Conditions: Osteopenia
Keywords: Low bone mass Post-menopausal women Bone mineral density Bone structure Bone turnover Bone-loading exercises calcium and vitamin D risedronate
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 276
Healthy volunteers: no

Brief summary:
The purpose of this study is to identify the best way to prevent bone loss in the first years after menopause. The HOPS study will compare bone loss at 12 months in women: 1) who take calcium and vitamin D only; 2) who take calcium and vitamin D plus the medication "risedronate"; or 3) who take calcium and vitamin D plus participate in bone-loading exercises. Our central hypothesis is that improvements in bone health will be greater in women randomized to bone-loading exercises with calcium and vitamin D compared to women who take calcium and vitamin D only or women who take calcium and vitamin D plus risedronate.

Detailed description:
This randomized controlled trial (RCT) will compare changes after 12 months in bone structure, bone mineral density (BMD), and bone turnover in women with low bone mass who are within 5 years of menopause. Women will be randomized to one control and 2 treatment groups (n =103 per group): 1) calcium + vitamin D (CaD) alone (Control); 2) Bisphosphonate (BP) plus optimal CaD (Risedronate); and 3) a bone loading exercise program plus optimal CaD (Exercise). Our central hypothesis is that improvements in bone health will be greater in subjects randomized to the exercise group compared to subjects in either the control or risedronate groups. Specific Aims: Aims 1, 2, and 3 are to compare control, risedronate, and exercise group subjects on changes in bone structure at the tibia and hip (measured by pQCT and Hip Structural Analysis) (Aim 1) ; on changes in BMD at the total hip, femoral neck, and spine (Aim 2); and on changes in serum markers of bone formation and resorption (Aim 3). In addition, Aim 4 will explore relationships between adherence to exercise (% sessions attended) or adherence to risedronate (% pills taken) and changes in bone structure.

Arms:
arm 1: Women randomized to the control group will receive calcium and vitamin D intake for 12 months. Calcium intake will be determined by analyzing 3 day dietary intake of calcium at baseline and then prescribing calcium carbonate supplements to ensure women have \~1200 mg of calcium daily. Vitamin D intake will be determined using baseline measures of Serum 25 (OH) D. Subjects who have serum D levels of 30 ng/ml or greater will be prescribed 1,000 IU vitamin D3 daily; subjects with levels of 20-29 ng/ml will be prescribed 2,000 IU Vitamin D3; and subjects with levels of 10-19 ng/ml will be prescribed 3,000 IU Vitamin D3. arm 2: Subjects in the risedronate group will take 35 mg of the bisphosphonate "risedronate" weekly for 12 months plus CaD. They will be asked to follow the protocol for administration of risedronate including taking the medication upon arising in the morning with an 8 ounce glass of water, remaining upright for at least 30 minutes, and having no oral intake except water for at least 30 minutes. arm 3: Subjects in the exercise group will participate in bone-loading exercises three times weekly in addition to taking CaD for 12 months. Women will exercise at community Young Men's Christian Association's fitness centers (YMCA) and exercises will be monitored by on-site Exercise Trainers. Exercises will consist of high-impact weight-bearing exercises (jogging with weighted vests) and resistance exercises for upper and lower extremities. Progressive increases in weight loads will be prescribed to provide maximal strength gains.

Interventions: intervention 1: Calcium Carbonate intervention 2: Vitamin D3 intervention 3: Risedronate intervention 4: Bone-loading exercises
Intervention descriptions: intervention 1: Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement) intervention 2: Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml. intervention 3: Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group. intervention 4: Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs.

Protocol document:
Prot_SAP_000.pdf: 
Bone Loading Exercises versus Risedronate on Bone Health in Postmenopausal Women 
 
Manual of Operations 
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Bone Loading Exercises versus Risedronate on Bone Health in Postmenopausal Women 
NINR Protocol Number: 378-14-FB 
NINR Grant Number: 
Principal Investigator: Nancy Waltman PhD, APRN-NP & Laura Bilek PhD, PT 
NINR Program Official:  Lynn Hardy 
 


Bone Loading Exercises versus Risedronate on Bone Health in Postmenopausal Women 
 
Manual of Operations 
Revised: 17 June 2015 
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TABLE OF CONTENTS 
{This table uses the Table of Contents function in Microsoft Word that will automatically update 
headings and page numbers used in the body of the report.  To update the Table of Contents and all 
cross-references in the document, press CTRL-A to select the entire document, then press F9.} 
PAGE 
TABLE OF CONTENTS ............................................................................................................... I 
LIST OF ABBREVIATIONS ........................................................................................................ III 
PROTOCOL SUMMARY ............................................................................................................ V 
1 
KEY ROLES AND CONTACT INFORMATION ................................................................... 9 
2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ....... 12 
2.1 
Background Information ........................................................................................ 12 
2.2 
Rationale .............................................................................................................. 12 
2.3 
Potential Risks and Benefits ................................................................................. 15 
2.3.1 
Potential Risks .......................................................................................... 15 
Risk of calcium supplementation. .......................................................................... 16 
2.3.2 Potential Benefits ......................................................................................... 18 
3 
OBJECTIVES ................................................................................................................... 19 
3.1 
Study Objectives ................................................................................................... 19 
3.2 
Study Outcome Measures .................................................................................... 19 
3.2.1 
Primary ...................................................................................................... 19 
3.2.2 
Secondary ................................................................................................. 20 
4 
STUDY DESIGN .............................................................................................................. 21 
5 
STUDY ENROLLMENT AND WITHDRAWAL .................................................................. 22 
5.1 
Subject Inclusion Criteria ...................................................................................... 22 
5.2 
Subject Exclusion Criteria ..................................................................................... 22 
5.3 
Treatment Assignment Procedures ....................................................................... 23 
5.4 
Subject Withdrawal ............................................................................................... 23 
5.4.1 
Reasons for Withdrawal ............................................................................ 23 
5.4.2 
Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention ............................................................................................... 23 
5.5 
Premature Termination or Suspension of Study .................................................... 23 
6 
STUDY INTERVENTION .................................................................................................. 24 
6.1 
Intervention(s) Description .................................................................................... 24 
6.2 
Administration of Intervention ................................................................................ 24 
6.3 
Intervention Fidelity and Assessment of Compliance ............................................ 28 
6.4 
Study Schedule ..................................................................................................... 28 
6.4.1 
Prescreening ............................................................................................. 28 
6.4.2 
Screening Visit .......................................................................................... 29 
6.4.3 
After Screening Visit .................................................................................. 31 
6.4.4 
Enrollment/Baseline .................................................................................. 31 


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6.4.5 
After Enrollment Visit ................................................................................. 34 
6.4.6 
Intermediate Visits ..................................................................................... 34 
7 
STUDY PROCEDURES /EVALUATIONS ........................................................................ 35 
7.1 
Study Procedures ................................................................................................. 35 
7.2 
Laboratory Procedures/Evaluations ...................................................................... 35 
7.2.1 
Clinical Laboratory Evaluations ................................................................. 35 
7.2.2 
Special Assays or Procedures ................................................................... 35 
7.2.3 
Specimen Preparation, Handling, and Storage .......................................... 35 
8 
ASSESSMENT OF SAFETY ............................................................................................ 37 
8.1.1 
Data .......................................................................................................... 37 
8.1.2 
Adverse Events ......................................................................................... 37 
STUDY OVERSIGHT ................................................................................................................ 38 
9 
CLINICAL SITE MONITORING ........................................................................................ 39 
10 
DATA ENTRY/STATISTICAL CONSIDERATIONS .......................................................... 40 
10.1 
Data Entry ............................................................................................................. 40 
10.2 
Sample Size Considerations ................................................................................. 40 
10.3 
Final Analysis Plan ............................................................................................... 40 
11 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................. 42 
DATA HANDLING AND RECORD KEEPING............................................................................ 43 
12 
LITERATURE REFERENCES .......................................................................................... 44 
APPENDICES ........................................................................................................................... 45 
APPENDIX B: PROTOCOLS .................................................................................................... 46 
APPENDIX B: FORMS .............................................................................................................. 51 
APPENDIX C: PACKETS .......................................................................................................... 56 
 


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LIST OF ABBREVIATIONS 
AE 
Adverse Events 
BCS 
Breast Cancer Survivor 
BMD 
Bone Mineral Density 
BSI 
Bone Strength Index 
BW 
Body Weight 
Ca 
Calcium 
CaD 
Calcium + Vitamin D 
CITI 
Collaborative Institutional Training Initiative 
CCORDA 
The College of Public Health and Center for Collaboration on Research Design 
and Analysis 
CLIA 
Clinical Laboratory Improvement Amendments 
CON 
College of Nursing 
CRC 
Clinical Research Center 
CSA 
Cross-Sectional Area 
CU 
Creighton University 
D 
Vitamin D 
DSCM 
Data and Safety Monitoring Committee 
DXA 
Dual Energy Absorptiometry 
ELISA 
Enzyme-Linked Immunosorbent Assay 
ET 
Exercise Trainer 
FRAX 
Fracture Risk Assessment 
FSH 
Follicle-Stimulating Hormone 
FQHC 
Federally Qualified Health Center 
HSA 
Hip Structural Analysis 
IA 
Iowa 
M 
Month 
N 
Number (typically refers to subjects) 
NE 
Nebraska 
NIH 
National Institute of Health 
NINR 
National Institute of Nursing Research 
NOCCC 
North Omaha Community Care Council 
NOF 
National Osteoporosis Foundation 
NTx 
N-terminal Telopeptide  


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ONJ 
Osteonecrosis of the Jaw 
ORC 
Osteoporosis Research Center 
PARQ 
PHC 
Physical Activity Readiness Questionnaire  
People’s Health Center 
pQTC 
Peripheral Quantitative Computed Tomography 
PI 
Principal Investigator 
PTH 
Parathyroid Hormone 
QCT 
Quantitative Computed Tomography 
RA 
Research Assistant 
RCT 
Randomized Controlled Trial 
RedCAP 
Research Electronic Data Capture 
Reps 
Repetitions 
RET 
Research Exercise Trainer 
RM 
Repetition Maximum 
RM-ANOVA 
Repeated Measures Analysis of Variance 
RN 
Research Nurse 
ROM 
Range of Motion 
RPE 
Rate of Perceived Exertion 
RSF 
Research Support Fund 
SAHP 
School of Allied Health Professionals 
SOCCC 
South Omaha Community Care Council 
ST 
Strength/Weight Training 
Steps 
Steps each leg 
TNMC 
The Nebraska Medical Center 
TSH 
Thyroid Stimulating Hormone 
UL 
Upper Limit 
UNMC 
University of Nebraska Medical Center 
US 
United States 
VCF 
Vertebral Compression Fracture 
Y 
YMCA 
 
 
 


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PROTOCOL SUMMARY 
Title: 
Bone Loading Exercises versus Risedronate on Bone Health in 
Postmenopausal Women 
Study moniker: 
Heartland Osteoporosis Prevention Study (HOPS) 
Précis: 
This stratified random study will compare 
changes in bone strength (bone structure, formation, and bone mineral 
density) at the hip and spine in women who take 12 months of either: 1) 
optimal calcium and vitamin D alone; 2) the bisphosphonate “risedronate” 
with calcium and vitamin D; or 3) a bone-loading exercise program with 
calcium and vitamin D. 
Objectives: 
 
Our long-term goal is to contribute development of clinical practice 
guidelines for the promotion of bone health in postmenopausal women 
with low bone mass, thus reducing the personal and societal burden of 
osteoporotic-related fractures. 
Specific Aims:  
Aim1: To compare Control, Risedronate, and Exercise group subjects on 
changes in bone structure at the tibia (bone strength index [BSI]: pQCT) 
and hip (femoral neck and shaft, intertrochanteric) (hip structural analysis: 
[HSA: DXA]) at baseline, 6, 12 months.  
 
Aim2. To compare Control, Risedronate, and Exercise group subjects on 
changes in BMD at the total hip, femoral neck, and spine (DXA) at baseline, 
6, 12 months.  
 
Aim3: To compare Control, Risedronate, and Exercise group subjects on 
changes in bone formation and resorption at baseline, 6, 12 months. 
(formation: AlkphaseB, resorption: Serum NTx). 
 
Aim4: To explore relationships between adherence to exercise (%sessions 
attended) or adherence to risedronate (% pills taken) and changes in bone 
structure at the tibia (BSI) and hip (HSA). 
Population: 
 
A total of N = 246 subjects are needed to achieve the proposed objectives. 
The subjects will be randomized and evenly allocated across three groups. 
In order to account for a realistic amount of attrition (20%), N = 309 
participants will be recruited for this study so that at least N = 246 should 
be retained if 20% of participants do not complete the study. In order to 
enroll 309 participants who meet criteria for the study, we are expecting 
to screen 900 women for eligibility.  
All subjects must: a) be women who are in their first 5 years of menopause 
(Menopause will be defined as either not having had a menstrual period in 
12 months or having had both ovaries removed. In addition, FSH testing 
will be conducted on women who are unsure of their menopause status); 
b) weigh 300 pounds or less; c) not use medications or have diagnoses that 


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would interact with the individual’s ability to adhere or safely complete 
any of the study components; d) have a T score between 1 and -2.49 at the 
femoral neck, total hip, or L1-L4 spine skeletal sites as measured by Dual 
Energy Absorptiometry (DXA); f) be 19 years of age or older; and g) have 
their health care providers permission to enroll in the study. 
Number of Sites: 
Intervention implementation and data collection will take place at the 
following sites: 
• 
University of Nebraska Medical Center  
• 
The Nebraska Medical Center  
• 
Creighton University Medical Center, Osteoporosis Research 
Center  
• 
Omaha, Lincoln, and Council Bluffs-based YMCAs 
Additionally, we will be contacting large organizations in Omaha, such as 
Mutual of Omaha, as well as community centers, medical facilities, etc. to 
determine interest in advertising this research study at their facilities. 
Therefore, information for recruitment purposes will be available to 
potential subjects at entities which choose to advertise information about 
the Heartland Osteoporosis Research Study. 
Description of  
Intervention: 
This proposed study has a randomized 3-group (2 treatment groups & 1 
control group), repeated measures experimental design.  
A computer generated code will be used to stratify subjects by exercise at 
baseline and then randomized to 3 groups (Control: n =103; Risedronate: n 
=103; Exercise: n =103) with assignments placed in sealed opaque 
envelopes for sequential use. All subjects will take dosages of calcium 
citrate supplements sufficient to ensure their total daily calcium 
(diet+supplements) is ~ 1200 mg daily and vitamin D3 supplements with 
daily dose to ensure serum levels of vitamin D [25 (OH)D] are between 30 
ng/mL and 80 ng/mL(optimal CaD). Subjects randomized to the 
Risedronate group will take optimal CaD daily and 150mg of oral 
risedronate once monthly for 12 months but will not participate in the 
exercise program. Subjects randomized to the Exercise group will take 
optimal CaD and also participate in 12 months of a bone-loading exercise 
program three times weekly at a local community-based YMCA (Y). To 
ensure the bone outcomes were not due to the CaD supplementation, a 
group taking only optimal CaD will serve as a control. While only women in 
the exercise group will participate in the structured bone-loading exercise 
program developed for this study, all women will be encouraged to 
participate in exercises and will be informed of the benefit of weight 
bearing and resistance exercises. The primary outcome will be bone 
structure at the tibia and hip and secondary outcomes are bone mineral 
density (BMD) and bone turnover. Repeated measures of primary and 
secondary outcome variables will be conducted at baseline, 6 and 12 
months to better understand response to intervention components with a 


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maximum difference expected at 12 months. An exercise intervention 
lasting 12 months or 2 to 3 bone turnover (resorption / formation) cycles is 
necessary in order to measure the effects of training on bone outcomes. 
Study Duration: 
Time from subject enrollment to completion of analysis is 4 years and 6 
months.  
Subject Participation 
Duration: 
Each subject will be asked to participate in the study for a total of 12 
months. 
Estimated Time to 
Complete Enrollment: 
Study enrollment will begin in Year 1, month 6 and continue through Year 
4, month 9. 


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SCHEMATIC OF STUDY DESIGN: 
 
See Protocol 1.Timeline for Data Collection, for details regarding collection of specific measures 
 
 
 
Prior to  
Enrollment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline 
 
 
 
3 months  
 
 
 
6 months 
 
 
 
12 months 
 
 
 
Prescreening: Prescreening form and PARQ 
Screening:  
Eligibility assessed by tests performed in the following order: 1) DXA; 2) laboratory analysis 
of CBC, serum vitamin D, calcium, creatinine, parathyroid hormone. Analysis of follicle stimulating 
hormone and/or thyroid stimulating hormone performed if necessary (See Section 7.1); 3) Fracture 
Risk Assessment; 4) Provider permission for participation  
Perform baseline assessments  
 
Post-Intervention assessments of outcome measures and safety 
Follow-up assessment of baseline outcome measures and safety 
Randomize 
Optimal CaD + 
Exercise  
N=103  
Optimal Calcium 
& vitamin D (CaD)  
N=103  
Assessments of subject compliance and evaluation of supplement dose  
 
Optimal CaD + 
Risedronate 
N= 103  


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1 KEY ROLES AND CONTACT INFORMATION 
Principal Investigator 
(PI):   
Nancy Waltman PhD, APRNNP 
Professor 
UNMC College of Nursing 
1230 0 Street, Suite 131 
PO Box 880220 
Lincoln, NE 68588-0220 
Work Phone: (402) 472-7354 
Cell Phone: (02) 613-4188 
Email: nwaltman@unmc.edu 
 
Laura Bilek PhD, PT 
Associate Professor 
Division of Physical Therapy Education 
Co-Chair, MSIA Graduate Program 
University of Nebraska Medical Center 
Omaha, NE 
Work Phone: (402) 559-6923 
Cell Phone: (402) 690-3524 
Email: lbilek@unmc.edu 
Secondary 
Investigators:  
Diane Cullen, PhD 
Email: dcullen@creighton.edu 
 
Joan Lappe, PhD, RN, FAAN 
Email: JoanLappe@creighton.edu  
 
Lynn Mack, MD 
Phone: 402-559-6208 
Pager: 402-888-2146 
Email: lmack@unmc.edu 
NINR Program 
Official:   
Lynn Hardy 
Institutions: 
 
 
 
 
 
 
 
 
 
 
Creighton University ORC 
 
UNMC, School of Allied Health Professions 
 
UNMC, College of Nursing—Lincoln Division 
 
 
YMCA:  
 
Council Bluffs YMCA 
YET: Ben Knauss 


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Institutions: (cont.) 
Phone: (712) 322-6606 
Email: bknauss@metroymca.org 
Supporting YET: Carrie McDonald 
Phone: (712) 322-6606 
 
Downtown YMCA 
YET: Dan Kohler 
Phone: (402) 301-8235 
Email: dkohler@metroymca.org 
Supporting YET: Stacey Centarri  
Phone: (402) 977-4303 
 
Maple Street YMCA 
YET: Susie Winegardner  
Phone: (402) 393-3700 
Email: swinegardner@metroymca.org 
Supporting YET:  Tara Brennan  
Phone: (402) 393-3700 
 
Sarpy YMCA 
YET: Theresa Lovings  
Phone: (402) 339-9861 
Email: tlovings@metroymca.org 
 
Southwest YMCA 
YET: Breann Lundblad 
Phone: (402) 334-8487 
Email: blundblad@metroymca.org 
 
Other Key Personnel: 
Project Coordinators: 
Meghan Langel 
Work Phone: (402) 559-6513 
Cell Phone: (515) 577-5329 
Email: meghan.langel@unmc.edu 
 
Melissa Meisinger 
Work Phone: (402) 559-5978 
Cell Phone: (402) 305-4809 
mel.meisinger@unmc.edu 
 
Margaret Begley 
Work Phone:  (402) 280-4578 
Email: mamb@creighton.edu 
 


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Creighton University ORC Clinic Supervisor: 
Jennifer Larsen 
Phone: (402) 280-4489 
Fax: (402)280-5173 
Email: JENNIFERLARSEN@creighton.edu 
 
Participating Personnel:  
Laura Krizan 
Email: LauraKrizan@creighton.edu 
 
Molly Lang 
Phone: (402) 559-6923 
Email: mslang@unmc.edu 
 
Kevin Kupzyk 
Phone: (402) 552-7262 
Email: Kevin.kupzyk@unmc.edu 
 
Ashlee Portelli-Trinidad 
Work Phone: (402) 559-6584 
Email: a.portellitrinidad@unmc.edu 
 


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2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE  
2.1 
Background Information 
Osteoporosis is a disease of fragile bones (decreased bone strength) and low bone mineral density 
(BMD). Approximately 18% of women with osteoporosis suffer a hip fracture and 22% die within a year 
of their fracture (1-3). Over 36 million post-menopausal American women have low bone mass (BMD T-
scores -1 to -2.49) which increases their risk for osteoporosis (BMD T-scores -2.50 or lower) (2). 
Improving bone strength and preventing further loss in BMD is critical in post-menopausal women with 
low bone mass as it is difficult to build significant bone without the influence of estrogen (4). 
Preventative treatments are especially important during the first five years post-menopause because 
women lose 2% of their BMD per year during this time. Calcium (Ca), vitamin D (D) and exercise are 
recommended for prevention of osteoporosis (5) and bisphosphonates (BPs) are prescribed to improve 
BMD in women with diagnosed osteoporosis (6). BPs may also be prescribed for women with low bone 
mass who are not yet osteoporotic, but are more controversial in this population due to the potential 
for adverse effects with their long-term use (7,8). Also, the best predictor of fracture is bone strength, 
and strength is determined by bone structure as well as BMD. While BPs are effective in improving bone 
density, findings on the effectiveness of BPs in improving bone structure are inconsistent (9). A bone 
loading exercise program (high-impact weight bearing and resistance training) promotes bone strength 
by improving bone structure and by promoting bone formation at sites of mechanical stress as well as by 
preserving BMD. This randomized controlled trial (RCT) will compare changes after 12 months in bone 
structure, BMD, and bone turnover in post-menopausal women with low bone mass randomized to one 
control and 2 treatment groups (N =103 per group): 1) optimal calcium + vitamin D (optimal CaD) alone 
(Control); 2) BP plus optimal CaD (Risedronate); and 3) a bone loading exercise program plus optimal 
CaD (Exercise). Bone-loading exercise programs for post-menopausal women with low bone mass may 
more effectively improve bone structure than either BPs or optimal CaD alone (9). Prescribing exercise 
programs and delaying use of BPs may prevent adverse effects from long-term use of BPs, and provide 
the opportunity for later use of BPs when they may be critically needed (8,15). Results of this study 
could be used in developing a clinical management pathway for women with low bone mass at their 
peak period of bone loss that would involve lifestyle modifications such as exercises prior to medications 
such as BPs. 
2.2 
Rationale 
Significance and Rationale for Sample Population. Osteoporosis and fractures result in significant 
morbidity and mortality in post-menopausal women with annual U.S. expenditures of approximately 
$19 billion (16-18). This problem will be even greater in the future, as the Surgeon General estimates the 
number of hip fractures in the United States could double or triple by the year 2040 (19). Our research 
aims to decrease the incidence of hip fractures by improving bone strength and preserving BMD in 
women with low bone mass (pre-osteoporotic) (20) during their first 5 years post menopause, a time of 
rapid and significant bone loss. 
 
Comparing Effectiveness of Exercise with BPs on Bone Strength. Calcium and vitamin D, exercise, and 
BPs are all used to address bone health in post-menopausal women. There is strong evidence that 
adequate CaD through dietary intake and/or supplementation are necessary to maintain bone health 
(21-26). Although CaD are more effective than no treatment, it frequently is not enough to prevent 


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progression of bone loss or to prevent osteoporosis. BPs such as risedronate are the medications of 
choice for treatment of post-menopausal osteoporosis, and studies have reported that use of 
risedronate attenuates the bone loss associated with menopause in osteoporotic women (27). BPs 
improve BMD by inhibiting bone resorption. However, long-term use of BPs can result in a freezing of 
bone resorption and turnover with significant accumulation of micro- damage in bone (28). This micro-
damage leads to increased risk of atypical hip and femur fractures (29-31). As a result, use of BPs in 
women with low bone mass is controversial, and providers are reluctant to prescribe BPs for greater 
than 5 years in women (32). Exercise programs combining resistance and high-impact weight bearing 
exercises can improve bone structure and increase bone formation at sites of mechanical stress (33) as 
well as maintain BMD. Participation in exercises improves the ratio of bone formation to resorption and 
improves bone structure by preserving trabecular and cortical structure, increasing thickness of cortical 
tissue, improving bone geometry and microarchitecture, and reorganizing bone collagen (34). Collagen 
reorganization during exercise maintains bone strength, even when BMD is decreased by as much as 
10% (34). Participation in exercises is not associated with freezing of bone turnover, and furthermore, 
exercise is associated with many other positive effects for post-menopausal women including increased 
insulin sensitivity, improved functional ability and decreased risk of falls and depression (35). If an 
effective exercise program could substitute for, or delay the use of BPs in post-menopausal women with 
low bone mass, not only would bone health improve through the lifespan, but women would benefit 
from the many other positive effects of exercise. 
 
Critical Need for Three Measures of Bone Strength. The gold standard for diagnosis of osteopenia and 
osteoporosis is BMD obtained from Dual Energy Absorptiometry (DXA) testing (36). However, the best 
predictor of fracture risk is bone strength. BMD is only one determinant of bone strength, and yet, most 
studies have relied on BMD as the sole measure for predicting fracture risk (37). Improved bone 
strength is a more realistic outcome for exercises than large increases in BMD (11). Greater increases in 
BMD have been reported with risedronate than with exercise in post-menopausal women. However, the 
magnitude of change in BMD may not equal the magnitude of change in fracture risk reduction. Marked 
reductions in fracture risk have been reported with small increases in BMD, likely because appropriate 
exercise training will improve bone strength as well as maintain BMD (38,39). 
This study will include three measures of bone status because the strength of bone depends not only on 
the amount of bone present (BMD) but also on bone structure or geometry and on positive bone 
turnover rates (ratio of bone formation to resorption) (40,41). Bone structure refers to the cortical and 
trabecular network of bone that is vital for maintaining maximum bone strength (10,42). Compared to 
pre-menopausal women, both cortical thickness and trabecular bone volume in post-menopausal 
women are substantially reduced (43). In the proposed study, bone structure will be measured at the 
tibia and hip (femoral neck and shaft, trochanter). Bone strength index (BSI), will be measured at the 4%, 
and 66% tibial sites using peripheral quantitative computed tomography (pQCT). BSI is based upon the 
total bone area, tissue density, bone porosity, and distribution or shape (moment of inertia) at that 
bone site and has been found to be a strong predictor of the torsion and bending strength of bones (9). 
Bone structure at the hip will be measured using Hip Structural Analysis (HSA) software and DXA testing 
(10). HSA measures the distribution of bone mass at the hip. The specific data collected includes the 
cross-sectional area [CSA] occupied by bone mineral, an index of bone strength against compression; 
section modulus [Z, mm3], an index of bone strength against bending; and centroid [mm], the distance 
from the center of the mass to the periphery (10,44). 


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Bone turnover is the process of removing old bone (resorption by osteoclasts) and replacing it with new 
bone (formation by osteoblasts) (40,41). In this study, resorption will be measured by Serum NTx 
(nmol/BCE/L) and formation by AlkphaseB (U/C). One remodeling cycle of resorption and formation 
takes up to six months with maybe 5-15% of total bone mass replaced per year. Menopause results in a 
brief period (~5 years) of accelerated turnover with resorption far exceeding formation (45). Increased 
resorption will result in bone loss. With exercise, there is new bone formation in areas of mechanical 
strain resulting in bones with greater bending strength in those regions (46). While weakening 
mechanical properties of bone (such as decreased bending strength) are possible with long-term use of 
BPs (>5 years) (29-31,47), long-term participation in targeted exercise training continually improves 
mechanical properties of bone over time. This provides the rationale for the comprehensive 
examination of bone (bone structure, BMD, and bone turnover) proposed in the study. 
This is one of few studies comparing the effectiveness of a bone-loading exercise program with BPs on 
bone strength. This is the first study to compare the efficacy of optimal CaD alone, or in combination 
with the BP, risedronate, or with combined resistance and weight-bearing exercises in improving bone 
structure and turnover and preserving BMD in women with low bone mass during the first 5 years post 
menopause. These comparisons are critical because they will determine whether standard practice 
should include a trial of lifestyle modification prior to BP prescriptions in this at risk population. Clinical 
management pathways for women who are at risk for other chronic illnesses such as hypertension or 
diabetes include trials of lifestyle modifications prior to prescriptions for medications. With the potential 
for adverse effects with long-term use of BPs and the potential bone strength benefits of exercise, 
studies should be conducted to determine if prescriptions for exercises are warranted prior to 
prescriptions for medications. 
 
This study will use a comprehensive evaluation of bone strength, bone structure, BMD and bone 
turnover- in comparing the efficacy of optimal CaD alone, with BPs, or with exercises. We believe that 
the impact of exercises on bone health has been underestimated because researchers have placed too 
much emphasis on BMD (48). 
 
This is the first study to optimize both calcium and vitamin D dosage. Our preliminary data and 
previous studies of others suggest that the efficacy of both BPs and exercises are improved with use of 
optimal CaD. Our results will provide more data on dosages of calcium required by post-menopausal 
women to supplement their dietary intakes, and dosages of vitamin D required for post-menopausal 
women to maintain serum levels at >30 ng/ml. 
 
Our results will provide more information on adherence to exercise in post-menopausal women with 
low bone mass and on use of cognitive/behavioral strategies including education, goal-setting, reducing 
barriers, and graphic feedback to promote adherence to exercise. 
 
This study was informed by findings on the efficacy of risedronate and resistance exercises in preserving 
BMD in post-menopausal women with low bone mass in our previous study, concerns about adverse 
effects with long-term use of BPs, the importance of other measures for bone health such as bone 
structure and turnover, studies reporting the high prevalence of vitamin D insufficiency in post-
menopausal women, and new information on the importance of optimal dose of vitamin D. 


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2.3 
Potential Risks and Benefits 
2.3.1 Potential Risks 
 
Risk of muscle soreness or injury with exercises. 
There may be temporary muscle soreness for up to two days following the initiation of, or increase in 
resistance training or bone loading exercises. Sudden forceful movements (seldom associated with 
progressive and monitored exercise programs) are the most common cause of musculoskeletal injury 
associated with exercise. In the previous RO1 study, some exercise subjects (< 10%) did complain of 
temporary muscle soreness with initiation of exercises or increase in weights lifted. If subjects 
complained of discomfort beyond the expected muscle soreness, exercises were not performed until the 
discomfort resolved. When subjects resumed exercises, they began with adapted exercises and lighter 
weights after another session with the YMCA Exercise Trainer (YET). No serious adverse effects occurred 
in the 110 subjects participating in exercises in the previous R01. 
 
Important precautions have been specified for this protocol to minimize and decrease the likelihood of 
any risk associated with the exercise program. Precautions include formulation of specific inclusion and 
exclusion criteria and monitoring of subjects for safe performance of exercises. In addition, the exercise 
program is initiated slowly and gradually, and the estimated 1 repetition maximum (1 RM) testing is not 
completed until week 2, providing the body time to acclimate to strength training before the max 
testing is performed. If subjects complain of discomfort or pain from the exercise program (more than 
the expected muscle soreness) the on-site YETs will seek consultation with the Research Exercise Trainer 
(RET) and Dr. Laura Bilek, Physical Therapist, and if necessary, refer subjects to their health care 
provider. The RET and Dr. Laura Bilek, PT, will make the decision to discontinue the exercise program 
after consulting with the health care provider and considering the desires of the subject. Generally, 
subjects will not discontinue exercises because of musculoskeletal problems, but this would be 
dependent on the nature and severity of the problem and the desires of the subject. If the 
musculoskeletal problem and/or persistent pain is/are not resolved, the subject may discontinue the 
exercise program. This subject will be considered off-protocol and will be asked to complete all tests and 
measurements as scheduled in alignment with intent-to-treat principles. 
 
If the problem and/or pain is/are resolved, subjects will be encouraged to resume the exercises. 
Subjects who are resuming their exercise program may need to begin with lighter weights, will need a 
consultation with the RET, and may require another supervised session with the RET and/or Dr. Bilek. 
 
Risk of cardiovascular events with exercises. 
There is a small risk of a cardiovascular event with exercise in persons with preexisting cardiovascular 
disease. The incidence of death during vigorous exercise in healthy adults is 1/15,000 to 18,000 per year. 
Exercise training is performed at a moderate intensity which has a much lower risk of cardiac events 
than vigorous exercise. 
 
The following precautions have been specified to reduce the infrequent risk of cardiovascular events 
with exercises: 


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• 
Subjects will be assessed for cardiac risk with the Physical Activity Readiness Questionnaire 
(PAR-Q) prior to study enrollment and those with high risk will be excluded from the study. 
• 
Approval from the health care provider is required prior to study enrollment 
• 
Study personnel (Research Project Coordinators (RPCs) or RET) will obtain blood pressures on all 
subjects at baseline, 6, and 12 months and will consult with the subjects provider for those with 
blood pressure greater than 140/90 
• 
RETs and on-site YETs will be CPR certified 
• 
All YMCAs are equipped with cardiac defibrillators 
No cardiovascular events occurred with women participating in exercises in the previous R01, and age 
range for subjects was 35 years to 75 years. 
 
Risk of fractures with exercises.  
Although the risk is much less than for patients with osteoporosis, patients with low bone mass are at 
increased risk of fracture, most notably, vertebral compression fracture (VCF). Movements most likely to 
precipitate a VCF are combined spinal flexion and rotation with load. So picking up a heavy object with 
one hand would be especially problematic. To minimize risk, we will: 
• 
minimize use of free weights and the need to lift heavy objects from the floor 
• 
use strength training machines that assist in stabilizing the body during the lifting motions 
• 
provide education on correct, upright posture during performance of all exercise to avoid 
loaded spinal flexion  
Risk of calcium supplementation. 
The Tolerable Upper Limit (UL) (highest level of daily intake of calcium from food, water and 
supplements that is likely to not pose any risks of adverse health effects for almost all of the general 
population) is currently established as greater than 2,500 mg per day. Risks of intake above the UL 
include hypercalcemia, impaired kidney function and decreased absorption of other minerals (iron, zinc, 
magnesium and phosphorus). Dietary intake of calcium will be monitored at baseline with the National 
Osteoporosis Foundation (NOF) Calcium Intake Estimate tool, and supplements will be prescribed to 
ensure subjects obtain approximately 1200 mg of total calcium (diet and supplements) daily which is 
well below the UL. In addition, serum calcium levels will be drawn at baseline. Kidney stones have 
occurred with high intakes of calcium, therefore, a daily fluid intake of at least 2,000 ccs will be 
encouraged. Participant will be counseled verbally and in writing not to take additional supplements of 
calcium beyond the study protocol to keep their intake below the UL. 
 
Risk of Vitamin D supplementation. 
Excessive amounts of vitamin D (D) can result in hypercalcemia. The current Recommended Daily 
Amount of D is 400-800 IU/day (or 2,800 to 5,600 per week), but studies have reported that D 
supplements of 4,000 IU per day are safe. In addition, subjects will be monitored for signs of D toxicity, 
i.e. hypercalcemia (nausea, vomiting, poor appetite, constipation, weakness and weight loss) at RPC 
visits throughout the study. At baseline, subjects will be prescribed optimal doses of D based on the 


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following protocol: Subjects who have serum D levels at 30 ng/ml or greater will be prescribed 1,000 IU 
daily; subjects with levels of 20-29 ng/ml will be prescribed 2,000 IU daily; and subjects with levels of 10-
19 ng/ml will be prescribed 3,000 IU daily. Subjects receiving 3,000 IU daily will have their serum levels 
rechecked at 3 months. Subjects will serum D level ≥ 60 ng/ml at screening will have levels rechecked at 
3 months, as well as calcium and albumin (calcium adjusted for albumin). All other subjects will have 
follow-up serum levels at 6 months. 
Participants will be counseled verbally and in writing not to take additional supplements of D beyond 
the study protocol to keep their intake below the UL. Subjects with a serum 25(OH) D level at baseline < 
10 ng/ml will be excluded from the study and can reapply when their serum levels are within normal 
limits. Participants with serum vitamin D greater than 60ng/ml at the time of screening will have serum 
levels rechecked at 3 months as well as analysis of serum calcium adjusted for albumin. If substantive 
problems occur related to administration of calcium or D or if serum levels of D elevate beyond 
acceptable levels, subjects will be asked to discontinue the supplements and will be referred to their 
health care provider for recommendation. 
 
Risk of risedronate. 
Reported adverse effects of BPs, including risedronate, are rare, but do include local damage to the 
mucous membrane, gastrointestinal bleeding, abdominal pain, perforating ulcers, vomiting, esophagitis, 
esophageal cancer, renal impairment at certain doses, severe bone, muscle, and joint pain, and atrial 
fibrillation (62). One serious adverse effect that was first reported with use of the BP zoledronic acid in 
high doses in cancer patients is osteonecrosis of the jaw (ONJ) (63).While short-term use of BPs is 
relatively safe for most women, the safety of long-term use of BPs (greater than five years) is unclear 
(64). The FDA recommends that providers be aware of a possible risk of atypical hip fractures in patients 
taking BPs long-term. 
 
To minimize adverse effects of risedronate, subjects will be instructed in the correct method for 
ingestion of the medication (upon arising in the morning with an 8 ounce glass of water or 2 hours after 
the last meal of the day, and subjects are to remain upright and have no oral intake except water for at 
least 30 minutes after taking risedronate). Serious side effects (recurring abdominal pain, gastritis, 
dysphagia or bone, joint, and muscle pain), will result in discontinuation of the drug. Subjects will be 
instructed to contact study personnel in the event of discomfort when taking this medication. RPC will 
confirm that the subject is taking medication as directed, and will ask Nancy Waltman PhD, APRN-NP or 
Jon Beck, Pharm.D to contact the participant if necessary. If the discomfort cannot be easily resolved, 
the subject will be referred to their health care provider for a decision on continuation of BPs. 
 
Risk of increased bone loss. 
Another concern is that postmenopausal women with low bone mass may experience more bone loss 
during the study and be at even greater risk for fractures (especially subjects in the control group). 
During the proposed study, DXA testing will be obtained at baseline 6, and 12 months, and all DXA 
results will be sent to the subjects' health care provider. If the subject has completed 6 months of the 
study and her BMD at the hip or spine has decreased to a T-score of -2.5 or below, the health care 
provider may decide to prescribe treatment with medications such as bisphosphonates. Subjects in the 
control or exercise groups who begin taking bisphosphonates during this study will be considered off-
protocol but will be asked to continue to participate in all testing for the study as scheduled. 
 


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PQCT and DXA testing. 
There is some radiation exposure with quantitative computed Tomography (QCT) testing, especially with 
axial QCT exams. Radiation doses received during a peripheral QCT (pQCT) exam (2.46 uSV) are much 
less than radiation dosages from axial QCT exams (30 60 uSV) or from radiation obtained annually from 
background radiation (2500 uSV). Risks associated with DXA bone density testing are minimal. DXAs are 
safe, non-invasive and painless. Subjects will have a DXA of the whole body at baseline, during which the 
subject is exposed to 20uSV, or a similar amount you would receive during a 2 hour airplane flight. 
Subjects will have a DXA of the hip and spine at 6 and 12 months, during which the subject is exposed to 
4.8uSV at each scan, or approximately 10% of the radiation required in a mammogram. 
 
Risks associated with obtaining blood and serum specimens. 
Risks from drawing blood are minimal with the most common being bruising or hematoma formation at 
the venous access site. This is minimized by proper technique and by the application of pressure at the 
site. A rare complication of obtaining serum specimens is infection at the venous access site. This is 
minimized with the use of sterile gloves, sterile needles, and antibacterial cleansing of the skin prior to 
the venipuncture. All venipuncture will be performed by experienced research nurses at the UNMC 
Clinical Research Center or trained study personnel to maintain quality, minimize variation in procedure 
and risk of infection. 
 
Risk of psychological discomfort. 
Risks associated with completing the questionnaires and journal include the potential for mild 
psychological stress related to questions on the forms. Subjects will be informed that they can refuse to 
answer any question that may be upsetting to them. 
 
Risk of loss of confidentiality. 
While not always possible, all measures will be taken to protect the subject’s identifiable and protected 
health information and research data. 
2.3.2 Potential Benefits 
Subjects may receive no benefits from participation in the study. No benefit is guaranteed. However, 
subjects with low bone mass who are at high risk of developing osteoporosis and osteoporotic fractures 
may improve bone structure and turnover and preserve BMD with optimal CaD alone, risedronate, or 
bone loading exercises. Subjects may benefit from receiving information on low bone mass and on 
effective interventions for improving bone health and prevention of osteoporosis 


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3 OBJECTIVES 
3.1 
Study Objectives 
Our long-term goal is to contribute to the development of clinical practice guidelines for the promotion 
of bone health in postmenopausal women with low bone mass. Our central hypothesis is that 
improvements in bone health will be greater in subjects randomized to the Exercise group compared to 
subjects in either the Control or Risedronate groups. 
Aim1: To compare Control, Risedronate, and Exercise group subjects on changes in bone structure at 
the tibia (bone strength index [BSI]: pQCT) and hip (femoral neck and shaft, intertrochanteric) 
(hipstructural analysis: [HSA: DXA]) at baseline, 6, 12 months. 
H1a: At 12 months, there will be significantly greater improvements in bone strength index (BSI) at the 
4% tibial site in Exercise subjects compared to subjects in either Risedronate or Control groups 
H1b: At 12 months, there will be significantly greater improvements in bone mass distribution (HSA; 
centroid, mm) at the femoral neck in Exercise subjects compared to subjects in either Risedronate or 
Control groups 
 
Aim2. To compare Control, Risedronate, and Exercise group subjects on changes in BMD at the total 
hip, femoral neck, and spine (DXA) at baseline, 6, and 12 months. 
H2a: At 12 months, there will be significantly greater improvements in BMD at the total hip, femoral 
neck, and spine in Exercise and Risedronate subjects compared to subjects in the Control group 
H2b: At least 80% of subjects in both the Exercise and Risedronate groups will have preserved BMD at 
the total hip, femoral neck, and spine. 
 
Aim3: To compare Control, Risedronate, and Exercise group subjects on changes in bone formation 
and resorption at baseline, 6, 12 months. (formation: AlkphaseB, resorption: Serum NTx). 
H3a:At 12 months there will be significantly greater decreases in serum markers of bone resorption 
(Serum NTx) in subjects in the Exercise and Risedronate groups compared to subjects in the Control 
group 
H3b: At 12 months, mean Serum NTx levels for subjects in both Exercise and Risedronate groups will 
have decreased to levels considered at low risk for fracture (< 12.6 nmol BCE/L) 
H3c:At 12 months, there will be significantly greater improvements in serum markers of bone formation 
(Alkphase B) in Exercise subjects compared to subjects in either Control or Risedronate group subjects 
 
Aim4: To explore relationships between adherence to exercise (%sessions attended) or adherence to 
risedronate (% pills taken) and changes in bone structure at the tibia (BSI) and hip (HSA). 
3.2 
Study Outcome Measures 
3.2.1 
Primary 
 


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Bone structure will serve as the primary outcome for this study and will be measured using peripheral 
quantitative computed tomography (pQCT) and Hip Structural Analysis (HSA) at baseline, 6 and 12M. 
PQCT will measure bone strength index (BSI) at the 4% and 66% tibial sites. BSI is based upon the total 
bone area, tissue density, bone porosity, and distribution or shape (moment of inertia) at that bone site 
and has been found to be a strong predictor of the torsion and bending strength of bones.(9) Bone 
structure at the hip will be measured using HSA software and DXA testing.(10) HSA specifically measures 
the distribution of bone mass at the hip. The data collected includes the cross-sectional area (CSA) 
occupied by bone mineral, an index of bone strength against compression; section modulus (Z, mm3), an 
index of bone strength against bending; and centroid (mm), the distance from the center of the mass to 
the periphery.(10, 45)  
 
3.2.2 
Secondary 
Bone turnover and BMD will serve as secondary outcomes and will be measured at baseline 6 and 
12M. Bone turnover will be measured by Serum NTx (nM BCE) and AlkphaseB (ng/ml). BMD will be 
measured using DXA.   
 


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4 STUDY DESIGN 
 
This study has a stratified, randomized 3-group (2 treatment groups & 1 control group), repeated 
measures experimental design. A computer generated code will be used for randomization to 3 groups 
(Control: n =103; Risedronate: n =103; Exercise: n =103) with assignments placed in sealed opaque 
envelopes for sequential use. All subjects will take dosages of calcium citrate supplements sufficient to 
ensure their total daily calcium (diet+supplements) is ~ 1200 mg daily and vitamin D3 supplements with 
daily dose to ensure serum levels of vitamin D [25 (OH)D] are between 30 ng/mL and 80 ng/mL(optimal 
CaD). Subjects randomized to the Risedronate group will take optimal CaD daily and 150mg of oral 
risedronate once monthly for 12 months but will not participate in the exercise program. Subjects 
randomized to the Exercise group will take optimal CaD and also participate in 12 months of a bone-
loading exercise program three times weekly at a local community-based Y. To ensure the bone 
outcomes were not due to the CaD supplementation, a group taking only optimal CaD will serve as a 
control. We believe it would be unethical for women at risk for further bone loss to have restrictions in 
physical activity for 12 months. Thus, while only women in the exercise group will participate in the 
structured bone-loading exercise program developed for this study, all women will be encouraged to 
participate in exercises and will be informed of the benefit of weight bearing and resistance exercises. 
The primary outcome will be bone structure at the tibia and hip and secondary outcomes are BMD 
and bone turnover. Repeated measures of primary and secondary outcome variables will be conducted 
at baseline, 6 and 12 months to better understand response to intervention components with a 
maximum difference expected at 12 months. An exercise intervention lasting 12 months or 2 to 3 bone 
turnover (resorption / formation) cycles is necessary in order to measure the effects of training on bone 
outcome 


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5 STUDY ENROLLMENT AND WITHDRAWAL 
5.1 
Subject Inclusion Criteria 
All subjects must: a) be women who are in their first 6 years of menopause (Menopause will be defined 
as either not having had a menstrual period in 12 months or having had both ovaries removed. In 
addition, FSH testing will be conducted on potential participants who are unsure of their menopause 
status); b) have a T score between 1 and -2.49 at the femoral neck, total hip, or L1-L4 spine skeletal sites 
as measured by DXA; c) be 19 years of age or older; and d) have their health care providers permission 
to enroll in the study. 
5.2 
Subject Exclusion Criteria 
Subjects will be excluded if they: a) have a 10 yr probability of hip fracture > 3% or major fracture >20% 
based on results of the FRAX tool; b) are currently taking or have taken bisphosphonates within the past 
6 months, estrogen replacement therapy, drugs affecting bone such as tamoxifen or aromatase 
inhibitors; c) weigh >300 lbs; d) serum 25(OH)D < 10 ng/ml e) have Pagets disease, heart disease, 
uncontrolled hypertension, renal disease, chronic fatigue syndrome, herniated disc, severe peripheral 
neuropathy, severe osteoarthritis, severe acid reflux or other concomitant conditions that prohibit 
participation in exercises, risedronate therapy, or use of CaD supplements; or f) have a T score below -
2.49 at the femoral neck, total hip, or L1-L4 spine skeletal sites as measured by DXA 
In the event of abnormal lab values at screening, personnel will consult Dr. Lynn Mack on 
appropriateness and safety of participation in the main study.  
Strategies for Recruitment and Retention 
Recruitment fliers and other print materials (see relevant attached documents) will be placed in 
physician and/or practitioner offices and community centers, and the principal investigators, RPCs 
(research project coordinator), RET (Research Exercise Trainer), RA (research assistant), and minority 
recruiter will solicit subjects during group presentations. In addition, subjects will be recruited through 
newspaper, radio ads, billboards, on-campus "electronic boards", via the Creighton University ORC's 
mailing list (women who have indicated interest in participating in future research), website and 
Facebook page. The website and Facebook page will be developed upon initiation of the project. In 
addition, we will utilize products such as pens, t-shirts, tote bags, etc. for advertising. No information 
will be distributed for viewing by potential subjects without prior IRB approval. Potential subjects will be 
provided a phone number or email to notify RPCs of their interest in the study. They will be interviewed 
by telephone by study personnel. They will be screened for eligibility and provided more information 
about the screening and main studies. Participants can also be screened for eligibility electronically by 
accessing the study website. If they meet the criteria for the study a screening study consent form/main 
study consent form, an informational handout regarding the research study (see One Page Study 
Summary form), a copy of "What do I need to know before being in a research study", and "The rights of 
research subjects" will be sent to these potential subjects. After 1-2 weeks, the RPCs or one of the 
principal investigators will meet with the subject at a face-to-face visit, follow the procedure for 
informed consent, and the potential subject will then be asked to sign a screening consent form for lab 
and diagnostic testing. Subjects will not be allowed to sign the screening consent form unless it is 
determined they are aware of the basic requirements of the main study. 


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5.3 
Treatment Assignment Procedures 
 
A computer generated code will be used for randomization to 3 groups (Control:n =103; Risedronate: n 
=103; Exercise: n =103) with assignments placed in sealed opaque envelopes for sequential use. 
5.4 
Subject Withdrawal 
5.4.1 
Reasons for Withdrawal 
Subjects are free to withdraw from participation in the study at any time upon request. 
An investigator may terminate a study subject’s participation in the study if: 
• 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
subject.  
• 
Laboratory values change to where medication is now needed and subject no longer qualifies 
for the group they were randomly assigned to 
• 
Musculoskeletal problems and/or pain occur and it is no longer safe for subject to continue with 
exercise protocol 
 
5.4.2 
Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention 
If taken off protocol for whatever reason, we will still ask subjects to complete all tests and 
measurements as scheduled in alignment with intent-to-treat principles. There will be no extra attempt 
made to replace the subject as attrition is accounted for in the total number recruited and consented.  
5.5 
Premature Termination or Suspension of Study 
This study may be suspended or prematurely terminated if there is sufficient reasonable cause.  Written 
notification, documenting the reason for study suspension or termination, will be provided by the 
suspending or terminating party to sponsor and regulatory authorities.  If the study is prematurely 
terminated or suspended, the principal investigator will promptly inform the IRB and will provide the 
reason(s) for the termination or suspension.  
Circumstances that may warrant termination include, but are not limited to: 
• 
Less than 50 subjects are accrued for each group within the 42 month recruiting period. 
• 
>10% of the subjects develop serious adverse events related to optimal CaD, risedronate, ore 
exercises. 
• 
50% attrition of subjects in either group occurs including BMD T-scores falling below -2.5.  


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6 STUDY INTERVENTION 
6.1 
Intervention(s) Description 
 
All subjects will take dosages of calcium citrate supplements sufficient to ensure their total daily calcium 
(diet + supplements) is ~1200 mg daily and will take vitamin D3 supplements with daily dose dependent 
on their serum levels of vitamin D (25 [OH]D) (optimal CaD). Subjects randomized to the Risedronate 
group will take optimal CaD daily and 150 mg of oral risedronate once every 4 weeks for 12 months but 
will not participate in the exercise program. Subjects randomized to the Exercise group will take optimal 
CaD and also participate in 12 months of a bone-loading exercise program three times weekly at a local 
community-based Y. To ensure the bone outcomes were not due to the CaD supplementation, a group 
taking only optimal CaD will serve as a control. The primary outcome will be bone structure at the tibia 
and hip and secondary outcomes are BMD and bone turnover. Assessors of these variables will be 
blinded to subject group. Repeated measures of primary and secondary outcome variables will be 
conducted at baseline, 6 and 12 months to better understand response to intervention components 
with a maximum difference expected at 12 months. 
6.2 
Administration of Intervention 
 
Optimal CaD 
 
All subjects will take calcium citrate supplements daily to ensure total intake (dietary and supplement) is 
~1200 mg. For optimal bone health, serum vitamin D levels are equal to or > 30 ng/ml. In the proposed 
study, all subjects will be prescribed optimal doses of vitamin D based on their serum 25(OH) D levels 
with a goal of reaching optimal serum levels of 30 ng/ml. To determine the optimal dose of D, serum 25 
(OH)D measures will be obtained for all subjects at baseline. Subjects who have serum D levels at 30 
ng/ml or greater will be prescribed 1,000 IU daily; subjects with levels of 20-29 ng/ml will be prescribed 
2,000 IU daily; and subjects with levels of 10-19 ng/ml will be prescribed 3,000 IU daily. Subjects 
receiving 3,000 IU daily will have their serum levels rechecked at 3 months. Participants with serum 
vitamin D greater than 60ng/ml at the time of screening will have serum levels rechecked at 3 months as 
well as analysis of serum calcium adjusted for albumin. All other subjects will have follow-up serum 
levels at 6 months. Time periods for assessing serum D were chosen because studies have reported that 
with daily dosing of D, it may take three months for plateau serum levels to be reached. The serum D 
criteria pertain to all 3 treatment groups. Patients with serum levels < 10 ng/ml have severe D 
deficiency, will be excluded from the study, and referred to their health care provider for management. 
 
See Protocol 2. CaD Delivery_RPC Responsibilities 
 
Risedronate 
Risedronate is a pyridinyl bisphosphonate with potent anti-resorptive activity which is approved at 
various dosages for the prevention and treatment of post-menopausal osteoporosis. Risedronate 
subjects will take 150 mg of oral risedronate monthly plus optimal CaD. Study personnel will contact 
subjects monthly to remind them to take their risedronate tablet. The National Osteoporosis Foundation 
(NOF) recommends that BPs be prescribed for all patients with vertebral or hip fractures, femoral neck 


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or spine T-scores of <-2.5 (dx of osteoporosis), and a 10-year high risk probability of fracture based on 
results of the Fracture Risk Assessment (FRAX) tool). The FDA recommends that providers be aware of a 
possible risk of atypical hip fractures in patients taking BPs long-term. Discontinuation of BPs after five 
years of treatment is becoming a common practice, particularly for patients at low risk of fracture. 
 
See Protocol 3. Risedronate Delivery_RPC Responsibilities 
 
Medication Calendar Cards 
CaD tablets will be supplied in Medication Calendar cards and dispensed by The Nebraska Medical 
Center (TNMC) outpatient pharmacy to study personnel. Calendar cards will be stored in Dr. Bilek's lab, 
in a locked cabinet and distributed to subjects at 3-month intervals. Medication Calendar cards, each 
containing a four-week supply of Ca and a second card containing D, will be distributed via mail or in 
person. Subjects in the risedronate group will receive additional cards containing risedronate. The 
medication risedronate requires a prescription. Prescriptions for risedronate will be written by Lynn 
Mack, MD (who serves as supervising physician on the study), dispensed to study personnel by TNMC 
outpatient pharmacy, and mailed to subjects or delivered in person. Tablets will be secured in individual 
bubbles on the cards. Subjects will be instructed to take their risedronate tablet at a minimum of seven 
days prior to the next scheduled dose (see Form 1. Calendar Card Instructions ). All cards will be 
collected by study personnel or returned by postage paid mail after each 4-week period. In 
circumstances which a participant does not wish to take study supplements, and would like to continue 
taking their own, personnel will monitor their adherence to taking optimal levels of calcium and vitamin 
D through taking their own vitamins and/or supplements (see Form 2. Blank Calendar). 
 
Bone-Loading Exercise Program In the proposed study, exercise participants will receive CaD 
per protocol as described for the Risedronate and Control participants. In addition, exercise participants 
will participate in an exercise intervention consisting of 1) high impact weight bearing exercise such as 
jogging and 2) resistance exercises three times weekly for 12 months at a community-based YMCA (Y) 
(There are 8 Y's based in Omaha, NE, 3 in Lincoln, NE, and 1 in Council Bluffs, IA). Each session will 
include warm up and cool down exercises consisting of 5 minutes of slow walking. 
 
 
Resistance Exercise (see Form 3. HOPS Exercise Booklet_Revised for details) 
1) Upper Extremity Exercises - Push Exercises (2 sets each): horizontal press, overhead press. 
2) Upper Extremity Exercises - Pull Exercises (2 sets each): latissimus pull, sitting row. 
3) Lower Extremity Exercises: (2 sets each)  
Group A (first six months): leg press, knee curl, and *side lunge 
Group B (second six months): leg press, knee curl, and *forward lunge 
4) Core Exercises: (2 sets each) 
Group A (first six months): *pelvic tilt, *side bridge,*superman 
Group B (second six months): *supine bridge, *side bridge, *pelvic tilt  
 (*indicates exercises using body weight for resistance.) 
 


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Exercises should be completed as follows (see Form 3. HOPS Exercise Booklet_Revised): 
Participants will alternate between colored exercises, i.e. Red is Upper Body, Blue is Lower Body, and 
Green is Core to allow the participant an effective use of time and also meet the required 2 minute rest 
before performing the same exercise again. One day of recovery is required between exercise sessions. 
There is no set order that the exercises need to be completed in, as long as they are all completed and 
with 2 minutes of rest between the same exercises (see Protocol 4. First Exercise Session Explanation 
and Documentation) 
 Initial resistance during week 1 will be based upon % of body weight values for each machine 
weight exercise (Form 4. Starting Load Values Based Upon Body Weight) along with participant feedback 
using the Borg 
rate of perceived 
exertion (RPE) 
scale (see Form 
5. Borg RPE 
scale). For body 
weight exercises, 
the participant 
will start out 
with the basic 
exercises 
options where 
offered. This 
acclimation of 
the machine 
weight exercises 
will prepare the 
participant for 
the estimated 1 
RM testing that will occur during week 2. Week 2 will be used to determine loads for weight machines. 
Strength will be assessed by determining the maximum load that can be lifted for 9 or less repetitions 
with good form (Protocol 5. Estimating 1RM). 
Progression will be prescribed based on the 
participant’s estimated 1 RM value and the YET 
HOPS excel spreadsheet or progression tables 
(Protocol 6. YET HOPS Exercise Schedule or 
Protocol 7. Progression and Increase Parameters 
for Exercise). Reassessment of 1 RM will occur at 
6 months. The purpose of 1 RM reassessment is 
to validate that the intervention is resulting in 
physiologic change and to evaluate if the 
workload is at a therapeutic potential (goal: workload > 70%of 1RM). Participants will be encouraged to 
increase workload to > 70% of 1 RM with a goal of reaching a resistance which results in volitional 
fatigue at 8-12 reps. Volitional fatigue is defined as the point at which the load cannot be lifted correctly 
with any additional repetitions. For those exercises using body weight for resistance, load will be added 
using a weighted vest, an advanced movement, or increased hold time. Both resistance and repetitions 
will be increased over time to participant tolerance.  
Table 2.  Resistance Training with Weight Machines:  Exercise Progression 
Week/Month 
Resistance 
Repetitions 
Sets 
Week 1 
Self-selected 
Progress to 15 reps 
1 
Week 2 
40% 1 RM or self-selected from 
week 1 (whatever is greater) 
Progress to 15 reps 
2 
Weeks 3-6 
Increase 5-10% 1 RM/week 
10–15 reps 
Increase load when reps=15 
2 
Goal: 70% of 1 RM during Week 6-minimum therapeutic 
threshold for increasing BMD 
Week 7 - 12 
Increase ~ 2-5%/week until 
volitional fatigue at 8–12 reps 
Volitional fatigue at 8–12 
reps 
2 
Increase load when reps > 12 on 2 consecutive sessions 
Goal:  Maintain resistance between 70–85% 1 RM 
6 & 12 months 
Complete 1 RM testing 
Confirm load >70% 1 RM  
Increase if needed 
Volitional fatigue at 8–12 
reps 
2 
Table 3. Body Weight Resistance Training:   
Exercise Progression 
Week/Month 
Resistance* 
Sets 
Reps* 
Weeks 1-2 
0% BW 
1 
5-12 
Weeks 3-4 
0% BW 
2 
8-12 
Month 2 
1-2% BW 
2 
8-12 
Month 3 
2-5% BW 
2 
8-12 
Month 4-12 
5-10% BW 
2 
8-12 
Increase load (% BW) when reps >12 on 2 consecutive sessions 
*BW=Body Weight; Reps=Repetitions 


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Impact Exercise-Jogging.  
In addition to resistance exercise, the exercise intervention will include high impact, weight bearing 
exercises with high ground reaction forces to promote bone remodeling. Participants will walk around a 
track, or any other open space, interspersed with short periods of jogging. After walking for 20-30 
seconds, participants will jog the prescribed number of steps and then return to walking. To avoid 
working at a vigorous intensity, participants will continue walking until they reach an RPE at or below 11 
on the Borg RPE scale provided. (see Protocol 8. Impact 
Jogging) 
To promote optimal performance, participants will be 
provided the Form 3. HOPS Exercise Booklet_Revised 
and Form 8. Exercise Log_Revised. The booklet will 
include detailed written and visual supportive 
instructions for each exercise including specific 
prescribed exercise session parameters to guide the 
participants. The exercise log applies corresponding 
colors to associate exercises with those in the booklet. 
The exercise log will also be a tool used  to detail the 
prescribed resistance, repetitions, sets, and steps to assure the participant is meeting  the goals set forth 
for them by the study. 
To promote optimal adherence and therapeutic potential of workload, a graphic feedback sheet will be 
provided to the participant (see Protocol 9. Graphic Feedback). The graphic feedback sheet will display 
graphs of the individual’s prior performance relative to study goals in order to improve adherence. For 
statistical analysis, adherence will be defined as the % training sessions attended; this will be calculated 
using the participant logs, which will be validated by Y electronic entrance documentation. 
Exercise participants can perform exercises at the Ys at any time during operating hours regardless of 
whether one of the study’s on-site YET coordinators are present (Protocol 10. Exercise Trainer Oversight 
Schedule_Revised). Even when YET coordinators are not present, other exercise specialists at the Y will 
always be present to answer general exercise questions or assist if problems arise with the exercise 
equipment.  
 
All exercises will be performed at a Y under the direction of Y exercise trainers (YETs) (see Form 10. 
YMCA Contact  Sheet for Participants_Version 3, Form 11. Availability of YETs). On-site YETs will 
communicate with each exercise participant every two weeks during the 12-month study, completing 
the Form 12. YET Documentation Form at each time of contact (see Protocol 11.Storing Exercise Docs at 
YMCAs). Communication between the RET and YET will be ongoing and will occur at specific, along with 
intermittent, times during the study. The RET and YET’s will also collectively use strategies regarding 
participant adherence to the exercise program (see Protocol 12.Addressing Missing Exercise Session, 
Adherence, Protocol 13. Addressing Continued Exercise Non-Compliance, Protocol 14. Exercise 
Group_Addressing Withdrawn or Off-Protocol Participants, Protocol 15. Exercise Group_Addressing 
Problems on YET Doc Form, Protocol 16. Using Barrier Intervention Strategies). 
During the 12-month study, the RET will visit on-site YET coordinators every two months and will 
monitor their performance. Coupled with orienting all Y staff members and providing additional in-
Table 4. Impact Jogging Progression 
Week/Month 
Resistance* 
Sets 
Steps* 
Weeks 1-2 
0% BW 
3-5 
4-6 
Weeks 3-4 
0% BW 
5-10 
6 
Month 2 
0% BW 
7-10 
6-10 
Month 3 
1-3% BW 
10 
6-10 
Month 4-5 
3-5% BW 
10 
6-10 
Month 6-8 
5-7% BW 
10 
6-10 
Month 9-12 
7-10% BW 
10 
6-10 
*BW=Body Weight; Steps=Steps Each Leg 


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depth training and supervision for on-site YET coordinators, the RET will be responsible for conducting 
the initial exercise participants training sessions during their first Y visit, performing the estimated 1RM 
testing, and helping maintain fidelity of the exercise intervention (see Protocol 10. Exercise Trainer 
Oversight Schedule_Revised 
Protocol 11.Storing Exercise Docs at YMCAs 
Protocol 12.Addressing Missing Exercise Session, Adherence 
Protocol 13. Addressing Continued Exercise Non-Compliance 
Protocol 14. Exercise Group_Addressing Withdrawn or Off-Protocol Participants 
Protocol 15. Exercise Group_Addressing Problems on YET Doc Form 
Protocol 16. Using Barrier Intervention Strategies 
Protocol 17. RET Protocol for YMCA Exercise Sessions by Visit 
Protocol 18. Scheduling YET Visits 
Protocol 19. Storing Scanned-In Exercise Documents 
  
6.3 
Intervention Fidelity and Assessment of Compliance  
 
Low adherence rates to exercises, risedronate, and CaD would impact fidelity of intervention 
components and limit generalizability of study results. 
According to Bandura, adherence is related to "task and barrier self-efficacy". Task self-efficacy is 
subject’s confidence in their ability to perform interventions such as exercises, and barrier self-efficacy is 
subjects confidence in their ability to overcome barriers to interventions. We will promote task and 
barrier self-efficacy through subject education, goal setting, reducing barriers, and by providing graphic 
feedback on goal achievements.  
Feedback sheets will be provided to subjects to demonstrate progress over time in adherence to 
interventions, 1RM measures, weight loads for exercises, and BMD. Scripts will be provided for assisting 
with goal-setting and reducing barriers to promote standardization across sites. Strategies for reducing 
barriers to adherence to exercises will be tailored to subjects based on their scores on the Barriers 
Interference instrument. 
 
6.4 
Study Schedule  
6.4.1 
Prescreening  
 
Potential subjects will be asked to respond to questions on the screening criteria form and Physical 
Activity Readiness Questionnaire (PARQ) either over the phone or electronically via our study website 
(see Form 1. Calendar Card Instructions Form 13. Prescreening Questionnaire.Web_Revised; Form 
14. Prescreening Qurestionnaire.Verbal_Revised see Protocol 20. Prescreening script). Use Protocol 21. 
Prescreening Procedure to guide this process. If potential subjects meet initial inclusion criteria, they will 
be mailed a packet of information including: current consent forms, Form 15. One Page Study 
Summary_3 , Form 16. What to Expect at your DXA, Form 17. Directions to CUMC ; for printing purposes 


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use Packet 1. Block Scheduled Screening Participant. Upon review of these forms, the potential subject 
will be scheduled to meet face to face to complete the Screening Consent Form at either the Creighton 
Osteoporosis Research Center or at UNMC (see Protocol 22. Steps to Take Prior to Screening Visit.  
6.4.2 
Screening Visit  
Reference Protocol 23. Block Screening Meeting and section below to conduct visit. 
 
To print the forms needed for completion of a screening visit, print Packet 2. Screening Visit. 
1. Participant arrives or ORC and is directed to waiting room for HOPS study. 
 
2. Immediately upon arrival, look in Screening Binder to identify the individual’s ID# and assigned 
RPC. Mark the participant’s folder and Form 18. Screening Visit Checklist with ID#, and use 
highlighter to mark folder tab with assigned RPC’s color.  
 
3. Step 1: Completion of Screening Consent  
a. RPC or Investigator greets the participant and reviews the consent form according to 
screening checklist and protocol (see Form 19. Screening Consent; see Form 18. 
Screening Visit Checklist) 
b. Screener signs Screening Consent form indicating informed consent. RPC or Investigator 
will sign as well.  
i. If participant decides they do not want to participate they are thanked for their 
time and may leave.  
4. Step 2: DXA 
a. HOPS personnel will walk participant down to ORC and let staff know that the 
participant is ready for their DXA.  
b. Hand Form 18. Screening Visit Checklist to participant or staff member. ORC staff will 
gather height, weight, and waist circumference while the participant is in the ORC 
completing their DXA and they will record this data on our Checklist. 
c. ORC personnel will complete DXA scan and record total Hip and lumber spine BMD, T-
scores. 
d. While participant is completing DXA, double check that all pages of the consent have 
been initialed (including signature page and last page!) and make a photocopy using the 
copy machine in the ORC. 
i. We keep the original document. Place the copy in a folder for the participant. 
e. After the DXA, the ORC personnel will direct participant back to the HOPS waiting room.  
f. Once results of DXA are generated ORC personnel will bring results of DXA to HOPS 
personnel  
i. ORC will provide an original and a copy. Place the copy in the participant’s folder 
and the original in our folder.  
5. Step 3: Questionnaires  
a. Whiel the participant is completing the DXA, personnel should open RedCap on the Ipad 
and assign an ID# according to the Protocol 24. RedCap Data Entry 
b. After returning from their DXA, the participant will complete the following 
questionnaires in RedCap according to the protocol on data entry: Form 20. 


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Osteoporosis Knowledge Test Revised (*must be 1st questionnaire), Form 21. 
Demographic Profile , Form 22. FRAX, Form 23. Screening Participants Contact 
Information Form_Revised , Form 24. Human Activity Profile Test (HAP) and Form 25. 
International Physical Activity Questionnaire (IPAQ)(see Protocol 25. Administering 
Osteo Knowledge Test ; Protocol 26. Administering FRAX;Protocol 27. Administering HAP 
Questionnaire; Protocol 28. Administering IPAQ 
6. Step 4: Reporting DXA Results  
a. Using the Form 26. Bone Mineral Density Report, report DXA results to participant.  
i. If DXA results indicate that the participant has either normal bone density, or 
that they are osteoporotic, inform participant that they do not qualify for HOPS  
E. Provide Form 27. Calcium FAQ, Form 28. Vitamin D FAQ, and Form 29. 
Osteoporosis Pamphlet 
F. If the screener is osteoporotic, HOPS personnel can refer them to a 
provider for follow up using the Protocol 29. Referral for Osteoporotic 
Screeners.  
G. Provide a flyer or two and ask participant to help spread the word about 
HOPS to friends and family.  
H. The participant is now finished and may leave.  
b. If the DXA shows that she has low bone mass (T score between-1 and -2.49), but not yet 
osteoporosis (T score < -2.5), the screening subject will be informed that they qualify for 
the next stage of screening, which includes a blood draw and blood pressure check. 
c. Confirm that screener wants to proceed with the next stage of screening and complete 
tasks outlined in #7: Step 5, immediately below.  
7. Step 5: Blood Draw, BP, and concluding visit:  
a. If the screener needs to have their blood drawn at the CRC: 
i. Take blood pressure using Protocol 30. Checking Resting Blood Pressure as a 
guide. Record results on Checklist. 
ii. Discuss an approximate date/time for blood draw so that we know when to 
expect communication from the CRC.  
iii. Hand them the following forms: Form 30. CRC Qualification, Form 31. CRC 
Directions with Map, Form 32. Further Questions Contact Sheet_Revised and 
Form 29. Osteoporosis Pamphlet 
iv. Inform participant that we will contact them once we receive the results of their 
lab work, and at that point, will send a letter to their provider regarding 
participation in HOPS (see Form 33. Provider Permission Letter_4).  
v. Allow participant to leave. 
vi. HOPS personnel should proceed with ordering blood draw by following the 
appropriate scenario in Protocol 31. Ordering Blood Draw 
b. If the screener has blood drawn on site at the Creighton ORC: 
i. Take blood pressure using Protocol 30. Checking Resting Blood Pressure as a 
guide. Record results on Checklist. 
ii. Blood draw performed by either Meghan or Ashlee  
E. Meghan and Ashlee are trained to perform phlebotomy and transport 
specimens, and will follow Protocol 32. Blood Draw Procedure, and 
Protocol 33. Blood Transportation Protocol, when performing 
venipuncture, labeling tubes, and transporting back to the TNMC lab 


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iii. If participant has questions or concerns about participation in HOPS, provide the 
Form 32. Further Questions Contact Sheet_Revised and Form 29. Osteoporosis 
Pamphlet, and advise that they contact one of the PIs before their enrollment 
visit  
iv. Inform participant that we will contact them once we receive the results of their 
lab work, and at that point, will send a letter to their provider regarding 
participation in HOPS (see Form 33. Provider Permission Letter_4).  
6.4.3 
After Screening Visit  
If the screener was not qualified, follow the Protocol 34. Steps to Take After Screening Visit to complete 
follow up paperwork.  
If the screener has qualified, the following tasks need completed after the screening consent visit:  
1. An order for analysis of the sample will need to be placed in One Chart immediately after the 
screening visit (or during screening consent visit, if personnel are able to remote in to their 
desktop). Use Protocol 35. Ordering Blood Tests in One Chart and Enrolling Participant. ***An 
order needs to be placed before any specimens are taken to the lab.  
2.  HOPS personnel will take one SST (gold top), one PST (green top), and one purple top tube to 
the TNMC lab. Personnel will keep one SST (gold top) tube and take it up to the lab to centrifuge 
and aliquot for storage (see Protocol 36. Blood Handling Procedure and Protocol 37. Serum NTx 
and Alkphase B Aliquot and Storage ).  
a. The following analyses will be performed using screening participants’ blood sample: 
CBC, serum vitamin D, serum calcium, serum creatinine, parathyroid hormone (PTH), 
follicle-stimulating hormone (FSH) if needed, and subjects diagnosed with a thyroid 
condition will also have a Thyroid Stimulating Hormone (TSH) test.  
b. At a later date, we will perform analysis of AlkphaseB, Serum NTx, and other soluble 
factors that may impact bone health (TBD), using the serum from the SST tube stored in 
Dr. Bilek’s -80 freezer.  
3. Immediately following this, or on the next business day, HOPS personnel should follow Protocol 
34. Steps to Take After Screening Visit to complete and/or initiate the remaining items that need 
completed for screening purposes, including verifying RedCap data, checking lab results, 
calculating FRAX, etc.  
4. If screening subjects remain eligible to participate after undergoing the steps listed above, study 
personnel will contact the individual's health care provider to request permission for the 
screening subject to participate in the Heartland Osteoporosis Prevention study (see Form 33. 
Provider Permission Letter_4; see Protocol 38. Sending Provider Permission Letter ) 
5. If permission is granted by the health care provider, the screening subject will be invited to 
enroll in the main study. The RPC schedules the participant for a time to come go to the ORC to 
fill out their main study consent, their PQCT, baseline questionnaires, and baseline education.  
6.4.4 
Enrollment/Baseline 
To print the forms needed for an enrollment visit, see Packet 3. Enrollment Visit Forms. All other forms 
needed for this visit are in RedCap. Checklists for this visit are printed and available at the ORC.   


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1. Complete process of informed consent to the Main Study (see Form 34. Main Study Consent; 
see Protocol 39. Main Study Consent Guidelines for Completion. ) 
2. Randomization: Open the next envelope (envelope on the “top” of the pile located in desk 
in HOPS office at ORC) and read treatment group out loud.  
3. Select the appropriate checklist (see Form 35. Enrollment Checklist Exercise, Form 36. 
Enrollment Checklist Control, Form 37. Enrollment Checklist Risedronate) 
4. Participant will complete Form 43. NOF Calcium Intake Estimate_Revised using paper and 
pencil (see Protocol 40. NOF Calcium Intake Calculator ) 
5. Walk the participant down to the ORC, where they will complete the PQCT. Leave study 
Checklist with the participant, so that the ORC personnel can initial that the Pqct has been 
completed. This scan takes approximately 5 minutes.  
6. During pQCT: 
1. Open RedCap complete the ID# assignment using Protocol 24. RedCap Data Entry 
(see also Packet 4. Control Group_All Enrollment Forms, Packet 5. Risedronate 
Group_All Enrollment Forms, Packet 6. Exercise Group_All Enrollment Forms, if you 
are using hard copy questionnaires).  
2. Locate appropriate Participant Manual (see Packet 7. Control Group_Participant 
Manual, Packet 8. Risedronate Group_Participant Manual, Packet 9. Exercise 
Group_Participant Manual). These are located in the ORC, although personnel will 
need to print copies of these periodically.  
 
Control Group Protocol: 
1. Participant Manual will contain the following: 
a. Form 15. One Page Study Summary_3 
b. Form 38. What is Osteoporosis 
c. Form 39. Exercise and Your Bones 
d. Form 40. Instructions for Calcium and Vitamin D 
e. Form 1. Calendar Card Instructions 
f. Form 41. Lexicomp Online Patient Education Cholecalciferol 
g. Form 42. Lexicomp Online Patient Education Calcium Citrate 
2. Participant will complete the Form 44. Health History Form in RedCap 
3. Research Project coordinator will educate participant on CaD referencing Form 45. Instructions 
for Calcium and Vitamin D Usage and using Protocol 42. Administering Edu CaD  as a guide.  
4. Participant will complete the Form 46. Goal Setting CaD form, Form 47. Task & Barrier 
Calcium  and Form 48. Task & Barrier VitD form in RedCap 
5. RPC will prescribe calcium and vitamin D on the Form 49. Calcium and Vitamin D Prescription 
Sheet using Protocol 41. Prescribing Calcium and Vitamin D. RPC will educate participant on 
usage of the cards using Form 1. Calendar Card Instructions document.  
6. Participants to be educated on mail back procedure and given SASE for convenience. 
Risedronate Group:  


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1. Participant Manual will contain the same documents as the Participant Manual Control plus the 
following:  
a. Form 50. Instructions for Taking Your Risedronate 
b. Form 51. Lexicomp Online Patient Education Risedronate 
7. Participant will complete Form 43. NOF Calcium Intake Estimate_Revised using paper and pencil 
(see Protocol 40. NOF Calcium Intake Calculator ) 
8. Participant will complete the Health History Form in RedCap 
2. Research Project coordinator will educate participant on CaD using Form 45. Instructions for 
Calcium and Vitamin D Usage as a guide (see Protocol 42. Administering Edu CaD  ) 
3. RPC will educate participant on Risedronate using Form 50. Instructions for Taking Your 
Risedronate as a guide (see Protocol 43. Administering Edu Risedronate). 
4. Participant will complete the Form 46. Goal Setting CaD form, Form 52. Goal Setting Risedronate 
form, Form 47. Task & Barrier Calcium  form, Form 48. Task & Barrier VitD form, and Form 53. 
Task & Barrier Risedronate form in RedCap 
5. RPC will prescribe calcium and vitamin D using forms and protocols referenced under “Control 
Group Protocol”, #6. 
6. Participants to be educated on mail back procedure and given SASE for convenience 
Exercise Group Protocol:  
1. Participant Manual will contain the same documents as the Participant Manual Control plus the 
following:  
a. Form 54. YMCA Membership Application 
b. Form 10. YMCA Contact  Sheet for Participants_Version 3 
2. Participant will complete Form 43. NOF Calcium Intake Estimate_Revised using paper and pencil 
(see Protocol 40. NOF Calcium Intake Calculator ) 
3. Participant will complete the Form 44. Health History Form in RedCap 
4. Research Project coordinator will educate participant on CaD using Form 45. Instructions for 
Calcium and Vitamin D Usage as a guide (see Protocol 42. Administering Edu CaD) 
5. Participant will complete the Form 46. Goal Setting CaD form, Form 47. Task & Barrier 
Calciumand Form 48. Task & Barrier VitD form in RedCap 
6. Participant will complete the Form 54. YMCA Membership Application and be introduced to 
Exercise program. Use Protocol 44. Steps to Take After Randomization to Exercise Group as a 
guide.  
7. RPC will prescribe calcium and vitamin D using forms and protocols referenced under “Control 
Group Protocol”, #6. 
8. Participants to be educated on mail back procedure and given SASE for convenience. 
 
Note: During week 2, RPC will complete the following instruments with the participant: 1. Form 
55. Goal Setting Exercise, 2. Form 56. Task and Barrier Exercise, and 3. Form 57. Barriers 
Interference Instrument, and the following educational materials: 1. Form 58. Reminder List for 
Exercises, 2. Form 59. Signs and Symptoms, 3. Form 60. Sore vs. Pain, 4. Form 61. Know the Facts 
About High BP, 5. Form 62. HOPS Posture 
 


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7. RPC will fill out Form 63. Payment Info Form. If personnel ID is unknown, ask participant to 
send via email or verify over the phone.  
8. RPC will give all participants a chance to ask any questions and ensure they understand the 
process of the study. RPC will remind participant that they will contact the participant in two 
weeks.  
6.4.5 
After Enrollment Visit 
Follow the steps listed in Protocol 45. Steps to Take After Enrollment Visit . This will include issuing the 
participant’s first payment. Use Protocol 46. Issuing Participant Payment Request , as a guide. 
If the participant was assigned to the Exercise group, make sure that the items outlined in Protocol 44. 
Steps to Take After Randomization to Exercise Group have been addressed.  
If the participant was randomized to the Risedronate group, follow the steps listed in Protocol 47. 
Acquiring Risedronate Rx , to attain a risedronate prescription for the participant.  
6.4.6 
Intermediate Visits 
 
Subjects will have follow up contact at 2 weeks, 3M, 6M, and 12M. Additional contact will be made 
between exercise participants and Melissa, the RET. Additional contact will occur between RPCs and 
participants as needed. If at any time during enrollment, a participant indicates that they have suffered 
a fracture, the participant will be asked to complete the Form 64. Fractures Documentation_Revised, 
and the participant’s provider will determine whether continuation in the study is appropriate.  
 
See Protocol 1.Timeline for Data Collection for details.   
 


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7 STUDY PROCEDURES /EVALUATIONS 
7.1 
Study Procedures 
 
See Protocol 1.Timeline for Data Collection for details.   
Protocol 48. Data Collection_Control Group, Protocol 49. Data Collection_Risedronate Group ,Protocol 
50. Data Collection_Exercise Group  for detailed data collection timelines according to treatment group.  
7.2 
Laboratory Procedures/Evaluations 
7.2.1 
Clinical Laboratory Evaluations 
Screening blood tests will include:  
• 
CBC 
• 
Serum vitamin D 
• 
Serum calcium 
• 
Serum creatinine 
• 
Parathyroid hormone 
• 
Follicle-stimulating hormone (if applicable) 
• 
Thyroid stimulating hormone (if applicable) 
• 
Additional serum drawn at screening will be stored and used for baseline analysis of Alkphase B 
and Serum NTx (markers of bone turnover) and other factors that may affect bone health 
 
Blood tests performed at 6 months: 
• 
Serum vitamin D 
• 
Alkphase B 
• 
Serum NTx 
 
Blood tests performed at 12 months:  
• 
Alkphase B 
• 
Serum NTx 
7.2.2 
Special Assays or Procedures 
• 
Dual energy x-ray absorptiometry (DXA) at screening(baseline), 6M, 12M 
o Hip Structural Analysis at screening (baseline), 6M, 12M 
o Trabecular Bone Score at screening, 6M, 12M  
• 
Peripheral quantitative computed tomography (pQCT) at baseline, 6M, 12M 
• 
Estimated 1 repetition maximum (1 RM) at 2 weeks, 6M 
7.2.3 
Specimen Preparation, Handling, and Storage 
Blood draws will be performed at either TNMC Clinical Research Center or at the Creighton Osteoporosis 
Research Center depending on subject availability and preference. Personnel will follow appropriate 
protocols for venipuncture and transportation of specimens (see Protocol 32. Blood Draw Procedure , 
and Protocol 33. Blood Transportation Protocol ). As indicated in Protocol 33. Blood Transportation 


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Protocol , some specimens will be stored in Dr. Bilek’s lab, while others will be analyzed by the TNMC 
laboratory. For specimens to be aliquoted and stored in Dr. Bilek’s lab and freezer space, use Protocol 
36. Blood Handling Procedure and Protocol 37. Serum NTx and Alkphase B Aliquot and Storage as a 
guide.  


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8 ASSESSMENT OF SAFETY 
8.1.1 
Data 
 
The location of the server is a password protected secured campus UNMC RedCap database server.This 
server is accessible from the external network, so researchers can design their surveys and provide a link 
to complete the survey that will work from any Internet-connected device, including mobile devices. 
This has a secure HTTPS connection. (Please see attached file named: RedCapServerInfoIRB.Docx, for 
more detailed information on the servers and firewall). 
 
Best practices are followed by UNMC IT where the web server and database server are two separate 
servers and both the web server and database server are securely located behind a firewall. (Please see 
attached file named:RedCapServerInfoIRB.Docx,for more detailed information.). 
 
Exercise logs used by subjects to document their exercises will be stored at individual Y's and then 
transported by study personnel every 4 weeks for entry into the online data base . On-site ET 
coordinators at Y's will monitor subject's adherence to exercises by examining subject exercise logs 
every 2 weeks during the study. Exercise logs must be stored at the Y's because they are used by 
subjects to document their exercises and by on-site ET coordinators to monitor fidelity of the exercise 
intervention. Hard copies of data will be kept locked in a file cabinet in the locked office of the study 
coordinator or the locked office of one of the PIs. Data will be transported in a locked briefcase. 
 
Research data will be linked to subjects by ID code number only. Each subject will be assigned an ID 
code for use on all study materials. The only link between a subject's name and ID code will be the 
consent form. A copy of the consent form will be kept in the PI's research office in a locked file separate 
from other study materials. 
As specified by the NIH, subject identifiers will be maintained for 7 years after the study is completed. 
Funding for the study is requested for 5 years, and study data will be kept for an additional 7 years. 
All electronic data will be destroyed with the assistance of the ITS and in accordance with UNMC 
Computer Use and Electronic Information Security Policy N0. 6051 
8.1.2 
Adverse Events 
If a subject is injured or has a medical problem as a direct result of being in this study, the subject has 
been instructed to immediately contact a member of the study personnel listed at the end of the 
consent form. 
 
The institution has no plans to pay for any required treatment or provide other compensation. If the 
subject has insurance, the insurance company may or may not pay the costs of medical treatment. If the 
subject does not have insurance, or if the insurance company refuses to pay, the subject will be 
expected to pay for the medical treatment. The subject will be informed that by participating in this 
research study, she has not given up any of her legal ri 


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STUDY OVERSIGHT 
The conduct and scientific integrity of this proposed clinical trial will be monitored by a Data and Safety 
Monitoring Committee (DSMC), comprised of the following persons: Joseph Norman, PT, PhD, Professor, 
Divison of Physical Therapy Education; Jane Meza, PhD, Professor College of Public Health Biostatistics; 
M. Patricia Leuschen, Professor Emeritus, School of Allied Health Professions; and Bernice Yates, RN, 
PhD, Professor, College of Nursing. The DSMC will audit the implementation of the protocol beginning 6 
months after the start of subject accrual. Since this trial is greater than minimal risk, it will be audited 
every 6 months. Each report will include monitoring of: compliance with informed consent and eligibility 
requirements, recruitment plan according to protocol, follow-up data collection according to protocol, 
expected and actual accrual, protocol violations, and patient withdrawals from the study. Per university 
policy, all serious adverse events (AE) will be reported to the UNMC IRB, the NIH, and to the DSM 
Committee within two business days after the investigators have been notified of the AE. The 
investigators will prepare a summarized report of these above-listed items and submit this report to the 
DSMC, with access to raw data if needed. A report from the DSMC audit will be sent to the investigators, 
the UNMC IRB, and NINR-NIH. 
The conduct and scientific integrity of this proposed clinical trial will be monitored by a Data and Safety 
Monitoring Committee (DSMC), comprised of the following persons: Joseph Norman, PT, PhD, Professor, 
Divison of Physical Therapy Education; Jane Meza, PhD, Professor College of Public Health Biostatistics; 
M. Patricia Leuschen, Professor Emeritus, School of Allied Health Professions;; and Bernice Yates, RN, 
PhD, Professor, College of Nursing. 


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9 CLINICAL SITE MONITORING 
The Research Project Coordinators (RPCs) and the Research Exercise Trainer (RET) (under the direction 
of the Co-PIs Dr Waltman and Dr Bilek) will conduct audits to monitor compliance with intervention and 
testing protocols and to monitor unanticipated problems involving risks to the subjects at random times 
and at least every 3 months of the study. Reports of violations will be submitted to the IRB as 
required.The conduct and scientific integrity of this proposed clinical trial will also be monitored by a 
Data and Safety Monitoring Committee (DSMC). The DSMC will audit the implementation of the 
protocol beginning 6 months after the start of subject accrual. Since this trial is greater than minimal 
risk, it will be audited every 6 months. Each report will include monitoring of: compliance with informed 
consent and eligibility requirements, recruitment plan according to protocol, follow-up data collection 
according to protocol, expected and actual accrual, protocol violations, and patient withdrawals from 
the study. Per university policy, all serious adverse events (AE) will be reported to the UNMC IRB, the 
NIH, and to the DSM Committee within two business days after the investigators have been notified of 
the AE. The investigators will prepare a summarized report of these above-listed items and submit this 
report to the DSMC, with access to raw data if needed. A report from the DSMC audit will be sent to the 
investigators, the UNMC IRB, and NINR-NIH.  
The same auditing plan will be used for external study sites involved in the study, including all "Y" 
facilities and the Creighton University Research Center. As described previously, audits will be conducted 
by the RPCs and RET (under the direction of the Co-PIs Dr Waltman and Dr Bilek) and also by the DSMC. 
 


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10 DATA ENTRY/STATISTICAL CONSIDERATIONS 
 
10.1 
Data Entry 
As indicated in Section 9.1.1, HOPS data will be entered and stored on a password protected, secured 
campus UNMC RedCAP database server. The server is accessible from an external network, therefore 
the database offers the capability to enter data off site. We will be utilizing Ipads to enter participant 
data offsite, and data will be entered by both HOPS personnel and participants. Styluses and keyboards 
have been purchased to increase ease of entry and to minimize error. Additionally, limitations have 
been set in RedCAP so that the database will notify the user any time a value outside of the normal 
range is submitted, allowing the user an opportunity to correct an error. In order to avoid any risk of 
violations of confidentiality, participants will have limited access to RedCAP, and will therefore, only be 
able to view the necessary forms.  
See Protocol 24. RedCap Data Entry for detailed directions on data entry and usage of the RedCAP 
database.  
10.2 
Sample Size Considerations 
A power analysis was conducted for the primary aim of the study since it involves the most complex 
analysis. Hypothesis 1a states that at 12 months, there will be significantly greater improvements in BSI 
at the 4% tibial site in subjects in the exercise group compared to subjects in the control or risedronate 
groups. Power for the repeated measures analysis of variance (RM-ANOVA) was determined using 
G*Power3.1.5. A within-between interaction will be the primary test of significance (time*group 
interaction). It is assumed that the exercise group will have significantly greater improvements in BSI 
than either the control or risedronate groups. Two groups were assumed for the purposes of the power 
analysis because the control and risedronate groups will be compared to the exercise group separately. 
The total sample size will then be the number determined plus one half to populate the three groups. 
We investigated effect size evidence from similar studies and a variety of effect sizes was observed. 
However, effect sizes were not reported in the studies that were deemed most similar to the planned 
study. This study compares an exercise group to control and risedronate groups, which is unique so a 
large expected effect size could not be assumed without further evidence. 
Therefore, a small effect size was assumed for this power analysis (f=.10; Cohen 1992). Assuming a 
significance level of .05, 3 time points, and an estimate of .5 for the correlation between time points, 
246 participants (82 per group) would be needed to have 80% power. 
10.3 
Final Analysis Plan 
Aim 1 hypotheses will be tested via RM-ANOVA models. Bone strength index at the tibia and bone mass 
distribution at the hip, the dependent variables of interest, will be measured at 6-month intervals (0, 6, 
and 12 months). A significant time*group interaction would indicate that the two groups being 
compared in each model have significantly different changes in bone structure over 12 months. Huynh-
Feldt corrected F-tests will be used in order to account for any possible violation of sphericity. It is 
hypothesized that the exercise group will have significantly greater improvements than the control or 
risedronate groups. Up to 20% attrition may be expected over the course of the study, but we expect it 


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to be less due to the use of cognitive behavioral strategies by Research Project Coordinators (RPC), the 
Research Exercise Trainer (RET), and ETs to promote exercise adherence and retention in the study. The 
method of handling missing data is not likely to have an effect with small amounts of missing data. 
However, If there is a higher than expected attrition rate, a maximum likelihood estimation method (e.g. 
mixed models) will be used instead of RM-ANOVA in order to utilize all available data and not delete 
cases in a listwise manner. 
 
Hypothesis 2a compares the groups changes in BMD and will also be analyzed using RM-ANOVA. 
Hypothesis 2b also involves BMD, but assesses the proportions of preservation of BMD in each group. It 
is expected that at least 80% of subjects in both the exercise+ and risedronate+ groups will have 
preserved BMD at the three skeletal sites, and that the control/CaD group will have a significantly lower 
proportion of participants preserving BMD over 12 months. In order to classify individuals into 
preserved vs. declined groups, change in BMD over 12 months will be compared to the least significant 
difference as defined by the Hologic DXA manufacturer for each respective skeletal site. Differences of 
proportion of preservation across groups will be assessed via chi-square tests, which would indicate if 
preservation of BMD was significantly different across groups. Aim 3 investigates the changes in bone 
formation and resorption over 12 months also using repeated-measures ANOVA. Alkphase B and Serum 
NTx will be measured at baseline, 6, and 12 months. 
 
The relationships of interest in Aim 4 will be explored by assessing the correlations between percentage 
of sessions attended, percentage of risedronate pills taken, and 12-month changes in bone structure at 
the tibia and hip. Assuming the variables are normally distributed, Pearson correlations will be used. 
Spearman rank correlations will be used if any of the variables are found to be non-normal. 
 


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11 ETHICS/PROTECTION OF HUMAN SUBJECTS 
See IRB Application 


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DATA HANDLING AND RECORD KEEPING 
See IRB Application 
 
 
 


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12 LITERATURE REFERENCES 
 


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APPENDICES 
APPENDIX B: PROTOCOLS .................................................................................................... 46 
APPENDIX B: FORMS .............................................................................................................. 51 
APPENDIX C: PACKETS .......................................................................................................... 56 


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APPENDIX B: PROTOCOLS 
Protocol 1.Timeline for Data Collection .....................................................................................48 
Protocol 2. CaD Delivery_RPC Responsibilities ........................................................................48 
Protocol 3. Risedronate Delivery_RPC Responsibilities ............................................................48 
Protocol 4. First Exercise Session Explanation and Documentation ..........................................48 
Protocol 5. Estimating 1RM .......................................................................................................48 
Protocol 6. YET HOPS Exercise Schedule ................................................................................48 
Protocol 7. Progression and Increase Parameters for Exercise .................................................48 
Protocol 8. Impact Jogging ........................................................................................................48 
Protocol 9. Graphic Feedback ...................................................................................................48 
Protocol 10. Exercise Trainer Oversight Schedule_Revised ......................................................48 
Protocol 11.Storing Exercise Docs at YMCAs ...........................................................................48 
Protocol 12.Addressing Missing Exercise Session, Adherence .................................................48 
Protocol 13. Addressing Continued Exercise Non-Compliance .................................................48 
Protocol 14. Exercise Group_Addressing Withdrawn or Off-Protocol Participants .....................48 
Protocol 15. Exercise Group_Addressing Problems on YET Doc Form .....................................48 
Protocol 16. Using Barrier Intervention Strategies .....................................................................48 
Protocol 17. RET Protocol for YMCA Exercise Sessions by Visit ..............................................48 
Protocol 18. Scheduling YET Visits ...........................................................................................48 
Protocol 19. Storing Scanned-In Exercise Documents ..............................................................48 
Protocol 20. Prescreening script ...............................................................................................48 
Protocol 21. Prescreening Procedure ........................................................................................48 
Protocol 22. Steps to Take Prior to Screening Visit ...................................................................48 
Protocol 23. Block Screening Meeting .......................................................................................48 
Protocol 24. RedCap Data Entry ...............................................................................................48 
Protocol 25. Administering Osteo Knowledge Test ....................................................................49 
Protocol 26. Administering FRAX ..............................................................................................49 
Protocol 27. Administering HAP Questionnaire .........................................................................49 
Protocol 28. Administering IPAQ ...............................................................................................49 
Protocol 29. Referral for Osteoporotic Screeners ......................................................................49 
Protocol 30. Checking Resting Blood Pressure .........................................................................49 
Protocol 31. Ordering Blood Draw .............................................................................................49 
Protocol 32. Blood Draw Procedure ..........................................................................................49 
Protocol 33. Blood Transportation Protocol ...............................................................................49 
Protocol 34. Steps to Take After Screening Visit .......................................................................49 
Protocol 35. Ordering Blood Tests in One Chart and Enrolling Participant ................................49 
Protocol 36. Blood Handling Procedure ....................................................................................49 
Protocol 37. Serum NTx and Alkphase B Aliquot and Storage ..................................................49 
Protocol 38. Sending Provider Permission Letter ......................................................................49 
Protocol 39. Main Study Consent Guidelines for Completion ....................................................49 
Protocol 40. NOF Calcium Intake Calculator .............................................................................49 


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Protocol 41. Prescribing Calcium and Vitamin D .......................................................................49 
Protocol 42. Administering Edu CaD .........................................................................................49 
Protocol 43. Administering Edu Risedronate .............................................................................49 
Protocol 44. Steps to Take After Randomization to Exercise Group ..........................................49 
Protocol 45. Steps to Take After Enrollment Visit ......................................................................49 
Protocol 46. Issuing Participant Payment Request ....................................................................49 
Protocol 47. Acquiring Risedronate Rx ......................................................................................49 
Protocol 48. Data Collection_Control Group ..............................................................................49 
Protocol 49. Data Collection_Risedronate Group ......................................................................50 
Protocol 50. Data Collection_Exercise Group ...........................................................................50 
 
 
 


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Protocol 1.Timeline for Data Collection 
Protocol 2. CaD Delivery_RPC Responsibilities 
Protocol 3. Risedronate Delivery_RPC Responsibilities 
Protocol 4. First Exercise Session Explanation and Documentation 
Protocol 5. Estimating 1RM 
Protocol 6. YET HOPS Exercise Schedule  
Protocol 7. Progression and Increase Parameters for Exercise  
Protocol 8. Impact Jogging 
Protocol 9. Graphic Feedback  
Protocol 10. Exercise Trainer Oversight Schedule_Revised 
Protocol 11.Storing Exercise Docs at YMCAs 
Protocol 12.Addressing Missing Exercise Session, Adherence 
Protocol 13. Addressing Continued Exercise Non-Compliance 
Protocol 14. Exercise Group_Addressing Withdrawn or Off-Protocol Participants 
Protocol 15. Exercise Group_Addressing Problems on YET Doc Form 
Protocol 16. Using Barrier Intervention Strategies 
Protocol 17. RET Protocol for YMCA Exercise Sessions by Visit 
Protocol 18. Scheduling YET Visits 
Protocol 19. Storing Scanned-In Exercise Documents 
Protocol 20. Prescreening script 
 
Protocol 21. Prescreening Procedure 
Protocol 22. Steps to Take Prior to Screening Visit 
Protocol 23. Block Screening Meeting 
Protocol 24. RedCap Data Entry 


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Protocol 25. Administering Osteo Knowledge Test 
Protocol 26. Administering FRAX 
Protocol 27. Administering HAP Questionnaire 
Protocol 28. Administering IPAQ 
Protocol 29. Referral for Osteoporotic Screeners 
Protocol 30. Checking Resting Blood Pressure 
Protocol 31. Ordering Blood Draw 
Protocol 32. Blood Draw Procedure 
Protocol 33. Blood Transportation Protocol 
Protocol 34. Steps to Take After Screening Visit 
Protocol 35. Ordering Blood Tests in One Chart and Enrolling Participant 
Protocol 36. Blood Handling Procedure 
Protocol 37. Serum NTx and Alkphase B Aliquot and Storage 
Protocol 38. Sending Provider Permission Letter 
Protocol 39. Main Study Consent Guidelines for Completion 
Protocol 40. NOF Calcium Intake Calculator 
Protocol 41. Prescribing Calcium and Vitamin D 
Protocol 42. Administering Edu CaD 
Protocol 43. Administering Edu Risedronate 
Protocol 44. Steps to Take After Randomization to Exercise Group 
Protocol 45. Steps to Take After Enrollment Visit 
Protocol 46. Issuing Participant Payment Request 
Protocol 47. Acquiring Risedronate Rx 
Protocol 48. Data Collection_Control Group 


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Protocol 49. Data Collection_Risedronate Group 
Protocol 50. Data Collection_Exercise Group 
 
 


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APPENDIX B: FORMS 
Form 1. Calendar Card Instructions ..........................................................................................53 
Form 2. Blank Calendar ............................................................................................................53 
Form 3. HOPS Exercise Booklet_Revised ................................................................................53 
Form 8. Exercise Log_Revised .................................................................................................53 
Form 9. Exercise Trainer Oversight schedule revised ...............................................................53 
Form 10. YMCA Contact  Sheet for Participants_Version 3.......................................................53 
Form 11. Availability of YETs ....................................................................................................53 
Form 12. YET Documentation Form ..........................................................................................53 
Form 13. Prescreening Questionnaire.Web_Revised ................................................................53 
Form 14. Prescreening Qurestionnaire.Verbal_Revised ............................................................53 
Form 15. One Page Study Summary_3.....................................................................................53 
Form 16. What to Expect at your DXA ......................................................................................53 
Form 17. Directions to CUMC ...................................................................................................53 
Form 18. Screening Visit Checklist ............................................................................................53 
Form 19. Screening Consent ....................................................................................................53 
Form 20. Osteoporosis Knowledge Test Revised ......................................................................53 
Form 21. Demographic Profile ..................................................................................................53 
Form 22. FRAX .........................................................................................................................53 
Form 23. Screening Participants Contact Information Form_Revised .......................................53 
Form 24. Human Activity Profile Test (HAP) .............................................................................53 
Form 25. International Physical Activity Questionnaire (IPAQ) ..................................................54 
Form 26. Bone Mineral Density Report .....................................................................................54 
Form 27. Calcium FAQ .............................................................................................................54 
Form 28. Vitamin D FAQ ...........................................................................................................54 
Form 29. Osteoporosis Pamphlet ..............................................................................................54 
Form 30. CRC Qualification ......................................................................................................54 
Form 31. CRC Directions with Map ...........................................................................................54 
Form 32. Further Questions Contact Sheet_Revised ................................................................54 
Form 33. Provider Permission Letter_4 .....................................................................................54 
Form 34. Main Study Consent ...................................................................................................54 
Form 35. Enrollment Checklist Exercise ....................................................................................54 
Form 36. Enrollment Checklist Control ......................................................................................54 
Form 37. Enrollment Checklist Risedronate ..............................................................................54 
Form 38. What is Osteoporosis .................................................................................................54 
Form 39. Exercise and Your Bones ...........................................................................................54 
Form 40. Instructions for Calcium and Vitamin D ......................................................................54 
Form 41. Lexicomp Online Patient Education Cholecalciferol ...................................................54 
Form 42. Lexicomp Online Patient Education Calcium Citrate ..................................................54 
Form 43. NOF Calcium Intake Estimate_Revised .....................................................................54 
Form 44. Health History Form ...................................................................................................54 
Form 45. Instructions for Calcium and Vitamin D Usage ...........................................................54 


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Form 46. Goal Setting CaD form ...............................................................................................54 
Form 47. Task & Barrier Calcium ..............................................................................................54 
Form 48. Task & Barrier VitD ....................................................................................................54 
Form 49. Calcium and Vitamin D Prescription Sheet .................................................................55 
Form 50. Instructions for Taking Your Risedronate ...................................................................55 
Form 51. Lexicomp Online Patient Education Risedronate .......................................................55 
Form 52. Goal Setting Risedronate ...........................................................................................55 
Form 53. Task & Barrier Risedronate ........................................................................................55 
Form 54. YMCA Membership Application ..................................................................................55 
Form 55. Goal Setting Exercise ................................................................................................55 
Form 56. Task and Barrier Exercise ..........................................................................................55 
Form 57. Barriers Interference Instrument .................................................................................55 
Form 58. Reminder List for Exercises .......................................................................................55 
Form 59. Signs and Symptoms .................................................................................................55 
Form 60. Sore vs. Pain .............................................................................................................55 
Form 61. Know the Facts About High BP ..................................................................................55 
Form 62. HOPS Posture ...........................................................................................................55 
Form 63. Payment Info Form ....................................................................................................55 
Form 64. Fractures Documentation_Revised ............................................................................55 
 
 


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Form 1. Calendar Card Instructions 
 
Form 2. Blank Calendar 
Form 3. HOPS Exercise Booklet_Revised 
Form 4. Starting Load Values Based Upon Body Weight 
Form 5. Borg RPE scale 
Form 6. YET HOPS Exercise Schedule 
Form 7. Progression and Increase Parameters for Exercise 
Form 8. Exercise Log_Revised 
Form 9. Exercise Trainer Oversight schedule revised 
Form 10. YMCA Contact  Sheet for Participants_Version 3 
Form 11. Availability of YETs 
Form 12. YET Documentation Form 
Form 13. Prescreening Questionnaire.Web_Revised 
Form 14. Prescreening Qurestionnaire.Verbal_Revised 
Form 15. One Page Study Summary_3 
Form 16. What to Expect at your DXA 
Form 17. Directions to CUMC 
Form 18. Screening Visit Checklist 
Form 19. Screening Consent 
Form 20. Osteoporosis Knowledge Test Revised 
Form 21. Demographic Profile 
Form 22. FRAX 
Form 23. Screening Participants Contact Information Form_Revised 
Form 24. Human Activity Profile Test (HAP) 


Bone Loading Exercises versus Risedronate on Bone Health in Postmenopausal Women 
 
Manual of Operations 
Revised: 17 June 2015 
 ________________________________________________________________________________________________________  
 
 ____________________________________________________________________________________________ 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
54 
 
Form 25. International Physical Activity Questionnaire (IPAQ) 
Form 26. Bone Mineral Density Report 
Form 27. Calcium FAQ 
Form 28. Vitamin D FAQ 
Form 29. Osteoporosis Pamphlet 
Form 30. CRC Qualification 
Form 31. CRC Directions with Map 
Form 32. Further Questions Contact Sheet_Revised 
Form 33. Provider Permission Letter_4 
Form 34. Main Study Consent 
Form 35. Enrollment Checklist Exercise 
Form 36. Enrollment Checklist Control 
Form 37. Enrollment Checklist Risedronate 
Form 38. What is Osteoporosis  
Form 39. Exercise and Your Bones 
Form 40. Instructions for Calcium and Vitamin D 
Form 41. Lexicomp Online Patient Education Cholecalciferol 
Form 42. Lexicomp Online Patient Education Calcium Citrate 
Form 43. NOF Calcium Intake Estimate_Revised 
Form 44. Health History Form 
Form 45. Instructions for Calcium and Vitamin D Usage 
Form 46. Goal Setting CaD form 
Form 47. Task & Barrier Calcium  
Form 48. Task & Barrier VitD 


Bone Loading Exercises versus Risedronate on Bone Health in Postmenopausal Women 
 
Manual of Operations 
Revised: 17 June 2015 
 ________________________________________________________________________________________________________  
 
 ____________________________________________________________________________________________ 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
55 
 
Form 49. Calcium and Vitamin D Prescription Sheet 
Form 50. Instructions for Taking Your Risedronate 
Form 51. Lexicomp Online Patient Education Risedronate 
Form 52. Goal Setting Risedronate 
Form 53. Task & Barrier Risedronate 
Form 54. YMCA Membership Application 
Form 55. Goal Setting Exercise 
Form 56. Task and Barrier Exercise 
Form 57. Barriers Interference Instrument 
Form 58. Reminder List for Exercises 
Form 59. Signs and Symptoms 
Form 60. Sore vs. Pain 
Form 61. Know the Facts About High BP 
Form 62. HOPS Posture 
Form 63. Payment Info Form 
Form 64. Fractures Documentation_Revised 
 


Bone Loading Exercises versus Risedronate on Bone Health in Postmenopausal Women 
 
Manual of Operations 
Revised: 17 June 2015 
 ________________________________________________________________________________________________________  
 
 ____________________________________________________________________________________________ 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
56 
 
APPENDIX C: PACKETS 
Packet 1. Block Scheduled Screening Participant .....................................................................57 
Packet 2. Screening Visit Forms ...............................................................................................57 
Packet 3. Enrollment Visit Forms ..............................................................................................57 
Packet 4. Control Group_All Enrollment Forms .........................................................................57 
Packet 5. Risedronate Group_All Enrollment Forms .................................................................57 
Packet 6. Exercise Group_All Enrollment Forms .......................................................................57 
Packet 7. Control Group_Participant Manual ............................................................................57 
Packet 8. Risedronate Group_Participant Manual .....................................................................57 
Packet 9. Exercise Group_Participant Manual ..........................................................................57 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Bone Loading Exercises versus Risedronate on Bone Health in Postmenopausal Women 
 
Manual of Operations 
Revised: 17 June 2015 
 ________________________________________________________________________________________________________  
 
 ____________________________________________________________________________________________ 
Based on NIDCR Clinical Trial (Interventional) Protocol Template v4.0 - 20140103 
57 
 
Packet 1. Block Scheduled Screening Participant 
Packet 2. Screening Visit Forms 
Packet 3. Enrollment Visit Forms 
Packet 4. Control Group_All Enrollment Forms 
Packet 5. Risedronate Group_All Enrollment Forms 
Packet 6. Exercise Group_All Enrollment Forms 
Packet 7. Control Group_Participant Manual 
Packet 8. Risedronate Group_Participant Manual 
Packet 9. Exercise Group_Participant Manual 
 
 
 

ICF_001.pdf: 
 
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ADULT CONSENT - CLINICAL BIOMEDICAL
Main Study Consent
Title of this Research Study
Invitation
You are invited to take part in this research study. You have a copy of the following,
which is meant to help you decide whether or not to take part:
Informed consent form
"What Do I need to Know Before Being in a Research Study?"
The Rights of Research Subjects
Why are you being asked to be in this research study?
You are being invited to take part in this study because:
the results of your screening examination indicate you are eligible to
participate (have low bone mass and blood tests were normal)
you are 19 years old or older
you have started menopause within the last 5 years
you are not at high risk for fracture
you weigh less than 300 lbs
you are healthy
A total of 309 post-menopausal women will be enrolled in this study.
What is the reason for doing this research study?
There is a period of rapid bone loss in the first years after menopause. This makes
women at high risk of developing osteoporosis and fractures. The purpose of the
Heartland Osteoporosis Prevention study is to identify the best way to maintain
healthy bones in the first years after menopause. The Heartland Osteoporosis
Prevention study will compare the bone health of women who take calcium and
vitamin D only to women taking calcium and vitamin D plus medication (risedronate)
or exercise.
What will be done during this research study?
If you consent to participate in the study, you will be randomly assigned to one of
three study treatment groups: 1) calcium and vitamin D supplements only, 2) calcium
and vitamin D supplements plus medication to prevent bone loss (risedronate), or 3)
calcium and vitamin D supplements plus exercise to prevent bone loss.
You will be asked to complete the following assessments at the time points indicated
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below:
Assessments at Baseline:
1. pQCT (peripheral quantitative computed tomography): This is a CT scan to
measure bone structure. The test will be completed on your lower leg in two
areas. You will sit in a chair with your lower leg in the machine that assesses
your bone. This will take approximately 15 minutes. The pQCT is performed
for research only and the results have no value to your health care.
Therefore, the results of these tests will not be sent to you or your healthcare
provider.
2. Diet History: The investigators will calculate how much calcium you get from
your diet. This will be used to prescribe the correct amount of calcium you
need to get the recommended 1200 mg/day.
3. Medical History: Study personnel will interview you to get a complete medical
history including medications and supplements that you take.
4. Self-Efficacy Questionnaires: You will fill out questionnaires related to your
confidence in completing the interventions assigned to your study treatment
group. For example if you are in the exercise group, the questionnaire asks
about your confidence in performing exercise the number of times per week
as prescribed. This information is used to inform the strategies used by the
investigators to help you become more confident in your ability to manage the
intervention.
5. Goal Setting Questionnaire: You will fill out questionnaires related to setting
goals for completing the interventions assigned to your study treatment
group. This information is used to inform the strategies used by the
investigators to help you become more confident in your ability to manage the
intervention.
6. Barrier Questionnaire: You only fill out this questionnaire if you are in the
exercise group. It evaluates barriers to completing exercises, and your results
help the investigators design strategies to make it easier for you to participate
in exercise.
7. One Repetition Maximum (1 RM): If you are in the exercise group, your
strength will be evaluated by performing a test which estimates the maximum
amount of weight you can lift. This is used to prescribe weight loads for
resistance training.
Assessments at 2 weeks:
1. You will be interviewed by study personnel to identify problems/issues with
the study.
Assessments at 3 months:
1. If the vitamin D in your blood is very low or very high, you will be asked to
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return at 3 months to have it checked again. If it is very high, we will also
check your calcium and albumin at 3 months. If it is minimally low or normal,
you do not have blood drawn.
2. You will complete the Self-Efficacy questionnaires and if you are in the
exercise group, you complete the Barrier questionnaire.
3. You will complete the Goal-Setting questionnaire.
4. You will be interviewed by study personnel to identify problems/issues with
the study.
If a blood test is not required, assessments at 3 months can be completed over the
phone.
Assessments at 6 months:
1. You will complete a DXA (dual energy x-ray absorptiometry): This is a test to
measure the bone density of your hip and back. You do not have to prepare
for the test. You will lie on your back while the machine moves over you. The
test will take about 30 minutes. Your results will be sent to your healthcare
provider. In addition to bone density, investigators will calculate estimates of
the strength of your bone using the DXA results. The results of these tests will
not be sent to your provider because results have no use in the treatment of
patients clinically.
2. You will complete a pQCT scan of your lower leg.
3. We will assess bone repair status. Bone is constantly breaking down and
repairing itself. That is how it stays healthy and strong. Investigators will
measure markers in your blood which indicate the status of this process.
These tests are performed in the investigator's lab for research only and the
results have no value to your health care. Therefore, the results of these tests
will not be sent to you or your healthcare provider.
4. We will assess your vitamin D level. Your results will be sent to your
healthcare provider.
5. The research exercise trainer will assess your 1 RM if you are in the exercise
group.
6. Study personnel will complete a medical screening: blood pressure, height
weight, waist circumference and document any changes in health or
fractures.
7. You will complete questionnaires to document your regular physical activity
patterns.
8. You will complete the Self-Efficacy questionnaires, and if you are in the
exercise group, you complete the Barrier questionnaire.
9. You will complete the Goal-Setting questionnaires.
10. You will be interviewed by study personnel to identify problems/issues with
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the study.
Assessments at 12 months (end of the study):
1. You will have a DXA, estimates of the strength of your bone, pQCT, and
blood tests to evaluate your bone repair status. Results of the DXA will be
sent to your healthcare provider.
2. Study personnel will complete a medical screening: blood pressure, height
weight, waist circumference and document any changes in health or
fractures.
3. You will complete questionnaires to document your regular physical activity
patterns.
4. You will complete the Self-Efficacy questionnaires, and if you are in the
exercise group, you complete the Barrier questionnaire.
5. You will be interviewed by study personnel to identify problems/issues with
the study.
You will report any broken bones occurring during the study to the investigators when
they happen.
INTERVENTIONS
At the first visit you will receive education on bone health and use of calcium and
vitamin D supplements. You will be provided with medication cards with tablets in
individual bubbles that are dated. This will help you to take the pills prescribed every
day. You will be given "calcium" medication cards with the correct amount of calcium
based on your diet history test. You will be given "vitamin D" medication cards that
have tablets with the correct amount of vitamin D based on your blood test. Because
calcium is best absorbed when taken without certain foods, you will be given
instructions on the best way to take this supplement. You will return all medication
cards with unused pills to the investigators every 4 weeks in the postage-paid,
addressed envelopes provided.
Group Specific Interventions
All groups will take the calcium and vitamin D as described above. All groups will
receive calcium and vitamin D supplements at three month intervals either in person,
or via mail. Below describes additional, study treatment group specific interventions.
Group 1) calcium and vitamin D supplements only
At two weeks and 3 months study personnel will contact you to see how you are
doing. The 3 month visit can be a phone call or face-to-face visit depending on how
you are doing. If you have problems, study personnel will help you find ways to take
the prescribed calcium and vitamin D.
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You will return for 6 and 12 month assessments as described above.
Group 2) calcium and vitamin D supplements plus medication to prevent bone loss,
"risedronate"
You will be prescribed risedronate, a medication that prevents bone loss, and it will
be mailed to you shortly after your initial visit. Study personnel will also give you
instructions for how to safely take this medication and help prevent side effects. The
correct method is to take the risedronate with an 8 ounce glass of water, either upon
arising in the morning or 2 hours after the last meal of the day. You are to remain
upright and have no oral intake except water for at least 30 minutes after taking
risedronate. Risedronate is to be taken once a month. You will receive your
risedronate prescription at three month intervals, either in the mail or in person.
At two weeks and 3 months, study personnel will contact you to see how you are
doing. The 3 month visit can be a phone call or face-to-face visit depending on how
you are doing. You are asked to contact study personnel in the event of discomfort
when taking this medication.
Study personnel will help you find ways to take the prescribed calcium, vitamin D and
risedronate.
You will return for 6 and 12 month assessments as described above.
Group 3) calcium and vitamin D supplements plus exercise
In addition to taking calcium and vitamin D, the research exercise trainer (RET) will
prescribe and teach you an exercise program to prevent bone loss. Exercises will
then be completed at an Omaha metro area or Lincoln area YMCA of your choice or
at the Salvation Army Kroc Center, at times of your choice, three times per week.
Exercises will consist of weight lifting exercises and jogging with a weighted vest to
stress the bones in your legs and back. Those with joint replacement of the hip
and/or knee will complete "step-up" exercises instead of the jogging and leg press
exercise machine. You will be provided with a detailed instruction manual and an
exercise log which you complete each time you exercise. The exercise trainers at the
YMCA or Kroc Center will be available upon request to assist and will review your
progress every two weeks. From this information, trainers will instruct you on how to
increase your exercises. The RET will also monitor your exercise logs and progress.
She will schedule a visit if you are having problems with the exercises.
At two weeks and 3 months, study personnel will contact you to see how you are
doing. The 3 month visit can be a phone call or face-to-face visit depending on how
you are doing. The study personnel will help you find ways to take the prescribed
calcium, vitamin D and exercises as instructed.
You will return for assessments at 6 and 12 months as described above.
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What are the possible risks of being in this research study?
The following are potential risks you could experience during this study:
DXA and pQCT exams: DXA and pQCTs are relatively safe, non-invasive, and
painless procedures. The risk associated with these tests is radiation exposure.
However, the risk is small. You have already completed a whole body DXA as part of
the screening process. As part of the main study you will complete a pQCT at
baseline, 6 and 12 months, and additional DXAs of your whole body at 6 and 12
months.The additional exposure for the pQCT and DXA combined after enrollment in
the main study is approximately 45usv and equivalent to the radiation you would
receive during an airplane flight from New York City to Los Angeles. To prevent
unnecessary radiation exposure, you will wear a lead apron over the majority of your
body, including the breasts, during the pQCT tests.
Blood draws:There is risk of bruising and infection with any blood draw. The study
personnel are all highly skilled and trained and will use strict processes to prevent
bruising (pressure on the blood draw site) and the spread of germs.
Exercise
Muscle Soreness or injury: It is common to have muscle soreness after starting a
new exercise program. This can often be alleviated by starting the exercise program
slowly. Although injury can occur, exercises will be performed on strength training
machines which help control your movements, lessening the chance of injury.
Fracture: A fracture in the bodies of the spine (vertebral compression fracture) can
occur with exercise even in women with low bone mass (early stages of
osteoporosis). The movement most likely to contribute to this fracture is bending and
twisting with something heavy in your hand. Your exercise instruction will stress good
posture and correct performance of the exercises to avoid these movements which
stress the spine.
Heart problems with exercise: There is a slight risk of heart attack and even death
with exercise, however, the overall risk is very low. The risk is greatest with vigorous
exercise. The instructions for exercise teach you how to exercise at a moderate
intensity and avoid exercise habits which raise your blood pressure and cause stress
while exercising.
Calcium and Vitamin D supplementation
Vitamin D supplements are relatively safe. Too much calcium can be harmful.
Stomach upset, constipation, and kidney stones have occurred with high intakes of
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calcium. You are encouraged to take at least 8 glasses of water a day while you are
taking calcium and vitamin D supplements. You should not take additional
supplements of calcium and vitamin D supplements above those of the study
protocol.
Risedronate medication to prevent bone loss
Risks associated with this medication are not common but include: 1) damage to the
lining of your mouth, stomach and the tube between, possibly resulting in bleeding, 2)
stomach ulcers, 3) abdominal pain, 4) esophageal cancer, 5) vomiting, 6) kidney
impairment, 7) severe joint, muscle or joint pain, irregular heart rhythm. Long term
use is associated with a small increase risk in unusual fractures, however, typical hip
fracture rates are decreased when this medication is used properly. The most
common side effect for persons taking this medicine is upset stomach. Please
contact study personnel in the event of discomfort when taking this medication.
The medication is harmful to the fetus, however, this is not a factor for you since you
are post-menopausal.
Questionnaires
There is minimal risk of psychological discomfort when you answer questions on the
questionnaires or during interviews. You are free not to answer any of the questions
on the questionnaires or you can stop the interview at any time if you feel
uncomfortable.
It is possible that other rare side effects could occur which are not described in this
consent form. It is also possible that you could have a side effect that has not
occurred before.
What are the possible benefits to you?
Because you have low bone mass you are at higher risk for developing osteoporosis
and fractures. You may be able to improve your bone health with the study treatment
you receive (calcium and vitamin D supplements alone, or with risedronate or
exercises).
Or, you may not get any benefit from being in this research study.
What are the possible benefits to other people?
Findings from this study may identify better ways to help women prevent bone loss
and potentially prevent osteoporotic fractures during the first years after menopause.
What are the alternatives to being in this research study?
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Instead of being in this research study, you can choose not to participate.
The National Osteoporosis Foundation recommends that post-menopausal women
take calcium and vitamin D supplements and increase activity. It is not typical for a
primary care provider to refer to a specialist with expertise in exercise programs with
specific bone building capacity, however, you could seek out specialists on your own
to advise on an appropriate bone building exercise program.
It is not a standard of care to test bone mineral density in all post-menopausal
women. The National Osteoporosis Foundation recommends testing for women over
65 and those at high risk of osteoporosis or fracture. If you chose not to participate,
you would need to discuss with your primary care provider the benefits of having a
DXA test and you (or your insurance company) would be responsible for the cost.
The National Osteoporosis Foundation recommends initiation of medication to
prevent bone loss such as risedronate when a woman has osteoporosis. However, in
practice, many primary care providers prescribe the medication when a women has
low bone mass or is osteopenic. If you chose not to be in this study, you and your
primary care provider would determine if medication was indicated and when to begin
medication.
What will being in this research study cost you?
There is no cost to you to be in this research study.
Will you be paid for being in this research study?
If you live less than 50 miles from Omaha, you will be paid $50 for each assessment
completed: at baseline, 6 months and 12 months. If you live further than 50 miles
from Omaha, you will receive $75 for each assessment completed to compensate for
additional time spent traveling. If you are in the exercise group, you will be provided a
12 month YMCA or Kroc Center membership so you can access the facility to
exercise for the purpose of the study. If you are in the "calcium/vitamin D only" or
"risedronate" group, you will receive a 6 month YMCA or Kroc Center membership at
the completion of the study if you would like. If you complete less than 6 months of
the study, you will receive a 3 month membership voucher instead of a 6 month
voucher.
In order to compensate you for your participation in this research study, we are
required to obtain your social security number per UNMC accounting practices. If you
choose not to provide your social security number you can still participate in the
research study but we will not be able to compensate you for your participation.
Who is paying for this research?
This research is being paid for by grant funds from the National Institute of Health.
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UNMC receives money from the National Institute of Health to conduct this study.
What should you do if you are injured or have a medical problem during this
research study?
Your welfare is the main concern of every member of the research team. If you are
injured or have a medical problem as a direct result of being in this study, you should
immediately contact one of the people listed at the end of this consent form.
Emergency medical treatment for this injury or problem will be available at the
Nebraska Medical Center. If there is not sufficient time, you should seek care from a
local health care provider.
UNMC has no plans to pay for any required treatment or provide other compensation.
If you have insurance, your insurance company may or may not pay the costs of
medical treatment. If you do not have insurance, or if your insurance company
refuses to pay, you will be expected to pay for the medical treatment.
Agreeing to this does not mean you have given up any of your legal rights.
How will information about you be protected?
You have rights regarding the protection and privacy of your medical information
collected before and during this research. This medical information is called
"protected health information" (PHI). PHI used in this study may include your medical
record number, address, birth date, medical history, the results of physical exams,
blood tests, x-rays as well as the results of other diagnostic medical or research
procedures. Only the minimum amount of PHI will be collected for this research. Your
research and medical records will be maintained in a secure manner.
Who will have access to information about you?
By signing this consent form, you are allowing the research team to have access to
your PHI. The research team includes the investigators listed on this consent form
and other personnel involved in this specific study at the Institution.
Your PHI will be used only for the purpose(s) described in the section What is the
reason for doing this research study?
You are also allowing the research team to share your PHI, as necessary, with other
people or groups listed below:
The UNMC Institutional Review Board (IRB)
Institutional officials designated by the UNMC IRB
Federal law requires that your information may be shared with these groups:
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The HHS Office of Human Research Protections (OHRP)
The Food and Drug Administration (FDA)
National Institutes of Health (NIH)
The HIPAA Privacy Rule requires the following groups to protect your PHI:
Researchers at Creighton University.
Your PHI may also be shared with the following groups. However, these
organization(s) do not have the same obligation to protect your PHI:
National Institutes of Health, which sponsors this research and provides funds
the Institution to conduct this research
Data and Safety Monitoring Committee (DSMC)
You are authorizing us to use and disclose your PHI for as long as the research
study is being conducted.You may cancel your authorization for further collection of
PHI for use in this research at any time by contacting the principal investigator in
writing. However, the PHI which is included in the research data obtained to date
may still be used. If you cancel this authorization, you will no longer be able to
participate in this research.
How will results of the research be made available to you during and after the
study is finished?
You can search this website at any time. In most cases, the results of the research
can be made available to you when the study is completed, and all the results are
analyzed by the investigator or the sponsor of the research. The information from this
study may be published in scientific journals or presented at scientific meetings, but
your identity will be kept strictly confidential.
If you want the results of the study, contact the Principal Investigator at the phone
number given at the end of this form or by writing to the Principal Investigator at the
following address:
Nancy Waltman, PhD, APRN-NP
UNMC, College of Nursing, Lincoln
1230 O Street
Lincoln, NE 68588-0220
Laura Bilek, PhD, PT
School of Allied Health Professions
984420 NE Medical Center
Omaha, NE 68198-4000
A description of this clinical trial will be available on www.ClinicalTrials.gov, as
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required by U.S. law. This website will not include information that can identify you. At
most, the website will include a summary of the results.
What will happen if you decide not to be in this research study?
You can decide not to be in this research study. Deciding not to be in this research
will not affect your medical care or your relationship with the investigator or UNMC.
Your doctor will still take care of you and you will not lose any benefits to which you
are entitled.
What will happen if you decide to stop participating once you start?
You can stop participating in this research (withdraw) at any time by contacting the
Principal Investigator or any other research staff.
Deciding to withdraw will otherwise not affect your care or your relationship with the
investigator or UNMC. You will not lose any benefits to which you are entitled.
For your safety, please talk to the research team before you stop taking any study
drugs or stop other related procedures. They will advise you how to withdraw safely.
Will you be given any important information during the study?
You will be informed promptly if the research team gets any new information during
this research study that may affect whether you would want to continue being in the
study.
What should you do if you have any questions about the study?
You have been given a copy of "What Do I Need to Know Before Being in a
Research Study?" If you have any questions at any time about this study, you should
contact the Principal Investigator or any of the study personnel listed on this consent
form or any other documents that you have been given.
What are your rights as a research participant?
You have rights as a research subject. These rights have been explained in this
consent form and in The Rights of Research Subjects that you have been given. If
you have any questions concerning your rights or complaints about the research, you
can contact any of the following:
The investigator or other study personnel
Institutional Review Board (IRB)
Telephone: (402) 559-6463
Email: IRBORA@unmc.edu
Mail: UNMC Institutional Review Board, 987830 Nebraska Medical
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Center, Omaha, NE 68198-7830
Research Subject Advocate
Telephone: (402) 559-6941
Email: unmcrsa@unmc.edu
Documentation of informed consent
You are freely making a decision whether to be in this research study. Signing this
form means that:
You have read and understood this consent form.
You have had the consent form explained to you.
You have been given a copy of The Rights of Research Subjects
You have had your questions answered.
You have decided to be in the research study.
If you have any questions during the study, you have been directed to talk to
one of the investigators listed below on this consent form.
You will be given a signed and dated copy of this consent form to keep.
Signature of Subject ___________________________
Date ___________
My signature certifies that all the elements of informed consent described on this
consent form have been explained fully to the subject. In my judgment, the subject
possesses the legal capacity to give informed consent to participate in this research
and is voluntarily and knowingly giving informed consent to participate.
Signature of Person obtaining consent ___________________________
Date ___________
Authorized Study Personnel
Principal
* Waltman, Nancy
phone: 402-472-7354
alt #: 402-472-7354
degree: RN, APRN-NP, PhD
 
 
Secondary
* Bilek, Laura
phone: 402-559-6923
alt #: 402-402-6923
 
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degree: PT, PhD
 
Participating Personnel
* Ward, Jolene
alt #: 402-559-6584
degree: RN, MEd
 
 
Other Coordinator
 Stubby, Julie
alt email: jas@creighton.edu
alt #: 402-280-4958
degree: RN BSN
 
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