Conditions: Bariatric Surgery Candidate Bone Loss Weight Loss
Keywords: Bone Health
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 24
Healthy volunteers: yes

Brief summary:
This is a pilot project to determine the feasibility of recruiting, enrolling, treating, and following 24 older sleeve gastrectomy patients into a randomized controlled trial (RCT) examining the efficacy of bisphosphonate use versus placebo in the prevention of surgical weight loss associated loss of bone mass and quality.

Detailed description:
This pilot study is a RCT, involving 24 participants randomized to Risedronate or placebo capsules for 24 weeks. All subjects planning a sleeve gastrectomy (SG) procedure will be approached during their pre-surgical evaluation for possible participation in the study. Eligible participants will be referred onto the study coordinator to read/sign an IRB-approved informed consent prior to enrollment.

Two in-person baseline assessment visits \[baseline visit 1 (BV1), baseline visit 2 (BV2)\] occurring 1-6 weeks prior to surgery, and two in-person follow up assessment visits \[follow up visit 1 (FV1) and follow up visit 2 (FV2)\] occurring ±2 weeks from their 23-week post-surgery date will be conducted, as well as monthly medication compliance reminders and adverse event reporting via phone. Optional additional exploratory assessments include CT-derive bone health and blood-based biomarkers, as well as 12-month DXA, CT, and blood assessments. The Wake Forest WMC, under the direction of Drs. Ard and Fernandez, will serve as a source of recruitment for potential study participants.

Arms:
arm 1: Experimental: Risedronate sodium,150 mg capsule once every 4 weeks for 24 weeks. arm 2: Active comparator: Identical 150 mg placebo capsules once every 4 weeks for 24 weeks.

Interventions: intervention 1: Risedronate Sodium 150 MG intervention 2: Placebo
Intervention descriptions: intervention 1: Subjects randomized to the Risedronate group will take a 150 mg capsule of oral Risedronate once every 4 weeks for 24 weeks (6 doses), beginning 1 week prior to surgery and dispensed in blinded capsules from the WFSM research pharmacy. intervention 2: Participants randomized to the placebo group will receive 150 mg placebo capsule once every 4 weeks for 24 weeks (6 doses), beginning 1 week prior to surgery and dispensed in blinded capsules from the WFSM research pharmacy.

Protocol document:
ICF_000.pdf: 
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Adult Consent Form
Version: 5/28/20
IRB Template Version 6.7.2017
Informed Consent Form to Participate in Research
Wake Forest University Department of Health and Exercise Science and Wake 
Forest Baptist Health Weight Management Center
Title: Weight Loss with Risedronate for Bone Health 
(WE RISE)
Principal Investigators: Kristen Beavers, PhD and Jamy Ard, MD
Participant Name:   
INTRODUCTION
You are invited to be in a research study. Research studies are designed to gain scientific 
knowledge that may help other people in the future. You are being asked to take part in this study 
because you will undergo a vertical sleeve gastrectomy for weight loss. Your participation is 
voluntary. Please take your time in making your decision as to whether or not you wish to 
participate. Ask your study doctor or the study staff to explain any words or information 
contained in this informed consent document that you do not understand. You may also discuss 
the study with your friends and family.
WHY IS THIS STUDY BEING DONE?
The purpose of this research study is to examine the effect of a medication (Risedronate) on 
changes in bone density and quality against those not receiving the medication to see which is 
better. Risedronate is a medication that prevents bone breakdown and has been approved by the 
US Food and Drug Administration (FDA) for the prevention and treatment of osteoporosis in 
older men and women. However, Risedronate has not been approved for the prevention of 
bone loss following vertical sleeve gastrectomy.
In this study 6, once-a-month doses of 150 mg Risedronate will be compared to 6, once-a-month 
doses of placebo. A placebo is a substance, like a sugar pill, that is not thought to have any effect 
on your disease or condition. In this study you will either receive the active study medication, 
Risedronate, or a placebo which is not active. Placebos are used in research studies to see if the 
drug being studied really does have an effect.
How Many People Will Take Part in the Study?
A total of 24 people will take part in this study. To identify this number of participants, we 
may need to screen as many as 50 because some people will not qualify for the study.
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WHAT IS INVOLVED IN THE STUDY?
If you agree to participate in this study by signing this consent form, you will be asked to 
participate in two, in-person baseline assessment visits [baseline visit 1 (BV1), baseline visit 2 
(BV2)] occurring 1-6 weeks prior to surgery, and two, in-person follow up assessment visits 
[follow up visit 1 (FV1) and follow up visit 2 (FV2)] occurring in the month following your last 
medication date. During this period, you will also receive monthly medication dosage reminders 
and adverse event inquiries by phone. In addition, you will have the option to attend a two-part, 
12-month follow up assessment visits (FV3 and FV4) following the study intervention that would 
occur within a month and a half of your surgical anniversary date. For convenience and if 
feasible, both of these visits could possibly be scheduled on the same day.
The details about all study visits and procedures are provided below. We will make every effort 
to follow the visit procedures in the order they are outlined below; however, it may be necessary 
at times to make changes to accommodate different schedules.
Screening/Baseline Visit 1 (BV1)/Follow-up Visit 2
This visit will take place at the Wake Forest University Human Performance Lab. After agreeing 
to participate in the study by signing this Informed Consent form, we will collect a baseline 
measure of your height and weight, have you complete forms asking about your social 
background and medical history (including likelihood of pregnancy) and take inventory of the 
medications that you use. This will take about an hour. If you report that you are pregnant, you 
will not be allowed to continue with the study.
If you meet the study eligibility requirements, we will have you undergo scans of your body that 
measure the amount of bone, muscle, and fat at that same visit. This scan uses a Dual Energy X- 
ray Absorptiometry (DXA) machine. This procedure is a type of x-ray that is painless, but 
involves a very low dose of radiation. This involves use of a scanner that will pass across your 
body while you are lying quietly on a padded table for the duration of each scan (5-10 minutes), 
for a total of up to 30 minutes. For the majority of the scan time, you will be lying down and will 
not be able to get up until the scan is complete. Radiation exposure information can be found in 
the risks section of this document below. If the DXA scan results show that you have 
osteoporosis (weakening bone structure) we will inform you and you will not be eligible to 
continue with the study. Your results will be sent to Dr. Jamy Ard who will offer to refer you to a 
bone evaluation clinic. If you are eligible to continue, we will schedule you for another DXA scan 
to take place after you complete the active part of the study. This entire first visit will take about 
two hours.
Baseline Visit 2 (BV2)/Follow-up Visit 2
Within a 1-2 week period of the BV1 visit, you will be scheduled for a fasting blood draw and 
computed tomography (CT) scan of your abdomen and upper thigh before you begin the WE RISE 
study intervention. These visits will take place at the Clinical Research Unit (CRU) and Outpatient 
Radiology clinic, both located at Wake Forest Baptist Medical Center. For the blood test, you will be 
asked to go to the CRU in the morning between 7 and 9 am. You will be asked to fast (not eat or 
drink anything but water) for at least 12-hours prior to this visit. There, the study nurse will draw
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about 2 teaspoons of blood from a vein in your arm. The total amount of blood withdrawn during 
the study will be approximately 4 teaspoons. This blood will be tested to measure two markers of 
bone metabolism. After this, you will be offered a light snack.
The CT scan is painless and will help us to determine the quality and strength of your spine and 
hip bones (more details provided in the Risks Section of this form). For this test you will lie on a 
narrow, motorized table that slides through the opening into a tunnel. Straps and pillows may be 
used to help you stay in position. While the table moves you into the scanner, detectors and the 
X-ray tube rotate around you. You may hear buzzing, clicking and whirring noises. The whole 
procedure typically takes about 30 minutes but the visit itself will last about 1 hour to complete.
We will schedule you for one more blood draw and CT scan to take place after completing the 
active part of the study. After this you will be asked to complete a Participant Satisfaction Survey 
to see how satisfied you were with the study procedures.
Optional One-year Follow-up Visits 3 and 4 (FV3 and FV4)
These final two testing visits are optional. If you agree to participate you will be asked to return 12 
months after the 6-month medication intervention has ended to undergo similar procedures as in the 
Follow-up Visits 1 and 2 except that all procedures may take place on the same day. These follow-
up assessments will occur at both the Wake Forest University Human Performance Lab on the Wake 
Forest University campus, and at the Outpatient Radiology clinic located at Wake Forest Baptist 
Medical Center. The blood draw for this visit may occur in the Clinical Research Unit (as done 
previously) or it may take place at the Wake Forest University Human Performance Lab.. Refusing 
to participate will not result in any penalty or loss of benefits to which you are entitled.
Do you wish to participate in the One-Year Follow-up Visits 3 and 4?
[  ] Yes
[   ] No
 
Initials
Randomization and Intervention
After you have competed the two, baseline testing visits, you will be randomized into one of the 
study groups described below. Randomization means that you are put into a group by chance. It is 
like flipping a coin. You will have an equal chance of being placed in either group. Based on your 
randomized group assignment, either to the Risedronate group or placebo group, you will be 
asked to take one, 150 mg oral dose of encapsulated Risedronate or a placebo capsule every 
month for 6 months (a total of 6 doses). Under the direction of the study doctor, one bottle 
containing 6 pills will be provided to you prior to surgery. Also, you will be provided a written 
schedule of the dates when these doses are due to be taken over the course of the 6-month 
intervention. In addition, you will receive a monthly reminder call when each dose is due. At this 
time you will be asked to report any side effects that you may be experiencing and if of child- 
bearing potential, asked if you are pregnant. If you report that you are pregnant, you will not be 
allowed to continue with the study.
Neither you nor the investigator nor study staff will know which study drug you are receiving. 
This is done so that a fair evaluation of results can be made. This information is available to the 
researchers if needed in an emergency.
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Institutional Review Board 
IRB Number: IRB00048310
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Storage of Biological Tissue
If you agree to participate in this study, we will draw 2-3 teaspoons of the blood to use for future 
research. This sample will be kept and may be used in future research to learn more about other 
diseases. Your sample will be obtained in the Clinical Research Unit at Wake Forest University Baptist 
Medical Center. The sample will be stored at the Pepper Center Repository of the Biogerontology 
Laboratory under the supervision of Barbara Nicklas, PhD and it will be given only to researchers 
approved by Dr. Kristen Beavers. An Institutional Review Board (IRB) must also approve any future 
research study using your tissue sample. In order to participate in this study, you must be willing to 
provide this sample for future research.
Your blood sample will be stored with a unique identifier and will not include any identifiable 
information about you such as your name, address, telephone number, social security number, 
medical record number or any of the identifiers outlined in the HIPAA Privacy Rule. The unique 
identifier will be a randomly assigned number and only the principal investigator will have access to 
the code that links the unique identifier to you. Your name, address, social security number, etc., will 
never be disclosed to future researchers and neither will the code that links your identifiers to the 
sample.
In the future, people who do research may need to know more about your health. While the study 
investigator may give reports about your health, he/she will NOT be given your name, address, 
phone number, or any other identifying information about who you are, unless you agree to be 
contacted in the future.
 
YES you many contact for future research studies
 
NO I do not want to be contacted regarding future research studies.
HOW LONG WILL I BE IN THE STUDY?
If you agree to participate in the 6-month study, you will be in the study for about 7-8 months until 
the final study testing is complete. If you agree to participate in the optional 12-month assessment 
visit you would be in the study for approximately 10.5-13.5 months.
You can stop participating at any time. If you decide to stop participating in the study we encourage 
you to talk to the investigators or study staff first to learn about any potential health or safety 
consequences.
WHAT ARE THE RISKS OF THE STUDY?
Being in this study involves some risk to you. You should discuss the risk of being in this study 
with the study staff. Risks and side effects related to the procedures or medication we are 
studying include:
Blood draw
Blood tests are done 2 times for the 6-month study and 3 times if participating in the 12-month
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assessment visit. Blood tests can sometimes cause bruising, bleeding, and pain where the needle 
goes in. Sometimes, some people become dizzy, lightheaded or feel faint. Infection may occur 
on rare occasions. Frequent donation of blood can result in low iron in your blood (iron deficient 
anemia).
Body measurements and radiation
Health risks of the 6-month assessment procedures include exposure to radiation from the two 
DXA and two CT scans. If participating in the additional 12-month assessment visit this number 
will increase to three DXA and three CT scans. The amount of radiation that you will receive 
from these procedures is small and is similar to that received from clinical x-ray and nuclear 
medicine studies. The amount of radiation exposure that you will receive from the 6-month study 
is equivalent to a uniform whole body exposure of 966 millirem which is equal to 3.22 times the 
amount of natural background radiation that the average person in the United States receives each 
year (300 millirem).If you decide to also participate in the additional 12-month assessment the 
amount of exposure would increase to 1449 millirem or 4.83 times the amount of annual 
background radiation that the average person in the United States receives.
If the baseline DXA scan reveals that you have osteoporosis (weakening bone structure) in one or 
more regions of your body, you will be excluded from study participation and referred to Dr.
Jamy Ard to offer referral to a bone evaluation clinic.
Please be aware that this radiation exposure is necessary for this research study only and is not 
essential for your medical care. Wake Forest Baptist Health’s Radiation Safety Committee, a 
group of experts on radiation matters, has reviewed the use of radiation in this research study and 
has approved this use as being necessary to obtain the research information desired. The potential 
long-term risk from these radiation doses is uncertain, but these doses have never been associated 
with any definite adverse effects. Thus, the risk to you, if any, is estimated to be slight. The scans 
are being conducted only for the purpose of research. It is a different test than what is used in the 
clinical setting to detect or discover medical conditions. It is not a substitute for a clinical scan.
Research personnel will analyze the scan only for the specified research findings. If we should 
happen to see an abnormal finding that may be harmful to your health, we will notify you.
Unexpected findings on the limited research scan will occasionally allow early discovery of a 
medical condition (such as osteoporosis) for which you may need treatment. They may also cause 
undue worry or result in additional testing, sometimes costly, which may or may not benefit your 
health. If you participate in this study, you will be exposed to amounts of radiation above what 
you would normally receive in daily life. To be sure that you do not receive an unhealthy amount 
of radiation from your participation in this study, you should let your study doctor know if you 
have had, or are going to have, any other scans or x-rays as part of your medical or dental care. It 
is very important that you let the study doctor know if you already are participating in, or plan to 
participate in, any other research study that involves radiation exposure.
Medication Intervention
The medication being evaluated as a part of this study has known common side effects, such as skin 
rash (7.9%), mild stomach pain or upset stomach (2.9% to 12.2%), flu-like symptoms (up to 9.8%), 
muscle pain (5.9% to 28%), nausea (3.6% to 3.9%), diarrhea (4.9% to 10.8%), or constipation (2.9
% to 12.9%). Potentially serious side effects associated with the medication are abnormal heart beat
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(men 2%), arm and leg swelling (8.2%), bone pain (5.3%), kidney stones (3%), osteonecrosis of the 
jaw. You will be contacted by phone on a monthly basis in order to track these possible adverse 
effects. Additionally, we will review your medial record, including routine lab work performed at 
the Weight Management Center’s post-operative follow-up visits, to monitor medication safety. To 
minimize potential risk of gastrointestinal irritation from the study medication, persons with a prior 
history of severe reflux will be excluded from study participation and all active participants will be 
instructed to swallow the medication with 6 to 8 ounces of water at least 30 minutes prior to the 
first food or drink of the day while in an upright position. Participants will be further instructed not 
to lie down for at least 30 minutes after taking the drug and avoid taking vitamins, mineral 
supplements, or antacids at the same time.
The placebo medication used in the study has no known consequences; however, if you are not 
randomized to the active medication group, it is possible that you will not see any improvement 
in the quality and strength of your bones over the study period.
To minimize risks related to study tests, all study tests will be conducted by trained and certified 
staff. Safety precautions will be taken during all testing. When there are medically relevant 
findings, you will be informed and advised to consult your physician. We can send copies of your 
test results to your personal physician. Even if you do not wish to have any of your medical 
information sent to your physician, you can still participate in this research study.
Do you request that we send important medical findings from your study tests/exams to 
your personal physician?
[  ] Yes
[  ] No
 
Initials
If you decide to stop participating in the study treatment intervention for any reason, there will be no 
consequences other than the possibility that you may not see any change in your bone quality or 
strength.
There also may be other side effects that we cannot predict. You should tell the research staff 
about all the medications, vitamins and supplements you take and any medical conditions you 
have. This may help avoid side effects, interactions and other risks. Taking part in this research 
study may involve providing information that you consider confidential or private. Efforts, such 
as coding research records, keeping research records secure and allowing only authorized people 
to have access to research records, will be made to keep your information safe.
Reproductive Risks and other Issues to Participating in Research
Due to unknown risks and potential harm to the unborn fetus, sexually active women of 
childbearing potential must use a reliable method of birth control while participating in this 
study. Reliable methods of birth control are: abstinence (not having sex), oral contraceptives, 
intrauterine device (IUD), DepoProvera, tubal ligation, or vasectomy of the partner (with 
confirmed negative sperm counts) in a monogamous relationship (same partner). An acceptable, 
although less reliable, method involves the careful use of condoms and spermicidal foam or gel
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and/or a cervical cap or sponge. We encourage you to discuss this issue further with your 
physicians if you have any questions.
Contraceptive Measures for Male
Your participation in this research study may damage your sperm, which could cause harm to a child 
that you may father while on this study. Such harm may be currently unforeseeable. If you are 
sexually active, you must agree to use a medically acceptable form of birth control in order to be in 
this study and for an undetermined period of time following the study. There are currently no data on 
potential damage to sperm in humans taking Risendronate. Medically acceptable contraceptives 
include: (1) surgical sterilization (such as a vasectomy), or (2) a condom used with a spermicide.
Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not 
acceptable methods for routine use. You should inform your partner of the potential for harm to an 
unborn child. She should know that if pregnancy occurs, you will need to report it to the study 
doctor, and she should also promptly notify her doctor.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
If you agree to take part in this study, there may or may not be direct benefit to you. We hope the 
information learned from this study will benefit other people in the future. The benefits of 
participating in this study may be a reduction in bone loss during active weight loss, which may 
be critical in reducing long-term fracture risk in bariatric surgery patients. Because individuals 
respond differently to therapy, no one can know in advance if it will be helpful in your particular 
case. In addition, you will be paid $50 for completing both baseline testing visits and an 
additional $150 for completing all follow-up testing visits ($50 for the 6 month follow up 
assessments, and $100 for the 12 month follow up assessments).”
WHAT OTHER CHOICES ARE THERE?
This is not a treatment study. Your alternative is not to participate.
WHAT ARE THE COSTS?
All study costs, including the study medications and procedures related directly to the study, will 
be paid for by the study. Costs for your regular medical care, which are not related to this study, 
will be your own responsibility.
WILL YOUR RESEARCH RECORDS BE CONFIDENTIAL?
The results of this research study may be presented at scientific or medical meetings or published 
in scientific journals. Your identity and/or your personal health information will not be disclosed 
unless it is authorized by you, required by law, or necessary to protect the safety of yourself or 
others. There is always some risk that even de-identified information might be re-identified.
Participant information may also be provided to Federal and other regulatory agencies as 
required. The Food and Drug Administration (FDA), for example, may inspect research records
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and learn your identity if this study falls within its jurisdiction. The purpose of this research study 
is to obtain data or information on the safety and/or effectiveness of Risedronate; the results will 
be provided to the sponsor, the Food and Drug Administration and other federal and regulatory 
agencies as required.
WILL YOU BE PAID FOR PARTICIPATING?
You will be paid $50 after completing the two baseline screening visits and another $50 after 
completing the two, 6 month follow-up testing visits. If you agree to participate in both parts of 
the one-year follow-up testing, you will be paid an additional $100. All reimbursements are made 
by a check mailed to your home.
To receive payment, you must provide your social security number, name and address so that we 
can comply with IRS (Internal Revenue Service) reporting requirements. When payments are 
reported to the IRS we do not let them know what the payment is for, only that you have been 
paid. If you do not wish to provide this information you can still take part in this study but you 
will not be paid.
WHO IS SPONSORING THIS STUDY?
This study is being sponsored by the Center for Diabetes, Obesity, and Metabolism at Wake 
Forest School of Medicine, the Wake Forest University Health Sciences Weight Management 
Center, and the Wake Forest University Department of Health and Exercise Science. The 
sponsors are providing money or other support to help conduct this study. The researchers do not, 
however, hold a direct financial interest in the sponsor or the product being studied.
WHAT HAPPENS IF YOU EXPERIENCE AN INJURY OR ILLNESS AS A
RESULT OF PARTICIPATING IN THIS STUDY?
Should you experience a physical injury or illness as a direct result of your participation in this 
study, Wake Forest University School of Medicine maintains limited research insurance coverage for 
the usual and customary medical fees for reasonable and necessary treatment of such injuries or 
illnesses. To the extent research insurance coverage is available under this policy the reasonable costs 
of these necessary medical services will be paid, up to a maximum of $25,000. Wake Forest 
University Baptist Medical Center holds the insurance policy for this coverage. It provides a 
maximum of $25,000 coverage for each claim and is limited to a total of $250,000 for all claims in 
any one year. The Wake Forest University School of Medicine, and the North Carolina Baptist 
Hospitals, Incorporated do not assume responsibility to pay for these medical services or to provide 
any other compensation for such injury or illness. Additional information may be obtained from the 
Medical Center’s Director of Risk and Insurance Management, at 
.
If you are injured, the insurer may require information such as your name, social security number, 
and date of birth in order to pay for your care. This is because the insurer is required by law to 
report any payments made to cover the care of any persons who are members of a government 
insurance plan to the Department of Health and Human Services.
You do not give up any legal rights as a research participant by signing this consent form. For
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more information on medical treatment for research related injuries or to report a study related 
illness, adverse event, or injury you should you should call Dr. Kristen Beavers at 
 
Department of Health and Exercise Science, Wake Forest University, or Dr. Jamy Ard, 
MD, Weight Management Center at 
. After hours call 
 
.
What About My Health Information?
In this research study, any new information we collect from you and/or information we get from 
your medical records or other facilities about your health or behaviors is considered Protected 
Health Information. The information we will collect for this research study includes: personal 
demographic data, race, social and health information, and bone health assessment data.
We will make every effort to keep your Protected Health Information private. We will store 
records of your Protected Health Information in a cabinet in a locked office or on a password 
protected computer. Your personal health information and information that identifies you (“your 
health information”) may be given to others during and after the study. This is for reasons such as 
to carry out the study, to determine the results of the study, to make sure the study is being done 
correctly, to provide required reports and to get approval for new products.
Some of the people, agencies and businesses that may receive and use your health information are 
the research sponsor; representatives of the sponsor assisting with the research; investigators at 
other sites who are assisting with the research; central laboratories, reading centers or analysis 
centers; the Institutional Review Board; representatives of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital; representatives from government agencies such as 
the Food and Drug Administration (FDA), the Department of Health and Human Services 
(DHHS) and similar agencies in other countries.
Some of these people, agencies and businesses may further disclose your health information. If 
disclosed by them, your health information may no longer be covered by federal or state privacy 
regulations. Your health information may be disclosed if required by law. Your health 
information may be used to create information that does not directly identify you. This 
information may be used by other researchers. You will not be directly identified in any 
publication or presentation that may result from this study unless there are photographs or 
recorded media which are identifiable.
Monitors, auditors, IRB or other regulatory agencies will be granted direct access to the 
participant’s original medical record for verification of clinical trial procedures or data, without 
violating confidentiality of the participant and to the extent permitted by other applicable laws.
If required by law or court order, we might also have to share your Protected Health Information 
with a judge, law enforcement officer, government agencies, or others. If your Protected Health 
Information is shared with any of these groups it may no longer be protected by federal or state 
privacy rules.
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Any Protected Health Information collected from you in this study that is maintained in the 
research records will be kept for at least six years after the study is finished. At that time any 
research information not already in your medical record will either be destroyed or it will be de- 
identified. You will not be able to obtain a copy of your Protected Health Information in the 
research records until all activities in the study are completely finished.
You can tell Dr. Kristen Beavers or Dr. Jamy Ard that you want to take away your permission to 
use and share your Protected Health Information at any time by sending a letter to either of these 
addresses:
Kristen Beavers, PhD
 
Jamy Ard, MD
 
However, if you take away permission to use your Protected Health Information you will not be 
able to be in the study any longer. We will stop collecting any more information about you, but 
any information we have already collected can still be used for the purposes of the research 
study.
By signing this form you give us permission to use your Protected Health Information for this 
study.
If you choose to participate in this study, your medical record at Wake Forest University Baptist 
Medical Center will indicate that you are enrolled in a clinical trial. Information about the research 
and any medications or devices you are being given as a participant may also be included in your 
medical record. This part of the medical record will only be available to people who have authorized 
access to your medical record. If you are not a patient at this Medical Center, a medical record will 
be created for you anyway to ensure that this important information is available to doctors in case of 
an emergency.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 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. You can search this Web site at any time.
Laboratory test results and other medical reports created as a result of your participation in the 
research study may be entered into the computer systems of Wake Forest University Health 
Sciences and North Carolina Baptist Hospital. These will be kept secure, with access to this 
information limited to individuals with proper authority, but who may not be directly involved 
with this research study.
A North Carolina Baptist Hospital (NCBH) medical record will be created for all study
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00048310
Meeting Date Approved 6/2/2020          
Version Valid Until: 12/29/2020


Page 11 of 11
Adult Consent Form
Version: 5/28/20
IRB Template Version 6.7.2017
participants. Information about your participation in the study will be placed in the NCBH 
medical record, along with any routine medical test results that were obtained at NCBH as part 
of this study.
WHAT ARE MY RIGHTS AS A RESEARCH STUDY PARTICIPANT?
Taking part in this study is voluntary. You may choose not to take part or you may leave the study 
at any time. Refusing to participate or leaving the study will not result in any penalty or loss of 
benefits to which you are entitled. If you decide to stop participating in the study we encourage 
you to talk to the investigators or study staff first to learn about any potential health or safety 
consequences. The investigators also have the right to stop your participation in the study at any 
time. This could be because it is in your best medical interest, your condition worsened, new 
information becomes available, you had an unexpected reaction, you failed to follow instructions, 
or because the entire study has been stopped. You will be given any new information we become 
aware of that would affect your willingness to continue to participate in the study.
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
For questions about the study or in the event of a research-related injury, contact the study 
investigator, call Dr. Kristen Beavers at 
, Department of Health and Exercise 
Science, Wake Forest University, or Dr. Jamy Ard, MD, Weight Management Center at 
 
. After hours call 
.
The Institutional Review Board (IRB) is a group of people who review the research to protect 
your rights. If you have a question about your rights as a research participant, or you would like 
to discuss problems or concerns, have questions or want to offer input, or you want to obtain 
additional information, you should contact the Chairman of the IRB at 
. You will 
be given a copy of this signed consent form.
SIGNATURES
I agree to take part in this study. I authorize the use and disclosure of my health information as 
described in this consent and authorization form. If I have not already received a copy of the 
Privacy Notice, I may request one or one will be made available to me. I have had a chance to 
ask questions about being in this study and have those questions answered. By signing this 
consent and authorization form, I am not releasing or agreeing to release the investigator, the 
sponsor, the institution or its agents from liability for negligence.
Subject Name (Printed):  
Subject Signature: 
Date: 
Time: 
am pm
Person Obtaining Consent (Printed):  
Person Obtaining Consent: 
Date: 
Time: 
am pm
WFU School of Medicine 
Institutional Review Board 
IRB Number: IRB00048310
Meeting Date Approved 6/2/2020          
Version Valid Until: 12/29/2020

SAP_002.pdf: 
Study Title:  Effect of bisphosphonate use on surgical weight loss associated bone loss in older adults 
with morbid obesity (WEight loss with RISEdronate for bone health; WE RISE) 
IRB00048310 
NCT03411902 
Date:  12/29/20 
Principal Investigator, Co-investigator(s): Co-PIs: Kristen Beavers and Jamy Ard. Co-Is: Adolfo 
Fernandez, Daniel Beavers, Ashley Weaver, and Laura Flores 
 
 
 
 
Statistical Analysis Plan 
 
Baseline characteristics were summarized overall and by randomized treatment group as means and 
standard deviations (mean±SD) for continuous variables or counts and percentages [n (%)] for discrete 
variables. Treatment effects of risedronate versus placebo were estimated using a mixed linear model fit 
with treatment assignment, visit, and treatment by visit interaction, adjusted for baseline characteristics of 
each outcome and assuming an unstructured covariance. Groups were compared using contrast statements 
at six and 12 months, with change over six months being the primary comparison. All statistical analyses 
were performed using SAS v9.4 (SAS Institute, Cary, NC) with significance based on a Type I error rate 
of 0.05. Because the study was designed as a pilot to determine feasibility and gather evidence for future 
work, analyses were not adjusted for multiple outcomes, and findings are not considered confirmatory. 
 

Prot_001.pdf: 
Protocol version: 10/1/20 
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1 
Study Title:  Effect of bisphosphonate use on surgical weight loss associated bone loss in older adults 
with morbid obesity (WEight loss with RISEdronate for bone health; WE RISE) 
IRB00048310 
NCT03411902 
Date:  10/1/20 
Principal Investigator, Co-investigator(s): Co-PIs: Kristen Beavers and Jamy Ard. Co-Is: Adolfo 
Fernandez, Daniel Beavers, Ashley Weaver, and Laura Flores 
Sponsor or Funding Source: Internal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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2 
Background, Rationale and Context 
  
1.   Significance 
1.A. Osteoporosis is a significant public health problem in older adults with obesity, which may be 
exacerbated with weight loss. Worldwide, one in three women and one in five men over the age of 50 
will experience an osteoporotic fracture in their lifetimes,1 with prevalence highest among those who are 
overweight and obese.2 Osteoporosis-related fractures of the hip and spine are the leading causes of injury 
in older adults, compromising both quality and expectancy of life. Bone mineral density (BMD) is a 
strong predictor of future osteoporotic fracture, with observational data consistently linking weight loss in 
late life with loss of BMD and increased fracture risk, regardless of intentionality of weight loss or initial 
body weight.3,4 This finding is echoed in the randomized controlled trial literature, where dietary-induced 
weight loss interventions of at least 6 months in duration are consistently associated with small, but 
significant, decreases in total hip BMD (on the order of 0.010-0.015 g/cm2 and conferring a 10-15% 
increase in fracture risk).5 Accordingly, greater weight loss exacerbates this decline in BMD and 
subsequent risk of fracture,6–8 with meta-analytic data showing BMD at the hip and spine is reduced by 
0.1 g/cm2 in the year following bariatric surgery (yielding ~35% weight loss),9 representing a 10% decline 
from pretreatment values, 10 times what is expected from lifestyle-based interventions, and similar in 
magnitude to what is seen in studies of unloading. Alarmingly, emerging long-term data suggest that bone 
loss continues in these patients even after weight stabilizes,9,10 with deterioration seen up to 5 years post-
surgery.11 Thus, of mounting concern to clinicians and patients, despite well recognized improvements in 
body weight and cardiometabolic indices, collective evidence suggests bariatric surgery irreversibly 
increases skeletal fragility and fracture risk, providing impetus to identify effective strategies to minimize 
bone loss during active weight loss in these patients. 
 
1.B. Bisphosphonate use reduces osteoporotic fracture risk and may be effective in minimizing 
surgical weight loss associated bone loss. Several FDA-approved pharmacotherapeutic options for 
osteoporosis are available at this time, and include: antiresorptive agents (i.e., bisphosphonates), selective 
estrogen receptor modulators (i.e., raloxifene), and hormonal agents (i.e., estrogen, teraparatide). 
Bisphosphonates are the most commonly prescribed drug to treat osteoporosis, and act by inhibiting 
activity of osteoclast cells, thereby decreasing the rate of bone resorption.12 Among oral bisphosphonates, 
Alendronate and Risedronate have been shown to reduce the number of vertebral and hip fractures,13 with 
Risedronate associated with significantly lower incidence of gastric and esophageal ulcers than 
Alendronate.14 Clinical practice guidelines support the consideration of oral bisphosphonate use in 
bariatric surgery patients with osteoporosis (provided that concerns about absorption or potential 
anastomotic ulceration are obviated),15 but no studies have examined the efficacy of oral bisphosphonate 
use to prophylactically attenuate surgical weight loss associated bone loss. Because weight loss is 
associated with a significant increase in bone resorption,16,17 bisphosphonate use may prove effective at 
countering bone loss during active weight loss, which may be critical in reducing long-term fracture risk 
in bariatric surgery patients.  
 
1.C. Current evidence on the effect of surgical-induced weight loss on measures of bone health are 
limited to traditional BMD metrics, select procedures, and younger populations. Dual-energy x-ray 
absorptiometry (DXA) acquired areal (a)BMD is the primary metric by which osteoporosis is assessed. 
However, more than half of all fractures occur in persons without osteoporosis (defined by aBMD), 18 
indicating aBMD alone cannot sufficiently quantify all future fracture risk. Furthermore, acquisition of 
aBMD in the context of obesity and weight loss is limited by methodological issues (e.g., influence of 
adipose tissue on aBMD measurement, overall reduction in precision). Increasingly, volumetric BMD 
(vBMD) obtained with quantitative computed tomography (CT) is used to complement DXA-acquired 
aBMD estimates,19 as less concern exists about obesity and weight loss-induced measurement error.20 
Further, CT allows for assessment of additional parameters of bone quality, including structure and 
strength, which add to fracture risk predictive power.21–23 In addition to CT-derived measures of bone 


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3 
quality, integration of biomarkers of bone metabolism with skeletal imaging data provide an early and 
sensitive measure of bone remodeling, and positively correlate with BMD and fracture risk. 24 
 
Studies assessing the effect of bariatric surgery on bone quality are less numerous and consistent than 
DXA studies,7,10–14 and most are limited to data collected following the Roux-en-Y gastric bypass 
(RYBG) procedure and at peripheral sites (i.e., radius and tibia). Recently, there has been a national shift 
away from RYGB procedures in favor of sleeve gastrectomy (SG; comprises 50% of surgical weight loss 
procedures performed at Wake Forest Weight Management Clinic [WMC]).28 This may have important 
implications on bone health, as nutrient deficiencies and ulcerations are less likely with SG; however, 
little empirical evidence exists to guide clinical understanding. To our knowledge only one study, 
conducted in primarily young to middle-aged adults, has been published examining the effects of SG (and 
RYGB) gastrectomy on aBMD and vBMD.29 Authors report losses of hip and spine aBMD and vBMD in 
both groups, with potentially greater hip losses experienced in the RYGB group; although, findings 
warrant replication, particularly in older adults as they are at elevated risk of fracture.   
Objectives 
The main objective of this pilot project is to determine the feasibility of recruiting, enrolling, treating, and 
following 24 older SG patients into a randomized controlled trial (RCT) examining the efficacy of 
bisphosphonate use (versus placebo) in the prevention of surgical weight loss associated loss of bone 
mass and quality. 
 
Methods and Measures 
 
Design and Setting 
This pilot study is a RCT, involving 24 participants randomized to consume Risedronate or placebo 
capsules for 24 weeks, and then followed for an additional 6 months. Two in-person baseline assessment 
visits [baseline visit 1 (BV1), baseline visit 2 (BV2)] occurring 1-6 weeks prior to surgery, two in-person 
6 month follow up assessment visits [follow up visit 1 (FV1) and follow up visit 2 (FV2)] occurring 
within 1 month of their last pill date, and two, in-person 12 month follow up legacy assessment visits 
(FV3 and FV4) occurring within 1.5 months of their surgical anniversary date, as well as monthly 
medication compliance reminders and adverse event reporting during the active intervention period via 
phone (see Table 1). The Wake Forest WMC, under the direction of Drs. Ard and Fernandez, will serve 
as a source of recruitment for potential study participants. 
 
Table 1. Proposed Study Assessment Timeline. 
 
Location: 
WFU 
WFSM 
WFU 
WFU 
WFSM 
WFU 
WFSM 
Week/Month Number: 
-6 to -3 
-3 to -1 
-1 to 
+23 
Within 1 month 
following last pill date 
Within 1.5 months of 
their surgery date 
anniversary  
 
BV1 
BV2 
INT 
FV1 
FV2 
FV3 
FV4 
Informed Consent   
x 
 
 
 
 
 
 
Demographic Characteristics 
x 
 
 
 
 
 
 
Medical History/Medication Use 
x 
 
x 
 
 
 
 
BMD/FRAX Questionnaire 
x 
 
 
x 
 
x 
 
DXA Assessment (total body 
and regional BMD) 
x 
 
 
x 
 
x 
 
CT Assessment (hip/spine 
vBMD and bone quality) 
 
x 
 
 
x 
 
x 
Fasting Blood Draw for   
 
x 
 
 
x 
 
x 


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4 
Biomarkers of bone turnover 
Monthly Medication 
Compliance reminders and 
Adverse Event Collection 
  
 
x 
 
 
 
 
Participation Satisfaction Survey 
 
 
 
 
x 
 
 
 
Participant Recruitment and Subject Selection Criteria 
All subjects planning a SG procedure will be approached during their pre-surgical evaluation for possible 
participation in the study. Phase I exclusion criteria will be evaluated by phone screen and include age 
<40 years, baseline weight >450 pounds (DXA limit), chronic anti-reflux treatment, history of medical 
disorders known to affect bone metabolism, use of bone‐active medications, or a known allergy to 
Risedronate. Participants who are given Phase I clearance will be further evaluated by the study physician 
(Drs. Ard/Fernandez, Phase II clearance) for potential eligibility (see Table 2). Eligible participants will 
be referred onto the study coordinator to read/sign an IRB-approved informed consent prior to enrollment.  
 
Table 2. Proposed Inclusion and Exclusion Criteria. 
 
Clearance Criteria 
Inclusion 
Exclusion 
Assessment 
Phase I 
Sleeve Gastrectomy  
Yes 
 
Referred from WMC
Age 
40-79 years  
 
Self-report 
Weight Status 
 
Weight greater than 450 lbs (DXA 
limit) 
Scale 
Medication use 
 
Regular use of growth hormones, oral
steroids, or prescription osteoporosis 
medications; known allergies to 
bisphosphonates. Unstable gastric 
reflux requiring 2 or more additional 
doses per month of anti-reflux 
medication. 
Medical Record 
Research participation Willing to provide 
informed consent; 
agree to all study 
procedures and 
assessments. 
Current participation in other research
study; Unable to provide own 
transportation to study visits; unable 
to position on scanner independently.
Self-report 
Phase II 
Physician Clearance 
Study MD 
approves safe 
participation. 
Participant presents with clinical 
contraindications (i.e. creatinine 
clearance <30, hypocalcemia, 
osteoporosis, pregnancy, esophageal 
abnormalities, increased risk of 
ulceration or electrolyte 
abnormalities) 
Medical Record or 
study baseline DXA 
scan 
 
Sample Size 
Twenty-four patients will be recruited to participate, with 12 randomized to the Risedronate group and 12 
randomized to the placebo group, blocking by gender. Because this pilot is focused on feasibility and 
gathering evidence to inform future studies, all analyses are exploratory rather than confirmatory. 
 
Interventions and Interactions 
Risedronate is a pyridinyl bisphosphonate with potent anti-resorptive activity30,31 which was approved at 
the 150 mg monthly dose for the prevention and treatment of post-menopausal osteoporosis.32 Subjects 
randomized to the Risedronate group will take a 150 mg capsule of oral Risedronate once every 4 weeks 
for 24 weeks (6 doses), beginning 1 week prior to surgery. One bottle containing 6 blinded capsules will 
be dispensed from the WFSM research pharmacy to each participant at the second baseline visit (BV2). 


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Participants will be instructed to follow label instructions for the proper method of medication intake to 
minimize GI discomfort (i.e., take medication with 6-8 oz of plain water, remain upright for the next 30 
minutes, avoid taking vitamins, mineral supplements, or antacids at the same time). Supplemental calcium 
and vitamin D will be provided to participants as a part of their post-surgical care and participants will be 
asked to take these supplements at least 30 minutes after taking the study medication. Participants 
randomized to the placebo group will receive identical placebo capsules and follow the same dosing 
protocol as the active treatment group, with both participants and study staff blinded to treatment 
allocation. To aid in compliance and safety monitoring, participants will receive monthly phone 
reminders to take their medications and will be queried for potential pregnancy (if applicable) and any 
new adverse events. After completing the active intervention period, subjects will return for follow up 
testing (i.e. FV1, FV2) and then return to free living conditions. Because bone remodeling requires a 
minimum of 4-6 months and continues for at least 12 months,33 subjects will be asked to return within the 
one month following their surgical date anniversary date for additional follow up testing (FV3, FV4) to 
examine intervention legacy effects. 
 
Assessments 
DXA-Acquired Outcome Measures  
All DXA-acquired outcome measures will be assessed at BV1 and FV1. If obtainable, total body 
composition as well as areal BMD of the total hip, femoral neck, lumbar spine and distal radius and 
Trabecular Bone Score of the lumbar spine will be determined by DXA (iDXA, GE Medical Systems, 
Madison, WI), housed within the Wake Forest University Department of Health and Exercise Science. All 
scans will be performed and analyzed in accordance with national recommendations by an International 
Society for Clinical Densitometry (ISCD) trained DXA technologist.  
 
CT-Acquired Outcome Measures 
All CT-acquired outcome measures will be assessed at BV2 and FV2. Single-energy helical CT scans of 
the femurs and lumbar spine will be acquired on a Siemens SOMATOM Definition Flash dual source CT 
scanner, housed within the WFSM, Department of Radiology. The scan coverage for the lumbar spine 
will be from the top of L1 through the base of L5, and the bilateral femur scan will cover the region from 
the superior acetabulum to mid-femur. Both scans will be conducted at SFOV 50 cm, 120 KVp, 350 mA, 
1 mm helical with a pitch of 1, and a gantry speed 0.8 second, standard reconstruction, with secondary 
reconstruction set at 0.625 mm thick, bone algorithm.  A 5-port bone mineral calibration phantom 
(Mindways Software, Inc., Austin, TX) will be imaged in every scan to allow for measurement of 
vBMD.34 Quality assurance and processing of CT images for cortical thickness and finite element derived 
strength estimates will be performed according to published methodology by Dr. Weaver (select examples 
in Figure 1).35,36 
  
A) 
B) 
C) 
Figure 1. A) Exemplar lumbar CT with Mindways phantom. B) Lumbar and hip vBMD measurement in 
QCT ProTM. C) Older male from experienced cortical thinning relative to baseline (left) following 6.8% 
weight loss over 18 months (right). 
 
Biomarkers of Bone Turnover 
Blood samples will be collected at BV2 and FV2 via venipuncture after an overnight fast (of ≥10 hours) 
and abstinence from physical activity for the previous 24 hours. After centrifugation for 20 minutes at 
4 mm
3 mm
2 mm
1 mm
0 mm


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6 
4ºC, aliquots of serum will be stored at -70ºC. Analyses of a bone formation marker (Procollagen Type 1 
N-Terminal Propeptide, P1NP), and a bone resorption marker (C-Terminal Telopeptide of Type 1 
Collagen, CTX) will be performed, by technicians in the ELISA Core laboratory using commercially 
available ELISAs (Neo Scientific, Cambridge, MA) as done previously.37 
 
Baseline and Covariate Measures 
Self-reported demographic information (i.e., age, gender, ethnicity, socioeconomic status) will be 
assessed at BV1. Participants will be queried at BV1 and FV1 on medical information relevant to assess 
10-year major osteoporotic and hip fracture risk using the FRAX tool.38 We will also record medication 
use by asking participants to bring in all medications (including nutritional supplements) and electronic 
medical records will be reviewed to assess co-morbid conditions. 
 
Analytic Plan  
This pilot is focused on feasibility and gathering evidence to inform future studies; thus, all analyses are 
considered exploratory rather than confirmatory. Baseline characteristics will be summarized using 
descriptive measures both overall and by gender at baseline. Feasibility will be based on retention of 
participants at follow-up visits. Follow-up treatment effect estimates at 6 and 12 months on bone metrics 
will yield means, standard deviations, and within-person correlations for use in power estimates for future 
clinical trials. Secondary analyses will examine change in bone metrics predicted by the magnitude of 
weight lost using linear regression models and adjusted for baseline values, as well as whether 
associations differ across demographic (i.e. gender, race) subgroups. Dr. Daniel Beavers will oversee all 
statistical analyses. 
 
Human Subjects Protection 
 
Subject Recruitment Methods 
The WMC will serve as the source of recruitment for potential study participants. Based on 216 sleeve 
gastrectomy procedures performed in FY2016 (average age 44.5 years), we expect a total recruitment 
pool of 18 participants/month, of which we anticipate a 35% recruitment rate to our study. Thus, 
enrollment of 6 participants/month with a baseline assessment (occurring 3-6 weeks prior to surgery) and 
follow up assessment occurring in the month following their last pill date, will allow us to recruit 20-24 
participants within the allotted time period. All subjects planning a SG procedure will be approached 
during their pre-surgical evaluation by the WMC Surgery Coordinator for possible participation in the 
study. Contact information interested participants will be referred to the study coordinator for phone 
screen, eligibility (see Table 2), and potential scheduling of BV1. 
 
 
Sources of Research Material 
Participants will self-report personal information on paper survey forms including personal demographic 
data, race, health information, psychological, social, and study satisfaction data.  Results will also be 
recorded in a computer database.  Data from the paper forms will be entered into an electronic database 
on a computer workstation.  All material and data will be obtained solely for research purposes. 
 
Informed Consent 
Interested participants who are eligible via a telephone screening interview, are invited to a baseline visit. 
The informed consent process will follow the procedures of the WFSM Institutional Review Board. The 
study interviewers explain the purpose, methods and extent of the study to prospective participants. The 
potential participant is asked to read the informed consent form and ask questions. The form is written in 
simple easy to understand language. We require study staff to review all of the key aspects of the study 
verbally with the potential participants. Staff are provided with a structured checklist for this purpose. Staff 
are then required to question potential participants to ascertain whether s/he has understood the information. 


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Potential participants who are illiterate or have impaired vision must have the consent read to them, 
followed by review of the checklist, opportunity for questions, and discussion. A copy of the signed and 
dated consent form will be given to participants, and the original document will be placed in subjects’ 
individual study files, which will be stored in a secure location. In compliance with the Health Insurance 
Portability and Accountability Act (HIPAA) and the Standards for Privacy of Individually Identifiable 
Health Information of the Department of Health and Human Services, we will access personal health 
information only after obtaining informed consent. 
 
According to the NIH and the Office of Human Research Protection (OHRP) guidelines, the informed 
consent will contain the following elements: 
1. A statement that the study involves research. 
2. An explanation of the purposes of the research. 
3. The expected duration of the subject's participation. 
4. A description of the procedures to be followed. 
5. Identification of any procedures which are experimental. 
6. A description of any reasonably foreseeable risks or discomforts to the subject. 
7. A description of any benefits to the subject that may reasonably be expected from the research. 
8. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be 
advantageous to the subject. 
9. A statement describing the extent to which confidentiality of records identifying the subject will be 
maintained. 
10. An explanation of whether any compensation and any medical treatments are available if a 
research-related injury occurs and, what these consist of, or where further information is obtained. 
11. An explanation of whom to contact for answers to pertinent questions about the research and 
research subjects' rights, and whom to contact in the event of a research-related injury. 
12. A statement that participation is voluntary, refusal to participate will involve no penalty or loss of 
benefits to which the subject is otherwise entitled, and the subject may discontinue participation at 
any time without penalty or loss of benefits, to which the subject is otherwise entitled. 
13. Anticipated circumstances under which subject participation may be terminated by the investigator 
without regard to the subject's consent. 
14. Any additional costs to the subject that may result from participation in the research. 
15. The consequences of a subject's decision to withdraw from the research and procedures for orderly 
termination of participation by the subject. 
16. A statement that significant new findings developed during the course of the research, which may 
relate to the subject's willingness to continue participation, will be provided to the subject. 
17. The approximate number of subjects involved in the study. 
 
Potential Risks 
There are inherent potential risks to human subjects who participate in any research study and the 
potential risks to study participants in this study are listed below. Any injuries or illnesses (severe adverse 
events) during the course of a participant’s enrollment in the study will be monitored regularly at monthly 
intervention sessions. A health risk of the study testing may be discovery of osteoporosis at during the 
DXA scan. Subjects who are identified as having hip or spine T-score value(s) of >-2.5 at baseline will be 
excluded from study participation. Participants identified as osteoporotic at any DXA assessment will be 
offered referral to a bone evaluation clinic. Health risks of the intervention include rare, but serious, side 
effects from taking Risedronate, including chest pain, difficulty or pain when swallowing, pain or burning 
under the ribs or in the back, new or worsening heartburn, severe or ongoing indigestion, severe joint, 
bone, or muscle pain, new or unusual pain in the thigh or hip, or jaw pain, numbness, or swelling. Less 
serious side effects may include mild stomach pain or upset stomach, flu-like symptoms, muscle pain, 
diarrhea, constipation, mild joint or back pain, or headache. Health risks of the assessment procedures 
include exposure to radiation from the DXA and CT scans. The amount of radiation that participants will 


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8 
receive from these procedures is equivalent to a uniform whole body dose of 1449 mrem, or 29% of the 
yearly radiation exposure limit allowed for a radiation worker (5000 mrem). 
 
Safety Measures During the Intervention and Assessments 
To control risk of further bone loss, persons identified as having osteoporosis will be excluded from study 
participation. To minimize potential risk of GI irritation, persons with a prior history of severe reflux will 
be excluded from study participation and all active participants will be instructed to take the medication 
following manufacturer recommendations (i.e., take the medication with 6-8 oz of plain water and remain 
upright for the next 30 minutes). To minimize assessment associated risk, all study assessments will be 
conducted by trained and certified staff. Safety precautions will be taken during all testing by applying 
standardized stopping criteria. If the participant reports pain, tightness or pressure in the chest, feeling faint, 
lightheaded or dizzy, or any other medical problems, the test will be stopped. When there are medically 
relevant findings, the participant will be told the cause for concern, and may be advised to consult his or her 
physician. If given permission by the participant, a letter will be sent to her primary care physician stating 
the concern. Because of the potential for pregnancy in some participants during the study, urinary 
pregnancy tests will be administered before each DXA/CT assessment, and all women of childbearing 
potential will be provided with monthly pregnancy tests, upon request. Should pregnancy be detected, 
participants will discontinue the intervention immediately and will not complete follow up DXA or CT 
assessments. However, because sleeve gastrectomy patients are advised not to become pregnant at least 12 
months following their surgery, the estimated pregnancy risk is slight. 
 
Confidentiality and Privacy 
Data will be used only in aggregate and no identifying characteristics of individuals will be published or 
presented. Results of testing will be sent to participant's private physicians if participants agree to this. 
Confidentiality of data is maintained by using research identification numbers which uniquely identify each 
individual. The information collected from participants in this study has a low potential for abuse because 
the data does not address sensitive issues. Nevertheless, appropriate measures are taken to prevent 
unauthorized use of study information. Data other than demographic information do not use names as an 
identifier. The research ID number is used. The research records are kept in locked cabinets in the 
Department of Health and Exercise Science, WFU. The files matching the participants' names and 
demographic information with the research ID numbers are kept in a separate room and locked file that uses 
a different key from that of all other files. Files may not be obtained from the research unit by persons other 
than research personnel, who are asked to sign a document agreeing to maintain the confidentiality of the 
information. After the study is completed, the local data will be stored with other completed research 
studies in a secured storage area. 
 
 
Data and Safety Monitoring 
The Co-PIs (Drs. Kristen Beavers and Jamy Ard) will be responsible for the overall monitoring of the 
data and safety of study participants.  The Co-PIs will be assisted by other members of the study staff. 
 
Reporting of Unanticipated Problems, Adverse Events or Deviations 
Any unanticipated problems, serious and unexpected adverse events, deviations or protocol changes will 
be promptly reported by the Co-PIs or designated member of the research team to the IRB and sponsor or 
appropriate government agency if appropriate. 
 
References 
 
1.  
Facts and Statistics | International Osteoporosis Foundation [Internet]. [cited 2017 Mar 29]. 
Available from: https://www.iofbonehealth.org/facts-statistics 


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2.  
Nielson CM, Srikanth P, Orwoll ES. Obesity and fracture in men and women: an epidemiologic 
perspective. J Bone Miner Res. 2012 Jan;27(1):1–10. PMID: 23348758 
3.  
Ensrud KE, Ewing SK, Stone KL, Cauley JA, Bowman PJ, Cummings SR. Intentional and 
unintentional weight loss increase bone loss and hip fracture risk in older women. J Am Geriatr Soc. 
2003 Dec;51(12):1740–1747. PMID: 14687352 
4.  
Shapses SA, Sukumar D. Bone metabolism in obesity and weight loss. Annu Rev Nutr. 2012 Aug 
21;32(1):287–309. PMID: 22809104 
5.  
Zibellini J, Seimon RV, Lee CM, Gibson AA, Hsu MS, Shapses SA, Nguyen TV, Sainsbury A. 
Does diet-induced weight loss lead to bone loss in overweight or obese adults? A systematic review 
and meta-analysis of clinical trials. J Bone Miner Res. 2015 Dec 1;30(12):2168–2178. PMID: 
26012544 
6.  
Lu C-W, Chang Y-K, Chang H-H, Kuo C-S, Huang C-T, Hsu C-C, Huang K-C. Fracture Risk After 
Bariatric Surgery: A 12-Year Nationwide Cohort Study. Medicine (Baltimore). 2015 
Dec;94(48):e2087. PMCID: PMC4674195 
7.  
Nakamura KM, Haglind EGC, Clowes JA, Achenbach SJ, Atkinson EJ, Melton LJ, Kennel KA. 
Fracture risk following bariatric surgery: a population-based study. Osteoporos Int J Establ Result 
Coop Eur Found Osteoporos Natl Osteoporos Found USA. 2014 Jan;25(1):151–158. PMCID: 
PMC3939838 
8.  
Yu EW, Lee MP, Landon JE, Lindeman KG, Kim SC. Fracture Risk After Bariatric Surgery: Roux-
en-Y Gastric Bypass Versus Adjustable Gastric Banding. J Bone Miner Res Off J Am Soc Bone 
Miner Res. 2017 Jun;32(6):1229–1236. PMCID: PMC5466471 
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