Heartland Osteoporosis Prevention Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized Control Trial of Bone Loading Exercises Versus Risedronate on Bone Health in Post-Menopausal Women

Conditions
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Osteopenia

Intervention / Treatment
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* Drug: Calcium Carbonate
* Drug: Vitamin D3
* Drug: Risedronate
* Behavioral: Bone-loading exercises


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women who are in their first 5 years of menopause Have a T score between -1 and -2.49 at the femoral neck, total hip, or L1-L4 spine Be 19 years of age or older Have their health care provider's permission to enroll in the study. Exclusion Criteria: Have osteoporosis Have a 10 yr probability of hip fracture >3% or major fracture >20% based on results of the fracture risk assessment (FRAX) tool Currently take bisphosphonates, estrogen replacement therapy, glucocorticosteroids, or other drugs affecting bone Currently participate in a resistance training or high impact weight bearing exercise program three or more times weekly Weigh >300 lbs Have abnormal results for the following laboratory tests: serum 25(OH)D; serum creatinine; serum calcium; parathyroid hormone (PTH); thyroid stimulating hormone (TSH). Have Paget's disease, heart disease, uncontrolled hypertension, renal disease, or other concomitant conditions that prohibit participation in exercises, risedronate therapy, or use of CaD supplements.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized to 3 treatment groups: Calcium + vitamin D only; risedronate and calcium + vitamin D; bone building exercises and calcium + vitamin D
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>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. | Drug: Calcium Carbonate<br>* Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)<br>* Other names: generic;Drug: Vitamin D3<br>* Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.<br>* Other names: generic;|
| Experimental: Risedronate<br>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. | Drug: Calcium Carbonate<br>* Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)<br>* Other names: generic;Drug: Vitamin D3<br>* Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.<br>* Other names: generic;Drug: Risedronate<br>* Risedronate 35 mg orally will be ingested weekly by subjects in Risedronate group.<br>* Other names: Actonel;|
| Experimental: Exercise<br>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. | Drug: Calcium Carbonate<br>* Used as daily supplement to ensure subject obtains 1200 mg of calcium per day (diet + supplement)<br>* Other names: generic;Drug: Vitamin D3<br>* Subjects will receive Vitamin D3 supplements to ensure serum level of Vitamin D is at least 30 ng/ml.<br>* Other names: generic;Behavioral: Bone-loading exercises<br>* Subjects will participate in bone loading exercises (weight-bearing and resistance) three times weekly at community YMCAs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bone Strength Index of the Distal Tibia Based on Randomization to Control, Risedronate, or Exercise Group. | Change in Bone Strength Index (BSI) of the distal tibia based on randomization to Control, Risedronate, or Exercise group. BSI (mg2/mm4) at the 4% tibial site will be measured using peripheral quantitative computed tomography (pQCT). | Baseline, 6, and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Bone Mineral Density (BMD) at the Spine (L1-L4) Based on Randomization to Control, Risedronate, or Exercise Group. | Bone mineral density is the gold standard for diagnosis of low bone mass and osteoporosis and will be measured at the spine using Dual Energy X-ray Absorptiometry (DXA). | Baseline,6, and 12 months | 
| Change in Serum Measures of Bone Resorption (Serum NTx) Based on Randomization to Control, Risedronate, or Exercise Group. | Bone turnover is the process of removing old bone (resorption by osteoclasts) and replacing it with new bone (formation by osteoblasts). Menopause results in a brief period ( 5 years) of accelerated turnover with resorption far exceeding formation. In this study, resorption will be measured by Serum NTx. | Baseline, 6, 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low bone mass, Post-menopausal women, Bone mineral density, Bone structure, Bone turnover, Bone-loading exercises, calcium and vitamin D, risedronate