Protocol for a randomized controlled trial to compare bone-loading exercises with risedronate for preventing bone loss in osteopenic postmenopausal women

BACKGROUND In the United States, over 34 million American post-menopausal women have low bone mass (osteopenia) which increases their risk of osteoporosis and fractures. Calcium, vitamin D and exercise are recommended for prevention of osteoporosis, and bisphosphonates (BPs) are prescribed in women with osteoporosis. BPs may also be prescribed for women with low bone mass, but are more controversial due to the potential for adverse effects with long-term use. A bone loading exercise program (high-impact weight bearing and resistance training) promotes bone strength by preserving bone mineral density (BMD), improving bone structure, and by promoting bone formation at sites of mechanical stress. METHODS/DESIGN The sample for this study will be 309 women with low bone mass who are within 5 years post-menopause. Subjects are stratified by exercise history (≥2 high intensity exercise sessions per week; < 2 sessions per week) and randomized to a control or one of two treatment groups: 1) calcium + vitamin D (CaD) alone (Control); 2) a BP plus CaD (Risedronate); or 3) a bone loading exercise program plus CaD (Exercise). After 12 months of treatment, changes in bone structure, BMD, and bone turnover will be compared in the 3 groups. Primary outcomes for the study are bone structure measures (Bone Strength Index [BSI] at the tibia and Hip Structural Analysis [HSA] scores). Secondary outcomes are BMD at the hip and spine and serum biomarkers of bone formation (alkaline phosphase, AlkphaseB) and resorption (Serum N-terminal telopeptide, NTx). Our central hypothesis is that improvements in bone strength will be greater in subjects randomized to the Exercise group compared to subjects in either Control or Risedronate groups. DISCUSSION Our research aims to decrease the risk of osteoporotic fractures by improving bone strength in women with low bone mass (pre-osteoporotic) during their first 5 years' post-menopause, a time of rapid and significant bone loss. 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. TRIAL REGISTRATION Clinicaltrials.gov NCT02186600 . Initial registration: 7/7/2014.