Bone Loading Exercises versus Risedronate on Bone Health in Post-Menopausal women

描述（由申请人提供）：超过3600万美国女性骨量低（骨矿物质密度[BMD] T评分-1至-2.49），并且进展为骨质疏松症（BMD T评分-2.50或更低）和骨折的风险非常高。骨质疏松症和骨折是美国的主要健康问题，每年花费190亿美元，而且问题还在不断扩大。我们的目标是通过提供证据来为护士和更广泛的医疗保健社区提供最佳实践指南，以证明在使用双膦酸盐（BP）药物之前是否应该对低骨量女性实施生活方式干预。在这项研究中，绝经前5年（快速和显著的骨丢失时间）的低骨量女性将随机分为3组（每组n =103）：1）最佳钙+维生素D（最佳CaD）单独（对照）; 2）BP加最佳CaD（利塞膦酸盐）;或3）每周三次骨负荷运动计划加最佳CaD（运动）。充足的钙和维生素D是骨骼所必需的;然而，它们通常不足以防止绝经后妇女骨质流失的进展。虽然BP适用于骨质疏松症女性，但其对早期骨质流失女性的使用存在争议。一个值得关注的问题是，长期使用BP可能会增加非典型髋关节和股骨骨折的风险。骨负荷锻炼计划通过改善机械应力部位的骨结构和骨形成以及通过保持BMD来促进骨健康。比较运动与BP的有效性是至关重要的，因为这将决定标准实践是否应包括在这一风险人群中BP处方之前的运动试验。如果一个有效的锻炼计划 可以替代或延迟使用BP，不仅可以在整个生命周期内改善骨骼健康，而且女性还可以从运动的许多其他积极影响中受益。我们的中心假设是，在参与12个月后，与对照组或利塞膦酸钠组相比，随机分配到运动组的受试者的骨强度改善更大。我们认为，骨折的最佳预测因素是骨强度，而骨强度是由骨结构和骨转换以及BMD决定的。因此，结局将包括胫骨和髋关节骨结构的变化（pQCT和髋关节结构分析）;全髋关节、股骨颈和脊柱的BMD;以及骨形成和骨吸收的血清标志物。由于受试者可能难以坚持锻炼和利塞膦酸钠，因此将使用教育、目标设定、图形反馈和针对性的障碍减少策略来促进依从性。Nancy Waltman博士拥有超过15年的经验和14篇关于运动对绝经后妇女骨骼影响的出版物。随着Bilek博士和其他专家顾问和合作研究者的加入，我们相信我们完全有资格进行这项研究。我们的建议与NINR战略计划一致，以支持患者自我管理，疾病预防和新技术应用（髋关节结构分析和pQCT）的研究。

DESCRIPTION (provided by applicant): Over 36 million American women have low bone mass (bone mineral density [BMD] T-scores -1 to -2.49) and are at very high risk for progression to osteoporosis (BMD T-scores -2.50 or lower) and fractures. Osteoporosis and fractures are major health problems in the U.S. with annual expenditures of $19 billion, and the problem is growing. Our goal is to provide nurses and the wider healthcare community best practice guidelines by contributing evidence as to whether a lifestyle intervention should be implemented for women with low bone mass prior to use of bisphosphonate (BP) medications. In this study, women with low bone mass in the first 5 years of menopause (a time of rapid and significant bone loss) will be randomized to 3 groups (n =103 per group): 1) optimal calcium + vitamin D (optimal CaD) alone (Control); 2) a BP plus optimal CaD (Risedronate); or 3) a three times weekly bone loading exercise program plus optimal CaD (Exercise). Adequate calcium and vitamin D are necessary for bone; however, they frequently are not enough to prevent progression of bone loss in post-menopausal women. Although BPs are indicated for women with osteoporosis, their use is controversial for women with early bone loss. One concern is that long-term use of BPs may increase risk for atypical hip and femur fractures. A bone loading exercise program promotes bone health by improving bone structure and bone formation at sites of mechanical stress as well as by preserving BMD. Comparing effectiveness of exercises with BPs is critical because this will determine whether standard practice should include a trial of exercises prior to BP prescriptions in this at risk population. If an effective exercise program could substitute for, or delay the use of BPs, not only would bone health improve throughout the lifespan, but women would benefit from the many other positive effects of exercise. Our central hypothesis is that after 12 months of participation, improvements in bone strength will be greater in subjects randomized to the Exercise group compared to subjects in either the Control or Risedronate groups. We believe that the best predictor of fracture is bone strength, and strength is determined by bone structure and turnover as well as BMD. Thus, outcomes will include changes in bone structure at the tibia and hip (pQCT and Hip Structural Analysis); BMD at the total hip, femoral neck, and spine; and serum markers of bone formation and resorption. Because adherence to exercises and risedronate may be difficult for subjects to accomplish, education, goal setting, graphic feedback, and targeted strategies for barrier reduction will be used to promote adherence. Dr. Nancy Waltman has over 15 years' experience and 14 publications on the impact of exercise on bone in post-menopausal women. With the addition of Dr. Bilek and other expert consultants and co-investigators, we believe we are well-qualified to conduct this study. Our proposal is consistent with the NINR strategic plan to support research for patient self-management, disease prevention, & application of new technology (Hip Structural Analysis and pQCT).