MULTINATIONAL, MULTICENTER, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 全世界每年约有160万例髋部骨折，仅美国就有近35万例。由于美国人口的老龄化，预计到2050年髋部骨折的数量将增加到70多万。虽然大多数髋部骨折预计发生在老年女性中，但至少30%的髋部骨折发生在男性中。髋部骨折的费用也在上升，目前每年花费超过125亿美元，预计在未来40年内，与髋部骨折相关的医疗保健费用将增加三倍。对于髋部骨折的幸存者来说，生活质量的变化是相当大的。在骨折后一年，超过50%的患者不能恢复到骨折前的功能水平。患有髋关节骨折的男性和女性发生后续骨折的风险很高，导致生活质量进一步恶化。双膦酸盐、降钙素、HRT或雷洛昔芬的抗吸收疗法已用于降低骨质疏松性椎体、髋关节和其他非椎体骨折的风险;维持或改善骨量;抑制过度骨转换。临床研究表明，在抗骨吸收方法中，双膦酸盐治疗为骨折高危的骨质疏松患者提供了最快速和有效的治疗，尽管尚未进行头对头骨折试验。口服双膦酸盐的低生物利用度及其对上皮组织的特征性化学毒性使得双膦酸盐类耐受性差，难以通过口服途径可靠地给药。帕米膦酸盐已被一些医生成功地用于标示外的骨质疏松症的IV治疗，但剂量给药需要每三个月延长IV输注，抗骨折疗效尚未测试，骨质疏松症适应症的治疗未经批准。申办者认为，唑来膦酸每年IV给药，联合标准钙和维生素D补充剂，将上级双膦酸盐口服给药或帕米膦酸盐IV给药，并将导致唑来膦酸抗骨折疗效的成功试验。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Approximately 1.6 million hip fractures occur worldwide each year, with almost 350,000 occurring in the United States alone. Due to the graying of the US population, the number of hip fractures is expected to rise to more than 700,000 by the year 2050. Although most of the hip fractures are expected to occur in elderly women, at least 30% of the total number of fractured hips will occur in men. The cost of hip fractures is also on the rise, with more than $12.5 billion currently being spent each year, and an expected three-fold rise in health care costs for osteoporosis-related fractures projected over the next 40 years. For the people who survive a hip fracture, the change in quality of life is considerable. At one year post fracture, more than 50% of patients do not return to pre-fracture functional levels. Men and women who have had an osteoporotic hip fracture are at high risk for subsequent fractures, leading to further deterioration in quality of life. Anti-resorptive therapies with bisphosphonates, calcitonins, HRT, or raloxifene have been used to reduce the risk of osteoporotic vertebral, hip, and other non-vertebral fractures; maintain or improve bone mass; and to suppress excessive bone turnover. Clinical studies suggest that among anti-resorptive approaches, bisphosphonate therapy provides the most rapid and effective therapy for osteoporotic patients at high risk of fracture, although no head-to-head fracture trials have been conducted. The low bioavailability of oral bisphosphonates and their characteristic chemical toxicity to epithelial tissue makes the bisphosphonate class poorly tolerated and difficult to administer reliably by the oral route. Pamidronate has been used successfully by some practitioners off-label as an IV treatment for osteoporosis, but dose administration requires a prolonged IV infusion every three months, anti-fracture efficacy remains untested, and the treatment of osteoporosis indications unapproved. The sponsor believes that annual IV dosing with zoledronic acid, combined with standard calcium and Vitamin D supplementation, will be superior to oral administration of bisphosphonates or IV administration of pamidronate, and will lead to a successful test of anti-fracture efficacy of zoledronic acid.