HORIZON-RFT

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。全世界每年约有160万例髋部骨折，仅美国就有近35万例。由于美国人口老龄化，预计到2050年，髋部骨折的数量将上升到70万以上。尽管预计大多数髋部骨折发生在老年女性身上，但髋部骨折总数的至少30%将发生在男性身上。髋部骨折的费用也在上升，目前每年花费超过125亿美元，预计未来40年，与骨质疏松症相关的骨折的医疗费用将增加三倍。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%的患者没有恢复到骨折前的功能水平。患有骨质疏松性髋部骨折的男性和女性继发骨折的风险很高，导致生活质量进一步恶化。使用双膦酸盐、降钙素、HRT或雷洛昔芬的抗吸收疗法已被用于降低骨质疏松性椎体、髋部和其他非椎体骨折的风险；维持或改善骨量；以及抑制过度的骨转换。临床研究表明，在抗吸收方法中，双膦酸盐疗法为骨折风险较高的骨质疏松症患者提供了最快、最有效的治疗方法，尽管尚未进行头对头骨折试验。口服双膦酸盐的生物利用度低，对上皮组织具有特有的化学毒性，使得双膦酸盐类药物耐受性差，难以通过口服途径可靠地给药。帕米磷酸钠已经被一些医生成功地用作标签外的静脉注射治疗骨质疏松症，但剂量给药需要每三个月长时间静脉输注，抗骨折疗效仍未测试，治疗骨质疏松症的适应症也未获批准。赞助商认为，每年静脉注射唑来膦酸，结合标准的钙和维生素D补充剂，将优于口服双磷酸盐或静脉注射帕米磷酸钠，并将导致唑来膦酸抗骨折疗效的成功测试。

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.