TREATMENT OF OSTEOPENIA IN ADULTS WITH CYSTIC FIBROSIS WITH ZOMETA

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。研究表明，在21岁以上的囊性纤维症患者中，有40%到70%的人在进行骨密度测量评估时患有腰椎或髋部的骨质疏松症或骨量减少(骨质疏松症：T-Score-1至-2.5；骨量减少：T-Score-1至-2.5)1；2 CF中的骨质疏松症会导致严重的骨折风险，与有严重骨质疏松症和既往骨折病史的绝经后女性相似。3骨质疏松症也是许多患有CF的成年人特别关注的问题，他们面临着肺移植的可能性，同时使用皮质类固醇可以显著恶化潜在的骨骼疾病。确定可用于预防骨质疏松症发展的新疗法将是CF护理的一大进步。先前关于慢性骨质疏松症的干预试验有限，主要集中在使用双膦酸盐治疗现有的严重骨质疏松症4。双膦酸类药物预防骨量减少进展为骨质疏松症的研究尚未完成。最近，一种新的静脉注射双膦酸盐被开发出来，它比帕米磷酸钠更有效，并被批准用于临床：唑来膦酸(Zometa)。今年2月发表在《新英格兰医学杂志》上的一项大型多中心研究表明，在患有骨量减少的绝经后妇女中，单次静脉注射5毫克唑来膦酸可导致破骨细胞抑制整整一年，并显著提高骨密度。我们建议的假设是，患有囊性纤维化和骨量减少的成年人的进行性骨密度丧失可以通过每年一次的15分钟静脉滴注唑来膦酸预防。我们的方案旨在确定与标准的维生素D和钙补充剂治疗相比，每年静脉注射一次唑来膦酸是否会改善骨量减少的CF成年人的骨密度。共有40名腰椎骨质疏松症患者(T-Score-1.0至-2.4)将参加一项为期三年的随机、双掩蔽、安慰剂对照的唑来膦酸研究。参与者将被随机分配接受5毫克的静脉注射唑来膦酸或安慰剂，为期三年。所有参与者都将接受800国际单位的维生素D和1500毫克元素钙的标准治疗。主要监测终点将是骨密度的变化以及骨吸收的血清和尿液标志物的变化。

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. Studies suggest that 40 to 70% of individuals with cystic fibrosis over the age of 21 have either osteoporosis or osteopenia in the lumbar spine or hip when assessed by bone densitometry (osteoporosis: T-score <-2.5; osteopenia: T-score -1 to -2.5).1;2 Osteoporosis in CF results in a significant risk of fracture, comparable to that seen in a post-menopausal woman with severe osteoporosis and history of a previous fracture.3 Osteoporosis is also of particular concern for the many adults with CF who face the possibility of lung transplantation and accompanying corticosteroid use that can dramatically worsen underlying bone disease. Identification of new therapies that could be utilized to prevent development of osteoporosis would be a major advance in CF care. Previous intervention trials in CF are limited and have predominately focused on the use of bisphosphonates for treatment of existing severe osteoporosis4. No studies of bisphosphonates to prevent progression of osteopenia to osteoporosis in CF have been done. Recently, a new intravenous bisphosphonate that is significantly more potent than pamidronate has been developed and approved for clinical use: zoledronic acid (Zometa). A large multi-center study published in February of this year in the New England Journal of Medicine5 demonstrated that a single intravenous infusion of 5 mg of zoledronic acid in post-menopausal women with osteopenia resulted in osteoclast suppression for a full year and significantly improved bone mineral density. The hypothesis of our proposal is that progressive loss of bone density in adults with cystic fibrosis and osteopenia can be prevented by a once yearly 15-minute intravenous infusion of zoledronic acid. Our protocol is designed to determine if once-yearly intravenous dosing of zoledronic acid in CF adults with osteopenia will improve bone density compared to standard therapy of vitamin D and calcium supplementation. A total of 40 individuals with CF and osteopenia of the lumbar spine (T-scores -1.0 to -2.4) will be enrolled in a three-year randomized, double-masked, placebo-controlled study of zoledronic acid. Participants will be randomized to receive either 5 mg of intravenous zoledronic acid or placebo infused annually for three years. All participants will receive standard therapy of 800 I.U. of vitamin D and 1500 mg of elemental calcium. Primary monitored endpoints will be changes in bone density and changes in serum and urine markers of bone resorption.