TREATMENT OF OSTEOPENIA IN ADULTS WITH CYSTIC FIBROSIS WITH ZOMETA

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。研究表明，40%至70%的21岁以上囊性纤维化患者在腰椎或髋部有骨质疏松症或骨量减少，（骨质疏松：T-评分<-2.5;骨质减少：T-评分-1至-2.5到1.1; 2 CF中的骨质疏松导致骨折的显著风险，与在一个帖子中看到的类似，患有严重骨质疏松症和既往骨质疏松症史的绝经期女性。3骨质疏松症也是许多面临肺部疾病可能性的CF成年人特别关注的问题。移植和伴随的皮质类固醇使用可显著恶化潜在的骨疾病。确定可用于预防骨质疏松症发展的新疗法将是CF护理的重大进展。以前的CF干预试验是有限的，主要集中在使用双膦酸盐治疗现有的严重糖尿病4。尚未进行双膦酸盐预防CF中骨量减少进展为骨质疏松症的研究。最近，一种比帕米膦酸盐更有效的新型静脉内双膦酸盐已被开发并批准用于临床用途：唑来膦酸（Zometa）。今年2月发表在《新英格兰医学杂志》5上的一项大型多中心研究表明，绝经后骨质减少妇女单次静脉输注5 mg唑来膦酸可抑制破骨细胞整整一年，并显著改善骨密度。我们建议的假设是，囊性纤维化和骨质减少的成年人骨密度的进行性丢失可以通过每年一次15分钟的唑来膦酸静脉输注来预防。我们的方案旨在确定与维生素D和钙补充剂的标准治疗相比，每年一次静脉注射唑来膦酸治疗骨质减少的CF成人是否会改善骨密度。共40名患有CF和腰椎骨质减少（T评分-1.0至-2.4）的个体将入组一项为期3年的唑来膦酸随机、双盲、安慰剂对照研究。受试者将随机接受5 mg唑来膦酸或安慰剂静脉注射，每年一次，持续三年。所有参与者将接受800 IU的标准治疗。维生素D和1500毫克的钙元素主要监测终点为骨密度变化以及骨吸收的血清和尿液标志物变化。

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.