TREATMENT OF OSTEOPENIA IN ADULTS WITH CYSTIC FIBROSIS WITH ZOMETA

用 Zometa 治疗患有囊性纤维化的成人骨质减少

• 批准号: 7378811
• 负责人: MICHAEL D. BOYLE
• 金额: $ 0.05万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378811
• 关键词: TREATMENT; OSTEOPENIA; ADULTS; CYSTIC; FIBROSIS

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.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。研究表明，40 - 70%的21岁以上囊性纤维化患者在骨密度测定时出现腰椎或髋关节骨质疏松或骨质减少（骨质疏松：t评分<-2.5；骨质减少：t评分-1至-2.5）。CF中的骨质疏松导致骨折的显著风险，与绝经后有严重骨质疏松和既往骨折史的妇女相当骨质疏松症也是许多CF成人患者特别关注的问题，他们可能面临肺移植和伴随的皮质类固醇使用，这可能会严重恶化潜在的骨骼疾病。确定新的治疗方法，可以用来预防骨质疏松症的发展将是CF治疗的一个重大进展。先前CF的干预试验是有限的，并且主要集中在使用双磷酸盐治疗现有的严重骨质疏松症4。目前还没有关于双膦酸盐预防CF患者骨质减少发展为骨质疏松症的研究。最近，一种比帕米膦酸更有效的新型静脉注射双膦酸盐被开发并批准用于临床：唑来膦酸（Zometa）。今年2月发表在《新英格兰医学杂志》（New England Journal of medicine）上的一项大型多中心研究表明，绝经后骨质减少的妇女单次静脉输注5mg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，患有囊性纤维化和骨质减少的成年人可以通过每年一次15分钟静脉输注唑来膦酸来预防骨密度的进行性损失。我们的方案旨在确定与维生素D和钙补充的标准治疗相比，每年一次静脉注射唑来膦酸是否能改善骨密度。共有40名CF和腰椎骨质减少患者（t评分-1.0至-2.4）将被纳入一项为期三年的随机、双盲、安慰剂对照的唑来膦酸研究。参与者将随机接受5毫克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国际单位维生素D和1500毫克元素钙的标准治疗。主要监测的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。