Bisphosphonate therapy for HIV-Associated osteopenia

描述（由申请人提供）：HIV相关骨质减少是最近认识到的健康问题。感染艾滋病毒的男子和妇女都受到影响。在最近一项针对一组HIV感染男性的研究中，与未接受蛋白酶抑制剂的受试者相比，接受蛋白酶抑制剂的受试者发生骨质减少和骨质疏松症的风险增加了一倍以上。此外，与年龄和体重相似的健康对照组相比，艾滋病毒感染妇女和艾滋病消瘦妇女的骨密度显著降低。此外，在该人群中报告了与骨质减少相关的显著发病率。据估计，在某些艾滋病毒感染群体中，这种疾病的流行率高达67.5%。 双膦酸盐已被广泛用于治疗骨质疏松症，并已被证明可以增加骨密度和降低骨折率。最近一项使用第三代双膦酸盐唑来膦酸盐静脉给药治疗绝经后骨质减少女性的研究表明，单次静脉给药唑来膦酸盐后一年内，骨密度得到有益改善，骨吸收显著减少。考虑到单次静脉给药的治疗保证和长期的健康益处，唑来膦酸盐似乎是具有复杂的药物治疗方案和医疗依从性问题的骨质减少性HIV感染受试者的理想治疗方案。 我们提出了一个双盲，安慰剂对照，随机对照试验，以评估静脉注射唑来膦酸盐在艾滋病毒感染的骨质疏松症患者的有效性。我们将确定唑来膦酸盐是否增加HIV相关骨质减少受试者的骨密度并减少持续的骨丢失。长期结果将包括唑来膦酸盐是否降低HIV感染受试者椎体骨折和其他骨质疏松相关疾病的风险。考虑到HIV感染患者中经常存在的多种药物，我们还将密切监测唑来膦酸盐治疗的安全性和抗逆转录病毒治疗受试者中潜在的药物相互作用。最后，这项初步研究所产生的数据将为今后的研究奠定基础，双膦酸盐治疗艾滋病毒感染者的骨病。

DESCRIPTION (provided by applicant): HIV-associated osteopenia is a recently recognized health problem. Both HIV-infected men and women are affected. In a recent study among a group of HIV-infected men, subjects taking protease inhibitors had more than double the risk of osteopenia and osteoporosis as compared with subjects not receiving protease inhibitors. In addition, HIV-infected women and women with AIDS wasting have significantly reduced bone density as compared to age and weight-similar healthy controls. Furthermore, significant morbidity associated with osteopenia has been reported in this population. The prevalence of this disease has been estimated as high as 67.5% in some HIV infected groups. Bisphosphonates have been widely used for treating osteoporosis and have been demonstrated to increase bone mineral density and reduce the rate of fracture. A recent study using intravenous zoledronate, a third-generation bisphosphonate, in postmenopausal women with osteopenia demonstrated beneficial improvements in bone density and significant reductions in bone resorption up to one year after single intravenous zoledronate dosing. Given the assurance of treatment delivery with single intravenous dosing and long-term health benefits, zoledronate appears to be an ideal treatment regimen for osteopenic HIV-infected subjects with complicated medical treatment regimens and medical compliance issues. We propose a double-blinded, placebo-controlled, randomized controlled trial to evaluate the effectiveness of intravenous zoledronate in HIV-infected subjects with osteopenia. We will determine whether zoledronate increases bone density and reduces ongoing bone loss in subjects with HIV-associated osteopenia. Long-term outcomes will include whether zoledronate reduces the risk of vertebral fracture and other osteopenia-associated morbidities in HIV-infected subjects. Given the polypharmacy often present in HIV-infected patients, we will also closely monitor the safety of zoledronate therapy and potential drug interactions in subjects on antiretroviral therapy. Finally, data generated by this pilot study will lay the foundation for future studies of bisphosphonate therapy in HIV-infected persons with bone disease.