Bisphosphonate therapy for HIV-Associated osteopenia

描述(由申请人提供)：HIV相关性骨量减少是最近认识到的一个健康问题。感染艾滋病毒的男性和女性都会受到影响。最近在一组感染HIV的男性中进行的一项研究显示，与不服用蛋白酶抑制剂的受试者相比，服用蛋白酶抑制剂的受试者患骨量减少和骨质疏松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，感染艾滋病毒的妇女和患有艾滋病的妇女的骨密度显著降低。此外，在该人群中已有与骨量减少相关的显著发病率的报道。据估计，在一些艾滋病毒感染人群中，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发生率。最近的一项研究表明，在绝经后骨量减少的妇女中使用第三代双磷酸盐静脉注射唑来膦酸盐，可以有效地改善骨密度，并显著减少骨吸收，最长可达一年。鉴于单次静脉给药的治疗效果和长期健康益处的保证，唑来膦酸盐似乎是一种理想的治疗方案，适用于有复杂的医疗方案和医疗依从性问题的骨量减少的艾滋病毒感染者。 我们提出了一项双盲、安慰剂对照、随机对照试验，以评估静脉注射唑来膦酸盐对患有骨量减少的HIV感染患者的疗效。我们将确定唑来膦酸盐是否能增加HIV相关性骨量减少患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了HIV感染者的脊椎骨折和其他骨量减少相关疾病的风险。鉴于HIV感染患者经常存在多种药物，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，这项初步研究产生的数据将为未来研究双膦酸盐治疗患有骨骼疾病的艾滋病毒感染者奠定基础。

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.