Madeddu G, Spanu A, Solinas P, Babudieri S, Calia G M, Lovigu C, Mannazzu M, Nuvoli S, Piras B, Bagella P, Mura M S, Madeddu G
Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Eur Rev Med Pharmacol Sci. 2015 Dec;19(23):4576-89.
To evaluate the changes in Bone Mineral Density (BMD) and bone remodelling markers in a group of HIV patients treated with HAART and controlled in a long follow-up and to identify possible risk factors for accelerated bone mass loss.
In a series of 172 HIV patients treated with HAART a total of 67 patients (44 males and 33 females) underwent repeated bone mineral density measurement by DEXA in lumbar spine and in femur; the patients were classified according to T-score WHO criteria. Serum bone alkaline phosphatase (BAP), by IRMA, and urine pyridinoline/deoxypyridinoline (PYD&DPD), by EIA, were also assayed in all cases.
At baseline, 62/67 patients were on HAART, while 5 were naïve; 44.8% were previous intravenous drug users (IVDU), 46.3% heterosexual and 8.9% homosexual, mean age being 40.2 ± 6.5 years, and 23.9% had previous AIDS diagnosis. Fifteen/67 (22.4%) of treated patients had osteoporosis and 25/67 (37.3%) osteopenia in spine and/or femur including 3 naïve, 27/67 (40.3%), including 2 naïve, had normal BMD in both sites. Fifty-one/67 patients were monitored during follow-up (56.8 ± 5.3 months); 27 (52.9%) of these (Group 1), received protease inhibitors (PI) and 24 (47.1%), including naïve, (Group 2) received not nucleoside reverse transcriptase inhibitors (NNRTI) for > 50% of follow-up period. In Group 1 patients, BMD reduction was observed after follow-up in respect of basal condition in both spine and femur, but significantly (p = 0.011) only for the latter. However, mean BMD values remained stable in both sites in Group 2 patients. Basal BAP and PYD&DPD levels were higher in Group 1 than Group 2, but not significantly. Moreover, only PYD&DPD levels at the follow-up evaluation were significantly (p = 0.031) higher in Group 1 than Group 2. Of the remaining 16/67 patients with osteoporosis/osteopenia, 10 received PI and 6 NNRTI and were treated with therapies that could increase bone density, in particular, 9 with Alendronate/Vitamin D/Calcium and 7 with only vitamin D/calcium; these patients were excluded from statistical analysis of 51 Group 1/Group 2 cases. In the 16 patients, after these specific treatments, mean spine and femur BMD increased over time, but significantly only in those cases including alendronate in their protocol.
The study showed that in HIV patients on HAART BMD decrease, even osteoporosis, can be present persisting over time, particularly in PI in respect of NNRTI treated patients. The pathogenesis is probably multifactorial, the different antiviral drugs seeming to differently affect bone metabolism. Alendronate/Vitamin D/Calcium therapy can be useful to slow down bone mass loss and also improve osteoporosis/osteopenia conditions, thus, reducing fracture risk also continuing HAART.
评估接受高效抗逆转录病毒治疗（HAART）并长期随访的一组HIV患者的骨矿物质密度（BMD）和骨重塑标志物的变化，并确定骨量加速流失的可能危险因素。
在172例接受HAART治疗的HIV患者中，共有67例患者（44例男性和33例女性）接受了双能X线吸收法（DEXA）对腰椎和股骨进行的重复骨矿物质密度测量；根据世界卫生组织（WHO）的T值标准对患者进行分类。所有病例均采用免疫放射分析（IRMA）检测血清骨碱性磷酸酶（BAP），采用酶免疫分析（EIA）检测尿吡啶啉/脱氧吡啶啉（PYD&DPD）。
基线时，67例患者中有62例接受HAART治疗，5例未接受治疗；44.8%为既往静脉吸毒者（IVDU），46.3%为异性恋者，8.9%为同性恋者，平均年龄为40.2±6.5岁，23.9%曾被诊断为艾滋病。67例接受治疗的患者中，15例（22.4%）在脊柱和/或股骨处患有骨质疏松症，25例（37.3%）患有骨量减少，其中包括3例未接受治疗者；67例中有27例（40.3%），包括2例未接受治疗者，两个部位的骨矿物质密度均正常。67例患者中有51例在随访期间接受监测（56.8±5.3个月）；其中27例（52.9%）（第1组）接受蛋白酶抑制剂（PI）治疗，24例（47.1%），包括未接受治疗者（第2组）在随访期超过50%的时间内接受非核苷类逆转录酶抑制剂（NNRTI）治疗。在第1组患者中，随访后观察到脊柱和股骨的骨矿物质密度相对于基础状态均有所降低，但仅股骨处显著降低（p = 0.011）。然而，第2组患者两个部位的平均骨矿物质密度值保持稳定。第1组患者的基础BAP和PYD&DPD水平高于第2组，但差异不显著。此外，仅在随访评估时第1组患者的PYD&DPD水平显著高于第⑵组（p = 0.031）。其余16例患有骨质疏松症/骨量减少的67例患者中，10例接受PI治疗，6例接受NNRTI治疗，并接受了可增加骨密度的治疗，特别是9例接受阿仑膦酸钠/维生素D/钙治疗，7例仅接受维生素D/钙治疗；这些患者被排除在对51例第1组/第2组病例的统计分析之外。在这16例患者中，经过这些特定治疗后，脊柱和股骨的平均骨矿物质密度随时间增加，但仅在治疗方案中包含阿仑膦酸钠的病例中显著增加。
研究表明，接受HAART治疗的HIV患者存在骨矿物质密度降低，甚至骨质疏松症，且可能随时间持续存在，特别是与接受NNRTI治疗的患者相比，接受PI治疗的患者更为明显。其发病机制可能是多因素的，不同的抗病毒药物似乎对骨代谢有不同影响。阿仑膦酸钠/维生素D/钙治疗可能有助于减缓骨量流失，并改善骨质疏松症/骨量减少状况，从而在继续进行HAART治疗的同时降低骨折风险。
