Fairfield W P, Finkelstein J S, Klibanski A, Grinspoon S K
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
J Clin Endocrinol Metab. 2001 May;86(5):2020-6. doi: 10.1210/jcem.86.5.7515.
Multiple endocrine and metabolic consequences of human immunodeficiency virus (HIV) infection exist that may contribute to bone loss in men with the acquired immune deficiency syndrome (AIDS) wasting syndrome. Recent studies suggest that anabolic strategies can increase lean body mass in men with AIDS wasting. Prior studies have not examined the effects of anabolic agents on bone mineral density (BMD) or bone turnover in these men. To determine the effects of testosterone and progressive resistance training on BMD and bone turnover in eugonadal men with AIDS wasting, we randomly assigned 54 eugonadal men with AIDS wasting (weight < 90% IBW or weight loss >10% from preillness baseline) to receive either testosterone enanthate (200 mg/week, im) or placebo and to progressive resistance training (3 times/week) or no training in a 2 x 2 factorial study design for 3 months. The BMD of the lumbar spine, proximal femur, and total body; lean body mass; and fat mass were measured by dual energy x-ray absorptiometry. Total body scans were repeated after 12 weeks of therapy. Baseline bone turnover and BMD were compared with those in 35 age-matched healthy non-HIV-infected control subjects. Compared with controls, lumbar spine BMD (1.021 +/- 0.018 vs. 1.084 +/- 0.025 g/cm(2); P = 0.04) and total hip BMD (0.951 +/- 0.017 vs. 1.070 +/- 0.019 g/cm(2); P < 0.0001) were reduced in men with AIDS wasting. T-scores were lower in men with AIDS wasting at the lumbar spine (-0.62 +/- 0.17 vs. -0.07 +/- 0.23, P = 0.05) and total hip (-0.65 +/- 0.11 vs. +0.20 +/- 0.014, P < 0.0001). Total hip T scores were less than -1.0 in 33% of men with AIDS wasting. Neither the use of protease inhibitors nor the duration of protease inhibitors use correlated with BMD. Serum osteocalcin levels were lower (3.63 +/- 0.29 vs. 4.54 +/- 0.31 nmol/L; P < 0.04) and urinary N-telopeptide excretion was higher (45.4 +/- 4.5 vs. 26.8 +/- 3.0 nmol BCE/mmol creatinine; P = 0.004) in men with AIDS wasting than in controls. Lumbar spine BMD, as assessed on regional total body dual energy x-ray absorptiometry scan, increased over the 12-week treatment period in response to testosterone (+2.4 +/- 1.3 vs. -1.3 +/- 1.0%, testosterone vs. placebo, respectively; P = 0.02), but not in response to training (+0.8 +/- 1.0 vs. +0.4 +/- 1.3%, training vs. no training; P = 0.70). Lumbar spine and total hip BMD are reduced in eugonadal men with AIDS wasting. Biochemical markers of bone turnover suggest that bone formation and bone resorption are uncoupled in these men. Testosterone administration, but not resistance training, over 3 months increases lumbar spine BMD in eugonadal men with AIDS wasting.
人类免疫缺陷病毒(HIV)感染存在多种内分泌和代谢后果,这可能导致获得性免疫缺陷综合征(AIDS)消瘦综合征男性出现骨质流失。最近的研究表明,合成代谢策略可增加患有AIDS消瘦的男性的瘦体重。先前的研究尚未考察合成代谢药物对这些男性骨矿物质密度(BMD)或骨转换的影响。为了确定睾酮和渐进性抗阻训练对性腺功能正常的AIDS消瘦男性的BMD和骨转换的影响,我们采用2×2析因研究设计,将54名性腺功能正常的AIDS消瘦男性(体重<90%理想体重或比病前基线体重减轻>10%)随机分为两组,分别接受庚酸睾酮(200mg/周,肌肉注射)或安慰剂,并进行渐进性抗阻训练(每周3次)或不训练,为期3个月。采用双能X线吸收法测量腰椎、股骨近端和全身的BMD、瘦体重和脂肪量。治疗12周后重复进行全身扫描。将基线骨转换和BMD与35名年龄匹配的健康未感染HIV的对照受试者进行比较。与对照组相比,AIDS消瘦男性的腰椎BMD(1.021±0.018 vs. 1.084±0.025g/cm²;P = 0.04)和全髋BMD(0.951±0.017 vs. 1.070±0.019g/cm²;P<0.0001)降低。AIDS消瘦男性腰椎(-0.62±0.17 vs. -0.07±0.23,P = 0.05)和全髋(-0.65±0.11 vs. +0.20±0.014,P<0.0001)的T值较低。33%的AIDS消瘦男性全髋T值小于-1.0。蛋白酶抑制剂的使用与否及使用时间均与BMD无关。与对照组相比,AIDS消瘦男性的血清骨钙素水平较低(3.63±0.29 vs. 4.54±0.31nmol/L;P<0.04),尿N-端肽排泄较高(45.4±4.5 vs. 26.8±3.0nmol BCE/mmol肌酐;P = 0.004)。在为期12周的治疗期间,根据全身双能X线吸收法扫描评估,腰椎BMD因睾酮而增加(分别为+2.4±1.3% vs. -1.3±1.%,睾酮组 vs. 安慰剂组;P = 0.02),但不因训练而增加(+0.8±1.0% vs. +0.4±1.3%,训练组 vs. 无训练组;P = 0.70)。性腺功能正常的AIDS消瘦男性的腰椎和全髋BMD降低。骨转换的生化标志物表明这些男性的骨形成和骨吸收失衡。在为期3个月的时间里,给予睾酮而非抗阻训练可增加性腺功能正常的AIDS消瘦男性的腰椎BMD。