Pearce G, Tabensky D A, Delmas P D, Baker H W, Seeman E
Austin and Repatriation Medical Center, University of Melbourne, Australia.
J Clin Endocrinol Metab. 1998 Mar;83(3):801-6. doi: 10.1210/jcem.83.3.4621.
Lack of consistent information concerning the pathophysiology of corticosteroid-related bone loss may be due to coexisting independent factors that influence bone mineral density (BMD). For example, the disease being treated may increase bone turnover and cause bone loss, and its severity may influence the dose of corticosteroids chosen. Similarly, disease remission due to the treatment or disease progression despite treatment may influence bone turnover and the rate of bone loss. The hormonal changes purportedly responsible for reduced bone formation or increased bone resorption may be the result of the disease, not the corticosteroids. To determine the pathophysiology of corticosteroid-related bone loss, we conducted a controlled, prospective study in men with no systemic illness treated with corticosteroids to reduce antisperm antibodies. We measured BMD using dual x-ray absorptiometry and circulating biochemical and hormonal determinants of bone turnover in 9 men before and during prednisolone treatment and in 10 age-matched controls. The results were expressed as the mean +/- SEM. There were no differences in BMD between the two groups at baseline. The patients received 50 mg prednisolone daily for 3.7 +/- 0.6 months (range, 1-6). BMD decreased by 4.6 +/- 0.8% at the lumbar spine (P = 0.0007), by 2.6 +/- 0.6% at the trochanter (P = 0.004), and by 4.8 +/- 1.9% at the Ward's triangle (P < 0.04). The decrease in lumbar spine BMD correlated with the cumulative dose of corticosteroids (r = -0.49; P = 0.03). Serum osteocalcin and skeletal alkaline phosphatase decreased by 28.5 +/- 15.5% (P = 0.08) and 24.2 +/- 8.6% (P < 0.03), respectively. The decrease in lumbar spine BMD correlated with the decrease in osteocalcin (r = -0.48; P < 0.02). Serum testosterone and sex hormone-binding globulin decreased by 28.6 +/- 4.4% (P < 0.003) and 28.5 +/- 8.3% (P < 0.007), respectively. The testosterone/sex hormone-binding globulin ratio did not change. The decrease in total testosterone correlated with the decrease in osteocalcin (r = -0.40; P = 0.05). There were no detectable changes in urinary C-telopeptide, serum PTH, or serum calcium. Estradiol decreased by 23.5 +/- 11.4% (P < 0.003). Corticosteroid therapy results in rapid bone loss, probably due to reduced bone formation. Neither increased bone resorption nor secondary hyperparathyroidism appears to contribute to the rapid bone loss. Whether the reduction in bone formation may be partly mediated by changes in sex steroids remains unclear.
关于皮质类固醇相关骨质流失的病理生理学缺乏一致的信息，这可能是由于存在影响骨矿物质密度（BMD）的独立共存因素。例如，正在治疗的疾病可能会增加骨转换并导致骨质流失，其严重程度可能会影响所选用的皮质类固醇剂量。同样，治疗导致的疾病缓解或治疗后疾病进展可能会影响骨转换和骨质流失率。据称导致骨形成减少或骨吸收增加的激素变化可能是疾病的结果，而非皮质类固醇所致。为了确定皮质类固醇相关骨质流失的病理生理学，我们对9名接受皮质类固醇治疗以降低抗精子抗体的无全身性疾病男性进行了一项对照前瞻性研究。我们在9名男性服用泼尼松龙治疗前和治疗期间以及10名年龄匹配的对照中，使用双能X线吸收法测量了BMD以及骨转换的循环生化和激素指标。结果以平均值±标准误表示。两组在基线时的BMD无差异。患者每日服用50mg泼尼松龙，持续3.7±0.6个月（范围1 - 6个月）。腰椎BMD下降了4.6±0.8%（P = 0.0007），转子处下降了2.6±0.6%（P = 0.004），沃德三角区下降了4.8±1.9%（P < 0.04）。腰椎BMD的下降与皮质类固醇的累积剂量相关（r = -0.49；P = 0.03）。血清骨钙素和骨特异性碱性磷酸酶分别下降了28.5±15.5%（P = 0.08）和24.2±8.6%（P < 0.03）。腰椎BMD的下降与骨钙素的下降相关（r = -0.48；P < 0.02）。血清睾酮和性激素结合球蛋白分别下降了28.6±4.4%（P < 0.003）和28.5±8.3%（P < 0.007）。睾酮/性激素结合球蛋白比值未改变。总睾酮的下降与骨钙素的下降相关（r = -0.40；P = 0.05）。尿C端肽、血清甲状旁腺激素（PTH）或血清钙未检测到变化。雌二醇下降了23.5±11.4%（P < 0.003）。皮质类固醇治疗导致快速骨质流失，可能是由于骨形成减少。骨吸收增加和继发性甲状旁腺功能亢进似乎均未导致快速骨质流失。骨形成减少是否可能部分由性类固醇变化介导仍不清楚。
