Picado C, Luengo M
Department de Medicina, Hospital Clinic i Universitari, Facultat de Medicina, Barcelona, Spain.
Drug Saf. 1996 Nov;15(5):347-59. doi: 10.2165/00002018-199615050-00005.
Osteoporosis is one of the most serious adverse effects experienced by patients receiving long term corticosteroid therapy. Bone loss occurs soon after corticosteroid therapy is initiated and results from a complex mechanism involving osteoblastic suppression and increased bone resorption. There are a number of factors that may increase the risk of corticosteroid-induced osteoporosis [smoking, excessive alcohol (ethanol) consumption, amenorrhoea, relative immobilisation, chronic obstructive pulmonary disease, inflammatory bowel disease, hypogonadism in men, organ transplantation]. The initial assessment of patients about to start taking corticosteroids should include measurement of spinal bone density, urinary calcium level and plasma calcifediol (25-hydroxycholecalciferol) level; serum testosterone levels should also be measured when hypogonadism is suspected. Many different drugs have been used to prevent osteoporosis in patients receiving long-term corticosteroid therapy, including thiazide diuretics, cholecalciferol (vitamin D) metabolites, bisphosphonates, calcitonin, fluoride, estrogens, anabolic steroids and progesterone. At present, however, published studies have failed to demonstrate a reduction in the rate of fracture using different preventive pharmacological therapies in patients being treated with corticosteroids on a continuous basis. Among the drugs studied, bisphosphonates (pamidronic acid and etidronic acid) and calcitonin appear to be effective in increasing bone density. Cholecalciferol preparations have been reported to be effective in some, but not all, studies. Limited data have shown positive results with thiazide diuretics, estrogen, progesterone and nandrolone. When treating patients with corticosteroids, the lowest effective dose should be used, with topical corticosteroids used whenever possible. Auranofin may be considered in patients with corticosteroid-dependent asthma. Patients should take as much physical activity as possible, maintain an adequate daily intake of calcium (1000 mg/day0 and cholecalciferol (400 to 800 U/day), stop smoking and avoid excessive alcohol intake. It is important to detect and treat hypogonadism in men, if present, and to replace gonadal hormones in postmenopausal women or amenorrhoeic premenopausal women, and to detect and correct cholecalciferol deficiency. A thiazide diuretic should be considered if hypercalciuria is present (urinary calcium excretion in excess of 4 mg/kg/day). High-risk patients and those with established osteoporosis should be treated with bisphosphonates (cyclical etidronic acid or intravenous pamidronic acid), nasal calcitonin, or calcifediol or calcitriol. Patients receiving cholecalciferol preparations should be carefully monitored for hypercalciuria and hypecalcaemia.
骨质疏松症是接受长期皮质类固醇治疗的患者所经历的最严重不良反应之一。皮质类固醇治疗开始后不久就会发生骨质流失，其机制复杂，涉及成骨细胞抑制和骨吸收增加。有许多因素可能增加皮质类固醇诱导的骨质疏松症的风险[吸烟、过量饮酒（乙醇）、闭经、相对固定不动、慢性阻塞性肺疾病、炎症性肠病、男性性腺功能减退、器官移植]。对即将开始服用皮质类固醇的患者进行的初始评估应包括测量脊柱骨密度、尿钙水平和血浆骨化二醇（25-羟胆钙化醇）水平；当怀疑有性腺功能减退时，还应测量血清睾酮水平。许多不同的药物已被用于预防接受长期皮质类固醇治疗患者的骨质疏松症，包括噻嗪类利尿剂、胆钙化醇（维生素D）代谢物、双膦酸盐、降钙素、氟化物、雌激素、合成代谢类固醇和孕酮。然而，目前已发表的研究未能证明在持续接受皮质类固醇治疗的患者中使用不同的预防性药物治疗能降低骨折发生率。在所研究的药物中，双膦酸盐（帕米膦酸和依替膦酸）和降钙素似乎对增加骨密度有效。胆钙化醇制剂在一些但并非所有研究中都被报道有效。有限的数据显示噻嗪类利尿剂、雌激素、孕酮和诺龙有积极效果。在治疗使用皮质类固醇的患者时，应使用最低有效剂量，尽可能使用局部皮质类固醇。对于依赖皮质类固醇治疗的哮喘患者可考虑使用金诺芬。患者应尽可能多进行体育活动，保持每日充足的钙摄入量（1000毫克/天）和胆钙化醇摄入量（400至800单位/天），戒烟并避免过量饮酒。重要的是，检测并治疗男性存在的性腺功能减退，对绝经后女性或绝经前闭经女性补充性腺激素，检测并纠正胆钙化醇缺乏。如果存在高钙尿症（尿钙排泄超过4毫克/千克/天），可考虑使用噻嗪类利尿剂。高危患者和已确诊骨质疏松症的患者应使用双膦酸盐（周期性依替膦酸或静脉注射帕米膦酸）、鼻用降钙素或骨化二醇或骨化三醇进行治疗。接受胆钙化醇制剂治疗的患者应密切监测高钙尿症和高钙血症。
