Gram J, Junker P, Nielsen H K, Bollerslev J
Department of Endocrinology, Odense University Hospital, Denmark.
Bone. 1998 Sep;23(3):297-302. doi: 10.1016/s8756-3282(98)00097-0.
To study the effects of treatment with glucocorticoid and calcitriol on biochemical markers of calcium and bone metabolism, 48 normal male volunteers (aged 21-54 years) were randomized to treatment for 7 days with either (A) prednisolone, 10 mg twice daily, (B) prednisolone, 10 mg twice daily, and calcitriol, 1 microg twice daily, (C) calcitriol 1 mg twice daily, or (D) placebo. The study period was 28 days. Renal calcium excretion increased (mean maximal increase +44.7%, p < 0.01) as well as serum parathyroid hormone (PTH) (max. +18.5%, p < 0.01) during prednisolone treatment. Concomitant treatment with calcitriol or calcitriol alone equally enhanced renal calcium excretion (max. +185.2%, p < 0.001) and decreased serum PTH (max. -43.1%, p < 0.001). Prednisolone administration was followed by prompt declines in markers of bone formation [serum osteocalcin (max. -34.7%, p < 0.001) and serum procollagen type I C-terminal propeptide (PICP) (max. -25.9%, p < 0.05)], whereas serum bone alkaline phosphatase (bone AP) remained unchanged. Calcitriol in combination with prednisolone attenuated the decrease in PICP (max. -8.9%, not significant), but it had no effect on osteocalcin (max. -40.1%, p < 0.001), and decreased bone AP (max. -22.2%, p < 0.05). Calcitriol alone increased osteocalcin (max. +37.8%, p < 0.03) and PICP (max. +26.0%, p < 0.05). Among markers of bone degradation, prednisolone suppressed serum C-terminal telopeptide of type I collagen (ICTP) (max. -28.4%, p < 0.001), but not the fasting renal excretion of hydroxyproline (OHP) and collagen type I N-terminal telopeptide (NTx). Calcitriol partially antagonized the decrease in ICTP (max. -17.2%, p < 0.001). Calcitriol alone had no effect on resorptive markers. Extraosseous matrix synthesis was suppressed by prednisolone evaluated by serum procollagen type III N-terminal propeptide (max. -30.8%, p < 0.001) and was not affected by concomitant treatment with calcitriol or calcitriol alone. In conclusion, short-term administration of prednisolone to healthy men leads to fast and protracted suppression of biochemical markers of bone formation and extraosseous connective tissue metabolism. The effect on bone was partially antagonized by simultaneous calcitriol treatment, and points toward a potential role of calcitriol in the prevention of steroid induced osteoporosis.
为研究糖皮质激素和骨化三醇治疗对钙及骨代谢生化指标的影响，将48名正常男性志愿者（年龄21 - 54岁）随机分为四组，分别接受为期7天的如下治疗：(A) 泼尼松龙，每日2次，每次10 mg；(B) 泼尼松龙，每日2次，每次10 mg，加骨化三醇，每日2次，每次1 μg；(C) 骨化三醇，每日2次，每次1 mg；(D) 安慰剂。研究周期为28天。泼尼松龙治疗期间，肾钙排泄增加（平均最大增幅 +44.7%，p < 0.01），血清甲状旁腺激素（PTH）也增加（最大增幅 +18.5%，p < 0.01）。骨化三醇与泼尼松龙联合治疗或单独使用骨化三醇均同等程度地增加肾钙排泄（最大增幅 +185.2%，p < 0.001）并降低血清PTH（最大降幅 -43.1%，p < 0.001）。给予泼尼松龙后，骨形成标志物迅速下降[血清骨钙素（最大降幅 -34.7%，p < 0.001）和血清I型前胶原C端前肽（PICP）（最大降幅 -25.9%，p < 0.05）]，而血清骨碱性磷酸酶（骨AP）保持不变。骨化三醇与泼尼松龙联合使用减弱了PICP的下降（最大降幅 -8.9%，无统计学意义），但对骨钙素无影响（最大降幅 -40.1%，p < 0.001），并降低了骨AP（最大降幅 -22.2%，p < 0.05）。单独使用骨化三醇增加了骨钙素（最大增幅 +37.8%，p < 0.03）和PICP（最大增幅 +26.0%，p < 0.05）。在骨降解标志物中，泼尼松龙抑制血清I型胶原C端肽（ICTP）（最大降幅 -28.4%，p < 0.001），但不影响空腹尿羟脯氨酸（OHP）和I型胶原N端肽（NTx）肾排泄。骨化三醇部分拮抗了ICTP的下降（最大降幅 -17.2%，p < 0.001）。单独使用骨化三醇对骨吸收标志物无影响。通过血清III型前胶原N端前肽评估，泼尼松龙抑制了骨外基质合成（最大降幅 -30.8%，p < 0.001），联合使用骨化三醇或单独使用骨化三醇对此无影响。总之，对健康男性短期给予泼尼松龙会导致骨形成和骨外结缔组织代谢生化标志物快速且持久的抑制。骨化三醇同时治疗可部分拮抗对骨的影响，提示骨化三醇在预防类固醇诱导的骨质疏松中可能具有潜在作用。
