Bishop N J, Ninkovic M, Alexander G J, Holmes S D, Milligan T, Price C, Compston J E
University of Cambridge Department of Medicine, Box 157, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, U.K.
Clin Sci (Lond). 1999 Aug;97(2):157-63.
Bone turnover, bone loss and fracture risk increase after liver transplantation. It has been postulated that peri-operative administration of a bisphosphonate might prevent bone loss and reduce fracture rate. We studied the effects of a single pre-operative dose of pamidronate on biochemical parameters of skeletal metabolism in the first month after liver transplantation. In a randomized, single-blind study, six of 12 patients with chronic liver disease received 60 mg of pamidronate intravenously on a single occasion 1-30 days before transplantation. Six other patients undergoing transplantation received no pamidronate. We measured serum calcium, phosphate, albumin, bone-specific alkaline phosphatase, plasma parathyroid hormone and tartrate-resistant acid phosphatase before pamidronate infusion and at frequent intervals during the first 30 post-operative days. In treated patients, plasma parathyroid hormone increased 12-fold over baseline values and remained elevated in comparison with baseline at days 26-30; serum calcium and phosphate fell significantly, returning to normal at around day 14 post-operatively. There were no significant changes in any parameter in the untreated group. No changes in bone formation or resorption markers were observed in either group. The large increase in plasma parathyroid hormone concentrations in the treated group is probably secondary to the fall in serum calcium. The magnitude of the increase is much greater than that seen after pamidronate infusion in other patient groups. The lack of change in, or correlation of, serum calcium and plasma parathyroid hormone in the untreated group suggests that additional factors release calcium from bone after liver transplantation, presumably by increasing bone resorption.
肝移植后骨转换、骨质流失和骨折风险增加。据推测,围手术期给予双膦酸盐可能预防骨质流失并降低骨折率。我们研究了术前单次给予帕米膦酸对肝移植后第一个月骨骼代谢生化参数的影响。在一项随机、单盲研究中,12例慢性肝病患者中有6例在移植前1 - 30天单次静脉注射60 mg帕米膦酸。另外6例接受移植的患者未接受帕米膦酸治疗。我们在输注帕米膦酸前以及术后第1个30天内定期测量血清钙、磷、白蛋白、骨特异性碱性磷酸酶、血浆甲状旁腺激素和抗酒石酸酸性磷酸酶。在治疗组患者中,血浆甲状旁腺激素比基线值增加了12倍,在术后第26 - 30天与基线相比仍保持升高;血清钙和磷显著下降,在术后约第14天恢复正常。未治疗组的任何参数均无显著变化。两组均未观察到骨形成或骨吸收标志物的变化。治疗组血浆甲状旁腺激素浓度的大幅增加可能继发于血清钙的下降。增加的幅度远大于其他患者组输注帕米膦酸后所见。未治疗组血清钙和血浆甲状旁腺激素缺乏变化或相关性表明,肝移植后还有其他因素从骨中释放钙,大概是通过增加骨吸收来实现的。