Bjøro K, Brandsaeter B, Wiencke K, Bjøro T, Godang K, Bollerslev J, Schrumpf E
Section of Hepatology and Gastroenterology, Dept. of Medicine, Rikshospitalet, NO-0027 Oslo, Norway.
Scand J Gastroenterol. 2003 Mar;38(3):320-7.
Metabolic bone disease is one of the major long-term complications in liver transplant recipients, but it remains unclear which patients are at highest risk for developing severe bone disease following transplantation.
A total of 46 consecutive, adult patients with chronic liver disease accepted for a liver transplantation waiting list were prospectively included in the study. The patients were classified into two groups: group A--chronic cholestatic liver disease (n = 28), and group B--chronic non-cholestatic liver disease (n = 18). Bone mineral density (BMD) was measured at acceptance for the waiting list and at 3, 12 and 36 months following transplantation. Markers of bone turnover (serum-bone specific alkaline phosphatases (bALP), s-osteocalcin, s-1-collagen-C-terminal telopeptide (1-CTP) and urine N-terminal telopeptides u-Ntx) were measured at acceptance and at 3, 6, 12, 24 and 36 months following transplantation. BMD and markers of bone turnover were compared with similar values in a matched control group of 42 healthy individuals.
BMD decreased significantly during the early post-transplantation period (median bone loss femoral neck (FN) 3 months post-transplant 8.5%). BMD levels declined slightly from 3 to 12 months following transplantation and increased thereafter. The relative bone loss was greatest among group B patients (relative bone loss FN 3 months post-transplant: group A, 8% versus group B, 13%; P = 0.04). At 36 months, 8/17 group A and 2/9 group B patients had BMD levels that exceeded the pretransplant levels (P = 0.12). The early bone loss was positively correlated with an increase in resorption markers (s-1-CTP and u-Ntx). Group B had higher levels of both s-1-CTP and u-Ntx at 3 and 6 months post-transplant than group A patients (P = 0.03). Bone formation markers increased slowly from 6 months post-transplant and onwards. Relative bone loss was positively correlated to total glucocorticoid dose during the first 3 months post-transplant. There were no differences in BMD between patients receiving tacrolimus versus those receiving cyclosporin A.
Bone loss following liver transplantation is considerable in patients with both cholestatic and non-cholestatic liver disease, the first group has the poorest starting-point while the latter group has the greatest bone loss following transplantation. Bone loss is closely correlated with biochemical markers of bone resorption and total dose of glucocorticoids given post-transplant.
代谢性骨病是肝移植受者主要的长期并发症之一，但目前仍不清楚哪些患者在移植后发生严重骨病的风险最高。
共有46例连续入选的成年慢性肝病患者被纳入肝移植等待名单并进行前瞻性研究。患者分为两组：A组——慢性胆汁淤积性肝病（n = 28），B组——慢性非胆汁淤积性肝病（n = 18）。在进入等待名单时以及移植后3、12和36个月测量骨密度（BMD）。在进入等待名单时以及移植后3、6、12、24和36个月测量骨转换标志物（血清骨特异性碱性磷酸酶（bALP）、骨钙素、I型胶原C端肽（1-CTP）和尿N端肽u-Ntx）。将BMD和骨转换标志物与42名健康个体的匹配对照组中的相似值进行比较。
移植后早期BMD显著下降（移植后3个月股骨颈（FN）中位骨丢失率为8.5%）。移植后3至12个月BMD水平略有下降，此后有所上升。B组患者的相对骨丢失最大（移植后3个月FN相对骨丢失率：A组为8%，B组为13%；P = 0.04）。在36个月时，17例A组患者中的8例和9例B组患者中的2例BMD水平超过移植前水平（P = 0.12）。早期骨丢失与吸收标志物（s-1-CTP和u-Ntx）的增加呈正相关。移植后3个月和6个月时，B组的s-1-CTP和u-Ntx水平均高于A组患者（P = 0.03）。骨形成标志物从移植后6个月起缓慢增加。相对骨丢失与移植后前3个月的糖皮质激素总剂量呈正相关。接受他克莫司的患者与接受环孢素A的患者之间的BMD没有差异。
胆汁淤积性和非胆汁淤积性肝病患者肝移植后均有明显的骨丢失，前者起始情况最差，而后者移植后骨丢失最大。骨丢失与骨吸收的生化标志物以及移植后给予的糖皮质激素总剂量密切相关。
