Fahrleitner-Pammer Astrid, Piswanger-Soelkner Jutta Claudia, Pieber Thomas Rudolf, Obermayer-Pietsch Barbara Maria, Pilz Stefan, Dimai Hans Peter, Prenner Guenther, Tscheliessnigg Karl-Heinz, Hauge Ellen, Portugaller Rupert Horst, Dobnig Harald
Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University of Graz, Graz, Austria.
J Bone Miner Res. 2009 Jul;24(7):1335-44. doi: 10.1359/jbmr.090216.
Bone loss and fractures are common complications after cardiac transplantation (CTP). The aim of this study was to investigate whether intravenous ibandronate is an effective preventive option. Thirty-five male cardiac transplant recipients received either ibandronate (IBN) 2 mg intravenously every 3 mo or matching placebo (CTR) in addition to 500 mg calcium carbonate and 400 IE vitamin D(3). Sera were collected at CTP and every 3 mo thereafter. At baseline and 6 and 12 mo, standardized spinal X-rays and BMD measurements were taken. Bone biopsies were taken at CTP and after 6 mo from six patients. In the IBN group, 13% of the patients sustained a new morphometric vertebral fracture compared with 53% in the CTR group (absolute risk reduction [ARR], 40%; relative risk reduction [RRR], 75%; p = 0.04). BMD remained unchanged with IBN treatment but in the CTR group decreased at the lumbar spine by 25% and at the femoral neck by 23% (both p < 0.0001) over the 1-yr period. Serum bone resorption markers carboxy-terminal telopeptide region of type I collagen (sCTX) and TRACP 5b were significantly increased in the CTR group and decreased in the IBN group at all time points compared with baseline. In contrast, both osteocalcin and bone-specific alkaline phosphatase levels showed, after a similar decrease over the first 3 mo in both groups, a marked rise in the CTR subjects and steadily declining levels in the IBN patients throughout the remainder of the study period. Three paired biopsies were available from each group. Despite the small sample size, a difference in the relative change of eroded surface (68% in the CTR versus -23% in the IBN group, p < 0.05) could be shown. Intravenous IBN reduced fractures, preserved bone mass, and prevented uncoupling of bone formation and resorption after CTP. The favorable effects on bone turnover were also supported by histomorphometric findings.
骨质流失和骨折是心脏移植（CTP）后的常见并发症。本研究的目的是调查静脉注射伊班膦酸钠是否为一种有效的预防选择。35名男性心脏移植受者除了服用500毫克碳酸钙和400国际单位维生素D(3)外，每3个月静脉注射2毫克伊班膦酸钠（IBN）或匹配的安慰剂（CTR）。在心脏移植时及之后每3个月采集血清。在基线、6个月和12个月时，进行标准化脊柱X线检查和骨密度测量。在心脏移植时和6个月后，从6名患者身上采集骨活检样本。在IBN组中，13%的患者出现了新的形态计量学椎体骨折，而CTR组为53%（绝对风险降低[ARR]，40%；相对风险降低[RRR]，75%；p = 0.04）。IBN治疗后骨密度保持不变，但在CTR组中，腰椎在1年期间下降了25%，股骨颈下降了23%（两者p < 0.0001）。与基线相比，CTR组血清骨吸收标志物I型胶原羧基末端肽区域（sCTX）和抗酒石酸酸性磷酸酶5b在所有时间点均显著升高，而IBN组则降低。相比之下，两组在前3个月均有类似程度的下降后，骨钙素和骨特异性碱性磷酸酶水平在CTR组受试者中显著升高，而在IBN组患者中在研究期的剩余时间内持续下降。每组有3对活检样本。尽管样本量小，但仍可显示侵蚀表面相对变化的差异（CTR组为68%，IBN组为 - 23%，p < 0.05）。静脉注射IBN可减少骨折、保留骨量，并防止心脏移植后骨形成和骨吸收的解偶联。组织形态计量学结果也支持对骨转换的有利影响。
