Giannini S, D'Angelo A, Carraro G, Nobile M, Rigotti P, Bonfante L, Marchini F, Zaninotto M, Dalle Carbonare L, Sartori L, Crepaldi G
Department of Medical and Surgical Sciences, University of Padova, Italy.
J Bone Miner Res. 2001 Nov;16(11):2111-7. doi: 10.1359/jbmr.2001.16.11.2111.
The aim of this study was to investigate the effects of alendronate, calcitriol, and calcium in bone loss after kidney transplantation. We enrolled 40 patients (27 men and 13 women, aged 44.2 +/- 11.6 years) who had received renal allograft at least 6 months before (time since transplant, 61.2 +/- 44.6 months). At baseline, parathyroid hormone (PTH) was elevated in 53% of the patients and the Z scores for bone alkaline phosphatase (b-ALP) and urinary type I collagen cross-linked N-telopeptide (u-NTX) were higher than expected (p < 0.001). T scores for the lumbar spine (-2.4 +/- 1.0), total femur (-2.0 +/- 0.7), and femoral neck (-2.2 +/- 0.6) were reduced (p < 0.001). After the first observation, patients were advised to adhere to a diet containing 980 mg of calcium daily and their clinical, biochemical, and densitometric parameters were reassessed 1 year later. During this period, bone density decreased at the spine (-2.6 +/- 5.7%;p < 0.01), total femur (-1.4 +/- 4.2%; p < 0.05), and femoral neck (-2.0 +/- 3.0%; p < 0.001). Then, the patients were randomized into two groups: (1) group A-10 mg/day of alendronate, 0.50 microg/day of calcitriol, and 500 mg/day of calcium carbonate; and (2) group B-0.50 microg/day of calcitriol and 500 mg/day of calcium carbonate. A further metabolic and densitometric reevaluation was performed after the 12-month treatment period. At the randomization time, group A and group B patients did not differ as to the main demographic and clinical variables. After treatment, bone turnover markers showed a nonsignificant fall in group B patients, while both b-ALP and u-NTX decreased significantly in alendronate-treated patients. Bone density of the spine (+5.0 +/- 4.4%), femoral neck (+4.5 +/- 4.9%), and total femur (+3.9 +/- 2.8%) increased significantly only in the alendronate-treated patients. However, no trend toward further bone loss was noticed in calcitriol and calcium only treated subjects. No drug-related major adverse effect was recorded in the two groups. We conclude that renal transplanted patients continue to loose bone even in the long-term after the graft. Alendronate normalizes bone turnover and increases bone density. The association of calcitriol to this therapy seems to be advantageous for better controlling the complex abnormalities of skeletal metabolism encountered in these subjects.
本研究的目的是调查阿仑膦酸钠、骨化三醇和钙对肾移植后骨质流失的影响。我们纳入了40例患者（27例男性和13例女性，年龄44.2±11.6岁），这些患者在至少6个月前接受了肾移植（移植后时间为61.2±44.6个月）。基线时，53%的患者甲状旁腺激素（PTH）升高，骨碱性磷酸酶（b-ALP）和尿I型胶原交联N-端肽（u-NTX）的Z评分高于预期（p<0.001）。腰椎（-2.4±1.0）、全股骨（-2.0±0.7）和股骨颈（-2.2±0.6）的T评分降低（p<0.001）。首次观察后，建议患者坚持每日摄入980mg钙的饮食，并在1年后重新评估其临床、生化和骨密度参数。在此期间，脊柱骨密度下降（-2.6±5.7%；p<0.01），全股骨（-1.4±4.2%；p<0.05），股骨颈（-2.0±3.0%；p<0.001）。然后，将患者随机分为两组：（1）A组——每日10mg阿仑膦酸钠、每日0.50μg骨化三醇和每日500mg碳酸钙；（2）B组——每日0.50μg骨化三醇和每日500mg碳酸钙。在12个月的治疗期后进行了进一步的代谢和骨密度重新评估。在随机分组时，A组和B组患者在主要人口统计学和临床变量方面没有差异。治疗后，骨转换标志物在B组患者中呈非显著性下降，而在接受阿仑膦酸钠治疗的患者中，b-ALP和u-NTX均显著下降。仅在接受阿仑膦酸钠治疗的患者中，脊柱（+5.0±4.4%）、股骨颈（+4.5±4.9%）和全股骨（+3.9±2.8%）的骨密度显著增加。然而，仅接受骨化三醇和钙治疗的受试者未发现有进一步骨质流失的趋势。两组均未记录到与药物相关的严重不良反应。我们得出结论，肾移植患者即使在移植后的长期内仍会持续骨质流失。阿仑膦酸钠可使骨转换正常化并增加骨密度。在这种治疗中加入骨化三醇似乎有利于更好地控制这些患者所遇到的复杂骨骼代谢异常。
