Grigg A P, Shuttleworth P, Reynolds J, Schwarer A P, Szer J, Bradstock K, Hui C, Herrmann R, Ebeling P R
Department of Medicine, University of Melbourne, Western Hospital, Footscray 3011, Australia.
J Clin Endocrinol Metab. 2006 Oct;91(10):3835-43. doi: 10.1210/jc.2006-0684. Epub 2006 Jul 11.
Rapid bone loss occurs from the proximal femur after allogeneic stem cell transplantation (alloSCT).
The objective of the study was to evaluate effects of high-dose pamidronate therapy on bone loss (BMD) after alloSCT.
This was a randomized, multicenter, open-label, 12-month prospective study of iv pamidronate (90 mg/month) beginning before conditioning vs. no pamidronate. All 116 patients also received calcitriol (0.25 microg/d) and calcium (1000 mg/d), which were continued for another year.
Primary objectives were to compare changes in BMD 12 months after alloSCT at the femoral neck, lumbar spine, and total hip between the treatment arms and assess influences of glucocorticoid and cyclosporin therapy on these changes.
Pamidronate reduced bone loss at the spine, femoral neck, and total hip by 5.6, 7.7, and 4.9% (all P < or = 0.003), respectively, at 12 months. However, BMD of the femoral neck and total hip was still 2.8 and 3.5% lower than baseline, respectively (P < 0.05) with pamidronate. Only differences at the total hip remained significant between the two groups at 24 months. Benefits were restricted to patients receiving an average daily prednisolone dose greater than 10 mg and cyclosporin therapy for more than 5 months within the first 6 months of alloSCT.
Pamidronate markedly reduced but did not completely prevent postallogeneic bone marrow transplantation bone loss. BMD benefits were greatest in patients on higher doses of immunosuppressive therapy, but most were lost 12 months after stopping pamidronate. Studies of more potent bisphosphonates or anabolic therapy with PTH after alloSCT are warranted with the aim of durable maintenance of bone mass.
异基因干细胞移植(alloSCT)后股骨近端会出现快速骨质流失。
本研究旨在评估大剂量帕米膦酸治疗对alloSCT后骨质流失(骨密度)的影响。
这是一项随机、多中心、开放标签的前瞻性研究,为期12个月,比较在预处理前开始静脉注射帕米膦酸(90毫克/月)与不使用帕米膦酸的情况。所有116名患者还接受骨化三醇(0.25微克/天)和钙(1000毫克/天),并持续使用一年。
主要目的是比较alloSCT 12个月后治疗组之间股骨颈、腰椎和全髋骨密度的变化,并评估糖皮质激素和环孢素治疗对这些变化的影响。
12个月时,帕米膦酸分别使脊柱、股骨颈和全髋的骨质流失减少了5.6%、7.7%和4.9%(所有P≤0.003)。然而,使用帕米膦酸时,股骨颈和全髋的骨密度仍分别比基线低2.8%和3.5%(P<0.05)。在24个月时,两组之间仅全髋的差异仍然显著。益处仅限于在alloSCT的前6个月内平均每日泼尼松龙剂量大于10毫克且接受环孢素治疗超过5个月的患者。
帕米膦酸显著减少但并未完全预防异基因骨髓移植后的骨质流失。骨密度益处对于接受更高剂量免疫抑制治疗的患者最大,但在停止使用帕米膦酸12个月后大部分益处丧失。有必要对alloSCT后更有效的双膦酸盐或用甲状旁腺激素进行促合成治疗进行研究,以期持久维持骨量。