Mechanisms of bone loss following allogeneic and autologous hemopoietic stem cell transplantation
Mechanisms of bone loss following allogeneic and autologous hemopoietic stem cell transplantation
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DOI：
10.1359/jbmr.1999.14.3.342
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发表时间：
1999-03-01
影响因子：
6.2
通讯作者：
Grigg, AP
中科院分区：
文献类型：
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作者：
Ebeling, PR;Thomas, DM;Grigg, AP
很大一部分患者将是骨髓移植(BMT)的长期幸存者，对他们晚期骨骼并发症的风险知之甚少。因此，我们评估了骨髓移植前的骨密度(BMD)、移植后骨密度的变化，以及长期存活者的骨丢失机制。我们进行了两项分析。第一项是对83名连续的BMT患者(38名女性，45名男性)的横断面研究，检查移植前立即测量的骨密度和骨转换之间的关系，以及一些疾病和患者变量。第二项是前瞻性研究，对39名患者(19名女性，20名男性)进行同种异体骨髓移植(异基因移植29例)和自体骨髓移植(自体移植10例)后的中位随访30个月(范围5-个月)，以确定骨丢失是否与糖皮质激素和环孢素A治疗移植物抗宿主病(GVHD)、高骨转换率或性腺功能减退有关。AUTO BMT患者作为对照组，观察GVHD治疗对骨密度的影响。在骨髓移植前，女性自体骨髓移植受者的脊柱和股骨颈(FN)骨密度分别比女性异基因骨髓移植受者低8.6%和14%(p=0.12和p=0.003)。尿骨吸收标记物高于性别和年龄匹配的正常对照组。以前接受糖皮质激素治疗的患者的FN骨密度也降低了8%。经糖皮质激素治疗的闭经妇女的腰椎(LS)和FN骨密度低于正常月经妇女和接受HRT的妇女。异基因骨髓移植后，患者的FN骨密度下降了11.7%，而自动骨髓移植后下降了1.1%(p<；0.001)。自体骨髓移植后，脊柱骨密度和全身骨矿含量分别下降3.9%和3.5%，而自体骨髓移植后分别增加1.5%(p=0.03)或不显著下降(-3.7%，p=NS)。异体骨髓移植后骨丢失与LS和FN处强的松龙累积剂量以及TBBMC的平均每日强的松龙剂量相关最好。在脊柱，强的松龙的骨丢失率为4%/10g，而FN的骨丢失率更大(9%/10g的强的松龙)。骨丢失也与环孢素治疗GVHD的持续时间和基线脱氧吡啶浓度呈负相关。4例发生股骨头血管坏死，1例异体骨髓移植患者发生椎体和肋骨骨折，但无一例自体骨髓移植患者发生骨折。总之，骨髓移植受者有继发性骨质疏松的风险，继发性骨质疏松与其基础疾病和/或化疗相关，特别是在女性自体移植受者和继发于GVHD及其治疗的同种异体移植受者中。
A significant proportion of patients will be long-term survivors of bone marrow transplantation (BMT) and little is known about their risk of late bony complications. We therefore evaluated bone mineral density (BMD) prior to BMT, post-transplantation changes in BMD, and mechanisms of bone loss in long-term survivors. We performed two analyses. The first was a cross-sectional study of 83 consecutive BMT patients (38 F, 45 M), examining the relationship between BMD and bone turnover, measured immediately prior to transplantation, and a number of disease and patient variables. The second was a prospective study of 39 patients (19F, 20 M) followed for a median of 30 months (range 5-64 months) following either allogeneic (allo, n = 29) or autologous (auto, n = 10) BMT to determine if bone loss was related to treatment of graft versus host disease (GVHD) with glucocorticoids and cyclosporine A, high bone turnover rates, or hypogonadism. Auto BMT recipients acted as a control group for effects of GVHD therapy on BMD. Prior to BMT, spinal and femoral neck (FN) BMDs were 8.6% and 14% lower in female auto BMT recipients than in female allo BMT recipients, respectively (p = 0.12 and p = 0.003). Urinary bone resorption markers were higher than in normal gender- and age-matched control subjects. Patients treated previously with glucocorticoids also had 8% lower FN BMD. Glucocorticoid-pretreated women with amenorrhoea had lower lumbar spine (LS) and FN BMDs than eumenorrheic women and women receiving HRT. Post-allo BMT, patients lost 11.7% of FN BMD compared with a nonsignificant decrease of 1.1% post-auto BMT (p < 0.001). Spinal BMD and total body bone mineral content (TBBMC) decreased by 3.9% and 3.5%, respectively, post-allo, compared with an increase (1.5%,p = 0.03) or nonsignificant decrease (-3.7%,p = NS), respectively, post-auto BMT. Post-allo BMT bone loss correlated best with the cumulative prednisolone dose at the LS and FN, and with average daily prednisolone dose for TBBMC. At the spine, the rate of bone loss was 4%/10 g of prednisolone, while the rate of bone loss at the FN was greater (9%/10 g of prednisolone). Bone loss was also negatively related to the duration of cyclosporine therapy for GVHD and baseline deoxypyridinoline concentrations. A vascular necrosis of the femoral head occurred in four, and vertebral and rib fractures occurred in one of the allo BMT patients, but in no auto BMT patients. In conclusion, BMT recipients are at risk of osteoporosis secondary to bone loss associated with their underlying illness and/or chemotherapy, particularly in female autograft recipients, and in allograft recipients secondary to GVHD and its treatment.