Department of Hematology at the Children's Hospital & Research Center, Oakland, CA, USA.
Bone. 2011 Jun 1;48(6):1305-12. doi: 10.1016/j.bone.2011.03.765. Epub 2011 Apr 5.
Previous reports using dual x-ray absorptiometry (DXA) suggest that up to 70% of adults with thalassemia major (Thal) have low bone mass. However, few studies have controlled for body size and pubertal delay, variables known to affect bone mass in this population. In this study, bone mineral content and areal density (BMC, aBMD) of the spine and whole body were assessed by DXA, and volumetric BMD and cortical geometries of the distal tibia by peripheral quantitative computed tomography (pQCT) in subjects with Thal (n = 25, 11 male, 10 to 30 years) and local controls (n=34, 15 male, 7 to 30 years). Z-scores for bone outcomes were calculated from reference data from a large sample of healthy children and young adults. Fasting blood and urine were collected, pubertal status determined by self-assessment and dietary intake and physical activity assessed by written questionnaires. Subjects with Thal were similar in age, but had lower height, weight and lean mass index Z-scores (all p < 0.001) compared to controls. DXA aBMD was significantly lower in Thal compared to controls at all sites. Adult Thal subjects (> 18 years, n = 11) had lower tibial trabecular vBMD (p = 0.03), cortical area, cortical BMC, cortical thickness, periosteal circumference and section modulus Z-scores (all p < 0.01) compared to controls. Cortical area, cortical BMC, cortical thickness, and periosteal circumference Z-scores (p = 0.02) were significantly lower in young Thal (≤ 18 years, n = 14) compared to controls. In separate multivariate models, tibial cortical area, BMC, and thickness and spine aBMD and whole body BMC Z-scores remained lower in Thal compared to controls after adjustment for gender, lean mass and/or growth deficits (all p < 0.01). Tanner stage was not predictive in these models. Osteocalcin, a marker of bone formation, was significantly reduced in Thal compared to controls after adjusting for age, puberty and whole body BMC (p=0.029). In summary, we have found evidence of skeletal deficits that cannot be dismissed as an artifact of small bone size or delayed maturity alone. Given that reduced bone density and strength are associated with increased risk of fracture, therapies focused on increasing bone formation and bone size in younger patients are worthy of further evaluation.
先前的研究报告表明，多达 70%的重型地中海贫血症（Thal）成人存在骨量低的问题。然而，很少有研究能够控制体型和青春期延迟等变量，这些变量已知会影响该人群的骨量。在这项研究中，我们使用双能 X 线吸收法（DXA）评估了 Thal 患者（n=25，男性 11 名，年龄 10-30 岁）和当地对照者（n=34，男性 15 名，年龄 7-30 岁）的脊柱和全身的骨矿物质含量和面积密度（BMC、aBMD），并通过外周定量计算机断层扫描（pQCT）评估了远端胫骨的体积 BMD 和皮质几何形状。从大量健康儿童和年轻人的参考数据中计算出骨结局的 Z 分数。采集空腹血液和尿液样本，通过自我评估确定青春期状态，并通过书面问卷评估饮食摄入和身体活动情况。与对照组相比，Thal 患者的年龄相似，但身高、体重和瘦体重指数 Z 分数较低（均 p<0.001）。与对照组相比，所有部位的 DXA aBMD 在 Thal 患者中均显著降低。11 名（>18 岁）成年 Thal 患者的胫骨小梁 vBMD（p=0.03）、皮质面积、皮质 BMC、皮质厚度、骨膜周长和截面模数 Z 分数（均 p<0.01）均显著低于对照组。与对照组相比，14 名年轻 Thal 患者（≤18 岁）的皮质面积、皮质 BMC、皮质厚度和骨膜周长 Z 分数（p=0.02）显著降低。在单独的多元模型中，在调整性别、瘦体重和/或生长缺陷后，Thal 患者的胫骨皮质面积、BMC 和厚度、脊柱 aBMD 和全身 BMC Z 分数仍低于对照组（均 p<0.01）。在这些模型中，Tanner 分期没有预测性。调整年龄、青春期和全身 BMC 后，Thal 患者的骨钙素（一种骨形成标志物）水平显著低于对照组（p=0.029）。综上所述，我们发现了不能仅归因于骨大小或成熟延迟的骨骼缺陷证据。鉴于骨密度和强度降低与骨折风险增加相关，因此针对年轻患者增加骨形成和骨大小的治疗方法值得进一步评估。
