Morabito Nunziata, Gaudio Agostino, Lasco Antonino, Atteritano Marco, Pizzoleo Maria Antonia, Cincotta Maria, La Rosa Mariangela, Guarino Roberta, Meo Anna, Frisina Nicola
Department of Internal Medicine, University of Messina, Messina, Italy.
J Bone Miner Res. 2004 May;19(5):722-7. doi: 10.1359/JBMR.040113. Epub 2004 Jan 12.
Osteoporosis represents an important cause of morbidity in adult thalassemic patients, and its pathogenesis has not, as yet, been completely clarified. In our study, we observed that thalassemic patients showed a significantly lower OPG/RANKL ratio than normal subjects. These data are extremely important for the possible therapeutic use of RANKL antagonists such as OPG in thalassemia-induced osteoporosis.
Osteoporosis represents an important cause of morbidity in adult thalassemic patients who display increased fracture risk. The etiology of this bone disease is multifactorial, but it is thought that the main role is played by hypogonadism. The mechanisms by which the skeletal effects of sex steroids are mediated are still not fully understood. Recently, two new cytokines, osteoprotegerin (OPG) and RANKL, have been implicated in the pathogenesis of postmenopausal osteoporosis and other metabolic bone diseases. Thus, the aim of this study was to characterize the possible role of the OPG/RANKL system in thalassemia-related bone loss.
We measured, in 30 thalassemic patients and in 20 healthy control subjects, serum OPG and RANKL levels, and determined their correlations with bone turnover markers, BMD, sex steroid levels, erythropoietin, and hemoglobin.
Thalassemic patients had an unbalanced bone turnover with an increased resorption phase (shown by high levels of pyridinium cross-links) and a decreased neoformation phase (shown by the slightly low levels of osteocalcin). Moreover, they displayed lower BMD values than controls both at the lumbar and femoral level. As far as the OPG/RANKL system is concerned, thalassemic patients showed no differences in plasma levels of OPG compared with controls, and significantly higher plasma levels of RANKL, with a consequent significantly lower OPG/RANKL ratio.
Our data suggest that, in thalassemic patients, an altered modulation of the OPG/RANKL system, resulting in increased expression of RANKL by stromal or osteoblastic cells, could contribute to the enhanced osteoclastic bone resorption and bone loss characteristic of these patients.
骨质疏松症是成年地中海贫血患者发病的一个重要原因，其发病机制尚未完全阐明。在我们的研究中，我们观察到地中海贫血患者的骨保护素（OPG）/核因子κB受体活化因子配体（RANKL）比值显著低于正常受试者。这些数据对于RANKL拮抗剂如OPG在地中海贫血所致骨质疏松症中的可能治疗应用极为重要。
骨质疏松症是成年地中海贫血患者发病的一个重要原因，这些患者骨折风险增加。这种骨病的病因是多因素的，但认为主要作用是由性腺功能减退发挥的。性类固醇的骨骼效应介导机制仍未完全了解。最近，两种新的细胞因子，骨保护素（OPG）和RANKL，已被认为与绝经后骨质疏松症和其他代谢性骨病的发病机制有关。因此，本研究的目的是确定OPG/RANKL系统在地中海贫血相关骨质流失中的可能作用。
我们测量了30例地中海贫血患者和20例健康对照受试者的血清OPG和RANKL水平，并确定了它们与骨转换标志物、骨密度、性类固醇水平、促红细胞生成素和血红蛋白的相关性。
地中海贫血患者的骨转换不平衡，吸收期增加（以吡啶交联水平高为表现），新形成期减少（以骨钙素水平略低为表现）。此外，他们在腰椎和股骨水平的骨密度值均低于对照组。就OPG/RANKL系统而言，地中海贫血患者与对照组相比，血浆OPG水平无差异，血浆RANKL水平显著更高，因此OPG/RANKL比值显著更低。
我们的数据表明，在地中海贫血患者中，OPG/RANKL系统的调节改变，导致基质细胞或成骨细胞中RANKL表达增加可能促成了这些患者特有的破骨细胞骨吸收增强和骨质流失。
