Compston Juliet E
School of Clinical Medicine, University of Cambridge, Cambridge CB2 2QQ, UK.
Bone. 2007 Jun;40(6):1447-52. doi: 10.1016/j.bone.2006.09.008. Epub 2006 Oct 12.
Intermittent administration of parathyroid hormone peptides has anabolic skeletal effects and reduces fracture risk in postmenopausal women with osteoporosis but the cellular and structural mechanisms by which these effects are mediated have not been fully established. In cancellous and endocortical bone, there is evidence that both modelling and remodelling-based formation contribute to the increase in bone mass although the contribution of these at different time points in the response to PTH has not been established. Despite the large increase in spine bone mineral density, however, significant increases in iliac crest cancellous bone volume and trabecular thickness have not been consistently demonstrated, possibly reflecting site-specific differences in PTH-induced skeletal effects and/or the large sampling and measurement variance associated with assessment of iliac crest cancellous bone volume and structure. In iliac crest cortical bone, increased cortical thickness has been demonstrated, due at least in part to increased endosteal bone formation; there is also some evidence for increased formation on periosteal surfaces. At some sites an increase in cortical porosity may also occur and the overall effects on cortical bone strength, particularly at the hip, remain to be established. Studies in iliac crest bone indicate a trend towards a lower mineralisation density of bone matrix and increased heterogeneity of mineralisation, consistent with new bone formation. In addition, there is a reduction in mineral crystallinity and a shift towards more divalent collagen cross-links, indicating a change towards a younger bone profile. The potential clinical implications of these effects on bone are currently unknown. The stimulatory effect of PTH peptides on bone formation may favour their use in low turnover bone disease and in states of advanced bone loss. Furthermore, if beneficial effects on cortical bone strength are confirmed, efficacy at non-vertebral sites might be superior to those observed with antiresorptive drugs. Better definition of the effects of intermittent PTH administration on cancellous and cortical bone remodelling and structure at different skeletal sites may inform these speculations and is an important area for future research.
间歇性给予甲状旁腺激素肽对骨骼具有合成代谢作用，并可降低绝经后骨质疏松症女性的骨折风险，但介导这些作用的细胞和结构机制尚未完全明确。在松质骨和内皮质骨中，有证据表明基于建模和重塑的形成过程均有助于骨量增加，尽管在对甲状旁腺激素反应的不同时间点，它们的贡献尚未明确。然而，尽管脊柱骨矿物质密度大幅增加，但髂嵴松质骨体积和小梁厚度并未始终如一地显著增加，这可能反映了甲状旁腺激素诱导的骨骼效应的部位特异性差异和/或与髂嵴松质骨体积和结构评估相关的较大采样和测量方差。在髂嵴皮质骨中，已证实皮质厚度增加，至少部分归因于骨内膜骨形成增加；也有一些证据表明骨膜表面形成增加。在某些部位，皮质孔隙率也可能增加，而对皮质骨强度的总体影响，尤其是在髋部，仍有待确定。对髂嵴骨的研究表明，骨基质矿化密度有降低趋势，矿化异质性增加，这与新骨形成一致。此外，矿物质结晶度降低，向更多二价胶原交联转变，表明骨形态向更年轻的方向变化。这些对骨骼的影响的潜在临床意义目前尚不清楚。甲状旁腺激素肽对骨形成的刺激作用可能有利于其在低转换骨病和严重骨丢失状态中的应用。此外，如果对皮质骨强度的有益作用得到证实，在非椎体部位的疗效可能优于抗吸收药物。更好地定义间歇性给予甲状旁腺激素对不同骨骼部位松质骨和皮质骨重塑及结构的影响，可能为这些推测提供依据，并且是未来研究的一个重要领域。
