Bourrin S, Ammann P, Bonjour J P, Rizzoli R
Division of Bone Diseases, WHO Collaborating Center for Osteoporosis and Bone Diseases, Department of Internal Medicine, University Hospital, Geneva, Switzerland.
Bone. 2002 Jan;30(1):195-200. doi: 10.1016/s8756-3282(01)00661-5.
Various bisphosphonates and the selective estrogen receptor modulator (SERM) raloxifene are approved treatments of postmenopausal osteoporosis. They increase bone mineral density (BMD), decrease bone turnover, and reduce vertebral fracture incidence through different cellular mechanisms. We investigated the bone cellular activities, architecture, mineral content/density, and strength of ovariectomized (ovx) rats on a long-term bisphosphonate or SERM treatment, at doses of either agent correcting bone strength. Eleven weeks postovariectomy, 6-month-old rats were treated with the SERM MDL 103,323 or with the bisphosphonate pamidronate for 5 months. Doses of pamidronate and MDL 103,323 were selected from previous studies showing correction of the ovx-induced decrease of ultimate strength of proximal tibia. Ultimate and yield strengths, BMD, and histomorphometric parameters were all quantified at the same site, i.e., the proximal tibia metaphysis. Long-term pamidronate decreases bone turnover and bone formation activity, leading to trabecular thinning. MDL 103,323 decreases bone turnover to a lesser extent, and slightly protects trabecular architecture by uncoupling bone resorption and formation activities. The yield strength is corrected by pamidronate, but not by MDL 103,323 treatment. However, neither compound restores the ovariectomy-induced cancellous bone loss. Total tissue area and cortical thickness are unchanged with pamidronate or MDL 103,323 treatment, indicating that cortical bone mass, thickness, and cross-sectional area are not modified. The discrepancy between proximal tibia BMD and mechanical resistance to fracture modifications, on the one hand, and cancellous bone volume, on the other hand, could be due to changes in the degree of mineralization of bone matrix and/or of the intrinsic properties of the bone matrix.
多种双膦酸盐和选择性雌激素受体调节剂（SERM）雷洛昔芬被批准用于治疗绝经后骨质疏松症。它们通过不同的细胞机制增加骨矿物质密度（BMD）、降低骨转换并减少椎体骨折发生率。我们研究了长期接受双膦酸盐或SERM治疗的去卵巢（ovx）大鼠的骨细胞活性、结构、矿物质含量/密度和强度，所用药物剂量均能纠正骨强度。卵巢切除术后11周，对6月龄大鼠用SERM MDL 103,323或双膦酸盐帕米膦酸治疗5个月。帕米膦酸和MDL 103,323的剂量是根据先前的研究选择的，这些研究表明其可纠正ovx诱导的胫骨近端极限强度降低。极限强度和屈服强度、BMD以及组织形态计量学参数均在同一部位即胫骨近端干骺端进行量化。长期使用帕米膦酸可降低骨转换和骨形成活性，导致小梁变薄。MDL 103,323在较小程度上降低骨转换，并通过解偶联骨吸收和形成活性对小梁结构起到轻微保护作用。帕米膦酸可纠正屈服强度，但MDL 103,323治疗则不能。然而，两种化合物均不能恢复去卵巢诱导的松质骨丢失。帕米膦酸或MDL 103,323治疗后，总组织面积和皮质厚度未发生变化，表明皮质骨质量、厚度和横截面积未改变。一方面胫骨近端BMD与骨折力学抵抗改变之间，另一方面与松质骨体积之间的差异，可能是由于骨基质矿化程度的变化和/或骨基质固有特性的改变所致。
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