Endocrine Center, Austin Health, University of Melbourne, Melbourne, Australia.
J Bone Miner Res. 2014 Feb;29(2):380-8. doi: 10.1002/jbmr.2101.
During early menopause, steady-state bone remodeling is perturbed; the number of basic multicellular units (BMUs) excavating cavities upon the endosteal surface exceeds the number (generated before menopause) concurrently refilling. Later in menopause, steady-state is restored; the many BMUs generated in early menopause refill as similarly large numbers of BMUs concurrently excavate new cavities. We hypothesized that risedronate reduces the number of cavities excavated. However, in younger postmenopausal women, the fewer cavities excavated will still exceed the fewer BMUs now refilling, so net porosity increases, but less than in controls. In older postmenopausal women, the fewer cavities excavated during treatment will be less than the many (generated during early menopause) now refilling, so net porosity decreases and trabecular volumetric bone mineral density (vBMD) increases. We recruited 324 postmenopausal women in two similarly designed double-blind placebo-controlled studies that included 161 younger (Group 1, ≤ 55 years) and 163 older (Group 2, ≥ 55 years) women randomized 2:1 to risedronate 35 mg/week or placebo. High-resolution peripheral computed tomography was used to image the distal radius and tibia. Cortical porosity was quantified using the StrAx1.0 software. Risedronate reduced serum carboxyterminal cross-linking telopeptide of type 1 bone collagen (CTX-1) and serum amino-terminal propeptide of type 1 procollagen (P1NP) by ∼50%. In the younger group, distal radius compact-appearing cortex porosity increased by 4.2% ± 1.6% (p = 0.01) in controls. This was prevented by risedronate. Trabecular vBMD decreased by 3.6% ± 1.4% (p = 0.02) in controls and decreased by 1.6% ± 0.6% (p = 0.005) in the risedronate-treated group. In the older group, changes did not achieve significance apart from a reduction in compact-appearing cortex porosity in the risedronate-treated group (0.9% ± 0.4%, p = 0.047). No between-group differences reached significance. Results were comparable at the distal tibia. Between-group differences were significant for compact-appearing cortex porosity (p = 0.005). Risedronate slows microstructural deterioration in younger and partly reverses it in older postmenopausal women, features likely to contribute to antifracture efficacy.
在绝经早期，稳态骨重塑受到干扰；在骨内膜表面挖掘腔的基本多细胞单位 (BMU) 的数量超过同时再填充的数量（绝经前生成的数量）。在绝经后期，稳态得到恢复；在绝经早期产生的许多 BMU 同时挖掘新腔的同时再填充。我们假设利塞膦酸钠可减少挖掘腔的数量。然而，在较年轻的绝经后妇女中，尽管挖掘的腔数量减少，但仍超过现在再填充的较少的 BMU 数量，因此净孔隙度增加，但不及对照组。在年龄较大的绝经后妇女中，治疗期间挖掘的腔数量将少于绝经早期产生的许多腔（现在正在再填充），因此净孔隙度减少，小梁体积骨矿物质密度（vBMD）增加。我们招募了 324 名绝经后妇女，参加了两项设计相似的双盲安慰剂对照研究，其中包括 161 名较年轻（组 1，≤55 岁）和 163 名年龄较大（组 2，≥55 岁）的妇女，按 2:1 的比例随机分配至利塞膦酸钠 35mg/周或安慰剂。使用高分辨率外周计算机断层扫描 (CT) 对远端桡骨和胫骨进行成像。使用 StrAx1.0 软件量化皮质骨孔隙率。利塞膦酸钠使血清羧基末端交联端肽 1 型胶原 (CTX-1) 和血清氨基末端前肽 1 型原胶原 (P1NP) 降低约 50%。在较年轻的组中，对照组桡骨致密外观皮质骨孔隙率增加 4.2%±1.6%（p=0.01）。利塞膦酸钠可预防这种情况。对照组的小梁 vBMD 降低 3.6%±1.4%（p=0.02），而利塞膦酸钠治疗组降低 1.6%±0.6%（p=0.005）。在年龄较大的组中，除了利塞膦酸钠治疗组致密外观皮质骨孔隙率降低 0.9%±0.4%（p=0.047）外，其他变化未达到显著水平。两组之间无差异达到显著水平。在远端胫骨处的结果相当。致密外观皮质骨孔隙率的组间差异具有显著性（p=0.005）。利塞膦酸钠可减缓年轻绝经后妇女的微结构恶化，并在一定程度上逆转其结构恶化，这可能有助于抗骨折疗效。
