D'Amelio P, Grimaldi A, Cristofaro M A, Ravazzoli M, Molinatti P A, Pescarmona G P, Isaia G C
Gerontology Section, Department of Surgical and Medical Disciplines, University of Torino, Corso Bramante 88/90, 10126, Torino, Italy.
Osteoporos Int. 2010 Oct;21(10):1741-50. doi: 10.1007/s00198-009-1129-1. Epub 2009 Dec 1.
This study evaluates the effect of alendronate on osteoclastogenesis, cytokine production, and bone resorption in postmenopausal women. We suggest that it acts on mature bone resorbing osteoclasts after 3 months of treatment, whereas, after 1 year, it diminishes their formation by reducing their precursors and serum RANKL.
Osteoclasts are the target cells of bisphosphonates, though the most drug-sensitive steps of their formation and activity have not been determined. The present study evaluates the effect of alendronate on osteoclastogenesis, cytokine production, and bone resorption in postmenopausal women.
The study was conducted on 35 osteoporotic women; 15 were pretreated with alendronate 70 mg/week, whereas, 20 were treated with calcium 1 g/day and vitamin D 800 IU/day. After 3 months, 30 received alendonate 70/mg, vitamin D 2800 IU/week, and calcium 1 g/day for 12 months (combined therapy), whereas, the other five patients remained on calcium 1 g/day and vitamin D 800 IU/day. The following parameters were assessed before and after therapy: changes in bone resorption markers, circulating osteoclast precursors, formation of osteoclasts in peripheral blood mononuclear cell cultures, their viability, and variations in cytokines production.
After 3 months of alendronate, there was no significant reduction in the number of osteoclast precursors, osteoclast formation and viability, and cytokine levels, whereas, there was a significant reduction of bone resorption markers. One year of the combined therapy, on the other hand, reduced osteoclast precursors, osteoclast formation, and serum RANKL, whereas, calcium plus vitamin D alone had no effect.
We suggest that alendronate mainly acts on mature bone resorbing osteoclasts in the short term, whereas, its long-term administration diminishes their formation by reducing their precursors and serum RANKL.
本研究评估阿仑膦酸钠对绝经后女性破骨细胞生成、细胞因子产生及骨吸收的影响。我们认为，治疗3个月后它作用于成熟的骨吸收破骨细胞，而1年后，它通过减少破骨细胞前体和血清RANKL来减少其形成。
破骨细胞是双膦酸盐的靶细胞，但其形成和活性中最药物敏感的步骤尚未确定。本研究评估阿仑膦酸钠对绝经后女性破骨细胞生成、细胞因子产生及骨吸收的影响。
该研究对35名骨质疏松女性进行；15名患者每周预先接受70mg阿仑膦酸钠治疗，而20名患者每天接受1g钙和800IU维生素D治疗。3个月后，30名患者接受70mg阿仑膦酸钠、每周2800IU维生素D和每天1g钙治疗12个月（联合治疗），而其他5名患者继续每天接受1g钙和800IU维生素D治疗。在治疗前后评估以下参数：骨吸收标志物的变化、循环破骨细胞前体、外周血单个核细胞培养中破骨细胞的形成、其活力以及细胞因子产生的变化。
阿仑膦酸钠治疗3个月后，破骨细胞前体数量、破骨细胞形成和活力以及细胞因子水平没有显著降低，而骨吸收标志物有显著降低。另一方面，联合治疗1年后，破骨细胞前体、破骨细胞形成和血清RANKL减少，而单独使用钙加维生素D没有效果。
我们认为，阿仑膦酸钠在短期内主要作用于成熟的骨吸收破骨细胞，而长期给药通过减少破骨细胞前体和血清RANKL来减少其形成。
