Marie Pierre J
INSERM U606 and University Paris 7, Lariboisière Hospital, 75475 Paris cedex 10, France.
Curr Opin Rheumatol. 2006 Jun;18 Suppl 1:S11-5. doi: 10.1097/01.bor.0000229522.89546.7b.
The increased bone remodeling in women after menopause induces an imbalance between bone resorption and formation, leading to decreased bone mass, altered bone microarchitecture, and increased fracture risk. Current antiosteoporotic drugs decrease bone remodeling or increase bone formation. Strontium ranelate (Protelos) is a newly developed antiosteoporotic drug that acts by reducing bone resorption and promoting bone formation, thereby inducing a positive bone balance. In rat and mouse culture models, strontium ranelate enhances preosteoblastic cell replication and bone formation markers. In contrast, it decreases rodent osteoclastic cell resorbing activity and human osteoclast differentiation, and increases rabbit osteoclast apoptosis. In vivo, strontium ranelate increases bone formation and reduces bone resorption in mice, resulting in increased vertebral bone mass. In rats, strontium ranelate increases bone mass and improves microarchitecture and bone geometry, resulting in increased bone resistance. In ovariectomized rats, strontium ranelate decreases bone resorption but maintains high bone formation, resulting in improved bone microarchitecture and increased bone mass and strength. In clinical trials, serum alkaline phosphatase levels increased whereas serum CTX levels simultaneously decreased in patients treated with Protelos versus placebo at all time-points. In these trials, histomorphometric analysis of bone biopsies showed that the osteoblast surface and mineral apposition rate increased whereas bone resorption parameters tended to decrease in treated patients compared to the placebo group. These preclinical and clinical data indicate that strontium ranelate acts by increasing bone formation and decreasing bone resorption, thus rebalancing bone turnover in favour of bone formation, an effect that results in increased bone mass and strength.
绝经后女性骨重塑增加会导致骨吸收与形成失衡，进而致使骨量减少、骨微结构改变以及骨折风险增加。目前的抗骨质疏松药物可减少骨重塑或增加骨形成。雷奈酸锶（普罗力）是一种新研发的抗骨质疏松药物，其作用机制是减少骨吸收并促进骨形成，从而实现正向骨平衡。在大鼠和小鼠培养模型中，雷奈酸锶可增强前成骨细胞复制及骨形成标志物。相反，它会降低啮齿动物破骨细胞的吸收活性以及人类破骨细胞分化，并增加兔破骨细胞凋亡。在体内，雷奈酸锶可增加小鼠的骨形成并减少骨吸收，从而增加椎骨骨量。在大鼠中，雷奈酸锶可增加骨量，改善微结构和骨几何形态，进而增强骨抗力。在去卵巢大鼠中，雷奈酸锶可减少骨吸收但维持高骨形成，从而改善骨微结构，增加骨量和强度。在临床试验中，与安慰剂相比，接受普罗力治疗的患者在所有时间点血清碱性磷酸酶水平均升高，而血清CTX水平同时降低。在这些试验中，对骨活检的组织形态计量学分析显示，与安慰剂组相比，治疗患者的成骨细胞表面和矿化沉积率增加，而骨吸收参数则趋于降低。这些临床前和临床数据表明，雷奈酸锶通过增加骨形成和减少骨吸收发挥作用，从而重新平衡骨转换，使其有利于骨形成，这种作用会导致骨量和强度增加。
