Strontium ranelate: a dual mode of action rebalancing bone turnover in favour of bone formation

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 (R)) 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.