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.