Osteoporosis associated with
estrogen deficiency results from an imbalance between
bone resorption and formation, causing deterioration of bone architecture and decreased bone mass. Anti-osteoporotic
therapies that have been developed so far include either anticatabolic or anabolic drugs.
Strontium ranelate is a newly developed
drug that induces opposite effects on
bone resorption and formation. This dual original mode of action was demonstrated in experimental studies on bone cells and pharmacological studies in animals. In vitro,
strontium ranelate was shown to decrease
bone resorption. This effect resulted from a decreased differentiation and resorbing activity of osteoclasts and increased osteoclast apoptosis. In contrast,
strontium ranelate was shown to enhance preosteoblastic cell replication and
collagen synthesis in culture without affecting bone mineralization. In vivo,
strontium ranelate promoted bone formation and reduced
bone resorption in intact mice, an effect which resulted in increased vertebral bone mass. Additionally,
strontium ranelate was found to reduce resorption and long bone loss induced by hind limb immobilization in rats. Finally,
strontium ranelate administration decreased
bone resorption and maintained bone formation in adult ovariectomized rats, which resulted in prevention of bone loss. In clinical trials (Spinal
Osteoporosis Therapeutic Intervention [SOTI]), bone
alkaline phosphatase levels increased, whereas C cross-linking telopeptide of
type I collagen (CTX) levels decreased in patients treated with
strontium ranelate compared with placebo at all time points. These pharmacological and clinical studies suggest that
strontium ranelate acts by increasing bone formation and decreasing
bone resorption and that these effects result in improved bone mass in vivo.