Strontium ranelate: A physiological approach for optimizing bone formation and resorption

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. (c) 2006 Elsevier Inc. All rights reserved.