A review on strontium ranelate long-term antifracture efficacy in the treatment of postmenopausal osteoporosis

Abstract

Osteoporotic fractures are one of the major causes of increased morbidity and mortality in postmenopausal women and the overall aging population. One of the major issues in the management of postmenopausal osteoporosis is to find a safe and effective treatment in the long term (>3 years) to achieve and maintain a reduction in the risk of fracture. Strontium ranelate (PROTELOS ® ) is a relatively novel drug, currently approved in Europe for the treatment of postmenopausal osteoporosis. Strontium ranelate is the first agent of a new therapeutic class in osteoporosis, capable of both promoting bone formation and, to a lesser extent, inhibiting bone resorption. This uncoupling in bone turnover results in a net gain in bone mineral density (BMD), bone quality improvement and reduction in risk of vertebral and nonvertebral fractures, as initially demonstrated in the preplanned long-term registrative trials SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis) at 5 years. Recently, open-label extensions of the SOTI and TROPOS trials up to 8 and, recently, 10 years have confirmed the sustained efficacy of strontium ranelate in increasing BMD, the long-term safety profile and the high compliance to treatment, independently from baseline BMD or other risk factors for osteoporotic fractures. Recent economic impact analyses have proved that long-term treatment with strontium ranelate is highly cost effective, especially in women older than 70 years of age. Histomorphometric analyses in animals and humans participating in the phase III trials have proved that the quality of mineralization is preserved in the long term and bone microarchitecture is ameliorated, with increased bone strength. Thus, strontium ranelate has been confirmed to be an effective compound for the long-term, chronic treatment of postmenopausal osteoporosis.

The calcium-sensing receptor in bone metabolism: from bench to bedside and back

“…On one hand, activators of the CaSR have the potential to inhibit PTH secretion and can be used in the treatment of parathyroid hyperfunction; on the other hand, CaSR inhibitors may induce transient PTH increases, which can be anabolic for bone. Strontium ranelate deserves a particular note as a divalent ion that can modulate bone metabolism favoring bone formation and decreasing resorption at least in part through modulation of the CaSR [84].…”

“…It displays a dual mechanism of action, namely, bone forming and anti-resorptive properties, which lead to short-and long-term reduction in vertebral and non-vertebral fractures, such as hip fractures [84,113].…”

Marine Natural Products: New Avenue in Treatment of Osteoporosis

“…Strontium ranelate is an antiresorptive and bone anabolic agent which has been approved for postmenopausal osteoporosis treatment in Europe (Cianferotti et al, 2013). Preliminary studies showed that strontium ranelate decreases osteoclast differentiation and function simultaneously promoting osteoblastogenesis and osteoblast activity.…”

Individualisierte Therapie der Osteoporose

“…Dieses Ergebnis bestätigten auch die Openlabel-Erweiterungen der Phase-III-Studien Spinal Osteoporosis Therapeutic Intervention (SOTI) und Treatment of Peripheral Osteoporosis (TROPOS), in denen eine kontinuierliche Zunahme der lumbalen Knochendichte über den gesamten Beobachtungszeitraum von 10 Jahren nachgewiesen wurde. Zudem war das relative Risiko für vertebrale Frakturen um 35 % und das für nichtvertebrale Frakturen um 38 % verringert [8].…”