Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants

Bain, Steven D.; Jerome, Christopher P.; Shen, Victor; Dupin-Roger, Isabelle; Ammann, Patrick

doi:10.1007/s00198-008-0815-8

Cited by 126 publications

(130 citation statements)

References 42 publications

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“…4 In animals, Sr prevents bone loss in OVX rats 7,8 and increases bone mass in intact rats 16 and monkeys. 17 However, information of the anabolic effect of Sr on trabecular bone is limited, especially at the structural and tissue level.…”

Section: Discussionmentioning

confidence: 99%

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In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells

Peng

Liu

Wang

et al. 2010

Journal Orthopaedic Research

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ABSTRACT:In vitro studies have demonstrated that strontium (Sr) could increase osteogenic differentiation of bone marrow stromal cells (BMSCs). We investigated the in vivo effect of Sr on BMSCs. Thirty-six female rats were randomly divided into the following groups: sham operated and treated with either vehicle (Sham þ Veh) or Sr compound (Sham þ Sr) and ovariectomized and treated with either vehicle (OVX þ Veh) or Sr compound (OVX þ Sr). Vehicle and Sr were orally administrated daily starting immediately after the surgery and continuing for 12 weeks. The anabolic effect of Sr on trabecular bone was determined at the structural and tissue level by microCT and histomorphometry, respectively. Colony formation assays demonstrated that BMSCs exhibited higher osteogenic colony but lower adipogenic colony in Sr-treated versus Veh-treated OVX rats. The mRNA level of osteogenic genes was higher, while the mRNA level of adipogenic genes was lower in BMSCs from Sr-treated versus Veh-treated Sham and OVX rats. The effect of Sr on rat BMSCs was reproducible in human BMSCs. Taken together, this study suggests that the anabolic effect of Sr on normal or osteoporotic bones is associated with increased osteoblastic differentiation of BMSCs. Keywords: strontium; osteoblastogenesis; adipogenesis; bone marrow stromal cells; osteoporosis Bone marrow stromal cells (BMSCs) can differentiate into a number of lineages, including osteoblasts, chondroblasts, and adipocytes. 1 This multipotent differentiation potential makes them good candidates to regenerate degenerating tissues and restore their function. Recent studies suggest that low magnitude mechanical signals can increase bone volume and reduce fat tissues in male mice by stimulating BMSCs proliferation and differentiation into an osteoblast lineage. 2 Moreover, Bortezomib (Bzb), a first-in-class proteasome inhibitor used to treat myeloma patients, exerts an anabolic effect on bone by stimulating the differentiation of BMSCs into osteoblasts, thus leading to new bone formation. 3 These studies indicate that modulation of in vivo lineage differentiation of BMSCs is a feasible approach to build bone volume, which may serve as a new strategy to treat postmenopausal osteoporosis.Strontium ranelate (SR), a new anti-osteoporosis agent, can decrease vertebral and nonvertebral fracture risks in postmenopausal women. [4][5][6] Previous studies on postmenopausal women showed that the serum bone formation marker was increased due to SR treatment as compared to placebo controls. 4 In OVX rats, SR treatment prevented bone loss by increasing the bone formation maker and decreasing the bone resorption marker. 7,8 The cellular and molecular mechanism of the anabolic effect of strontium (Sr) on bone remains poorly understood. In vitro studies suggest that Sr can promote osteoblast proliferation and differentiation. 9,10 Recent studies also demonstrated that Sr can increase in vitro osteogenic differentiation of BMSCs. 11,12 Based on the observation that Sr could increase osteoblastic differentiati...

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Section: Discussionmentioning

confidence: 99%

“…4 In OVX rats, SR treatment prevented bone loss by increasing the bone formation maker and decreasing the bone resorption marker. 7,8 The cellular and molecular mechanism of the anabolic effect of strontium (Sr) on bone remains poorly understood. In vitro studies suggest that Sr can promote osteoblast proliferation and differentiation.…”

mentioning

confidence: 99%

In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells

Peng

Liu

Wang

et al. 2010

Journal Orthopaedic Research

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show abstract

“…In OVX rats, strontium ranelate-treated animals exhibited increased bone formation and decreased bone resorption, resulting in prevention of trabecular bone loss, improved bone microarchitecture, and strength (33,34). In postmenopausal osteoporotic women, strontium ranelate treatment increased bone mineral apposition rate and improved trabecular microarchitecture (35), which was associated with reduced fracture risk (27,29).…”

Section: Present Anabolic Therapiesmentioning

confidence: 99%

Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

Marie¹,

Kassem²

2011

European Journal of Endocrinology

191

143

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Objective: Age-related bone loss is associated with significant changes in bone remodeling characterized by decreased trabecular and periosteal bone formation relative to bone resorption, resulting in bone fragility and increased risk of fractures. Prevention or reversal of age-related decrease in bone mass and increase in bone fragility has been based on inhibition of bone resorption using anticatabolic drugs. The current challenge is to promote osteoblastogenesis and bone formation to prevent age-related bone deterioration. Methods: A limited number of approved therapeutic molecules are available to activate bone formation. Therefore, there is a need for anabolic drugs that promote bone matrix apposition at the endosteal, endocortical, and periosteal envelopes by increasing the number of osteoblast precursor cells and/or the function of mature osteoblasts. In this study, we review current therapeutics promoting bone formation and anabolic molecules targeting signaling pathways involved in osteoblastogenesis, based on selected full-text articles searched on Medline search from 1990 to 2010. Results and discussion: We present current therapeutic approaches focused on intermittent parathyroid hormone and Wnt signaling agonists/antagonists. We also discuss novel approaches for prevention and treatment of defective bone formation and bone loss associated with aging and osteoporosis. These strategies targeting osteoblastic cell functions may prove to be useful in promoting bone formation and improving bone strength in the aging population.

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“…Studies in rats have demonstrated that in addition to the increase in bone mass, there is an increase in cortical thickness and an improvement in trabecular and cortical microarchitecture, leading to an increased bone quality and strength [Ammann et al 2004[Ammann et al , 2007. In ovariectomized rats, an established animal model for postmenopausal osteoporosis, strontium ranelate was able to prevent bone loss by decreasing bone resorption while maintaining bone formation not only in the short term [Marie et al 1993], but also in the long term [Bain et al 2009]. In this latter study, the ovariectomy-induced decline in bone mass, volume and strength was prevented by achieving a plasma concentration of strontium ranelate similar to that obtained in women with osteoporosis treated with the therapeutic daily dose of 2 g.…”

Section: Determinants At the Tissue Level: In Vivo Evidencementioning

confidence: 99%

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

Cianferotti

D’Asta

Brandi

2013

Therapeutic Advances in Musculoskeletal

101

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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.

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Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants

Cited by 126 publications

References 42 publications

In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells

In vivo anabolic effect of strontium on trabecular bone was associated with increased osteoblastogenesis of bone marrow stromal cells

Osteoblasts in osteoporosis: past, emerging, and future anabolic targets

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

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