The calcium-sensing receptor (CaR) is involved in strontium ranelate-induced osteoblast proliferation

Chattopadhyay, Naibedya; Quinn, Stephen; Kifor, Olga; Ye, Chianping; Brown, Edward M.

doi:10.1016/j.bcp.2007.04.020

Cited by 193 publications

(171 citation statements)

References 41 publications

Supporting

Mentioning

151

Contrasting

Unclassified

Order By: Relevance

“…CaSR has been shown to mediate, at least in part, strontiuminduced osteoblast proliferation [Chattopadhyay et al 2007;Caudrillier et al 2010], and osteoclast apoptosis [Hurtel-Lemaire et al 2009]. CaSR signaling has been shown to play a key role in mediating the modulation of the OPG/RANKL system by strontium.…”

Section: Determinants At the Cellular And Molecular Level: In Vitro Ementioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Determinants At the Cellular And Molecular Level: In Vitro Ementioning

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

View full text Add to dashboard Cite

show abstract

“…9),12), 13) Strontium ranelate (S129112-2, PROTELOS ® ) was invented for controlling the bone fracture of osteoporosis patients.…”

Section: +mentioning

confidence: 99%

Ion release from SrO-CaO-TiO2-P2O5 glasses in Tris buffer solution

Lee

Obata

Kasuga

2009

J. Ceram. Soc. Japan

View full text Add to dashboard Cite

SrO-containing calcium phosphate invert glasses, (60-x)CaO•xSrO•30P2O5•7Na2O•3TiO2 (mol%, x = 0 -60), which are expected to inhibit bone resorption by osteoclast and enhance bone formation, were prepared and their ion release behaviors in Tris buffer solution were estimated. The glass containing 20 mol% of SrO showed the smallest amount of the dissolved ions in the present work. Laser Raman spectra showed that the peaks of phosphate groups and TiOy polyhedral groups red-shifted with increasing the SrO content in the glasses. The shift was suggested to be due to decrease in bonding strength between cations and phosphate groups or TiOy polyhedral groups in the glasses. In the case of the glasses containing SrO over 20 mol%, no shifts of Raman peaks due to the TiOy polyhedra were observed. The TiOy (y = 4 or 6) polyhedra in the glasses can coordinate with cations up to 18 mol% since they contain 3 mol% of TiO2. Sr 2+ ions are supposed from the shift behavior of the Raman peaks to preferentially coordinate with the TiOy polyhedra; the formation of this structure would induce decrease in the ion amounts released from the glasses containing 0 -20 mol% of SrO.

show abstract

“…We emphasise that this concentration of Sr 2+ was already sufficient to cause near-total inhibition of bone mineralisation in our cell cultures, and thus, no additional effect was observed at the highest dose tested (1 mM). No data are available for local, extravascular concentrations of Sr 2+ in patients or animalsbut to us, it seems extremely unlikely that they would reach levels as high as the 9 mM Sr 2+ used in the paper cited by Xie and Ye [4]. Moreover, it seems inconceivable that such a large amount of Sr 2+ could somehow trigger bone formation (a process that involves mineralisation) when a 90-fold lower concentration was able to block bone mineralisation so convincingly.…”

mentioning

confidence: 88%

Strontium and osteoblast function

et al. 2015

View full text Add to dashboard Cite

Dear Editor, We thank Drs. Xie and Ye [1] for their interest in our paper [2] and address their main comments below.Firstly, we were careful to acknowledge the contrasting findings of other published studies, both in vitro and in vivo. We do not know of any evidence to support the assertion of Drs. Xie and Ye that BSr 2+ concentrations in biological microenvironment(s) play essential roles in bone formation^.Secondly, Drs. Xie and Ye are concerned that we did not study sufficiently high concentrations of Sr 2+ in our osteoblast experiments. We chose Sr 2+ concentrations that spanned the maximum circulating Sr 2+ level (about 0.1 mM), measured in patients treated with 2 g/day strontium ranelate [3]. We emphasise that this concentration of Sr 2+ was already sufficient to cause near-total inhibition of bone mineralisation in our cell cultures, and thus, no additional effect was observed at the highest dose tested (1 mM). No data are available for local, extravascular concentrations of Sr 2+ in patients or animalsbut to us, it seems extremely unlikely that they would reach levels as high as the 9 mM Sr 2+ used in the paper cited by Xie and Ye [4]. Moreover, it seems inconceivable that such a large amount of Sr 2+ could somehow trigger bone formation (a process that involves mineralisation) when a 90-fold lower concentration was able to block bone mineralisation so convincingly.Thirdly, Drs. Xie and Ye are troubled that we did not include Ca 2+ in our culture system. The formulation of the standard DMEM cell culture medium we used is widely available but we are happy to confirm that it does indeed contain Ca 2+ , added to a concentration of 1.8 mM. This calcium is, of course, required for the abundant matrix mineralisation evident in our control cultures.Lastly, we certainly did not state in our paper that Sr 2+ is a Bfoe of bone formation^. Rather, as we suggest in the discussion, Sr 2+ could potentially exert beneficial effects on bone by acting to limit secondary mineralisation, thus reducing stiffness or brittleness.

show abstract

The calcium-sensing receptor (CaR) is involved in strontium ranelate-induced osteoblast proliferation

Cited by 193 publications

References 41 publications

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

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

Ion release from SrO-CaO-TiO2-P2O5 glasses in Tris buffer solution

Strontium and osteoblast function

Contact Info

Product

Resources

About