生物活性

• 描述Extracellular calcium-sensing receptor (CaSR) is a heptahelical transmembrane-spanning G protein-coupled receptor (GPCR) that plays an essential role in maintaining extracellular calcium ion concentrations. Strontium ranelate is an agonist of CaR with an IC50 of 0.5 mM. It was shown that strontium ranelate treatment from 0.1 to 1 mM (Sr²⁺) for 5 days induced proliferation in mouse calvaria cells, and the mRNA expression of osteoblastic markers was significantly elevated after 22 days of treatment. On the contrary, 8 days of strontium ranelate treatment significantly decreased osteoclast differentiation in a dose-dependent manner, starting at 0.1 mM (Sr²⁺). Also in osteoclasts, reduced resorption was observed 48 hours after the treatment of 0.1 mM to 24 mM strontium ranelate (Sr²⁺)^[3]. A murine study showed that a dose of 1800 mg/kg/d of strontium ranelate significantly increased the trabecular bone volume by 59% in female mice and by 38% in male mice after 104 weeks of treatment^[4]. In adult ovariectomized rats, daily treatment of 625 mg/kg/day strontium ranelate for 52 weeks prevented their bone loss and micro-architecture deterioration^[5]. A phase 3 clinical trial in postmenopausal women showed that daily ingestion of 2 g strontium ranelate reduced the risk of new vertebral fractures by 49% in the first year and by 41% over three years^[6].
• 作用机制Strontium ranelate contains two atoms of stable strontium (Sr²⁺), which resembles Ca²⁺, acting as an agonist of calcium-sensing receptor^[7].

• 动物研究
  剂量	Rat: 25 mg/kg, 50 mg/kg[3] (p.o.) Dog: 25 mg/kg - 75 mg/kg[4] (p.o.)
  给药途径	p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02637180	-	-	Completed	-	Greece ... more >> NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS, MEDICAL SCHOOL, 2nd DEPARTMENT OF ORTHOPAEDIC SURGERY Athens, Attiki, Greece, 14233 Democritus University of Thrace, School of Medicine, Department of Orthopaedic Surgery Alexandroupolis, Evros, Greece, 68100 Orthopaedic Department, Faculty of Medicine, School of Health Sciences, University of Thessalia Larissa, Greece, 41110 Aristotle University of Thessaloniki, 3rd University Orthopaedic Department, Papageorgiou General Hospital Thessaloniki, Greece, 56403 Collapse <<
  NCT00409032	Osteoporosis	Phase 2	Completed	-	Denmark ... more >> PhaseOneTrials Hvidovre, Denmark, 2650 Odense University Hospital Odense, Denmark, 5000 United Kingdom Medinova Clinic Northwood, Middlesex, United Kingdom Synexus Wales Clinical Research Centre Cardiff, United Kingdom, CF14 5GJ Synexus Scotland Clinical Research Centre Glasgow, United Kingdom, G81 2DR Synexus Limited Reading Clinical Research Centre Reading, United Kingdom, RG2 7AG University of Sheffield Sheffield, United Kingdom, S5 7AU Synexus Crosby Clinical Research Centre Waterloo, United Kingdom, L22 0LG Synexus Wigan Clinical Research Centre Wigan, United Kingdom, WN1 1XX Collapse <<
  NCT00239629	Postmenopausal Osteoporosis	Phase 4	Completed	-	Czech Republic ... more >> For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Prague, Czech Republic, 128 21 Germany For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Hamburg, Germany, 20354 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Heidelberg, Germany, 69120 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Magdeburg, Germany, D-39110 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Vogelsang, Germany, 39245 Greece For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Kifissia, Greece, 145 61 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Thessaloniki, Greece, 56429 Israel For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Haifa, Israel, 31096 Mexico For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Guadalajara, Mexico, 44670 Spain For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Barcelona, Spain, 08025 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Madrid, Spain, 28041 Collapse <<

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• 参考文献

• [1] Guo X, Wei S, et al. Dose-dependent Effects of Strontium Ranelate on Ovariectomy Rat Bone Marrow Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells. Int J Biol Sci. 2016 Nov 25;12(12):1511-1522.

  [2] Fernandez JM, Molinuevo MS, et al. Strontium ranelate prevents the deleterious action of advanced glycation endproducts on osteoblastic cells via calcium channel activation. Eur J Pharmacol. 2013 Apr 15;706(1-3):41-7.

  [3] Bonnelye E, Chabadel A, Saltel F, Jurdic P. Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone. 2008 Jan;42(1):129-38.

  [4] Delannoy P, Bazot D, Marie PJ. Long-term treatment with strontium ranelate increases vertebral bone mass without deleterious effect in mice. Metabolism. 2002 Jul;51(7):906-11.

  [5] Bain SD, Jerome C, Shen V, Dupin-Roger I, Ammann P. Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants. Osteoporos Int. 2009 Aug;20(8):1417-28.

  [6] Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, Balogh A, Lemmel EM, Pors-Nielsen S, Rizzoli R, Genant HK, Reginster JY. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med. 2004 Jan 29;350(5):459-68.

  [7] Marie PJ. Strontium ranelate in osteoporosis and beyond: identifying molecular targets in bone cell biology. Mol Interv. 2010 Oct;10(5):305-12.

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