Does Local Application of Strontium Increase Osteogenesis and Biomaterial Osteointegration in Osteoporotic and Other Bone Tissue Conditions: Review of Literature

Open access


Osteoporosis and other pathological bone conditions can impair bone regeneration properties, consuming in increased morbidity and decreased quality of life. Changes of bone healing can result in poor osteointegration and surgical failures if implants are used. To overcome and facilitate bone regeneration, more attempts are made to develop an ideal synthetic scaffold with better biocompatibility, osteoconductivity, bioactivity, osteoinductivity and interconnected porosity. It is considered that strontium, being similar to calcium, can be incorporated into the mineral phase of the bone remodeling. This quality had led strontium to be used as an osteoporotic medication to improve quality of bone and to reduce the risk of bone fractures. Also local application of strontium has been widely used within different biomaterials in tissue engineering researches.

In this review authors wanted to provide an overview about strontium, its mechanisms of action in bone tissue and initiated changes of bone remodeling within biomaterials.


  • 1. Andersen OZ, Offermanns V, Sillassen M et al. Accelerated bone ingrowth by local delivery of strontium from surface functionalized titanium implants //. Biomaterials, 2013; 34(24): 5883-5890

  • 2. Atkins GJ, Welldon KJ, Halbout P et al. Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response // Osteoporos Int. 2009; 20(4):653-64

  • 3. Bakker AD, Zandieh-Doulabi B, Klein-Nulend J. Strontium ranelate affects signaling from mechanically-stimulated osteocytes towards osteoclasts and osteoblasts // Bone, 2013; 53(1): 112-119

  • 4. Billström GH, Blom AW, Larsson S et al. Application of scaffolds for bone regeneration strategies: Current trends and future directions // Injury, 2013; 44(1): 28-33

  • 5. Bose S, Fielding G, Tarafder S et al. Understanding of dopant – induced osteogenesis and angiogenesis in calcium phosphate ceramics // Trends in Biotechnology, 2013; 31 (10):594–605.

  • 6. Breart G, Cooper C, Meyer O et al. Osteoporosis and venous thromboembolism: a retrospective cohort study in the UK General Practice Research Database // Osteoporos Int. 2010;21(7):1181-7

  • 7. Caverzasio J, Thouverey C. Activation of FGF receptors is a new mechanism by which strontium ranelate induces osteoblastic cell growth // Cell Physiol Biochem. 2011;27(3-4):243-50

  • 8. Chen YW, Feng T, Shi GQ, et al. Interaction of endothelial cells with biodegradable strontium-doped calcium polyphosphate for bone tissue engineering // Applied Surface Science, 2008; 255(2): 331-335

  • 9. Chen YW, Shi GQ, Ding YL et al. In vitro study on the influence of strontium-doped calcium polyphosphate on the angiogenesis-related behaviors of HUVECs // J Mater Sci Mater Med, 2008; 19(7): 2655-2662

  • 10. Cho SW, Yang JY, Her SJ et al. Osteoblast-targeted overexpression of PPARgamma inhibited bone mass gain in male mice and accelerated ovariectomy-induced bone loss in female mice // J Bone Miner Res, 2011; 26(8): 1939-1952

  • 11. Dahl SG, Allain P, Marie PJ et al. Incorporation and distribution of strontium in bone // Bone, 2001; 28:446-453

  • 12. Donneau AF, Reginster JY. Cardiovascular safety of strontium ranelate: real-life assessment in clinical practice // Osteoporos Int. 2014; 25(2):397-8

  • 13. Elgali I, Turri A, Xia W et al. Guided bone regeneration using resorbable membrane and different bone substitutes: Early histological and molecular events // Acta Biomater, 2016; 29: 409-423

  • 14. Fernández JM, Molinuevo MS, Sedlinsky C, Strontium ranelate prevents the deleterious action of advanced glycation endproducts on osteoblastic cells via calcium channel activation // Eur J Pharmacol, 2013; 706(1-3): 41-47

  • 15. Fromigué O, Haÿ E, Barbara A et al. Essential role of nuclear factor of activated T cells (NFAT)-mediated Wnt signaling in osteoblast differentiation induced by strontium ranelate // J Biol Chem, 2010; 285(33): 25251-25258

  • 16. Fromigué O, Haÿ E, Barbara A et al. Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate // J Cell Mol Med, 2009; 13(8B): 2189-2199

  • 17. Gu Z, Zhang X, Li L et al. Acceleration of segmental bone regeneration in a rabbit model by strontium-doped calcium polyphosphate scaffold through stimulating VEGF and bFGF secretion from osteoblasts // Mater Sci Eng C Mater Biol Appl, 2013; 33(1): 274-281

  • 18. Gu Z, Xie H, Li L et al. Application of strontium-doped calcium polyphosphate scaffold on angiogenesis for bone tissue engineering // J Mater Sci Mater Med, 2013; 24(5): 1251-1260

  • 19. Guan RG, Cipriano AF, Zhao ZY et al. Development and evaluation of a magnesium-zinc-strontium alloy for biomedical applications--alloy processing, microstructure, mechanical properties, and biodegradation // Mater Sci Eng C Mater Biol Appl, 2013; 33(7): 3661-3669

  • 20. Hao J, Acharya A, Chen K, et al. Novel bioresorbable strontium hydroxyapatite membrane for guided bone regeneration // Clin Oral Implants Res, 2015; 26(1): 1-7

  • 21. Iolascon G, Frizzi L, Di Pietro G et al. Bone quality and bone strength: benefits of the bone-forming approach // Clin Cases Miner Bone Metab. 2014;11(1): 20–24

  • 22. Isaac J, Nohra J, Lao J et al. Effects of strontium-doped bioactive glass on the differentiation of cultured osteogenic cells // Eur Cell Mater, 2011; 21: 130-143

  • 23. Kuang GM, Yau WP, Lu WW et al. Local application of strontium in a calcium phosphate cement system accelerates healing of soft tissue tendon grafts in anterior cruciate ligament reconstruction: experiment using a rabbit model // Am J Sports Med, 2014; 42(12): 2996-3002

  • 24. Li Y, Li J, Zhu S et al. Effects of strontium on proliferation and differentiation of rat bone marrow mesenchymal stem cells // Biochem Biophys Res Commun, 2012; 418(4): 725-730

  • 25. Lin K, Xia L, Li H et al. Enhanced osteoporotic bone regeneration by strontium-substituted calcium silicate bioactive ceramics // Biomaterials, 2013; 34(38): 10028-10042

  • 26. Liu C, Zhang Y, Wang L et al. A Strontium-Modified Titanium Surface Produced by a New Method and Its Biocompatibility In Vitro // PLoS One, 2015; 10(11): e0140669

  • 27. Marie PJ. Strontium ranelate: a novel mode of action optimizing bone formation // Osteoporosis Int, 2005; 16: 7-10

  • 28. Meunier PJ, Roux C, Seeman E et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis // N Engl J Med. 2004; 350(5):459-68

  • 29. Neves N, Campos BB, Almeida IF et al. Strontium-rich injectable hybrid system for bone regeneration // Mater Sci Eng C Mater Biol Appl, 2016; 59: 818-827

  • 30. Ni GX, Lu WW, Chiu KY et al. Strontium-containing hydroxyapatite (Sr-HA) bioactive cement for primary hip replacement: an in vivo study// J Biomed Mater Res B Appl Biomater, 2006;77(2): 409-415

  • 31. Nielsen SP. Review – the biological role of strontium // Bone, 2004; 35(3):583–588

  • 32. Panzavolta S, Torricelli P, Sturba L et al. Setting properties and in vitro bioactivity of strontium-enriched gelatin-calcium phosphate bone cements // J Biomed Mater Res A, 2008; 84(4): 965-972

  • 33. Park JW, Kang DG, Hanawa T. New bone formation induced by surface strontium-modified ceramic bone graft substitute // Oral Diseases, 2016; 22(1): 53-61

  • 34. Pelletier JP, Kapoor M, Fahmi H et al. Strontium ranelate reduces the progression of experimental dog osteoarthritis by inhibiting the expression of key proteases in cartilage and of IL-1β in the synovium // Ann Rheum Dis, 2013; 72(2): 250-257

  • 35. Pelletier JP, Roubille C, Raynauld JP et al. Disease-modifying effect of strontium ranelate in a subset of patients from the Phase III knee osteoarthritis study SEKOIA using quantitative MRI: reduction in bone marrow lesions protects against cartilage loss // Ann Rheum Dis, 2015; 74(2): 422-429

  • 36. Peng S, Zhou G, Luk KD et al. Strontium promotes osteogenic differentiation of mesenchymal stem cells through the Ras/MAPK signaling pathway // Cell Physiol Biochem, 2009; 23(1-3): 165-174

  • 37. Peng S, Liu XS, Huang S et al. The cross-talk between osteoclasts and osteoblasts in response to strontium treatment: involvement of osteoprotegerin // Bone. 2011; 49(6):1290-8

  • 38. Qiu K, Zhao XJ, Wan CX et al. Effect of strontium ions on the growth of ROS17/2.8 cells on porous calcium polyphosphate scaffolds // Biomaterials, 2006, 27(8): 1277-1286

  • 39. Querido W, Farina M, Anselme K. Strontium ranelate improves the interaction of osteoblastic cells with titanium substrates: Increase in cell proliferation, differentiation and matrix mineralization // Biomatter, 2015; 5: e1027847

  • 40. Ray S, Thormann U, Sommer U et al. Effects of macroporous, strontium loaded xerogel-scaffolds on new bone formation in critical-size metaphyseal fracture defects in ovariectomized rats // Injury, 2016; 47(1): 52-61

  • 41. Reginster JY, Badurski J, Bellamy N et al. Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial // Ann Rheum Dis. 2013; 72(2):179-86

  • 42. Reginster JY, Brandi ML, Cannata-Andía J et al. The position of strontium ranelate in today’s management of osteoporosis //Osteoporos Int. 2015; 26 (6):1667–1671

  • 43. Reginster JY, Deroisy R, Jupsin I. Strontium ranelate: a new paradigm in the treatment of osteoporosis // Drugs Today (Barc). 2003; 39(2):89-101

  • 44. Römer P, Desaga B, Proff P et al. Strontium promotes cell proliferation and suppresses IL-6 expression in human PDL cells // Ann Anat, 2012; 194(2): 208-211

  • 45. Rivadeneira F, Mäkitie O. Osteoporosis and Bone Mass Disorders: From Gene Pathways to Treatments // Trends Endocrinol. Metab. 2016 ( (2016) 262–281.

  • 46. Rucci N. Molecular biology of bone remodeling // Clin. Cases Miner. Bone Metab. 2008; (5): 49-56

  • 47. Rybchyn MS, Slater M, Conigrave AD et al. An Akt-dependent increase in canonical Wnt signaling and a decrease in sclerostin protein levels are involved in strontium ranelate-induced osteogenic effects in human osteoblasts // J Biol Chem, 2011; 286(27): 23771-23779

  • 48. Saidak Z, Haÿ E, Marty C et al. Strontium ranelate rebalances bone marrow adipogenesis and osteoblastogenesis in senescent osteopenic mice through NFATc/Maf and Wnt signaling // Aging Cell, 2012; 11(3): 467-474

  • 49. Saidak Z, Marie PJ. Strontium signaling: Molecular mechanisms and therapeutic implications in osteoporosis // Pharmacology & Therapeutics, 2012; (136): 216–226

  • 50. Singh S, Kumar D, Lal AK. Serum Osteocalcin as a Diagnostic Biomarker for Primary Osteoporosis in Women // J Clin Diagn Res, 2015; 9(8): 4–7

  • 51. Singh SS, Roy A, Lee BE. A study of strontium doped calcium phosphate coatings on AZ31 // Mater Sci Eng C Mater Biol Appl, 2014; 40: 357-365

  • 52. Tie D, Guan R, Liu H. An in vivo study on the metabolism and osteogenic activity of bioabsorbable Mg-1Sr alloy // Acta Biomater, 2016; 29: 455-467.

  • 53. Thormann U, Ray S, Sommer U et al. Bone formation induced by strontium modified calcium phosphate cement in critical-size metaphyseal fracture defects in ovariectomized rats // Biomaterials, 2013; 34(34): 8589-8598

  • 54. Verberckmoes SC, Debroe ME. Dose dependent effect of strontium on osteoblast function and mineralization // Kidney Int, 2003; 64:534-543

  • 55. Yang F, Yang D, Tu J et al. Strontium enhances osteogenic differentiation of mesenchymal stem cells and in vivo bone formation by activating Wnt/catenin signaling // Stem Cells, 2011; 29(6): 981-991

Acta Chirurgica Latviensis

The Journal of Riga Stradins University; Latvian Association of Surgeons; Latvian Association of Paediatric Surgeons

Journal Information


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 12 12 12
PDF Downloads 3 3 3