Abstract
The aim of this study was to evaluate the strontium incorporation into specific bones and teeth of rats treated with strontium ranelate. The relative strontium levels [Sr/(Ca + Sr) ratio] were obtained by synchrotron radiation micro X-ray fluorescence. The incisor teeth were further examined by energy dispersive X-ray spectroscopy (EDS) in a scanning electron microscope. The isolated mineral phase was investigated by EDS in a transmission electron microscope and X-ray diffraction. The strontium content was markedly increased in animals treated with strontium ranelate, with different incorporation levels found among specific bones, regions within the same bone and teeth. The highest strontium levels were observed in the iliac crest, mandible and calvaria, while the lowest were observed in the femoral diaphysis, lumbar vertebrae, rib and alveolar bone. The strontium content was higher in the femoral neck than in the diaphysis. The strontium levels also varied within the alveolar bone. High levels of strontium were found in the incisor tooth, with values similar to those in the iliac crest. Strontium was observed in both enamel and dentin. The strontium content of the molar tooth was negligible. Strontium was incorporated into the mineral substance, with up to one strontium replacing one out of 10 calcium ions within the apatite crystal lattice. The mineral from treated animals presented increased lattice parameters, which might be associated to their bone strontium contents. In conclusion, the incorporation of strontium occurred in different levels into distinct bones, regions within the same bone and teeth of rats treated with strontium ranelate.
Similar content being viewed by others
References
Ammann P (2005) Strontium ranelate: a novel mode of action leading to renewed bone quality. Osteoporos Int 16(Suppl 1):S11–S15
Marie PJ (2006) Strontium ranelate: a dual mode of action rebalancing bone turnover in favour of bone formation. Curr Opin Rheumatol 18(Suppl 1):S11–S15
Ammann P, Shen V, Robin B, Mauras Y, Bonjour JP, Rizzoli R (2004) Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J Bone Miner Res 19:2012–2020
Reginster JY, Felsenberg D, Boonen S, Diez-Perez A, Rizzoli R, Brandi ML, Spector TD, Brixen K, Goemaere S, Cormier C, Balogh A, Delmas PD, Meunier PJ (2008) Effects of long-term strontium ranelate treatment on the risk of nonvertebral and vertebral fractures in postmenopausal osteoporosis: results of a five-year, randomized, placebo-controlled trial. Arthritis Rheum 58:1687–1695
Meunier PJ, Roux C, Ortolani S, Diaz-Curiel M, Compston J, Marquis P, Cormier C, Isaia G, Badurski J, Wark JD, Collette J, Reginster JY (2009) Effects of long-term strontium ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis. Osteoporos Int 20:1663–1673
Dorozhkin SV (2009) Calcium orthophosphates in nature, biology and medicine. Materials 2:399–498
Pasteris JD, Wopenka B, Valsami-Jones E (2008) Bone and tooth mineralization: why apatite? Elements 4:97–104
Gedalia I (1975) Strontium uptake by the developing femur bone and deciduous dentition. J Dent Res 54(spec no. B):B125–B130
Li Z, Lu WW, Deng L, Chiu PK, Fang D, Lam RW, Leong JC, Luk KD (2010) The morphology and lattice structure of bone crystal after strontium treatment in goats. J Bone Miner Metab 28:25–34
Boivin G, Deloffre P, Perrat B, Panczer G, Boudeulle M, Mauras Y, Allain P, Tsouderos Y, Meunier PJ (1996) Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration. J Bone Miner Res 11:1302–1311
Farlay D, Boivin G, Panczer G, Lalande A, Meunier PJ (2005) Long-term strontium ranelate administration in monkeys preserves characteristics of bone mineral crystals and degree of mineralization of bone. J Bone Miner Res 20:1569–1578
Boivin G, Farlay D, Khebbab MT, Jaurand X, Delmas PD, Meunier PJ (2010) In osteoporotic women treated with strontium ranelate, strontium is located in bone formed during treatment with a maintained degree of mineralization. Osteoporos Int 21:667–677
Li C, Paris O, Siegel S, Roschger P, Paschalis EP, Klaushofer K, Fratzl P (2010) Strontium is incorporated into mineral crystals only in newly formed bone during strontium ranelate treatment. J Bone Miner Res 25:968–975
Roschger P, Manjubala I, Zoeger N, Meirer F, Simon R, Li C, Fratzl-Zelman N, Misof BM, Paschalis EP, Streli C, Fratzl P, Klaushofer K (2010) Bone material quality in transiliac bone biopsies of postmenopausal osteoporotic women after 3 years of strontium ranelate treatment. J Bone Miner Res 25:891–900
Dahl SG, Allain P, Marie PJ, Mauras Y, Boivin G, Ammann P, Tsouderos Y, Delmas PD, Christiansen C (2001) Incorporation and distribution of strontium in bone. Bone 28:446–453
Boivin G, Meunier PJ (2003) The mineralization of bone tissue: a forgotten dimension in osteoporosis research. Osteoporos Int 14(Suppl 3):S19–S24
Cazalbou S, Eichert D, Ranz X, Drouet C, Combes C, Harmand MF, Rey C (2005) Ion exchanges in apatites for biomedical application. J Mater Sci Mater Med 16:405–409
Cabrera WE, Schrooten I, De Broe ME, D’Haese PC (1999) Strontium and bone. J Bone Miner Res 14:661–668
Marie PJ, Hott M, Modrowski D, De Pollak C, Guillemain J, Deloffre P, Tsouderos Y (1993) An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats. J Bone Miner Res 8:607–615
Pemmer B, Hofstaetter JG, Meirer F, Smolek S, Wobrauschek P, Simon R, Fuchs RK, Allen MR, Condon KW, Reinwald S, Phipps RJ, Burr DB, Paschalis EP, Klaushofer K, Streli C, Roschger P (2011) Increased strontium uptake in trabecular bone of ovariectomized calcium-deficient rats treated with strontium ranelate or strontium chloride. J Synchrotron Radiat 18(pt 6):835–841
Pérez C, Radtke M, Sánchez HJ, Tolentino H, Neuenshwander R, Barg W, Rubio M, Bueno MIS, Raimundo IM, Rohwedder JJR (1999) Synchrotron radiation X-ray fluorescence at the LNLS beamline instrumentation and experiments. X-Ray Spectrom 28:320–326
Lopes RT, Lima I, Pereira GR, Pérez CA (2011) Synchrotron radiation X-ray microfluorescence techniques and biological applications. Pramana J Phys 76:271–279
Pérez CA, Sánchez HJ, Barrea RA, Grenón M, Abraham J (2004) Microscopic X-ray fluorescence analysis of human dental calculus using synchrotron radiation. J Anal At Spectrom 19:392–397
Solé VA, Papillon E, Cotte M, Walter Ph, Susini J (2007) A multiplatform code for the analysis of energy-dispersive X-ray fluorescence spectra. Spectrochim Acta Part B 62:63–68
Weiner S, Price PA (1986) Disaggregation of bone into crystals. Calcif Tissue Int 39:365–375
Mahamid J, Sharir A, Addadi L, Weiner S (2008) Amorphous calcium phosphate is a major component of the forming fin bones of zebrafish: indications for an amorphous precursor phase. Proc Natl Acad Sci USA 105:12748–12753
Shih WJWM, Hon MH (2005) Morphology and crystallinity of the nanosized hydroxyapatite synthesized by hydrolysis using cetyltrimethylammonium bromide (CTAB) as a surfactant. J Cryst Growth 275:e2339–e2344
Rey C, Combes C, Drouet C, Glimcher MJ (2009) Bone mineral: update on chemical composition and structure. Osteoporos Int 20:1013–1021
Fraser R, Harrison M, Ibbertson K (1960) The rate of calcium turnover in bone. Measurement by a tracer test using stable strontium. Q J Med 29:85–111
Reeve J, Wootton R, Hesp B (1976) A new method for calculating the accretion rate of bone calcium and some observations on the suitability of strontium-85 as a tracer for bone calcium. Calcif Tissue Res (2):121–135
Reeve J, Arlot M, Wootton R, Edouard C, Tellez M, Hesp R, Green JR, Meunier PJ (1988) Skeletal blood flow, iliac histomorphometry, and strontium kinetics in osteoporosis: a relationship between blood flow and corrected apposition rate. J Clin Endocrinol Metab 66:1124–1131
Kirkeby OJ, Berg-Larsen T (1991) Regional blood flow and strontium-85 incorporation rate in the rat hindlimb skeleton. J Orthop Res 9:862–868
Schour I, Massler M (1942) The teeth. In: Griffith JQ, Farris EJ (eds) The rat in laboratory investigation. J. B. Lippincott, Philadelphia, pp 104–165
Addison WHF, Appleton JL (1915) The structure and growth of the incisor teeth of the albino rat. J Morphol 26:43–96
Robinson C, Connell S, Kirkham J, Brookes SJ, Shore RC, Smith AM (2004) The effect of fluoride on the developing tooth. Caries Res 38:268–276
Acknowledgments
We gratefully acknowledge the assistance and expertise of C. A. Pérez (LNLS) in the SRμXRF analyses, V. C. A. Moraes (CBPF) in the XRD analyses and M. M. Medeiros (UFRJ) in the sample preparation procedures. This study was supported by the Brazilian agencies CNPq, FAPERJ, CAPES and FINEP.
Author information
Authors and Affiliations
Corresponding author
Additional information
Josianne P. Oliveira and William Querido contributed equally to this study.
The authors have stated that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Oliveira, J.P., Querido, W., Caldas, R.J. et al. Strontium Is Incorporated in Different Levels into Bones and Teeth of Rats Treated with Strontium Ranelate. Calcif Tissue Int 91, 186–195 (2012). https://doi.org/10.1007/s00223-012-9625-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00223-012-9625-2