Bone material quality in transiliac bone biopsies of postmenopausal osteoporotic women after 3 years of strontium ranelate treatment

Strontium ranelate (SrR) is a relatively new treatment for osteoporosis. In this study we investigated its potential impact on human bone material quality in transiliac bone biopsies from postmenopausal osteoporotic women treated 3 years with calcium and vitamin D plus either 2 g SrR per day or placebo. Bone mineralization density distribution (BMDD), strontium (Sr) concentration, collagen cross‐link ratio, and indentation modulus were analyzed by quantitative backscattered electron imaging, electron‐induced X‐ray fluorescence analysis, synchrotron radiation induced micro X‐ray fluorescence elemental mapping, Fourier transform infrared imaging, and nanoindentation, respectively. The BMDD of SrR‐treated patients was shifted to higher atomic numbers (Zmean +1.5%, p < .05 versus placebo). We observed Sr being preferentially incorporated in bone packets formed during SrR treatment up to 6% atom fraction [Sr/(Sr + Ca)] depending on the SrR serum levels of the individuals (correlation r = 0.84, p = .018). Collagen cross‐link ratio was preserved in SR‐treated bone. The indentation modulus was significantly decreased in younger versus older bone packets for both placebo‐ (−20.5%, p < .0001) and SrR‐treated individuals (−24.3%, p < .001), whereas no differences were found between the treatment groups. In conclusion, our findings indicate that after SrR treatment, Sr is heterogeneously distributed in bone and preferentially present in bone packets formed during treatment. The effect of SrR on BMDD seems to be due mainly to the uptake of Sr and not to changes in bone calcium content. Taken together, these data provide evidence that the investigated bone quality determinants at tissue level were preserved in postmenopausal osteoporotic women after 3‐year treatment with 2 g SrR per day plus calcium and vitamin D. © 2010 American Society for Bone and Mineral Research

[1]  P. Delmas,et al.  In osteoporotic women treated with strontium ranelate, strontium is located in bone formed during treatment with a maintained degree of mineralization , 2010, Osteoporosis International.

[2]  P. Fratzl,et al.  Strontium is incorporated into mineral crystals only in newly formed bone during strontium ranelate treatment , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[3]  Y. Tsouderos,et al.  Re: "Effect of long-term treatment with strontium ranelate on bone strontium content" by Bärenholdt et al. (Bone, 2009). , 2009, Bone.

[4]  N. Kolthoff,et al.  Reply to Letter Re: “Effect of long term treatment with strontium ranelate on bone strontium content” by Bärenholdt et al. (Bone, 2009) , 2009 .

[5]  M. Rybchyn,et al.  Osteoblasts play key roles in the mechanisms of action of strontium ranelate , 2009, British journal of pharmacology.

[6]  N. Kolthoff,et al.  Effect of long-term treatment with strontium ranelate on bone strontium content. , 2009, Bone.

[7]  S. Bain,et al.  Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants , 2009, Osteoporosis International.

[8]  D. Slosman,et al.  Monitoring strontium ranelate therapy in patients with osteoporosis , 2009, Osteoporosis International.

[9]  E. Brown,et al.  The Calcium-sensing Receptor Is Involved in Strontium Ranelate-induced Osteoclast Apoptosis , 2009, Journal of Biological Chemistry.

[10]  T. Spector,et al.  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. , 2008, Arthritis and rheumatism.

[11]  D. Burr,et al.  Strontium ranelate does not stimulate bone formation in ovariectomized rats , 2008, Osteoporosis International.

[12]  P. Fratzl,et al.  Bone mineralization density distribution in health and disease. , 2008, Bone.

[13]  H. Genant,et al.  Histomorphometric and μCT Analysis of Bone Biopsies From Postmenopausal Osteoporotic Women Treated With Strontium Ranelate , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[14]  René Rizzoli,et al.  Strontium Ranelate Treatment Improves Trabecular and Cortical Intrinsic Bone Tissue Quality, a Determinant of Bone Strength , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[15]  Paul Roschger,et al.  Evidence that Treatment with Risedronate in Women with Postmenopausal Osteoporosis Affects Bone Mineralization and Bone Volume , 2007, Calcified Tissue International.

[16]  G. Blake,et al.  The correction of BMD measurements for bone strontium content. , 2007, Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry.

[17]  P. Fratzl,et al.  Bone Material Properties in Trabecular Bone From Human Iliac Crest Biopsies After 3‐ and 5‐Year Treatment With Risedronate , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[18]  P. Fratzl,et al.  Lead accumulation in tidemark of articular cartilage. , 2006, Osteoarthritis and cartilage.

[19]  T. Spector,et al.  Strontium Ranelate Reduces the Risk of Vertebral Fractures in Patients With Osteopenia , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[20]  P. Marie Strontium ranelate: a physiological approach for optimizing bone formation and resorption. , 2006, Bone.

[21]  P. Meunier,et al.  Long‐Term Strontium Ranelate Administration in Monkeys Preserves Characteristics of Bone Mineral Crystals and Degree of Mineralization of Bone , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[22]  D. Donley,et al.  Bone mineral and collagen quality in iliac crest biopsies of patients given teriparatide: new results from the fracture prevention trial. , 2005, The Journal of clinical endocrinology and metabolism.

[23]  J. Reginster,et al.  Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study. , 2005, The Journal of clinical endocrinology and metabolism.

[24]  P. Fratzl,et al.  Two different correlations between nanoindentation modulus and mineral content in the bone-cartilage interface. , 2005, Journal of structural biology.

[25]  R. Rizzoli,et al.  Strontium Ranelate Improves Bone Resistance by Increasing Bone Mass and Improving Architecture in Intact Female Rats , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[26]  T. Spector,et al.  Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies , 2004, The New England journal of medicine.

[27]  R. Recker,et al.  Distribution of Collagen Cross‐Links in Normal Human Trabecular Bone , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[28]  P. Meunier,et al.  The mineralization of bone tissue: a forgotten dimension in osteoporosis research , 2003, Osteoporosis International.

[29]  P. Fratzl,et al.  Constant mineralization density distribution in cancellous human bone. , 2003, Bone.

[30]  R Mendelsohn,et al.  Spectroscopic Characterization of Collagen Cross‐Links in Bone , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[31]  P. Fratzl,et al.  Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. , 2001, Bone.

[32]  C. Christiansen,et al.  Incorporation and distribution of strontium in bone. , 2001, Bone.

[33]  S. Goldstein,et al.  Elastic modulus and hardness of cortical and trabecular bone lamellae measured by nanoindentation in the human femur. , 1999, Journal of biomechanics.

[34]  P. Fratzl,et al.  Validation of quantitative backscattered electron imaging for the measurement of mineral density distribution in human bone biopsies. , 1998, Bone.

[35]  P. Meunier,et al.  Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[36]  P. Marie,et al.  Strontium increases vertebral bone volume in rats at a low dose that does not induce detectable mineralization defect. , 1996, Bone.

[37]  H. Plenk,et al.  A new scanning electron microscopy approach to the quantification of bone mineral distribution: backscattered electron image grey-levels correlated to calcium K alpha-line intensities. , 1995, Scanning microscopy.

[38]  G. Pharr,et al.  An improved technique for determining hardness and elastic modulus using load and displacement sensing indentation experiments , 1992 .

[39]  S. C. Skoryna Effects of oral supplementation with stable strontium. , 1981, Canadian Medical Association journal.

[40]  H. DeLuca,et al.  Strontium Induced Rickets: Metabolic Basis , 1971, Science.

[41]  E. Storey Intermittent bone changes and multiple cartilage defects in chronic strontium rickets in rats. , 1962, The Journal of bone and joint surgery. British volume.

[42]  A. Sobel,et al.  The nature of the injury to the calcifying mechanism in rickets due to strontium. , 1935, The Biochemical journal.

[43]  G. Falkenberg,et al.  Determination of the elemental distribution in human joint bones by SR micro XRF , 2008 .