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1.
Bone ; 64: 18-24, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24662618

ABSTRACT

Our purpose was to evaluate the impact of strontium ranelate (SrRan) on bone mineral quality at both tissue and bone structural unit (BSU) levels. Thirty iliac bone samples (dehydrated then embedded) were taken from monkeys who received 0 (controls), 200, 500 or 1250 mg/kg/day of SrRan for 52 weeks and were sacrificed either at the end of administration (treated animals, n=16) or 10 weeks later (reverse animals, n=14). Degree of mineralization (DMB), heterogeneity index of mineralization (HI), Vickers microhardness (Hv) and focal bone strontium content (BSC) were measured globally at tissue level and focally on the same 923 BSUs. Mineral and collagen characteristics, as well as chemometric analyses were performed on younger and older tissues in cortical bone and cancellous bone in 737 other BSUs. At tissue level, SrRan preserved material properties. At BSU level, BSC increased (significant) dose dependently in treated and reverse animals. DMB and Hv were greater in older than in younger bone in controls and treated animals. In treated animals, DMB was positively correlated with Hv and inversely correlated with the BSC. Thus, younger BSUs were less mineralized and less hard than older BSUs independently from the presence of strontium. Mineral maturity, crystallinity index, mineralization index, carbonation and collagen maturity were not modified by SrRan. Chemometry confirmed the absence of a direct effect of strontium on mineralization. Thus, surrogates of micro- and nano-structural mineral properties were not altered by SrRan and remained at a physiological level.


Subject(s)
Bone Density Conservation Agents/pharmacology , Bone Density/drug effects , Ilium/drug effects , Thiophenes/pharmacology , Animals , Macaca fascicularis , Spectroscopy, Fourier Transform Infrared/methods
2.
J Trace Elem Med Biol ; 26(2-3): 153-6, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22565017

ABSTRACT

Strontium ranelate (2g/day) appears to be a safe and efficient treatment of osteoporosis (OP), reducing the risks of both vertebral and non-vertebral fractures (including hip) in a wide variety of patients. Thus, the agent can now be considered as a first-line option to treat women at risk of OP fractures, whatever their age and the severity of the disease. A long-term treatment with strontium ranelate in OP women leads to a continued increase in bone mineral density at spine and hip levels, and a sustained antifracture efficacy. The mode of action of strontium ranelate involves a dissociation between bone resorption and formation, as the bone formation rate is increased and not influenced by the antiresorptive action of the agent. Strontium is heterogeneously distributed in bone tissue: it is absent from old bone tissue and is exclusively present in bone formed during the treatment. Total area containing strontium in bone tissue increases during treatment, although the focal bone strontium content is constant. Whatever the duration of treatment and the content of strontium in bone, the degree of mineralization is maintained in a normal range. Furthermore, no change at crystal level is detected up to 3 years of treatment.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Organometallic Compounds/therapeutic use , Osteoporosis/drug therapy , Thiophenes/therapeutic use , Female , Humans , Osteoporosis/diagnostic imaging , Osteoporosis, Postmenopausal/diagnostic imaging , Osteoporosis, Postmenopausal/drug therapy , Radiography
3.
Eur J Endocrinol ; 165(3): 469-76, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21690207

ABSTRACT

OBJECTIVE: To investigate interactions between strontium (Sr) and bone mineral and its effects on mineralization in osteoporotic women treated long-term with Sr ranelate (SrRan). DESIGN: In this study, 34 iliac bone biopsies were analyzed after 2, 12, 24, 36, 48, and 60 months of treatment with SrRan. METHODS: Sr global distribution was analyzed by X-ray cartography and the percentage of bone area containing Sr was calculated in the bone samples. The focal distribution of Sr in all bone samples was investigated by X-ray microanalysis. The degree of mineralization was assessed by quantitative microradiography. RESULTS: Absent from old bone formed before the beginning of treatment, Sr was exclusively present in bone formed during this treatment with a much higher focal Sr content in new bone structural units than in old ones. A progressive increase in the extent of areas containing Sr was observed during treatment. The focal bone Sr content in recently formed bone was constant over treatment. Secondary mineralization was maintained at a normal level during treatment. CONCLUSION: Thus, the quality of bone mineralization (density and heterogeneity at tissue level) was preserved after a long-term treatment with SrRan.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone and Bones/metabolism , Organometallic Compounds/therapeutic use , Osteoporosis, Postmenopausal/drug therapy , Osteoporosis, Postmenopausal/pathology , Strontium/pharmacokinetics , Thiophenes/therapeutic use , Aged , Biopsy , Bone Density , Bone and Bones/pathology , Calcification, Physiologic , Electron Probe Microanalysis , Female , Humans , Ilium/pathology , Osteoporosis, Postmenopausal/metabolism
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