Long-term strontium ranelate administration in monkeys preserves characteristics of bone mineral crystals and degree of mineralization of bone.
In monkeys, long-term strontium ranelate administration results in a dose-dependent bone strontium uptake (mainly into newly formed bone) that preserves the degree of mineralization of bone and the bone mineral at the crystal level, showing its safety at bone mineral level.


BACKGROUND
Strontium ranelate simultaneously increases bone formation and decreases bone resorption, leading to prevention of bone loss and increase in bone mass and bone strength in normal and ovariectomized rats. This study investigated the interactions of stable strontium (Sr) with bone mineral in monkeys after long-term strontium ranelate treatment and after a period of treatment withdrawal.


METHODS
Iliac bone was obtained from untreated monkeys, monkeys at the end of a 52-week strontium ranelate administration (200, 500, 1250 mg/kg/day orally), and in parallel groups 10 weeks after the end of strontium ranelate administration (same three doses; n = 3-7). Sr uptake and distribution in bone mineral were quantified by X-ray microanalysis, changes at the crystal level by X-ray diffraction, and the degree of mineralization of bone (DMB) by quantitative microradiography.


RESULTS
After strontium ranelate administration, dose-dependent Sr uptake occurred into cortical and cancellous bone, with higher content (1.6 times) in new than in old bone. This Sr uptake decreased (50%) 10 weeks after treatment withdrawal; the decrease occurred almost exclusively in new bone. At the end of strontium ranelate treatment and after its withdrawal, a preservation of crystal characteristics was observed, suggesting that Sr was only faintly linked to crystals by ionic substitution and of DMB.


CONCLUSIONS
These results show the absence of a deleterious effect of long-term strontium ranelate treatment on bone mineralization, confirming the histomorphometric observations made in postmenopausal osteoporotic women treated with strontium ranelate.
Farlay
Delphine
D
Laboratoire d'Histodynamique Osseuse, Faculté de Médecine R. Laennec, Université C. Bernard-Lyon 1, Lyon, France.
Boivin
Georges
G
Panczer
Gérard
G
Lalande
Agnès
A
Meunier
Pierre Jean
PJ
D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D000882:Haplorhini; D007477:Ions; D008252:Macaca fascicularis; D008297:Male; D008852:Microradiography; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000473:pathology; D013324:Strontium / Q000378:metabolism / Q000494:pharmacology; D013876:Thiophenes / Q000008:administration & dosage* / Q000494:pharmacology*; D013997:Time Factors; D014961:X-Ray Diffraction; D014965:X-Rays
D007477:Ions; D009942:Organometallic Compounds; D013876:Thiophenes; C081587:strontium ranelate; D013324:Strontium