STRONTIUM DISTRIBUTION AND INTERACTIONS WITH BONE-MINERAL IN MONKEY ILIAC BONE AFTER STRONTIUM SALT (S-12911) ADMINISTRATION

The analysis of the interaction of strontium (Sr) with bone mineral is of interest because a new agent. containing Sr (S 12911) has shown po sitive effects on bone mass in various animal models of osteoporosis a nd is currently being developed for preventive and curative treatment of postmenopausal osteoporosis, Iliac bone samples were obtained from 20 mat monkeys: 4 untreated control animals, 12 animals sacrificed at the end of a 13-week treatment with high dose levels of S 12911 (750, 275, or 100 mg/kg/day orally), and 4 animals sacrificed 6 weeks after the end of a 13-week treatment with S 12911 (750 or 100 mg/kg/day oral ly), The distribution of Sr was determined and quantified by X-ray mic roanalysis, Changes at the crystal level were evaluated by Ii-ray diff raction and Raman microspectrometry, In the control animals, traces of Sr were found to be homogeneously distributed throughout the bone tis sue, In the treated monkeys, Sr could only be detected in calcified ma trix, In monkeys sacrificed at the end of the treatment, Sr was found to be dose-dependently incorporated into the mineral substance of the compact and cancellous bone, Sr was heterogeneously distributed with t hree to four times more Sr in new than in old compact bone, and approx imately two and a half times more Sr in new than in old cancellous bon e, The bone Sr content dramatically decreased in the animals sacrifice d 6 weeks after the end of the treatment, Diffraction showed no signif icant changes in the characteristics of the crystal lattice, Sr appear ed to be easily exchangeable from bone mineral and was slightly linked to mature crystals through ionic substitutions, Even at the highest d ose level tested, less than 1 calcium ion out of 10 was substituted by 1 Sr ion in each crystal, In conclusion taken up by bone, Sr was hete rogeneously distributed with a higher concentration in new than in old bone but induced no major modifications of the bone mineral (crystall inity, crystal structure) at the crystal level, As a result, a treatme nt with S 12911 Sr salt should not induce any alteration of bone miner al.