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 positive effects on bone mass in various animal models of osteoporosis and is currently being developed for preventive and curative treatment of postmenopausal osteoporosis. Iliac bone samples were obtained from 20 male 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 orally). The distribution of Sr was determined and quantified by X-ray microanalysis. Changes at the crystal level were evaluated by X-ray diffraction and Raman microspectrometry. In the control animals, traces of Sr were found to be homogeneously distributed throughout the bone tissue. In the treated monkeys, Sr could only be detected in calcified matrix. 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 three to four times more Sr in new than in old compact bone, and approximately two and a half times more Sr in new than in old cancellous bone. The bone Sr content dramatically decreased in the animals sacrificed 6 weeks after the end of the treatment. Diffraction showed no significant changes in the characteristics of the crystal lattice. Sr appeared to be easily exchangeable from bone mineral and was slightly linked to mature crystals through ionic substitutions. Even at the highest dose 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 heterogeneously distributed with a higher concentration in new than in old bone but induced no major modifications of the bone mineral (crystallinity, crystal structure) at the crystal level. As a result, a treatment with S 12911 Sr salt should not induce any alteration of bone mineral.
Boivin
G
G
Laboratoire d'Histodynamique Osseuse, Faculte A. Carrel, Lyon, France.
Deloffre
P
P
Perrat
B
B
Panczer
G
G
Boudeulle
M
M
Mauras
Y
Y
Allain
P
P
Tsouderos
Y
Y
Meunier
P J
PJ
D000284:Administration, Oral; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004577:Electron Probe Microanalysis; D005260:Female; D006801:Humans; D007085:Ilium / Q000187:drug effects / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000517:prevention & control; D013052:Spectrometry, X-Ray Emission; D013059:Spectrum Analysis, Raman; D013324:Strontium / Q000378:metabolism; D013876:Thiophenes / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D014018:Tissue Distribution; D014475:Uncoupling Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D014961:X-Ray Diffraction
D009942:Organometallic Compounds; D013876:Thiophenes; D014475:Uncoupling Agents; C081587:strontium ranelate; D013324:Strontium