S 12911-2 inhibits osteoclastic bone resorption in vitro

The potential anti-osteoporotic activity of the strontium compound, S12911, was tested on osteoclast-like cells 21 and on cultured fetal mouse long bones. From 1 mM Sr2+, S12911 reduced both basal and stimulated bone resorption by decreasing osteoclast activity and ruffled border formation. The aim of this study was to evaluate the effects of S 12911-2 on osteoclastic bone resorption using in vitro systems. Osteoclast-like cells, produced in vitro by co-culture of mouse bone marrow cells with primary osteoblasts, were allowed to settle on dentine slices, and the area of resorption pits formed after 48 h was Sr2+ measured using an image analysis system. S 12911-2, at a minimal active concentration of 1 mMSr(2+) significantly reduced pit formation by these cells (p < 0.05). Pretreatment of slices for 48 h with S12911-2 (5 mM Sr2+) did not produce appreciable inhibition of resorption. Bone resorption in cultured fetal mouse long bones was assessed by measuring the release of pre-incorporated (45)calcium. S 12911-2 inhibited resorption in control cultures (18.9%, p: less than or equal to 0.05) and in bones cultured with the active form of vitamin D-3 [1,25(OH)(2)D-3] (44.5%, p less than or equal to 0.05). S 12911-2 had no effect on the number of osteoclasts observed histochemically in longitudinal sections prepared from fetal mouse long bones. Electron microscopy of mouse long bones treated with S 12911-2 (3 mM Sr2+) showed osteoclasts with clear zones facing the bone surface, but without well-developed ruffled borders; untreated bones contained osteoclasts with normal ruffled borders. These results indicate that S 12911-2 inhibits osteoclast activity. This effect is directly linked to the presence of strontium, is effective on basal and stimulated resorption, and involves a decrease in ruffled border formation by osteoclasts.