ECTS2013 Poster Presentations Osteoporosis: treatment (64 abstracts)
University College London, London, UK.
Strontium ranelate (SrR) is now widely used for the prevention of osteoporotic fractures. The mechanisms by which this occurs, however, remain unclear. We investigated the actions of Sr2+ salts in bone-forming cultures of primary osteoblasts from rat calvariae. Osteoblasts were treated continuously with either SrR or SrCl2 for 14 days. Abundant, discretely mineralised trabecular bone structures formed in alizarin red-stained control cultures. Surprisingly, SrR at 10, 100 and 1000 μM inhibited mineralisation, assessed morphometrically, to 75, 16 (P<0.01) and 1% (P<0.001) of control values, respectively. SrCl2 at the same concentrations caused similar inhibitions. Collagen deposition and soluble collagen were unaffected by SrR or SrCl2 at any concentration up to 1 mM. Osteoblast cell number and alkaline phosphatase activity were also unaltered. The selective inhibitory action of Sr2+ salts on mineralisation was confirmed by inspection of unstained osteoblast cultures, revealing numerous unmineralised collagenous trabeculae. To study the effects of Sr2+ salts on osteoclast function, we cultured mouse marrow cells on ivory discs with 1 μM1 mM SrR or SrCl2 for 7 days in the presence of MCSF and RANKL. SrR dose-dependently reduced the number of multinucleated osteoclasts formed, with a 50% inhibition occurring at 1 mM; SrCl2 was somewhat less effective, eliciting a maximal 30% inhibition. Corresponding decreases in total resorption pit formation were observed, suggesting Sr2+ salts affect osteoclast formation rather than resorptive activity. Our osteoblast findings are consistent with the documented physicochemical inhibitory action of Sr2+ on mineralisation but contrast with reports that Sr2+ increases osteoblast activity and number in vitro. Osteoclast data fit with previous findings that showed modest reductions in osteoclast numbers by Sr2+ in vitro. Our results suggest that rather than acting as an agent that uncouples bone formation and resorption, Sr2+ acts as a global inhibitor of bone cell function, with particularly marked effects on mineralisation.