Bone Abstracts

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 μM–1 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.