Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast cultures and reduces numbers of osteoclasts in mouse marrow cultures

Abstract

SummaryThe basic mechanisms by which strontium ranelate acts on bone are still unclear. We show that an important action of strontium salts is to block calcification in cultures of osteoblasts, the bone-forming cells. These results suggest that strontium treatment could have previously overlooked effects on bone.IntroductionThe basic mechanisms of action of strontium ranelate (SrR) on bone have remained unclear. We studied the direct actions of Sr2+ salts in functional cultures of osteoblasts and osteoclasts.MethodsCultures of primary osteoblasts from rat calvariae and osteoclast-forming mouse marrow cells were treated continuously with either SrR or strontium chloride (SrCl2).ResultsAbundant, discretely mineralised ‘trabecular’ bone structures formed in control osteoblast cultures after 14 days. SrR at 0.01, 0.1 and 1 mM inhibited mineralisation to 59, 98 and 100 % (all p < 0.001) of control values, respectively. SrCl2 at the same concentrations caused similar inhibitions. Osteoblast cell numbers and alkaline phosphatase activity were unaltered. SrR dose-dependently reduced the formation of multinucleated osteoclasts from marrow mononuclear cells cultured on dentine for 8 days in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL), with a 50 % inhibition occurring at 1 mM; SrCl2 was slightly 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.ConclusionOur 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. 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. The potential effects of long-term Sr2+ on secondary mineralisation in bone deserve investigation.

Effects of micro/nano strontium‐loaded surface implants on osseointegration in ovariectomized sheep

“…For the loading of Sr, several studies have indicated that Sr can mainly improve the biological response of host bone for the following reasons: first, Sr can improve the biological response of bone through enhanced osteoblast differentiation by increasing many osteoblast markers (eg, ALP, COL‐1, bone sialoprotein, and OCN) . Second, Sr can improve the biological response of bone through inhibition of osteoclast function by decreasing functional expression of osteoclast markers and disrupting the cytoskeleton, which is essential for the resorbing activity of osteoclasts . Third, Sr loaded on the titanium surface can release to the implant‐tissue interface locally and directly, thus enabling effective absorption by bone tissues around the implant, which promotes bone formation and suppresses bone resorption …”

Effects of strontium ranelate on ligature‐induced periodontitis in estrogen‐deficient and estrogen‐sufficient rats

“…Therefore, the effects of strontium ranelate on alveolar bone metab- and number, some investigations failed to observe any effect of this medication on osteoblast numbers and indicated that strontium ranelate inhibits mineralization and decreases collagen cross-linking in bone. 38,39 Based on the current immunohistochemical findings, it is hypothesized that most of the histometric benefits induced by strontium ranelate on ligature-induced bone resorption rely on its anti-resorptive rather than its anabolic action. Therefore, the dual effects of strontium ranelate might be not verified under an infectiousinflammatory state and this medication may present differences in the mode of its action according to different environmental factors influencing bone metabolism.…”

Strontium ion attenuates lipopolysaccharide‐stimulated proinflammatory cytokine expression and lipopolysaccharide‐inhibited early osteogenic differentiation of human periodontal ligament cells

“…Nardone et al reported that Sr 2+ with different concentrations revealed the biphasic action of mineralization in vitro. Wornham et al demonstrated that Sr 2+ inhibited bone formation, especially the mineralization. In our study, we observed that the OPN gene expressions were upregulated for dozens of times when exposed to Sr 2+ .…”