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 strontium ranelate on wear particle‑induced aseptic loosening in female ovariectomized mice

“…In conclusion, SR and ALN have inhibitory effects on aseptic loosening in ovariectomized mice, and SR may affect osteogenesis and osteoclasts to inhibit aseptic loosening, in agreement with the results of Wornham et al (52). SR has a better inhibitory effect on aseptic loosening compared with ALN and may potentially serve as a treatment of aseptic loosening in patients with osteoporosis.…”

Effects of strontium ranelate on wear particle‑induced aseptic loosening in female ovariectomized mice

“…In conclusion, SR and ALN have inhibitory effects on aseptic loosening in ovariectomized mice, and SR may affect osteogenesis and osteoclasts to inhibit aseptic loosening, in agreement with the results of Wornham et al (52). SR has a better inhibitory effect on aseptic loosening compared with ALN and may potentially serve as a treatment of aseptic loosening in patients with osteoporosis.…”

Strontium inhibits osteoclastogenesis by enhancing LRP6 and β-catenin-mediated OPG targeted by miR-181d-5p

“…2a, b, c), indicating that strontium inhibited osteoclastogenesis. Taken together, these data supported previous studies (Bonnelye et al 2008;Roy and Bose 2012;Roy et al 2013;Takahashi et al 2003;Wornham et al 2014).…”

Gut microbiota, plasma metabolites, and osteoporosis: unraveling links via Mendelian randomization

“…Several studies, reinforcing our findings, indicate that the genus Ruminococcaceae UCG014 plays a beneficial role in the management and improvement of OP ( Liu et al, 2020 ; Ling et al, 2021 ; Wei et al, 2024 ). This beneficial effect aligns with recent research on strontium (Sr), a bioactive element recognized for its potential to enhance bone quality ( Schrooten et al, 2003 ; Wornham et al, 2014 ). One particular study has suggested that Ruminococcaceae UCG014 may enhance the bioavailability or efficacy of Sr. in mitigating bone loss ( Xi et al, 2023 ).…”

Effects of strontium ranelate on wear particle‑induced aseptic loosening in female ovariectomized mice

“…In conclusion, SR and ALN have inhibitory effects on aseptic loosening in ovariectomized mice, and SR may affect osteogenesis and osteoclasts to inhibit aseptic loosening, in agreement with the results of Wornham et al (52). SR has a better inhibitory effect on aseptic loosening compared with ALN and may potentially serve as a treatment of aseptic loosening in patients with osteoporosis.…”

Strontium inhibits osteoclastogenesis by enhancing LRP6 and β-catenin-mediated OPG targeted by miR-181d-5p

“…2a, b, c), indicating that strontium inhibited osteoclastogenesis. Taken together, these data supported previous studies (Bonnelye et al 2008;Roy and Bose 2012;Roy et al 2013;Takahashi et al 2003;Wornham et al 2014).…”

Gut microbiota, plasma metabolites, and osteoporosis: unraveling links via Mendelian randomization

“…Several studies, reinforcing our findings, indicate that the genus Ruminococcaceae UCG014 plays a beneficial role in the management and improvement of OP ( Liu et al, 2020 ; Ling et al, 2021 ; Wei et al, 2024 ). This beneficial effect aligns with recent research on strontium (Sr), a bioactive element recognized for its potential to enhance bone quality ( Schrooten et al, 2003 ; Wornham et al, 2014 ). One particular study has suggested that Ruminococcaceae UCG014 may enhance the bioavailability or efficacy of Sr. in mitigating bone loss ( Xi et al, 2023 ).…”

Effects of strontium ranelate on wear particle‑induced aseptic loosening in female ovariectomized mice

“…In conclusion, SR and ALN have inhibitory effects on aseptic loosening in ovariectomized mice, and SR may affect osteogenesis and osteoclasts to inhibit aseptic loosening, in agreement with the results of Wornham et al (52). SR has a better inhibitory effect on aseptic loosening compared with ALN and may potentially serve as a treatment of aseptic loosening in patients with osteoporosis.…”

Strontium inhibits osteoclastogenesis by enhancing LRP6 and β-catenin-mediated OPG targeted by miR-181d-5p

“…2a, b, c), indicating that strontium inhibited osteoclastogenesis. Taken together, these data supported previous studies (Bonnelye et al 2008;Roy and Bose 2012;Roy et al 2013;Takahashi et al 2003;Wornham et al 2014).…”

Gut microbiota, plasma metabolites, and osteoporosis: unraveling links via Mendelian randomization

“…Several studies, reinforcing our findings, indicate that the genus Ruminococcaceae UCG014 plays a beneficial role in the management and improvement of OP ( Liu et al, 2020 ; Ling et al, 2021 ; Wei et al, 2024 ). This beneficial effect aligns with recent research on strontium (Sr), a bioactive element recognized for its potential to enhance bone quality ( Schrooten et al, 2003 ; Wornham et al, 2014 ). One particular study has suggested that Ruminococcaceae UCG014 may enhance the bioavailability or efficacy of Sr. in mitigating bone loss ( Xi et al, 2023 ).…”