Bisphosphonates are used to treat bone disease characterised by increased bone resorption by inhibiting the activity of mature osteoclasts, resulting in decreased bone turnover. Bisphosphonates may reduce the population of osteoclast precursor cells (OPCs). Our aims were to investigate the effect of bisphosphonates on i) OPCs and ii) bone turnover in postmenopausal women with osteoporosis compared with healthy premenopausal women. Participants were 62 postmenopausal women (mean age 66) from a parallel group trial of bisphosphonates. They received ibandronate 150 mg/month (n=22), alendronate 70 mg/week (n=19) or risedronate 35 mg/week (n=19). Fasting blood was collected at baseline, weeks 1 and 48. 25 healthy premenopausal women (mean age 37) were recruited, blood was collected at baseline. Peripheral blood mononuclear cells were extracted and stained for CD14, M-CSFR, CD11b and TNFRII receptors. Flow cytometry was used to identify monocytes (CD14+) and OPCs (CD14+ and CD11b+ or M-CSF+ or TNFRII+). CTX was measured using the iSYS-IDS analyser (UK). After 48 weeks of treatment, there was a decrease in the percentage of OPCs expressing MCSFR and CD11b receptors by 53 and 49% respectively (P<0.01). CTX decreased by 62% after 1 week and by 83% after 48 weeks. OPCs expressing M-CSFR and CD11b were decreased with ibandronate and risedronate after 48 weeks (table) to the lower part of the premenopausal limits.
Significance from baseline tested using non-parametric Wilcoxon signed test. *P<0.05, **P<0.01 and ***P<0.001
|Baseline||Week 1||Week 48|
Bisphosphonates inhibit bone resorption in the short-term by direct action on mature osteoclasts. There is also a later effect mediated by a reduction in the population of circulating osteoclast precursors.
17 May 2014 - 20 May 2014