Purpose: Low fracture incidence has been demonstrated in women with postmenopausal osteoporosis treated with denosumab (DMAb) for up to 10 years in the FREEDOM Extension. Several assessments have evaluated effects of DMAb treatment at the tissue level and showed low remodelling consistent with mechanism of action. Here, we report the effects of DMAb on bone matrix mineralisation in women who underwent transiliac crest bone biopsy in FREEDOM.
Methods: FREEDOM was a 3-year randomised, double-blind, placebo (Pbo)-controlled study in postmenopausal women who received Pbo or 60 mg DMAb subcutaneously every 6 months. A subset of women underwent transiliac crest bone biopsies at year 2 and/or 3. Bone matrix mineralisation was assessed in a blinded fashion by digitised quantitative microradiography and analysed using a Matlab program. The mean degree of mineralisation of bone (DMB) and the heterogeneity index (HI) of the distribution of DMB were calculated for cancellous and cortical bone, endocortical and periosteal sub-compartments of cortical bone and total bone (cancellous and cortical combined).
Results: In this analysis, 72 bone biopsy samples (42 DMAb, 30 Pbo) from a subset of the FREEDOM bone biopsy assessment (n = 115) were evaluated and analysed. Treatment with DMAb resulted in a significant increase in mean DMB compared with Pbo-treated subjects (Figure) and these findings were consistent across cancellous and cortical compartments (p < 0.01). A significantly lower HI was observed in total bone and in all compartments assessed in the DMAb-treated group (p < 0.05), consistent with reduced bone turnover in response to DMAb therapy.
Conclusions: Treatment of women with postmenopausal osteoporosis with DMAb resulted in increased bone matrix mineralisation and a lower heterogeneity index compared with Pbo. These data are consistent with expected results based on observations with other antiresorptives and with mechanism of action.