Bone Abstracts (2016) 5 OC3.2 | DOI: 10.1530/boneabs.5.OC3.2

Effects of Denosumab (Dmab) on bone matrix mineralization: results from the phase 3 FREEDOM trial

David W Dempster1,2, Jacques P Brown3, Susan Yue4, Delphine Farlay5, Sebastien Rizzo5, Jenny Song4, Andrea Wang4, Rachel B Wagman4 & Georges Boivin5


1Columbia University, New York, New York, USA; 2Helen Hayes Hospital, West Haverstraw, New York, USA; 3Laval University and CHU de Quebec-(CHUL) Research Centre, Quebec City, Quebec, Canada; 4Amgen Inc., Thousand Oaks, California, USA; 5INSERM UMR 1033, Université de Lyon, Lyon, France.


Low fracture (FX) incidence has been demonstrated in women with postmenopausal osteoporosis (PMO) treated with DMAb for up to 10 years in the FREEDOM extension [Bone ASBMR 2015]. Bone biopsy-based assessment of DMAb’s effects at the tissue level has demonstrated a low remodelling rate consistent with DMAb’s mechanism of action (Reid JBMR 2010; Brown JBMR 2014). From FREEDOM, we report the effects of DMAb on bone matrix mineralization in women who underwent transiliac crest bone biopsy at year 2 and/or 3 (Reid JBMR 2010). Bone matrix mineralization was assessed in a blinded fashion by digitized quantitative microradiography and analyzed using a Matlab program (Montagner J X-Ray Sci Technol 2015). The mean degree of mineralization of bone (DMB) and 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. 72 of 115 biopsies (42 DMAb, 30 Placebo) from the FREEDOM bone biopsy sub-study were evaluated. Subject demographics were comparable to FREEDOM. DMAb resulted in a significant increase in mean DMB compared with Placebo (Table 1; findings consistent across cancellous and cortical compartments). 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. In women with PMO, DMAb resulted in increased bone matrix mineralization and a lower HI compared with Placebo. These data are consistent with expected results based on observations with other antiresorptives (Bala Eur J Endocrinol 2011) and with DMAb’s mechanism of action.

Table 1 Mean (SD) DMB by Location
DMAbPlaceboP-value*
Cancellous bone1.036 (0.035) [n=41]1.009 (0.034) [n=30]0.0014
Cortical bone1.100 (1.066) [n=42]1.066 (0.032) [n=30]0.0002
Endosteal1.106 (0.041) [n=31]1.074 (0.032) [n=22]0.0017
Periosteal1.095 (0.043) [n=31]1.067 (0.036) [n=22]0.0085
Total bone1.079 (0.035) [n=42]1.053 (0.030) [n=30]0.0009
*P-value of 2-sided Wilcoxon test for between-group comparison in DMB

Article tools

My recent searches

No recent searches.