Effects of up to 10 years of denosumab treatment on bone matrix mineralisation: Results from the FREEDOM Extension — ASN Events
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Effects of up to 10 years of denosumab treatment on bone matrix mineralisation: Results from the FREEDOM Extension (#159)

Jeff Hassall 1 , David W Dempster 2 3 , Jacques P Brown 4 , Susan Yue 5 , Sebastien Rizzo 6 , Delphine Farlay 6 , Rachel B Wagman 5 , Andrea Wang 5 , Xiang Yin 5 , Georges Boivin 6
  1. Amgen Australia, Kew, VIC, Australia
  2. Columbia University, New York, NY, USA
  3. Helen Hayes Hospital, West Haverstraw, NY, USA
  4. Laval University and CHU de Quebec-(CHUL) Research Centre, Quebec City, QC, Canada
  5. Amgen Inc, Thousand Oaks, CA, USA
  6. INSERM, UMR 1033, Univ Lyon, , Université Claude Bernard Lyon 1, Lyon, France

Aim: Report bone matrix mineralisation indices at years 2 and 7 of the FREEDOM Ext, representing 5 and 10 years of DMAb treatment, respectively.

Methods: Transiliac bone biopsies were performed at year 2 and/or 3 of FREEDOM (Reid JBMR 2010) and years 2 (Brown JBMR2015) and 7 (Dempster ASBMR 2016) of the Ext. Bone matrix mineralisation was assessed by digitised quantitative microradiography in a blinded fashion and analysed using a Matlab program (Montagner J X-Ray Sci Technol 2015). The mean degree of mineralisation of bone (DMB) and heterogeneity index (HI) of DMB were calculated for cancellous and cortical bone, endocortical and periosteal cortical sub-compartments, and total bone, which are compared between treatment groups and between time points.

Results: Biopsies from 72 women in FREEDOM (30 placebo, 42 DMAb at 2 or 3 years) and 28 and 21 women in the Ext who had received DMAb for a total of 5 and 10 years, respectively, were evaluated. Subject demographics in this sub-study were comparable to FREEDOM. Through 10 years, DMAb resulted in significant increases in mean DMB and a significantly lower HI in total bone compared with placebo (p<0.05, Fig.). There were no significant differences in mean DMB or HI between 5 and 10 years of DMAb treatment; DMB and HI plateaued between 5 and 10 years. Similar results were seen in all bone compartments assessed.

Conclusions: These data suggest mean DMB reaches a maximum by year 5. Clinical outcomes (BMD gains and low fracture incidence) with DMAb through 5 years likely reflect closing of the remodeling space and increases in secondary mineralisation of bone matrix. Additional mechanisms may contribute to long-term clinical outcomes, including reduction in cortical porosity and preservation of modeling-based bone formation.