E-Poster Presentation ESA-SRB-ANZBMS 2021

Bone matrix quality in transiliac biopsies from post-menopausal osteoporotic (PMOP) women treated with denosumab (DMab) for up to 10 years (FREEDOM and FREEDOM Extension Trials) (#734)

Arkadi Chines 1 , Delphine Farlay 2 , Sebastian Rizzo 2 , David Demster 3 4 , Shuang Huang 1 , Li Chen 1 , Jacques P Brown 5 , Georges Boivin 2
  1. Amgen Inc, Thousand Oaks, CA, USA
  2. Team Bone and Chronic Diseases, INSERM, Lyon, France
  3. Department of Pathology and Cell Biology, Columbia University, New York, NY, USA
  4. Helen Hayes Hospital, West Haverstraw, NY, USA
  5. CHU de Québec (CHUL) Research Centre, Laval University, Quebec City, Canada

In PMOP women, DMAb therapy through 10 years (y) is associated with continued BMD gains and low fracture incidence. Until 5y, DMAb significantly increased the degree of mineralisation of bone (DMB) compared with placebo (Pbo), then plateaued through 10y in both cortical (Ct) and cancellous (Cc) bone. We assess the microhardness (Hv) of bone reflecting elastic and plastic deformations by DMB and the quality of mineral and organic matrix in bone biopsies from PMOP women treated with DMAb for up to 10y.

Assessments were performed blindly on 1) 72 iliac bone samples from patients treated for 2/3 y either Pbo or DMAb, and 2) 49 iliac bone samples from patients treated for 5y (N=28) or 10y (N=21) with DMAb.

After 2/3y, Ct Hv was significantly higher in DMAb than Pbo (Table) with increased mineral/matrix ratio but without significant variation of other quality of mineral and organic matrix variables. At 5y and 10y, mineral/matrix ratio, mineral maturity (transformation of precursors into apatite crystals), crystallinity (size/perfection of crystals), were higher compared to 2/3y of DMAb, supporting transition to more mature crystals (within physiological range). However, Hv was significantly lower at 5y and 10y than to 2/3y while Cc collagen maturity was increased.

In conclusion, DMAb improves bone Hv after 2/3y, mainly by changes in bone matrix mineralisation characteristics that are consistent with DMAb’s mechanism of action as a potent remodelling inhibitor. However, persistently low state of bone remodelling at 5y and 10y is associated with reduced bone Hv, suggesting aging of the poorly remodelled organic matrix (non-collagenous proteins or other factors could be involved). At the organ level, DMAb preserves modelling-based bone formation at weight-bearing sites and leads to continued BMD gains and low fracture rate up to 10y.

 

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