Effect of 10 years of denosumab treatment on bone histology and histomorphometry in the FREEDOM extension study — ASN Events
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Effect of 10 years of denosumab treatment on bone histology and histomorphometry in the FREEDOM extension study (#51)

Astrid Fahrleitner-Pammer 1 , David Dempster 2 3 , Nadia Daizadeh 4 , Jens-Erik Beck Jensen 5 , David Kendler 6 , Ivo Valter 7 , Rachel B Wagman 4 , Susan Yue 4 , Jacques P Brown 8
  1. Medical University Graz, Graz, Austria, Graz, Austria
  2. Columbia University, New York, NY, USA
  3. Helen Hayes Hospital, West Haverstraw, NY, USA
  4. Amgen Inc, Thousand Oaks, CA, USA
  5. Hvidovre University Hospital, Hvidovre, Denmark
  6. University of British Columbia, Vancouver, BC, Canada
  7. Center for Clinical and Basic Research, Tallinn, Estonia
  8. Laval University and CHU de Québec (CHUL), Quebec City, QC, Canada

Aim: Report bone biopsy data in subjects with 10 years of DMAb treatment.

Methods: A subset of subjects with 10 years of DMAb exposure in FREEDOM/FREEDOM Extension underwent tetracycline/demeclocycline labeling prior to their bone biopsy visit (6 months after their last DMAb dose). Samples were prepared and analysed as described previously (Reid JBMR 2010). Data were summarised using descriptive statistics.

Results:  22 biopsies were evaluable for qualitative histology. All specimens showed normally mineralised lamellar bone; there was no evidence of pathologic findings, including osteomalacia, woven bone, or marrow fibrosis. 21 biopsies were evaluable for histomorphometry. These showed DMAb anti-resorptive effects were maintained over time. Indicators associated with bone formation/structure were similar to those at years 2/3 and year 5 of DMAb treatment (Table). The presence of tetracycline labels was reviewed in all biopsies. The percentage of samples with any tetracycline label in trabecular bone steadily increased from 34% in year 2/3, to 43% in year 5, and 77% in year 10 of DMAb treatment; the percentage of samples with any label in cortical bone has remained steady from 57%, to 64%, and 55%, respectively. Double tetracycline labeling of trabecular or cortical bone was found in 7 (32%) subjects at year 10.

Conclusion: Bone histology showed normal bone microarchitecture, and histomorphometry was consistent with DMAb mechanism of action. There was no evidence of progression in the degree of low remodeling with long-term exposure to DMAb.