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SAT0487 Denosumab (DMAB) Effect on Bone Histology and Histomorphometry in Men with Low Bone Mineral Density (BMD)
  1. D. Dempster1,2,
  2. D.L. Kendler3,
  3. S. Boonen4,
  4. M. Bolognese5,
  5. R. Chapurlat6,
  6. S. Goemaere7,
  7. L. Hyldstrup8,
  8. E.M. Lewiecki9,
  9. P. Miller10,
  10. Y.-C. Yang11,
  11. R. Wagman11,
  12. B. Langdahl12
  1. 1Columbia University, New York
  2. 2Helen Hayes Hospital, West Haverstraw, United States
  3. 3University of British Columbia, Vancouver, Canada
  4. 4Leuven University, Leuven, Belgium
  5. 5Bethesda Health Research Center, Bethesda, United States
  6. 6Hopital Edouard Herriot, Lyon, France
  7. 7Ghent University Hospital, Ghent, Belgium
  8. 8Hvidovre Hospital, Hvidovre, Denmark
  9. 9New Mexico Clinical Research and Osteoporosis Center, Albuquerque
  10. 10Colorado Center for Bone Research, Lakewood
  11. 11Amgen, Thousand Oaks, United States
  12. 12Aarhus University Hospital, Aarhus, Denmark

Abstract

Background In the ADAMO trial in men with low BMD, DMAb treatment for 1 yr significantly increased BMD and reduced bone resorption vs placebo (Pbo) (Orwoll, JCEM 2012). Transiliac bone biopsies from women with postmenopausal osteoporosis (PMO) treated with DMAb for up to 5 yrs had normal bone quality and decreased remodeling at the tissue level (Reid, JBMR 2010; Brown, JBMR 2012)

Objectives To confirm bone histology and histomorphometry effects of DMAb among men treated for 1 yr in men

Methods Following labeling with tetracycline or demeclocycline, transiliac bone biopsy was performed as a substudy of the ADAMO trial ≤30 d before the yr-1 visit. For biopsies with only single labels in trabecular bone within the measurable field (20mm2), mineral apposition rate was imputed as 0.3μm/d

Results Among 29 subjects (17 DMAb; 12 Pbo) in the bone biopsy substudy, mean (SD) time from last DMAb dose to first label dose was 5.0 (0.5) months. Qualitative bone histology, assessed in all samples, showed normally mineralized lamellar bone. Structural indices, including cancellous bone volume and trabecular number and surface, were similar between treatment groups

Table 1.

Cancellous bone histomorphometry after 12 months of DMAb or Pbo

Consistent with the mechanism of action, bone remodeling was decreased in DMAb-treated subjects; 12/17 (71%) DMAb- and all Pbo-treated subjects had specimens with double labels in trabecular and/or cortical compartments; 6 DMAb- and 12 Pbo-treated subjects were evaluable for dynamic trabecular bone parameters. Static and dynamic remodeling indices were lower in DMAb- than Pbo-treated subjects, consistent with reduced bone turnover with DMAb.

Conclusions DMAb for 1 yr in men with low BMD resulted in qualitatively normal bone with reduced bone turnover. These findings are consistent with those from women with PMO treated with DMAb for 1, 2, 3 or 5 yrs.

Acknowledgements Study sponsor and abstract preparation Amgen/GSK

Disclosure of Interest D. Dempster Consultant for: Amgen, D. Kendler Grant/research support: Amgen, Eli Lilly, Novartis, Pfizer, GSK, J&J, Consultant for: Amgen, Eli Lilly, Novartis, Pfizer, Warner Chilcott, S. Boonen Grant/research support: Amgen and Novartis, M. Bolognese Grant/research support: Amgen, Eli Lilly, GenenTech, Consultant for: Eli Lilly, NOF, VIVUS, R. Chapurlat Grant/research support: Merck, Consultant for: Novartis, Amgen, Roche, Pfizer, S. Goemaere: None declared, L. Hyldstrup Consultant for: Amgen, Novartis, Takeda, E. M. Lewiecki Grant/research support: Amgen, Lilly, Merck, Consultant for: Amgen, Lilly, Merck, Novarits, P. Miller Grant/research support: Amgen, Eli Lilly, Merck, Radius, Consultant for: Amgen, Eli Lilly, Merck, Warner-Chilcott, Y.-C. Yang Shareholder of: Amgen, Employee of: Amgen, R. Wagman Shareholder of: Amgen, Employee of: Amgen, B. Langdahl Grant/research support: Amgen, MSD, Eli Lilly, Consultant for: Amgen, MSD, Eli Lilly, Speakers bureau: Amgen, MSD, Eli Lilly

DOI 10.1136/annrheumdis-2014-eular.1181

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