Microarchitectural deterioration of cortical and trabecular bone: Differing effects of denosumab and alendronate |
| |
| Authors: | Ego Seeman Pierre D Delmas David A Hanley Deborah Sellmeyer Angela M Cheung Elizabeth Shane Ann Kearns Thierry Thomas Steven K Boyd Stephanie Boutroy Cesar Bogado Sharmila Majumdar Michelle Fan Cesar Libanati Jose Zanchetta |
| |
| Institution: | 1. Austin Health, University of Melbourne, Melbourne, Australia;2. INSERM U831 and University of Lyon, Lyon, France;3. University of Calgary, Calgary, Alberta, Canada;4. Johns Hopkins University, Baltimore, MD, USA;5. University Health Network and University of Toronto, Toronto, Ontario, Canada;6. Columbia Presbyterian Medical Center, New York, NY, USA;7. Mayo Clinic, Rochester, MN, USA;8. INSERM U890 and University Hospital, Saint‐Etienne, France;9. Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina;10. University of California, San Francisco, San Francisco, CA, USA;11. Amgen, Inc., Thousand Oaks, CA, USA |
| |
| Abstract: | The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause. Denosumab suppresses remodeling more than alendronate, leading to greater gains in areal bone mineral density (aBMD). These greater gains may reflect differing effects of each drug on bone microarchitecture and strength. In a phase 2 double‐blind pilot study, 247 postmenopausal women were randomized to denosumab (60 mg subcutaneous 6 monthly), alendronate (70 mg oral weekly), or placebo for 12 months. All received daily calcium and vitamin D. Morphologic changes were assessed using high‐resolution peripheral quantitative computed tomography (HR‐pQCT) at the distal radius and distal tibia and QCT at the distal radius. Denosumab decreased serum C‐telopeptide more rapidly and markedly than alendronate. In the placebo arm, total, cortical, and trabecular BMD and cortical thickness decreased (?2.1% to ?0.8%) at the distal radius after 12 months. Alendronate prevented the decline (?0.6% to 2.4%, p = .051 to <.001 versus placebo), whereas denosumab prevented the decline or improved these variables (0.3% to 3.4%, p < .001 versus placebo). Changes in total and cortical BMD were greater with denosumab than with alendronate (p ≤ .024). Similar changes in these parameters were observed at the tibia. The polar moment of inertia also increased more in the denosumab than alendronate or placebo groups (p < .001). Adverse events did not differ by group. These data suggest that structural decay owing to bone remodeling and progression of bone fragility may be prevented more effectively with denosumab. © 2010 American Society for Bone and Mineral Research |
| |
| Keywords: | denosumab alendronate HR‐pQCT volumetric bone mineral density cortical thickness |
|
|
