Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate

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

Research output: Contribution to journalArticlepeer-review

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 (60mg subcutaneous 6 monthly), alendronate (70mg 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.

Original languageEnglish (US)
Pages (from-to)1886-1894
Number of pages9
JournalJournal of Bone and Mineral Research
Volume25
Issue number8
DOIs
StatePublished - Aug 2010

Keywords

  • Alendronate
  • Cortical thickness
  • Denosumab
  • HR-PQCT
  • Volumetric bone mineral density

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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