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


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 < or = .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.

SUBMITTER: Seeman E 

PROVIDER: S-EPMC4445722 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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

Seeman Ego E   Delmas Pierre D PD   Hanley David A DA   Sellmeyer Deborah D   Cheung Angela M AM   Shane Elizabeth E   Kearns Ann A   Thomas Thierry T   Boyd Steven K SK   Boutroy Stephanie S   Bogado Cesar C   Majumdar Sharmila S   Fan Michelle M   Libanati Cesar C   Zanchetta Jose J  

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20100801 8


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  ...[more]

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