title: 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.
authors.affiliation: Austin Health, University of Melbourne, Melbourne, Australia. egos@unimelb.edu.au
authors.forename: Ego
authors.initials: E
authors.lastname: Seeman
authors.forename: Pierre D
authors.initials: PD
authors.lastname: Delmas
authors.forename: David A
authors.initials: DA
authors.lastname: Hanley
authors.forename: Deborah
authors.initials: D
authors.lastname: Sellmeyer
authors.forename: Angela M
authors.initials: AM
authors.lastname: Cheung
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shane
authors.forename: Ann
authors.initials: A
authors.lastname: Kearns
authors.forename: Thierry
authors.initials: T
authors.lastname: Thomas
authors.forename: Steven K
authors.initials: SK
authors.lastname: Boyd
authors.forename: Stephanie
authors.initials: S
authors.lastname: Boutroy
authors.forename: Cesar
authors.initials: C
authors.lastname: Bogado
authors.forename: Sharmila
authors.initials: S
authors.lastname: Majumdar
authors.forename: Michelle
authors.initials: M
authors.lastname: Fan
authors.forename: Cesar
authors.initials: C
authors.lastname: Libanati
authors.forename: Jose
authors.initials: J
authors.lastname: Zanchetta
mesh_terms: D000368:Aged; D019386:Alendronate / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology*; D003710:Demography; D000069448:Denosumab; D005260:Female; D006801:Humans; D008875:Middle Aged; D053245:RANK Ligand / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D053245:RANK Ligand; D000069448:Denosumab; D019386:Alendronate