Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive
rheumatoid arthritis.
Author(s): Sharp JT, Tsuji W, Ory P, Harper-Barek C, Wang H, Newmark R.
Affiliation(s): Amgen Inc., Seattle, Washington, USA.
Publication date & source: 2010, Arthritis Care Res (Hoboken). , 62(4):537-44
OBJECTIVE: Osteoclast-mediated bone loss in the hand predicts future bone
erosions in patients with rheumatoid arthritis (RA). Osteoclast activity depends
on RANKL, which is inhibited by denosumab, an investigational fully human
monoclonal antibody against RANKL. We measured metacarpal shaft cortical bone
thickness using a novel computer-based technique, digital x-ray radiogrammetry
(DXR), to evaluate the effects of denosumab on cortical bone in RA.
METHODS: Patients (n = 227) with active, erosive RA were randomized to receive
subcutaneous denosumab 60 mg or 180 mg or placebo every 6 months. All patients
received stable doses of methotrexate and daily calcium and vitamin D. For this
blinded post hoc analysis (n = 218), cortical bone loss was determined by DXR
using computer-assisted measurement of cortical thickness and shaft width at 21
midshaft levels of the second through fourth metacarpal bones of both hands.
RESULTS: At 12 months, patients receiving denosumab had significantly less
metacarpal bone loss versus placebo (denosumab 60 mg: -0.0034, denosumab 180 mg:
0.0001 gain, placebo: -0.0108; P < or = 0.01 for both denosumab doses).
Twelve-month decreases from baseline greater than the smallest detectable change
occurred in 2 patients in the denosumab 180 mg group, 9 patients in the denosumab
60 mg group, and 12 patients in the placebo group. Negative correlation was
significant between static cortical thickness ratios and static erosion scores (6
and 12 months), and for placebo, between changes in erosion scores and changes in
cortical thickness ratio.
CONCLUSION: Twice-yearly injections of denosumab with ongoing methotrexate
treatment significantly reduced cortical bone loss in RA patients for up to 12
months. These results add to the growing evidence supporting the clinical utility
of DXR.
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