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Explore This IssueMarch 2021
“Denosumab is already a well-established licensed drug for the indications of osteoporosis and metastatic bone lesions in cancer, and has been shown to be effective in reducing erosions in inflammatory arthritis,” Dr. Mark J.M. Wilkinson of the University of Sheffield, U.K., tells Reuters Health by email. “Here we tested the drug in the setting of osteolysis after hip replacement, a condition that currently has no effective non-surgical treatment.”
“We demonstrate the biological concept that the drug is 90% effective in reducing osteoclast numbers within these osteolytic lesions,” he says.
“The drug does not currently have licensing authorization for this indication,” he says. “Our next step would be to confirm that this biological efficacy translates into a clinically measurable benefit by reducing symptoms and re-operation rates in a phase 3 clinical trial, subject to attracting the necessary clinical trial funding.”
As reported in The Lancet Rheumatology, Dr. Wilkinson and colleagues conducted a phase 2 randomized, placebo-controlled, proof-of-concept study of patients scheduled for revision surgery for symptomatic osteolysis.1
The primary outcome was the between-group difference in osteoclast number per mm of bone surface of biopsies taken from the osteolytic membrane-bone interface at surgery eight weeks after the intervention.
Twenty-four patients were randomly assigned to subcutaneous denosumab (60 mg single dose) or placebo. Patients had a mean age of 72; 60% of denosumab patients were men, as were 83% of those on placebo.
There were 83% fewer osteoclasts at the osteolysis membrane-bone interface in the denosumab group: median 0.05 per mm vs. 0.30 mm for placebo.
Further, the length of the osteoclast surface was 87% shorter (0.14% vs. 1.04%); the length of the eroded surface was 72% shorter (0.22% vs. 0.78%); the osteoblast number was 90% fewer (0.04 per mm vs. 0.41 per mm); and the length of the osteoblast surface was 91% shorter (0.05% vs. 0.53%).
Thirteen patients were included in the safety analysis. “No life-threatening or disabling adverse events, or deaths were recorded,” the author’s state.
Dr. Hannu Aro of the University of Turku and Turku University Hospital, Finland, author of a related editorial, called the study “good news.” He noted by email that osteolysis is caused by wear particles and is “a frequent complication of conventional polyethylene bearing surfaces. Current material options are more wear resistant, but the problem still exists.”2
“Current surgical guidelines remain controversial and overshadowed by unexpectedly high rates of surgical complications,” he tells Reuters Health. “If the implant is still well fixed, the clinician and the patient are faced with difficult decisions in timing revision surgery.”