A phase 2 trial from investigators in the UK suggests use of denosumab, a human monoclonal antibody, could drastically reduce the rate of revision procedures after hip replacements.
Research from a team at the University of Sheffield and Sheffield Teaching Hospitals suggests use of denosumab could drastically reduce the number of revision procedures following hip replacements.
Results of the study indicate use of the osteoporosis therapy could help prevent the incidence of osteolysis and was able to eliminate approximately 90% of the cells responsible for bone loss in patients who were scheduled to have revision hip surgery.
"For decades scientists have been looking for a therapy that will help to protect vulnerable areas of bone and prevent revision surgery which not only has huge cost implications for the NHS, but also causes pain and reduces mobility for patients," said Mark Wilkinson, MBChB, PhD, a professor in the University of Sheffield's Department of Oncology and Metabolism, in a statement. "This study is a significant breakthrough as we've demonstrated there is a drug, already available and successful in the treatment of osteoporosis, which has the potential to prevent up to half of all revised replacement surgeries which are caused by osteolysis.”
With revision surgery posing a serious risk to patients and creating an additional cost burden, Wilkinson and a team of colleagues set out to establish whether any existing therapies could mitigate the impact of osteolysis in a clinical trial. The current study was designed as a phase 2 trial examining use of the human monoclonal antibody denosumab on osteolytic lesion activity in patients undergoing revision total hip arthroplasty surgery.
For their double-blind, placebo-controlled, proof of concept superiority trial, investigators enrolled patients aged 30 years and older and scheduled for revision surgery for symptomatic, radiographically confirmed osteolysis. These patients were randomized in a 1:1 ratio to subcutaneous denosumab at a 60 mg dose or placebo therapy. The primary outcome of the trial was the between-group difference in osteoclast number per millimeter of bone surface of biopsies taken from the osteolytic membrane–bone interface at surgery 8 weeks later, which was measured using quantitative histomorphometry in all patients who underwent revision surgery.
From December 12, 2012 through June 24, 2018, investigators assessed 51 patients for eligibility and 24 were ultimately included in the study. Investigators noted 2 of the 24 patients had their revision surgery cancelled for unrelated reasons and 22 patients were included in the final analyses. Of the 22 included, 12 were randomized to placebo therapy and 10 were assigned to the denosumab group. Of note, exclusion criteria for the study included currently using or having a history of using oral bisphosphonate, having an eGFR less than 30, and being pregnant or breast feeding, among others.
Upon analysis, results indicated there were 83% fewer osteoclasts at the osteolysis membrane-bone interface in the denosumab group compared to the placebo group (median, 0.05 per mm [IQR, 0.11] vs 0.30 mm [0.40]; P=.011). There were no deaths or treatment-related serious adverse events observed during the study. Overall, 7 adverse events, including one severe adverse events, occurred among 4 of the 11 patients randomized to denosumab. Among those in the placebo arm, 10 adverse events, including 3 severe adverse events, occurred in 5 of 13 patients randomized to placebo therapy.
"It is very clear from our bone biopsies and bone imaging that the injection stops the bone absorbing the micro-plastic particles from the replacement joint and therefore could prevent the bone from being eaten away and the need for revision surgery,” Wilkinson added.
This study, “Effect of denosumab on osteolytic lesion activity after total hip arthroplasty: a single-centre, randomised, double-blind, placebo-controlled, proof of concept trial,” was published in The Lancet Rheumatology.