A new proof-of-concept study suggests that a single injection of denosumab (Prolia, Amgen), frequently used to treat osteoporosis, may reduce the need for revision surgery in patients with symptomatic osteolysis following total hip arthroplasty. Aseptic loosening is the result of wear-induced osteolysis caused by the prosthetic hip and is a major contributor to the need for revision surgery in many parts of the world.
A single injection of denosumab (Prolia, Amgen), frequently used to treat osteoporosis, may reduce the need for revision surgery in patients with symptomatic osteolysis following total hip arthroplasty, a new proof-of-concept study suggests.
Aseptic loosening is the result of wear-induced osteolysis caused by the prosthetic hip and is a major contributor to the need for revision surgery in many parts of the world.
"The only established treatment for prosthesis-related osteolysis after joint replacement is revision surgery, which carries substantially greater morbidity and mortality than primary joint replacement," say Mohit M. Mahatma, MRes, of the University of Sheffield, UK, and colleagues in their article published online January 11 in Lancet Rheumatology.
As well as an increased risk of infection and other complications, revision surgery is much more costly than a first-time operation, they add.
"The results of this proof-of-concept clinical trial indicate that denosumab is effective at reducing bone resorption activity within osteolytic lesion tissue and is well tolerated within the limitations of the single dose used here," they conclude.
Commenting on the findings, Antonia Chen, MD, associate professor of orthopedic surgery, Harvard Medical School, Boston, Massachusetts, emphasized that further studies are needed to assess the effectiveness of this strategy to reduce the need for hip revision surgery.
Nevertheless, "osteolysis is still unfortunately a problem we do have to deal with and we do not have any other way to prevent it," she told Medscape Medical News. "So it's a good start...although further studies are definitely needed," Chen added.
In an accompanying editorial, Hannu Aro, MD, Turku University Hospital in Finland, agrees: "Without a doubt, the trial is a breakthrough, but it represents only the first step in the development of pharmacological therapy aiming to slow, prevent, or even reverse the process of wear-induced periprosthetic osteolysis."
Small Single-Center Study
The phase 2, single-center, randomized, controlled trial involved 22 patients who had previously undergone hip replacement surgery at Sheffield Teaching Hospitals and were scheduled for revision surgery due to symptomatic osteolysis. They were randomized to a single subcutaneous injection of denosumab at a dose of 60 mg or placebo on their second hospital visit.
"The primary outcome was the between-group difference in the number of osteoclasts per mm of osteolytic membrane at the osteolytic membrane-bone interface at week 8," the authors note.
At this timepoint, there were 83% fewer osteoclasts at the interface in the denosumab group compared with placebo, at a median of 0.05 per mm in the treatment group compared with 0.30 per mm in the placebo group (P = .011).
Secondary histological outcomes were also significantly improved in favor of the denosumab group compared with placebo (Table 1).