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Drugs, biologics may play a role in treating osteolysis
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While alternative bearing surfaces have received most of the attention and have the most clinical data, researchers are investigating the use of pharmacological agents to treat osteolysis. Harry E. Rubash, MD, and Arun Shanbhag, PhD, received the 1997 John Charnley award for a study demonstrating that alendronate (Fosamax; Merck) significantly reduced osteolysis in a canine model.
Edward Schwarz, PhD, of the Center for Musculoskeletal Research at the University of Rochester School of Medicine and Dentistry, is conducting research into the efficacy of tumor necrosis factor alpha (TNF-alpha) antagonists. “The osteolysis that we see in joints of patients with rheumatoid arthritis (RA) is very reminiscent, in many respects, of osteolysis that we see in patients with periprosthetic aseptic loosening,” he said. “Based on two decades of research on the biologic response in RA, we now know the major factors and clearly the most important is TNF-alpha.”
Three possible biologics
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The FDA has approved three biologics for RA that may be efficacious in treating osteolysis: etanercept (Enbrel; Amgen Inc.), infliximab (Remicade; Centocor Inc.) and adalimumab (Humira; Abbott Laboratories). Schwarz was the lead author of a pilot study in the Journal of Orthopaedic Research in 2003 that compared etanercept to placebo in the treatment of established osteolysis in 20 patients who had undergone hip replacement surgery. The goal of the study was to establish a measurement to determine drug efficacy, and another study is planned.
Schwarz is also planning a study of what he believes to be the most promising biologic for osteolysis. AMG 162, which is being developed by Amgen Inc. to treat osteoporosis, is a human monoclonal antibody that targets the receptor activator of nuclear factor kappa B ligand (RANKL). RANKL is a key mediator of the resorptive phase of bone remodeling.
“I think once anti-RANK ligand is available, patients will probably show up in a clinic with a 2-mm line on an x-ray and be receiving two doses of anti-RANK ligand a year to prevent the progression of their osteolysis,” Schwarz told Orthopedics Today.
Will pharmacology work?
William J. Maloney, MD, of Stanford University School of Medicine in Palo Alto, Calif., disagrees. “I don’t think pharmacology is going to cure this; I think this is a materials issue.” Maloney and colleagues presented a poster at the recent meeting of the Orthopaedic Research Society that studied the efficacy of alendronate in inhibiting the progression of periprosthetic osteolysis.
The multicenter, randomized, placebo-controlled trial followed 123 patients treated with alendronate for up to six months. The study showed that the drug did not have an effect on quantitative osteolytic measurements.
“Bisphosphonates are actually effective in blunting the response to particles, but they are not effective in treating osteolysis once it occurs. I can’t see us prophylactically treating every patient who has a total joint replacement with bisphosphonates,” Maloney said.
Dr. Schwarz is a paid consultant for a company mentioned in the article.