SEATTLE – Women with knee osteoarthritis who took bisphosphonates were 27% less likely to undergo joint replacement surgery than were women who didn’t take bisphosphonates in a U.K. cohort study of 3,928 propensity-matched users and nonusers, according to a report at the World Congress on Osteoarthritis.
“In older women with incident knee osteoarthritis, incident bisphosphonate use may be associated with lower risk of knee replacement than in nonusers,” said Dr. Tuhina Neogi of Boston University.
Dr. Tuhina Neogi
Dr. Neogi and her colleagues used data from The Health Improvement Network (THIN), a U.K. database of primary care patients, to identify women aged 50-89 years who received a diagnosis of knee osteoarthritis between 2003 and 2012. Patients were excluded if they were poor surgical candidates or were taking disease-modifying antirheumatic drugs, biologic agents, or other bone-active agents.
The researchers compared 1,964 women who subsequently started bisphosphonate therapy with 1,964 propensity score–matched women who did not. In 85% of the former, the bisphosphonate was alendronate, marketed as Fosamax in the United States.
During a mean follow-up of 3 years, the incidence rate of knee replacement was 21 cases per 1,000 patient-years among bisphosphonate users and 29 cases per 1,000 patient-years among nonusers, according to results reported at the meeting, which was sponsored by Osteoarthritis Research Society International.
In adjusted analyses, users had a significantly lower relative risk of undergoing this surgery (hazard ratio, 0.73), reported Dr. Neogi, who disclosed that she had no relevant conflicts of interest.
Sensitivity analyses showed an even stronger association in a separate cohort of patients matched by age, body mass index, and the duration of osteoarthritis (hazard ratio, 0.33) and a nonsignificant benefit when bisphosphonate users were instead compared against an active user group of women who initiated any other bone-modulating therapy.
“Now of course this is observational data from electronic medical records, so we cannot rule out the potential for residual bias,” she acknowledged. “Our sensitivity analyses were fairly consistent and provide some reassurance, but nonetheless, the magnitude of effect is still likely to be biased due to residual confounding.”
In an interview, Dr. Rik Lories, one of the session’s comoderators and a professor at the University of Leuven, Belgium, said that the study “is still far from practice changing. But the great thing about this research is that we are starting to split up what you would call the osteoarthritic diseases, taking osteoarthritis as the outcome [and showing] the underlying mechanisms of the different phenotypes being different.”
Dr. Rik Lories
Dr. Neogi noted that subchrondral bone changes are prominent in knee osteoarthritis and that mechanical factors play a central role in the disease. At the same time, findings of trials of antiresorptive agents, including bisphosphonates, in knee osteoarthritis have been conflicting.
“There are a number of limitations to this study, including the fact that The Health Improvement Network does not have bone mineral density results. We tried to address this by accounting for a prior diagnosis of osteoporosis, fracture history, potential risk for fractures, body mass index, age, number of bone mineral density tests ordered, et cetera,” Dr. Neogi said. “Another limitation is that of the secular trends in use of bone-modulating agents over this time frame, and that precluded robust evaluation of the active user comparator analysis.
“Bone mineral density is still a major potential confounder here that can’t be adequately addressed,” she acknowledged.