The use of bone-specific drugs (BSDs) is associated with an increased risk for osteonecrosis of sites other than the jaw, according to study results published in the Journal of Bone and Mineral Research.

Previous studies have reported that the use of BSDs is associated with an increased risk for osteonecrosis of the jaw. However, as only limited and mixed data are available on the association between BSDs and osteonecrosis of other sites, the goal of the current study was to determine this risk in a Swedish nationwide cohort.

Using registry data on all residents of Sweden aged >50 years on December 31, 2005, the researchers completed 2 studies. The first, a cohort study, included patients prescribed a BSD between 2006 and 2017 and nonusers matched for birth year, sex, history of hip fracture, and Swedish or foreign origin. The second, a case-control study, included patients diagnosed with osteonecrosis between 2006 and 2017 who were matched with individuals without a history of osteonecrosis for year, sex, and Swedish or foreign origin.

The cohort study was the main analysis of this study and included 217,387 patients (mean age, 73.2 years; 79.0% women) who dispensed a BSD during the study period and the same number of randomly selected matched nonusers. The most common first dispensed BSD was alendronate (83.2%), followed by risedronate (7.5%), denosumab (2.9%), and zoledronic acid (2.4%).


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A total of 1970 patients were diagnosed with osteonecrosis during the follow-up, and the most common sites were the hip (992 patients [50.3% of all cases]), knee/lower leg (288 patients [14.6%]), and shoulder/upper arm (130 patients [6.6%]).

During a mean treatment duration of 2.8 years, osteonecrosis was diagnosed in 983 BSD users (incidence rate of 16.1 cases per 10,000 person-years) and 214 nonusers (incidence rate of 3.5 cases per 10,000 person-years) and the adjusted risk was 4-fold higher for BSD users (adjusted hazard ratio [HR], 4.02; 95% CI, 3.32-4.87).

Patients with a femoral neck fracture who were not treated with total hip arthroplasty or hemiarthroplasty developed osteonecrosis at a rate of 1.4% per year if they had received a BSD compared with 0.6% if they had not received a BSD. Use of a BSD was not associated with osteonecrosis in patients with a femoral neck fracture that was not treated with total hip arthroplasty or hemiarthroplasty.

Zoledronic acid (HR, 1.95; 95% CI, 1.31-2.91) and denosumab (HR, 1.93; 95% CI, 1.33-2.79) were associated with a higher risk for osteonecrosis compared with less potent BSDs, including alendronate and risedronate. In denosumab treatment, the risk for osteonecrosis was significantly greater in patients receiving 120 mg vs 60 mg (HR, 2.95; 95% CI, 1.70-5.14).

With regard to the risk for osteonecrosis after treatment cessation, the researchers reported that the risk decreased with increasing time since treatment cessation. Risk for osteonecrosis was 4-fold greater in the first 2 years after cessation and was <2-fold greater at >5 years after the end of therapy.

The case-control study included 12,614 patients with a history of osteonecrosis during the study period and the same number of randomly selected matched control individuals. The results from the cohort study were confirmed in the case-control study, as 19.1% of osteonecrosis cases had previously been dispensed a BSD compared with 7.9% of control individuals (adjusted odds ratio, 1.83; 95% CI, 1.63-2.05).

The study had several limitations, according to the researchers, including the observational design, small number of cases, missing data on medications given during inpatient and outpatient care as opposed to only those collected at pharmacies, and potential inaccuracy of diagnoses or dates of diagnosis for all cases of osteonecrosis.

“[U]se of BSDs, especially more potent BSDs, is associated with increased risk of osteonecrosis of sites other than the jaw. This increased risk decreases after the final dose of BSD,” concluded the researchers.

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Reference

Nordström P, Bergman J, Ballin M, Björk S, Nordström A. Bone-specific drugs and osteonecrosis of sites other than the jaw: a nationwide cohort study [published online May 7, 2020]. J Bone Miner Res. doi:10.1002/jbmr.4040