Thiazide Diuretics May Increase Knee Replacement Risk in Osteoarthritis

Among patients with knee osteoarthritis, the use of thiazide diuretics is associated with a higher risk of knee replacement surgery than with the use of loop diuretics, possibly due to the effect of thiazide diuretics on bone mineral density and serum magnesium, according to study results published in Osteoarthritis and Cartilage.

The use of thiazide diuretics has been associated with higher bone mineral density and possibly lower levels of serum magnesium than the use of loop diuretics; both low serum magnesium and high bone mineral density have been linked to a higher prevalence of knee osteoarthritis. This population-based cohort study included patients in the United Kingdom, ages 50 and older, who were diagnosed with knee osteoarthritis in The Health Improvement Network, a general practitioner electronic medical record database. Researchers compared the risk of knee replacement surgery, over 5 years, among patients initiating loop or thiazide diuretics. All the patients followed initiated diuretics after diagnosis to mitigate potential selection bias as both bone mineral density and magnesium are chronic factors that are likely occur before osteoarthritis diagnosis.

Both groups comprised of 3488 patients, 59% were women with a mean age of 73 years. Among thiazide diuretic initiators, 359 (28.6/1000 person-years [PY]) knee replacements occurred during the follow-up period compared with 283 (24.1/1000 PY) among loop diuretic initiators. The risk difference of incident knee replacement in thiazide initiators compared with loop initiators was 4.5 (95% CI, 1.08-1.47) per 1000 PY, with a corresponding hazard ratio [HR] of 1.26 (95% CI, 1.08-1.47). The adherence-adjusted HR of knee replacement for continuous thiazide diuretic use was 1.44 (95% CI, 1.21-1.72).

The associations were not materially changed by sensitivity analyses that excluded potential confounders like chronic kidney disease (HR, 1.27; 95% CI, 1.08-1.49) and extreme propensity scores (HR, 1.30; 95% CI, 1.11-1.52), or restricted analysis to patients with incident knee osteoarthritis (HR, 1.23; 95% CI, 1.02-1.48).

Limitations of this study included potential selection bias and the fact that bone mineral density and serum magnesium are chronic factors that are likely occur prior to osteoarthritis.

Study investigators concluded that if these findings can be replicated in future studies and found to be causal, then it could suggest that thiazide diuretics may unfavorably impact knee osteoarthritis progression. Researchers also concluded that “this study may shed light on our understanding of the biological mechanisms linking thiazide use to the risk of knee [osteoarthritis] progression. If future studies could collect data on thiazide use, bone mineral density, serum levels of magnesium, as well as changes in knee structures and symptoms, we could assess to what [extent] the effect of thiazide use on the risk of knee [osteoarthritis] progression is mediated via effects on [bone mineral density] or magnesium levels; such insight could help guide the development of targeted treatment strategies for knee [osteoarthritis] prevention and progression.”

Reference

Wei J, Neogi T, Terkeltaub R, et al. Thiazide diuretics and risk of knee replacement surgery among patients with knee osteoarthritis: a general population-based cohort study [published online June 8, 2019]. Osteoarthritis Cartilage. doi:10.1016/j.joca.2019.05.020