Statin use tied to joint replacement risk

A French study presented at EULAR 2024 reveals an association between statin treatment and an increased risk of total joint replacement in individuals with knee and hip osteoarthritis (OA).

“In our study, the use of statins is associated with a higher risk of [knee and hip] prostheses in a population [of individuals aged] between 40 and 75 years,” said Dr Christian Roux from the University Cote d’Azur, Nice, France, during his presentation at EULAR 2024.

Compared with individuals who were not treated with statins, those on statins had a significantly higher risk of knee (hazard ratio [HR], 1.49, 95 percent confidence interval [CI], 1.44–1.55) or hip replacement (HR, 1.38, 95 percent CI, 1.34–1.44; p<0.0001 for both). These results were derived from logistic regression after adjustments for age, sex, and comorbidities had been made. [EULAR 2024, abstract OP0281]

These results were further confirmed on sensibility analysis using a propensity score for both knee and hip prostheses fitting (HR, 1.22, 95 percent CI, 1.18–1.28; p<0.0001 for both outcomes). These findings indicate that the risk of knee and hip prosthesis was 22-percent greater among those who were treated with statins, noted Roux.

Beyond lipid-lowering properties

“[Although] the role of cholesterol metabolism has not been fully investigated … the proinflammatory effect of lipids and adipokine-linked pro-inflammatory cytokines and pathways have been shown to be associated with the pathogenesis of OA,” said Roux. “Therefore, lipid metabolism could be attractive targets for OA management.”

Statins are the most effective lipid-lowering agents, but they have more than just cholesterol-lowering properties, Roux stressed. “Statins have shown a strong effect [against] cardiovascular mortality … The anti-inflammatory effect of statins has been well-known for many years and has led to discussions on its use in rheumatoid arthritis.”

Furthermore, the effects of statins on cartilage has been shown in animal models, demonstrating its ability to reduce the synthesis of certain metalloproteases, Roux continued.

Roux and colleagues set out to evaluate the risk of total knee or hip replacement in patients treated with statins and compared it against those who had no statin treatment in a French National Health Insurance cohort comprising >1M individuals. Of these, 274,801 patients have received statins (mean age 60.2 years, 58.1 percent men) while 795,491 have not (mean age 56.1 years, 48.1 men).

A third of statin-treated patients had cardiovascular disease, while a quarter had diabetes. The corresponding percentages in the no-statin group were 7 and 7.7 percent, respectively. About 20 percent of the overall cohort were undergoing treatment for hypertension. “There was more comorbidities in the statin group as expected,” commented Roux.

The most commonly used statin was atorvastatin (63 percent), followed by simvastatin (16 percent), pravastatin (13 percent), rosuvastatin (7 percent), and fluvastatin (1 percent).

A total of 5,788 knee replacements and 5,347 hip replacements were performed in the statin group during follow-up. In the no-statin group, the corresponding numbers were 9,928 and 10,170, respectively.

Conflicting evidence

The link between statins and OA progression remains unclear, as evidence on their association are conflicting. According to Roux, some studies show little effect, a few demonstrated an increased OA risk, but most studies reveal no effect. Even meta-analyses reflect contradicting results, he added.

“[Although] the literature is confusing, our study confirms the results of the few studies showing an increased [risk] of OA progression,” said Roux.

“Different hypotheses may be discussed. The answer probably lies in the pleiotropic effect of statins and activation of specific pathways,” he concluded.