Levothyroxine Associated With Decreased Muscle Mass Among Patients at Risk for Knee OA

Levothyroxine use in patients at risk for knee osteoarthritis (OA) is associated with decreased quadriceps muscle mass and, therefore, an increased risk for knee OA occurrence over time, according to results of an exploratory analysis published in Arthritis Research & Therapy.

More than 7% of the US population receives treatment with levothyroxine, making it one of the most frequently prescribed medications in the country. However, levothyroxine use is often associated with a decrease in muscle mass, particularly in the thighs, among adults at risk for knee OA.

Using  data from the Osteoarthritis Initiative (OAI), researchers analyzed the association between changes in thigh muscle mass and levothyroxine use in patients at risk for knee OA over a 4-year period (ClinicalTrials.gov Identifier: NCT00080171).

Patients receiving levothyroxine were propensity score-matched with nonusers in 1:2/3 ratio. Multilevel linear mixed-effect regression models were used to compare longitudinal changes in thigh muscle mass and composition between patients using vs not using levothyroxine.

In total, 1043 knees/thighs were matched and included in the study (266 levothyroxine users vs 777 nonusers). There were no significant differences in baseline magnetic resonance imaging (MRI) biomarkers for thigh muscle composition between both the groups.

Regression models revealed levothyroxine use was associated with a decrease in both quadriceps (mean difference, -16.06 mm²/year; 95% CI, -26.70 to -5.41 mm²/year) and total thigh muscles (mean difference, -22.23 mm²/year; 95% CI, -40.25 to -4.21 mm²/year) cross-sectional areas (CSA).

Researchers further evaluated the association between levothyroxine use and risk for knee OA incidence over an 8-year period. Levothyroxine use was linked to increased risk for knee OA incidence according to radiographic data (hazard ratio [HR], 1.78; 95% CI, 1.15-2.75). In addition, patients who used levothyroxine were at increased risk of developing symptomatic knee OA (HR, 1.93; 95% CI, 1.19-3.13). 

According to mediation analysis, a 4-year decrease in quadriceps CSA partially mediated the association between increased radiographic and symptomatic knee OA incidence and levothyroxine use.

The study was limited by lack of data examining the association between underlying thyroid dysfunction and muscle degeneration among patients receiving levothyroxine.

The study authors noted, “This study showed that levothyroxine use may be associated with loss of quadriceps muscle mass which may also partially mediate the increased risk of [knee] OA radiographic and symptomatic incidence in these participants.”

They concluded, “Further trials and prospectively designed observational studies are certainly warranted to assess the role of underlying thyroid function as a potential confounder or effect modifier on muscle changes and [knee] OA risk.”