LEVOTHYROXINE USE MAY BE ASSOCIATED WITH LONGITUDINAL QUADRICEPS ATROPHY AND SUBSEQUENT KNEE OA RISK: PRELIMINARY ANALYSIS FROM OAI COHORT

Abstract

Levothyroxine, the primary treatment for hypothyroidism, is prescribed for more than 7% of Americans. Levothyroxine use, or the underlying hypothyroidism can be associated with musculoskeletal symptoms; however, no prior work has investigated this association using sensitive biomarkers. We examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in participants at-risk of knee OA and their mediatory role in subsequent knee OA radiographic and symptomatic incidence. Thighs and knees of OAI participants without established radiographic knee OA were included. Levothyroxine users were defined as self-reported use at all annual follow-up visits until the 4th-year and were matched with nonusers for potential confounders using 1:2/3 propensity-score (PS) matching. We developed and validated a deep learning method for automated thigh segmentation and assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intramuscular adipose tissue (intra-MAT), contractile percentage, and specific force (force per CSA). We further assessed whether levothyroxine use is associated with an 8-year risk of standard knee OA radiographic and symptomatic incidence. Finally, we assessed whether the association between levothyroxine use and knee OA incidence is mediated via muscle changes. We included 1485 matched thighs/knees (387:1098 users:non-users; age: 62±9 years, female/male:3.1). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI:-15.46mm2/year, -25.11– -5.82) but not thigh muscles’ composition biomarkers. Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR):1.59, 1.15–2.20) and symptomatic knee OA incidence (HR:1.60, 1.12–2.29). A decrease in quadriceps CSA partially mediated the increased risk of knee OA incidence associated with levothyroxine use. Our exploratory analyses suggest that levothyroxine users might have increased risk of thigh muscle atrophy and subsequent knee OA. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier and therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal thigh muscles atrophy and associated knee OA incidence risk. NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under Award Number R01AR079620-01. AG reported receiving funding from Merck Serono, AstraZeneca, Galapagos, Pfizer, Roche, TissueGene (for consultation), and Boston Imaging Core Lab (as the president and stockholder). SD reported that he received funding from Toshiba Medical Systems (for consultation) and grants from GERRAF and Carestream Health (for a clinical trial study). Authors acknowledge OAI staff and team. CORRESPONDENCE ADDRESS: sdemehri1@jhmi.edu .