Levothyroxine use and bone loss: Longitudinal analysis among euthyroid men and women from the Baltimore Longitudinal Study of Aging.

BACKGROUND: Levothyroxine (LT4) is among the most frequently prescribed medications worldwide and the leading cause of thyrotoxicosis, a known risk factor for lower bone density and fracture. However, the skeletal consequences of LT4 use in biochemically euthyroid individuals remain poorly characterized. METHODS: Data are from the Baltimore Longitudinal Study of Aging (BLSA). Eligible participants were euthyroid at all study visits and either consistently or never used LT4 throughout follow-up. Sex-stratified propensity score matching (1:3 ratio) balanced LT4-users and non-users on demographic, physiologic, medical and sex-specific factors. BMD was measured by dual-energy X-ray absorptiometry and linear mixed-effects models with piecewise linear age splines were used to estimate age-specific BMD trajectories. RESULTS: We included 108 men (31 LT4-users, 77 non-users) and 202 women (53 LT4-users, 149 non-users) analyzed in four age-strata: (<60, 60-69, 70-79, ≥80). Among men, annual BMD change was similar between LT4-users and non-users across all age strata. Among women, LT4-users experienced significantly greater BMD decline than non-users in two age groups: <60 (difference: -0.010 g/cm2/year; 95% CI -0.015 to -0.006) and 70-79 (difference: -0.003 g/cm2/year; 95% CI -0.005 to -0.001). CONCLUSIONS: Findings raise the possibility that LT4 therapy may be a factor in bone loss, particularly among women in late-middle and early old-age. Even the potential for a deleterious effect should be included in a pragmatic assessment of LT4 treatment indications and monitoring to avoid overtreatment in vulnerable populations.