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

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.

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.

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).

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.