Skeletal Effects of Levothyroxine for Subclinical Hypothyroidism in Older Adults: A TRUST Randomized Trial Nested Study.

CONTEXT

Both thyroid dysfunction and levothyroxine therapy (LT4) have been associated with bone loss, but studies on the effect of LT4 for subclinical hypothyroidism (SHypo) on bone yielded conflicting results.

OBJECTIVE

To assess the effect of LT4 treatment on bone mineral density (BMD), Trabecular Bone Score (TBS), and bone turnover markers (BTMs) in older adults with SHypo.

DESIGN AND INTERVENTION

Planned nested substudy of the double-blind placebo-controlled TRUST trial. Participants with SHypo were randomized to LT4 with dose titration vs. placebo with computerized mock titration.

SETTING AND PARTICIPANTS

196 community-dwelling adults over 65 years enrolled at the Swiss TRUST sites had baseline and 1-year follow-up bone examinations; 4 participants withdrew due to adverse events not related to treatment.

MAIN OUTCOME MEASURES

One-year percent changes of BMD, TBS, and two serum BTMs (sCTX and P1NP). Student's t-test for unadjusted analyses, and linear regression adjusted for clinical center and sex, were performed.

RESULTS

Mean age was 74.3y ± 5.7, 45.4% were women, and 19.6% were osteoporotic. The unadjusted 1-year change in lumbar spine BMD was similar between LT4 (+0.8%) and placebo-treated groups (-0.6%; between-groups difference +1.4%: 95%CI -0.1 to 2.9, p=0.059). Likewise, there were no between-group differences in 1-year change in TBS (-1.3%: 95%CI -3.1 to 0.6, p=0.19), total hip BMD (-0.2%: 95%CI -1.1 to 0.1, p=0.61), or BTMs levels (sCTX +24.1%: 95%CI -7.9 to 56.2, p=0.14), or after adjustment for clinical centers and sex.

CONCLUSIONS

Over one-year levothyroxine had no effect on bone health in older adults with SHypo.

REGISTRATION

ClinicalTrial.gov NCT01660126 and NCT02491008.