Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts.

Segna D, Bauer DC, Feller M, Schneider C, Fink HA, Aubert CE, Collet TH, da Costa BR, Fischer K, Peeters RP, Cappola AR, Blum MR, van Dorland HA, Robbins J, Naylor K, Eastell R, Uitterlinden AG, Rivadeneira Ramirez F, Gogakos A, Gussekloo J, Williams GR, Schwartz A, Cauley JA, Aujesky DA, Bischoff-Ferrari HA, Rodondi N, Thyroid Studies Collaboration. Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts. Journal of Internal Medicine. 2018 Jan 1; 283(1):56-72.

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Abstract:

BACKGROUND: Subclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear. OBJECTIVE: To investigate the association between subclinical thyroid dysfunction and bone loss. METHODS: Individual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45-4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (% BMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach. RESULTS: Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: % BMD = -0.18 (95% CI: -0.34, -0.02; I = 0%), with a nonstatistically significant pattern at the total hip: % BMD = -0.14 (95% CI: -0.38, 0.10; I = 53%), but not at the lumbar spine: % BMD = 0.03 (95% CI: -0.30, 0.36; I = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (% BMD = -0.59; [95% CI: -0.99, -0.19]) and total hip region (% BMD = -0.46 [95% CI: -1.05, -0.13]). In contrast, SHypo was not associated with bone loss at any site. CONCLUSION: Amongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk.