@article {7585, title = {Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts.}, journal = {J Intern Med}, volume = {283}, year = {2018}, month = {2018 Jan}, pages = {56-72}, 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 (\%ΔBMD) 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: \%ΔBMD = -0.18 (95\% CI: -0.34, -0.02; I2 = 0\%), with a nonstatistically significant pattern at the total hip: \%ΔBMD = -0.14 (95\% CI: -0.38, 0.10; I2 = 53\%), but not at the lumbar spine: \%ΔBMD = 0.03 (95\% CI: -0.30, 0.36; I2 = 25\%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (\%Δ BMD = -0.59; [95\% CI: -0.99, -0.19]) and total hip region (\%ΔBMD = -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.

}, keywords = {Aged, Asymptomatic Diseases, Bone Density, Female, Fractures, Bone, Humans, Hyperthyroidism, Hypothyroidism, Male, Risk Factors}, issn = {1365-2796}, doi = {10.1111/joim.12688}, author = {Segna, D and Bauer, D C and Feller, M and Schneider, C and Fink, H A and Aubert, C E and Collet, T-H and da Costa, B R and Fischer, K and Peeters, R P and Cappola, A R and Blum, M R and van Dorland, H A and Robbins, J and Naylor, K and Eastell, R and Uitterlinden, A G and Rivadeneira Ramirez, F and Gogakos, A and Gussekloo, J and Williams, G R and Schwartz, A and Cauley, J A and Aujesky, D A and Bischoff-Ferrari, H A and Rodondi, N} }