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

• Published in: Journal of internal medicine Vol. 283; no. 1; pp. 56 - 72
• Main Authors: Segna, D., Bauer, D. C., Feller, M., Schneider, C., Fink, H. A., Aubert, C. E., Collet, T.‐H., Costa, B. R., Fischer, K., Peeters, R. P., Cappola, A. R., Blum, M. R., Dorland, H. A., Robbins, J., Naylor, K., Eastell, R., Uitterlinden, A. G., Rivadeneira Ramirez, F., Gogakos, A., Gussekloo, J., Williams, G. R., Schwartz, A., Cauley, J. A., Aujesky, D. A., Bischoff‐Ferrari, H. A., Rodondi, N.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.01.2018
• Subjects: Absorptiometry; Adults; Aged; Asymptomatic Diseases; Biomedical materials; Bone Density; Bone loss; Bone mineral density; Data analysis; Data processing; Dual energy X-ray absorptiometry; Female; Femur; Fractures; Fractures, Bone - etiology; Fractures, Bone - metabolism; Fractures, Bone - prevention & control; Health risk assessment; Hip; Humans; Hyperthyroidism; Hyperthyroidism - diagnosis; Hyperthyroidism - epidemiology; Hyperthyroidism - metabolism; Hypothyroidism; Hypothyroidism - diagnosis; Hypothyroidism - epidemiology; Hypothyroidism - metabolism; Male; prospective studies; Regression analysis; Risk Factors; Spine; Spine (lumbar); Surgical implants; Thyroid; thyroid disease; Thyroid diseases; Thyroid gland; Thyroid-stimulating hormone; Thyroxine; thyroid disease; hyperthyroidism; hypothyroidism; bone loss; bone density; prospective studies
• ISSN: 0954-6820; 1365-2796
• DOI: 10.1111/joim.12688

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.