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

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.

The physiology of endocrine systems with ageing

“…15 However, a subsequent study showed that individuals aged 85 years with subclinical hyperthyroidism did not have a significantly worse 9-year survival than their euthyroid peers. 16 Further, subclinical hyperthyroidism is associated with an increased risk of atrial fibrillation, 17 hip and other fractures, 18 and dementia, 19 particularly among people with TSH concentrations that are lower than 0·10 mIU/L, and those with endogenous thyroid disease. In contrast, older individuals with subclinical hypothyroidism or higher TSH concentrations within the normal range have a lower mortality than do euthyroid individuals or people with lower TSH concentrations.…”

The Influence of Thyroid Pathology on Osteoporosis and Fracture Risk: A Review

“…Osteoporosis 5458 Subclinical hyperthyroidism is associated with lower BMD. 2018 [46] Fracture risk 314,146 Subclinical hyperthyroidism is associated with an increased risk of fracture. 2016 [44] Fracture risk 70,298 Subclinical hyperthyroidism is associated with an increased risk of fractures.…”

“…Subclinical hyperthyroidism and bone health. Subclinical hyperthyroidism is considered by most studies to be associated with a lower BMD and with an increased risk of fracture (Tables 1-3) [25,40,42,[44][45][46]. Only a few studies showed that subclinical hyperthyroidism is not predictive for incidental hip fracture (Tables 1-3) [23,40].…”

Thyroid Stimulating Hormone and Bone Mineral Density: Evidence From a Two-Sample Mendelian Randomization Study and a Candidate Gene Association Study

“…Furthermore, a similar relationship has been reported in individuals with subclinical hyperthyroidism (reduced circulating concentration of TSH but circulating fT4 within the normal reference range), and in euthyroid individuals with a relatively low TSH and relatively high fT4 within the normal reference range . Accordingly, individuals with subclinical hyperthyroidism had increased bone loss during prospective follow‐up compared to euthyroid individuals . In addition to effects of thyroid hormone on bone, some studies have suggested direct effects of TSH on bone .…”

“…(9,10) Accordingly, individuals with subclinical hyperthyroidism had increased bone loss during prospective follow-up compared to euthyroid individuals. (11) In addition to effects of thyroid hormone on bone, some studies have suggested direct effects of TSH on bone. (12,13) However, others have not confirmed these findings.…”