Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts
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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 inMEDLINE/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 percentageBMDchange (%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%) hadSHypo and 284 (5.2%) hadSHyper. During 36 569 person‐years of follow‐up, those withSHyper 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.
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Subclinical hyperthyroidism is associated with greater annual bone loss at the femoral neck but not at the lumbar spine in prospective cohorts.
“Subclinical hyperthyroidism was also associated with greater annual bone loss at the femoral neck but not at the lumbar spine in prospective cohorts (101)”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [101]
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Higher serum free thyroxine levels are associated with increased risk of hip fractures in older men
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Thyroid Disorders and Osteoporosis
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- Authors
- Segna, D., Bauer, D. C., Feller, M., Schneider, C., Fink, H. A., Aubert, C. E., Collet, T. ‐., da Costa, B. R., Fischer, K., Peeters, R. P., Cappola, A. R., Blum, M. R., van 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., & the Thyroid Studies Collaboration
- Affiliations
- University of Bern (CH)
- University of California, San Francisco (US)
- University of Minnesota (US)
- Centre Hospitalier Universitaire Vaudois (CH)
- Institute of Primary Health Care (BIHAM) University of Bern Bern Switzerland
- University of Zurich (CH)
- Erasmus MC (NL)
- University of Pennsylvania (US)
- Department of General Internal Medicine Inselspital, Bern University Hospital University of Bern Bern Switzerland
- University of California Davis Medical Center (US)
- University of Sheffield (GB)
- Department of Internal Medicine & Department of Epidemiology Erasmus Medical Center Rotterdam The Netherlands
- Imperial College London (GB)
- Leiden University Medical Center (NL)
- University of Pittsburgh (US)
- Centre on Aging and Mobility University of Zurich Zurich Switzerland
- Corresponding author
- Rodondi, N.
- ORCID
- Venue
- Journal of Internal Medicine
- Publisher
- Wiley
- Published
- 2017-10-16
- Volume
- 283
- Issue
- 1
- Pages
- 56-72
- ISSN
- 0954-6820 (ISSN-L)
- 1365-2796
- PMC
- PMC5739958
- OpenAlex
- W2766405024
- Cited by
- 87
- References
- 41
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 13 · 2021: 12 · 2020: 14 · 2019: 9 · 2018: 9
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Leiden Repository (Leiden University) (submittedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Open Access CRIS of the University of Bern
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNSF 320030‐150025, 320030‐172676, P3SMP3‐155318, PZ00P3‐167826)
- National Heart, Lung, and Blood Institute (HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295)
- National Institute of Neurological Disorders and Stroke
- National Institute on Aging (R01AG023629, N01‐AG‐6‐2101, N01‐AG‐6‐2103, N01‐AG‐6‐2106, R01‐AG028050)
- National Institute of Nursing Research (R01‐NR012459)
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Center for Advancing Translational Sciences
- Sanofi-Aventis Korea Company
- Eli Lilly and Company
- Novartis
- Pfizer
- Roche
- Erasmus Medisch Centrum
- Erasmus Universiteit Rotterdam
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- ZonMw
- Ministerie van Onderwijs, Cultuur en Wetenschap
- Ministerie van Volksgezondheid, Welzijn en Sport
- European Commission (FP7‐HEALTH‐2011)
- Arthritis Research UK
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- subclinical hyperthyroidism, subclinical hypothyroidism, subclinical thyroid dysfunction, bone mineral density, bone loss, femoral neck, total hip, lumbar spine, thyroid-stimulating hormone, fracture risk, osteoporosis, individual patient data meta-analysis, prospective cohort, older adults, sex differences, free thyroxine
- MeSH terms
- Aged, Female, Humans, Hyperthyroidism, Hypothyroidism, Male, Risk Factors, Bone Density, Fractures, Bone, Asymptomatic Diseases
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