Subclinical thyroid dysfunction and the risk for fractures: a systematic review and meta-analysis.

BACKGROUND

Data on the association between subclinical thyroid dysfunction and fractures conflict.

PURPOSE

To assess the risk for hip and nonspine fractures associated with subclinical thyroid dysfunction among prospective cohorts.

DATA SOURCES

Search of MEDLINE and EMBASE (1946 to 16 March 2014) and reference lists of retrieved articles without language restriction.

STUDY SELECTION

Two physicians screened and identified prospective cohorts that measured thyroid function and followed participants to assess fracture outcomes.

DATA EXTRACTION

One reviewer extracted data using a standardized protocol, and another verified data. Both reviewers independently assessed methodological quality of the studies.

DATA SYNTHESIS

The 7 population-based cohorts of heterogeneous quality included 50,245 participants with 1966 hip and 3281 nonspine fractures. In random-effects models that included the 5 higher-quality studies, the pooled adjusted hazard ratios (HRs) of participants with subclinical hyperthyroidism versus euthyrodism were 1.38 (95% CI, 0.92 to 2.07) for hip fractures and 1.20 (CI, 0.83 to 1.72) for nonspine fractures without statistical heterogeneity (P = 0.82 and 0.52, respectively; I2= 0%). Pooled estimates for the 7 cohorts were 1.26 (CI, 0.96 to 1.65) for hip fractures and 1.16 (CI, 0.95 to 1.42) for nonspine fractures. When thyroxine recipients were excluded, the HRs for participants with subclinical hyperthyroidism were 2.16 (CI, 0.87 to 5.37) for hip fractures and 1.43 (CI, 0.73 to 2.78) for nonspine fractures. For participants with subclinical hypothyroidism, HRs from higher-quality studies were 1.12 (CI, 0.83 to 1.51) for hip fractures and 1.04 (CI, 0.76 to 1.42) for nonspine fractures (P for heterogeneity = 0.69 and 0.88, respectively; I2 = 0%).

LIMITATIONS

Selective reporting cannot be excluded. Adjustment for potential common confounders varied and was not adequately done across all studies.

CONCLUSION

Subclinical hyperthyroidism might be associated with an increased risk for hip and nonspine fractures, but additional large, high-quality studies are needed.

PRIMARY FUNDING SOURCE

Swiss National Science Foundation.