Influence of Thyroid-stimulating Hormone Suppression Therapy on Bone Mineral Density in Patients with Differentiated Thyroid Cancer: A Meta-analysis

Abstract

Background: The effects of subclinical hyperthyroidism on bone mineral density (BMD) induced by thyroid-stimulating hormone (TSH) suppression therapy in patients with differentiated thyroid cancer (DTC) remains unclear. We conducted a meta-analysis to determine the influence of TSH suppression therapy on BMD.

Methods: We performed a systematic search to identify studies which included BMD measurement of femoral neck, total hip or lumbar spine in patients on TSH suppression therapy for DTC. Main outcome measures were difference of BMD of femoral neck, total hip or lumbar spine measured by dual energy X-ray absorptiometry between patients and controls.

Results: A systematic search yielded a total of 11 published controlled cross-sectional studies (including about 571 patients and 836 controls). TSH suppression therapy was associated with the lower BMD of total hip (weighted mean difference [WMD], -0.023; 95% confidence interval [CI], -0.047 to 0.000; P=0.050) and spine (WMD, -0.041; 95% CI, -0.057 to -0.026; P<0.001) in postmenopausal women with DTC, while it was not associated with that in premenopausal women and men with DTC.

Conclusions: Although the included studies were limited by small numbers, results suggested possible association between chronic TSH suppression therapy and the lower BMD of spine and total hip in postmenopausal women (but not in premenopausal women and men) with DTC. A large, well-designed study with long-term follow-up would provide further insight into the influence of TSH suppression therapy and loss of BMD.

Keywords: Bone density; Meta-analysis; Osteoporosis; Thyroid neoplasms.

Fig. 1. Preferred Reporting Items for Systematic review and Meta-analysis flow diagram details the process of relevant study selection. DTC, differentiated thyroid cancer; TSH, thyroid-stimulating hormone; DXA, dual-energy X-ray absorptiometry; BMD, bone mineral density.

Fig. 2. Forest plot of effect of thyroid-stimulating hormone suppression therapy on femoral neck, total hip, and lumbar spine bone mineral density in premenopausal women with differentiated thyroid cancer determined by fixed effects meta-analysis. Effect sizes are indicated as Hedges' g standardized mean differences and 95% confidence interval (CI). WMD, weighted mean difference.

Fig. 3. Forest plot of effect of thyroid-stimulating hormone suppression therapy on femoral neck, total hip, and lumbar spine bone mineral density in postmenopausal women with differentiated thyroid cancer determined by fixed effects meta-analysis. Effect sizes are indicated as Hedges' g standardized mean differences and 95% confidence interval (CI). WMD, weighted mean difference.

Fig. 4. Forest plot of effect of thyroid-stimulating hormone suppression therapy on femoral neck and lumbar spine bone mineral density in men with differentiated thyroid cancer determined by fixed effects meta-analysis. Effect sizes are indicated as Hedges' g standardized mean differences and 95% confidence interval (CI). WMD, weighted mean difference.

Fig. 5. The Begg's funnel plot and P-value by Egger's test shows publication bias of femoral neck, total hip, and lumbar spine bone mineral density in each group. (A–C) Premenopausal women, (D–F) postmenopausal women, and (G, H) men. WMD, weighted mean difference.