Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis

Abstract

CONTEXT As subclinical hyperthyroidism increases the risk of osteoporosis and fractures, concerns are growing about the long-term skeletal safety of thyrotropin (TSH) suppression therapy after total thyroidectomy in patients with differentiated thyroid cancer (DTC). OBJECTIVE We aimed to determine the effect of TSH suppression therapy on bone mineral density (BMD) in DTC patients. METHODS We searched PubMed, Embase, the Cochrane library, and other sources. Eligible observational studies included DTC patients who underwent TSH suppression therapy and BMD measurement. Two independent reviewers extracted data on the studies’ characteristics and outcomes and determined their risk of bias. Data were extracted from each study for postmenopausal/premenopausal women’s and men’s lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD and summed using a random-effects meta-analysis model. The weighted mean difference (WMD) with 95% confidence intervals (CI) are expressed for the differences in outcome measurements between groups. RESULTS Seventeen studies (739 patients and 1085 controls) were included for quantitative analysis. In postmenopausal women, TSH suppression therapy showed a significant decrease in LS BMD (-0.03; -0.05, -0.02), and a similar trend was seen in TH. In premenopausal women, TSH suppression therapy significantly increased LS BMD (0.04; 0.02, 0.06) and FN BMD (0.02; 0.01, 0.04). In men, there was no significant association between TSH suppression therapy and BMD at any site compared to the controls. CONCLUSION Evidence from observational studies suggests that postmenopausal women treated with TSH suppression therapy are at risk for lower BMD. Attention should be paid to long-term skeletal safety in DTC survivors.

Thyroid-stimulating Hormone Suppressive Therapy and Osteoporosis: A Review and Meta-analysis

“…[15] 2018 Spain Casecontrol 14 vs 84 1.00 ± 0.12 vs 0.98 ± 0.11, lumbar 14 vs 84 0.86 ± 0.12 vs 0.84 ± 0.15, lumbar 10 years BMD was higher among women with DTC who received thyroxine for TSH suppression, no difference in BMD was observed among males compared to their counterparts without TSH suppression. The current findings were similar to Ku and colleagues who conducted a meta-analysis and found similar results [25]. The current findings supported the conclusion of a recent meta-analysis that included only 11 studies and focused on Sudan Journal of Medical Sciences Hyder Osman Mirghani and Albaraa Altowigri the site of BMD, our study assessed additional women with osteopenia and a broad category of women without specification of menopausal status.…”

Effects of TSH suppressive therapy on bone mineral density (BMD) and bone turnover markers (BTMs) in patients with differentiated thyroid cancer in Northeast China: a prospective controlled cohort study

“…On the other hand, estrogen may provide some protection against bone loss and counteracts the resorptive effects of excess thyroid hormones in premenopausal patients with levothyroxine therapy [28]. The change of BTMs might provide an explanation for the higher BMD observed in premenopausal DTC patients than controls in this study, as well as in the above-mentioned metaanalyses [17,19]. The change of β-CTX was signi cantly different between postmenopausal DTC patients and controls, with a reduction in DTC patients and an increase in controls.…”

“…Therefore, our study suggested that TSH suppressive therapy had no adverse effects on BMD in premenopausal women. Two metaanalyses consistently reported FN-BMD and LS-BMD were signi cantly higher in patients with TSH suppressive therapy than in the control group [17,19]. The safety of TSH suppressive therapy in premenopausal women might contribute to the protective role of estrogen.…”

“…Consist with our results, Pei Zhang et al reported that although postmenopausal women with 2-year postoperative TSH suppressive therapy (TSH 0.3 µIU/mL) showed a 1.9 % reduction in the LS-BMD, there was no signi cant difference in the LS-BMD between patients with TSH suppressive therapy (TSH 0.3 µIU/mL) and non-suppressed TSH patients (TSH 0.3 µIU/mL) after postoperative 6, 12, and 24 months [10]. In another 2-year longitudinal study including 23 postmenopausal patients with TSH suppressive therapy, no signi cant difference was observed in BMD at either baseline or follow-up compared with healthy controls [16].A recent meta-analysis including 17 crosssectional studies reported that postmenopausal DTC patients receiving TSH suppressive therapy showed a signi cant decrease in LS-BMD, and a similar trend was seen in TH-BMD [17]. A large randomized controlled prospective cohort study by Sugitani et al compared the T-score of the lumbar spine in 120 women receiving TSH suppressive therapy with those who did not receive TSH suppressive therapy.…”

Biomarkers indicating tissue thyroid hormone status: ready to be implemented yet?

“…Furthermore, DIO3 is expressed in osteoclasts, osteoblasts and chondrocytes, whereas DIO2 is present in mature osteoblasts making it possible to regulate TH status at the tissue level. Research in thyroidectomized postmenopausal women using L-T4 showed that biochemical euthyroidism while treated may be associated with decreased bone mineral density (Ku et al 2021). This suggests that markers involved in bone metabolism could be of interest to determine bone TH status.…”