TSH suppression attenuates the early efficacy of zoledronic acid in osteoporosis

Abstract Summary TSH suppression was associated with an attenuated early skeletal response to zoledronic acid in postoperative DTC patients with osteoporosis. Objective This prospective study aimed to evaluate the impact of TSH suppression therapy on the early skeletal efficacy of zoledronic acid in patients with differentiated thyroid cancer (DTC), and to explore whether this response differs across subgroups. Methods Patients were divided into two groups: the osteoporosis with TSH suppression group (TSH + OP, n = 42) and the osteoporosis without TSH suppression group (TSH − OP, n = 67). Both groups received a single infusion of zoledronic acid (5 mg) along with daily calcium and calcitriol supplementation. Primary analyses compared changes in bone mineral density (BMD) and bone turnover markers(BTMs) at 6 and 9 months post-treatment. After propensity score matching (PSM), 36 patients from each group were included in the primary analyses. Exploratory subgroup analyses were conducted according to age and sex. Results After PSM, the TSH + OP group showed significantly less BMD improvement compared to the TSH − OP group. At 9 months, the intergroup differences in BMD change were -7.08 mg/cm 2 (lumbar, P = 0.02), -12.03 mg/cm 2 (left hip, P < 0.001) and -6.12 mg/cm 2 (femoral neck, P < 0.001). BTMs (PINP and β-CTX) remained higher in the TSH + OP group at all time points (all P < 0.01). Subgroup analyses suggested that these differences were primarily observed in postmenopausal patients. Conclusion TSH suppression therapy was associated with an attenuated early skeletal response to zoledronic acid in postoperative DTC patients with osteoporosis, with this attenuation being more pronounced at the hip and femoral neck. Exploratory subgroup analyses suggested that this attenuation was primarily observed in postmenopausal women. In patients undergoing TSH suppression, serum PINP and β-CTX are useful monitoring biomarkers.