The aim of this study was to examine different influences on bone degradation (estrogen status, thyroid function, parathyroid function, bone metastases) with special interest focusing on the significance of suppressive levothyroxine therapy (LT4) on bone degradation in patients with differentiated thyroid carcinoma (DTC). Two markers of bone degradation (ELItest NTx = U-NTx; Serum CrossLaps = S-CTx) were used (1) to quantify the influence of different metabolic influences on bone degradation and (2) to compare these two markers with each other. One hundred forty samples of 98 female patients ages 23-86 years were analyzed. The correlation between the two assays of bone degradation was high (r = 0.825; p < 0.001). Both assays demonstrated that estrogen deficiency, hyperparathyroidism, and bone metastases caused significant increases of bone degradation. A suppressive LT4 therapy, as used for patients with DTC, led to no significant increases of S-CTx and U-NTx. The study indicates that a well-controlled suppressive LT4 therapy has only a minor effect on the degree of bone degradation and that a possible estrogen deficiency in patients with DTC has a greater impact on bone degradation. Thus, female patients with DTC on suppressive LT4 therapy and estrogen deficiency may benefit from hormone replacement therapy, as patients with DTC and normal estrogen levels presented similar results to euthyroid controls.