PURPOSE: Differentiated thyroid carcinoma (DTC) is the most frequent endocrine cancer, with a high incidence in young population. Patients with postoperative DTC are usually considered with increased risk of bone loss, possibly due to the thyroid stimulating hormone (TSH) suppression therapy. However, it remains unclear whether vitamin D and calcium supplementation is beneficial on bone metabolism of young patients with vitamin D malnutrition after thyroidectomy of DTC. METHODS: In this one-year prospective study, adult men younger than 50 years or premenopausal women with DTC and vitamin D insufficiency or deficiency were enrolled after thyroidectomy, who were administered with daily supplements of 1000-2000 IU vitamin D3 and 600 mg of elemental calcium (calcium-D3) or not. Propensity score matching (PSM) was applied to identify baseline-matched cohorts. RESULTS: A total of 458 patients with a median age of 37 (range 21-50) years were enrolled, with 94 (20.5%) patients supplemented with calcium-D3. After PSM, we identified baseline-matched cohorts of 246 DTC patients, of which 82 patients were supplemented with calcium-D3 and 164 were not. After 12 months' supplementation, lower serum levels of β-CTX (0.27 ± 0.15 vs. 0.35 ± 0.18 ng/ml, P = 0.004), PTH (36.2 ± 12.7 vs. 45.2 ± 14.6 pg/ml, P < 0.001) and higher BMD at lumbar spine (1.8% vs. 0.7%, P = 0.050) and total hip (1.1% vs. -0.4%, P < 0.001) were observed compared to the control group. Among all the 458 patients, increase of 25OHD levels was closely associated with decrease of PTH, ALP and β-CTX levels and improvement in total hip BMD throughout the one-year study period. CONCLUSION: Vitamin D and calcium supplements can reduce PTH levels and bone loss, possibly contributing to protecting bone of young DTC patients with vitamin D malnutrition after thyroidectomy.