Background <p>Long-term thyroid hormone therapy raises concerns regarding potential adverse effects on bone health, including osteopenia and osteoporosis. We investigated the impact of levothyroxine therapy administered at either replacement or suppressive doses on bone mineral density (BMD) compared with healthy controls in young adults.</p> Methods <p>This cross-sectional study included 122 participants aged 20–50 years, in the three groups. Group 1 comprised 40 patients with hypothyroidism who had been treated with a replacement dose of levothyroxine for 3–5 years. Group 2 included 40 patients with thyroid cancer receiving a suppressive dose of levothyroxine for 3–5 years. Group 3 consisted of 42 healthy individuals as the control group. BMD was assessed in all participants using dual-energy x-ray absorptiometry (DXA), and results were compared across the groups.</p> Results <p>The mean femur Z-score was 0.74 ± 1.09 in the control group, 0.41 ± 0.73 in the replacement dose group, and − 0.43 ± 1.13 in the suppressive dose group. Statistical analysis demonstrated a significant difference in BMD between the suppressive dose group and the other two groups. Moreover, the prevalence of low bone density was markedly higher in patients receiving suppressive doses compared with those in both the replacement and control groups (<i>P</i> = 0.002).</p> Conclusions <p>Our findings indicate that long-term use of suppressive doses of levothyroxine is associated with an increased risk of reduced bone mass in thyroid cancer patients. In contrast, replacement doses in hypothyroid patients did not adversely affect bone density. We therefore recommend routine bone densitometry for patients undergoing suppressive therapy, regardless of age, enabling early detection and management of bone loss.</p> Clinical trial number <p>Not applicable.</p>