Changes in bone density and microarchitecture following treatment of Graves’ disease and the effects of vitamin D supplementation. A randomized clinical trial

Abstract

Summary: Thyrotoxicosis leads to loss of bone mass. Vitamin D is important to bone health. In this randomized, placebo-controlled trial, we showed that bone restoration did not improve when adding vitamin D supplementation to standard care of Graves’ disease thyrotoxicosis. Bone density and microarchitecture improved markedly with treatment of thyrotoxicosis. Purpose: Vitamin D is important to skeletal health and ensuring a replete vitamin D status is recommended. In thyrotoxicosis, bone turnover is increased and bone mass density (BMD) reduced. We examined whether vitamin D supplementation improves bone recovery in thyrotoxicosis caused by Graves’ disease (GD). Methods: Using a double-blinded design, hyperthyroid patients with GD were randomized to vitamin D3 70 µg/day (2800 IU) or similar placebo as add-on to antithyroid drugs (ATD). At baseline and 9 months, we measured BMD and bone architecture using DXA and high resolution peripheral quantitative computerized tomography. Bone turnover markers (BTM) were measured at 3 months also. Effect of vitamin D versus placebo and the response to ATD treatment were analyzed using linear mixed modelling. Results: Eighty-six GD patients were included (age 41 ± 14 years, 86% females). Compared to placebo, vitamin D3 did not improve BMD or microarchitecture. In response to ATD, BMD increased in the hip by 2% (95%CI: 1–4%). Cortical porosity decreased in tibia (− 7% [95%CI: − 12 to − 2%]) and radius [− 14% [95%CI: − 24 to − 3%]), and trabecular thickness increased (tibia (5% [95%CI: 2 − 9%]) and radius (4% [95%CI: 1–7%]). Changes in BTM, but not thyroid hormones, were associated with changes in BMD by DXA and with changes in the cortical compartment. Conclusion: In newly diagnosed GD, 9 months of high dose vitamin D3 supplementation does not offer benefit by improving skeletal health. Treatment of thyrotoxicosis is associated with the recovery of BMD and microarchitecture. Clinicaltrial.gov identifier: NCT02384668