The effect of oral colchicine and vitamin K1 on bone metabolism in patients with diabetes mellitus: A post-hoc analysis of a 2 × 2 factorial randomized controlled trial with 18F-sodium fluoride positron emission tomography.

PURPOSE: Diabetes mellitus (DM) confers an increased risk of fracture. Fracture risk stratification techniques are imperfect, and preventative therapies are sparse. We aimed to describe features associated with a dysfunctional bone metabolism determined by 18F-Sodium Fluoride Positron Emission Tomography (18F-NaF PET) in patients with DM and test the effects of vitamin K1 and colchicine therapy on vertebral 18F-NaF activity.

METHODS

This is a post-hoc analysis of a 2 × 2 factorial randomized double-blind placebo-controlled trial. Participants aged 50-80 with DM underwent 18F-NaF PET/CT imaging at baseline, 3 months of therapy with vitamin K1 (10mg/daily) or placebo, and colchicine (0.5 mg/day) or placebo and repeat 18F-NaF PET/CT. The 18F-NaF vertebral mean standardized uptake value (SUVmean) and the CT estimated bone mineral density (BMD) (in Hounsfield units) was evaluated from thoracic vertebra.

RESULTS

In total, 149 individuals (66.4 % male, mean age 65.5 ± 6.8 years) were included. Male sex (β -1.421, 95 % CI [-1.826, -1.016], p < 0.001), duration of DM in years (-0.021 [-0.039, -0.002], p = 0.030) and CT estimated vertebral BMD (0.011 [0.006, 0.015], p < 0.001) were independently associated with the SUVmean. The change in the SUVmean was similar between vitamin K1 or placebo groups (-0.07 ± 0.64 v 0.07 ± 0.69, p = 0.20). Participants receiving colchicine therapy had a greater reduction in the SUVmean, compared with placebo (-0.12 ± 0.72 v 0.11 ± 0.60, p = 0.039).

CONCLUSION

18F-NaF PET may be a useful measure of vertebral bone metabolism in people with DM. Three months of oral colchicine reduced the 18F-NaF vertebral SUVmean, whereas Vitamin K1 had no effect. The findings should be considered hypothesis generating.

TRIAL REGISTRATION: www.anzctr.org.au (ACTRN12616000024448).