Longitudinal study of vitamin D metabolites after long bone fracture

Animal models suggest a key role for dihydroxylated vitamin D metabolites in fracture healing, as evidenced by increases in serum concentration of 24R,25-dihydroxyvitamin D (24R,25[OH]₂D) after long bone fracture. Human studies investigating the kinetics of serum concentrations of 24R,25[OH]₂D, 1,25-dihydroxyvitamin D (1,25[OH]₂D) and their parent metabolite 25-hydroxyvitamin D (25[OH]D) are lacking. We, therefore, conducted a longitudinal study to determine whether total, free, or bioavailable concentrations of these vitamin D metabolites fluctuate in humans after long bone fracture. Twenty-eight patients with cross-shaft (diaphyseal) long bone fracture presenting to an emergency department in London, UK, were studied. Serum concentrations of 25(OH)D, 24R,25(OH)₂D, 1,25(OH)₂D, vitamin D binding protein, albumin, and calcium were determined within 48 hours of fracture and again at 1 and 6 weeks postfracture. Concentrations of free and bioavailable vitamin D metabolites were calculated using standard equations. No changes in mean serum concentrations of 25(OH)D or 24R,25(OH)₂D were seen at either follow-up time point versus baseline. In contrast, mean serum 1,25(OH)2 D concentration declined by 21% over the course of the study, from 68.5 pmol/L at baseline to 54.1 pmol/L at 6 weeks (p < 0.05). This decline was associated with an increase in mean serum corrected calcium concentration, from 2.32 mmol/L at baseline to 2.40 mmol/L at 1 week (p < 0.001) that was maintained at 6 weeks. No changes in free or bioavailable concentrations of any vitamin D metabolite investigated were seen over the course of the study. We conclude that serum 1,25(OH)₂D concentration declines after long bone fracture in humans but that the serum 24R,25(OH)₂D concentration does not fluctuate. The latter finding contrasts with those of animal models reporting increases in serum 24R,25(OH)₂D concentration after long bone fracture.