title: Longitudinal study of vitamin D metabolites after long bone fracture.
abstract: 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.
authors.affiliation: Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom, USA.
authors.forename: Adam D M
authors.initials: AD
authors.lastname: Briggs
authors.forename: Valerie
authors.initials: V
authors.lastname: Kuan
authors.forename: Claire L
authors.initials: CL
authors.lastname: Greiller
authors.forename: Beverley D
authors.initials: BD
authors.lastname: Maclaughlin
authors.forename: Manoj
authors.initials: M
authors.lastname: Ramachandran
authors.forename: Timothy
authors.initials: T
authors.lastname: Harris
authors.forename: Peter M
authors.initials: PM
authors.lastname: Timms
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Venton
authors.forename: Reinhold
authors.initials: R
authors.lastname: Vieth
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Norman
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Griffiths
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Martineau
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3 / Q000097:blood*; D000328:Adult; D000368:Aged; D000418:Albumins / Q000378:metabolism; D002117:Calcitriol / Q000097:blood*; D004636:Emergency Service, Hospital; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000097:blood* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008131:London; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014809:Vitamin D-Binding Protein / Q000097:blood
chemical_list: D000418:Albumins; D014809:Vitamin D-Binding Protein; D015650:24,25-Dihydroxyvitamin D 3; D002117:Calcitriol