24-25-dihydroxyvitamin-d-3 and Fractures--Bone

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.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Aged; Albumins; Calcitriol; Emergency Service, Hospital; Female; Follow-Up Studies; Fractures, Bone; Humans; London; Male; Middle Aged; Time Factors; Vitamin D-Binding Protein

While disorders of impaired vitamin D activation and action have long been appreciated, the consequences of abnormalities in pathways leading to the inactivation of vitamin D metabolites have only recently been identified. Two recent articles have shed new light on this area of vitamin D biology. The report by Martineau et al., published in the JCI, describes a pathway in which binding of the vitamin D metabolite 24R,25(OH)2D3 to its effector molecule FAM57B2 plays an important role in endochondral ossification during bone repair. This work follows, and adds to, another recent JCI publication by Roizen et al., showing that rapid inactivation of vitamin D metabolites causes vitamin D deficiency, leading to vitamin D-dependent rickets.

Topics: 24,25-Dihydroxyvitamin D 3; Fractures, Bone; Humans; Vitamin D; Vitamin D Deficiency

Blood levels of the active metabolites of vitamin D3, 25-hydroxycholecalciferol [25(OH)D3], 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and 24,25-dihydroxycholecalciferol [24,25(OH)2D3] were determined in seven patients. Two subjects suffered from delayed union of tibial fractures; one showed a delayed union after a proximal tibial osteotomy; one patient suffered from bilateral femoral neck fractures, of which one failed to unite and the other united late; two patients had multiple fractures that united normally; and one patient exhibited staged bilateral femoral neck fractures whose occurrence was separated by a short interval and which united without undue delay. The blood levels of 25(OH)D3 were within the normal range. A relative decrease in 24,25(OH)2D3 values was noted in all patients, whereas in three subjects the decrease was absolute, to non-detectable levels. A decrease in 1,25(OH)2D3 levels was noted in only two patients. We postulate that these changes reflect the consumption of these metabolites during healing at the fracture site.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Calcifediol; Calcitriol; Dihydroxycholecalciferols; Female; Fractures, Bone; Fractures, Ununited; Humans; Male; Middle Aged; Wound Healing

Vitamin D metabolite levels were measured in serum and bone samples obtained from 27 patients undergoing elective bony procedures and from 28 patients operated on after a fracture. Serum 25 hydroxyvitamin D3 (25-OH-D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) did not differ significantly between the elective and fracture patients, but serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was significantly reduced in the fracture patients. Very little 25-OH-D3 was found in bone, although it was the major vitamin D metabolite in serum (90%). In elective patients bone levels of 24,25(OH)2D3 and 1,25(OH)2D3 were similar to those in serum; however, in bone from around pertrochanteric fractures, but not from subcapital or patellar fractures, the concentrations of these compounds were considerably increased. These findings may shed light on the mechanism of callus formation and on the role of vitamin D metabolites in bone healing.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Aged; Bone and Bones; Calcifediol; Calcitriol; Dihydroxycholecalciferols; Fractures, Bone; Humans; Joints; Middle Aged; Vitamin D

In 41 geriatric patients with long bone fractures, a seasonal variation was observed in the serum levels of 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D [1,25(OH)2D], 24,25-dihydroxyvitamin D [24,25(OH)2D] and parathormone (PTH). The serum concentrations of vitamin D metabolites correlate positively, while that of PTH correlates negatively with day length and global solar radiation in southern Israel. Our data suggest that the higher serum levels of vitamin D metabolites during the summer suppress PTH secretion. During the winter, the reduction of serum levels of vitamin D metabolites due to decreased endogenous production was accompanied by an increase in serum PTH levels.

Topics: 24,25-Dihydroxyvitamin D 3; Aged; Calcifediol; Calcitriol; Dihydroxycholecalciferols; Female; Fractures, Bone; Humans; Israel; Male; Parathyroid Hormone; Seasons; Sunlight; Time Factors; Vitamin D

Previous investigations have suggested that a lower-than-normal serum 1,25(OH)2D is found in elderly women with postmenopausal osteoporosis. We examined the fundamental aspects of this theory by investigating serum vitamin D metabolites in four representative samples of Caucasian women. These included 44 early postmenopausal women divided into two subgroups: fast bone losers, that is, bone loss greater than 3%/year (n = 20), and "physiological" bone loss (n = 24); and 28 70-year-old women divided into two subgroups: with and without osteoporotic fractures. Serum 1,25(OH)2D concentrations were virtually the same in all groups thus contradicting the previous reports of low 1,25(OH)2D in elderly women. Furthermore, mean 25OHD and 24,25(OH)2D did not differ between the groups. We conclude that 1,25(OH)2D is unlikely to be significant in the development or treatment of a majority of women with postmenopausal osteoporosis.

Topics: 24,25-Dihydroxyvitamin D 3; Aged; Aging; Dihydroxycholecalciferols; Female; Fractures, Bone; Humans; Hydroxycholecalciferols; Menopause; Middle Aged; Osteolysis, Essential; Osteoporosis