Healing of rachitic lesions in chicks by 24R,25-dihydroxycholecalciferol administered locally into bone

Abstract

In an attempt to further define the nature of the active metabolite in bone formation, a series of experiments were conducted whereby vitamin D metabolites were administered locally in vivo into the proximal epiphyseal growth plate of the tibiae of rachitic chicks. Local administration of 3 micrograms of 24,25(OH)2D3 in vivo to D-deficient chicks resulted in disappearance of the rachitic lesions in the same leg. Administration of 1 microgram 1,25(OH)2D3 in a similar manner failed to show any sign of healing. Injection of 5 micrograms 25(OH)D3 was followed by recovery from rickets in both the injected right leg and in the vehicle-injected left tibia, although the recovery was more pronounced in the injected leg. Lower doses of 0.3 or 1 microgram 24,25(OH)2D3 failed to reverse the rachitic lesions and induced only minimal recovery. These findings suggest that 24,25(OH)2D3 at the higher doses has a direct local effect on cartilage and bone, while 1,25(OH)2D3 has no such effect in chicks. 25(OH)D3 is probably absorbed from the epiphyses into the blood stream and converted into the active metabolites, which were indeed detected in the blood to exert its systemic effects.

24, 25-Dihydroxycholecalciferol but not 25-hydroxycholecalciferol suppresses apolipoprotein A-I gene expression

“…However, studies using 24-hydroxylase knockout mice have shown that chondrogenesis requires this vitamin D metabolite (St-Arnaud et al, 1996;St-Arnaud, 1999). In addition, putative basal-lateral membrane receptors for 24, 25-(OH) 2 D 3 have been identified in carp and Atlantic cod enterocytes (Larsson et al, 2001), and experiments showing that 24, 25-(OH) 2 D 3 is involved in regulating endochondral ossification (Dickson and Maher, 1985;Lidor et al, 1987;Wientroub et al, 1987;Miyahara et al, 1994), have led to the belief that 24-hydroxylated vitamin D metabolites can have important biologic effects. Since previously published studies have shown that vitamin D receptor (VDR) activation can alter apo A-I expression (Wehmeier et al, 2005(Wehmeier et al, , 2008, the effect of 25-OHD 3 and its two major metabolites, 1, 25-(OH) 2 D 3 and 24, 25-(OH) 2 D 3 , were examined.…”

Vitamin D in Foot and Ankle Fracture Healing

“…Still, some research supports supplementation of other forms of vitamin D. The less active 24,25-dihydroxyvitamin D 3 has been shown to produce similar, or perhaps improved, healing efficacy versus what 1,25-dihydroxyvitamin D 3 , notably when administered locally at the fracture site 39,40 and, while somewhat out of the scope of this article, other supplements and modalities have been hypothesized and tested with animal models, with varying degrees of success. Iwamoto et al 31 performed a study on femoral fractures in rats utilizing vitamin K 2 supplementation.…”

Effect of modulating dietary vitamin D on the general bone health of rats during posterolateral spinal fusion

“…A randomized clinical trial reported an increase in local bone mineral density in osteoporotic proximal humerus fractures with supplementation of both calcium and vitamin D(13). Animal studies have demonstrated accumulation of vitamin D within the fracture callus (20,21). Fu et al reported an increase in bone volume with administration of vitamin D in a rat model.…”