Vitamin D Metabolism and Rickets in Domestic Animals

Abstract

Rickets and osteomalacia are increasing in prevalence in people because of cultural practices, breast-feeding, decreased sun exposure, and increased sunscreen usage. Several hereditary forms of rickets owing to either renal phosphate wasting or defects in vitamin D metabolism are also reported in people. Rickets is well recognized in domestic animals, but published reports are not always supported by microscopic findings, and diagnoses based on clinical signs and radiology are unreliable. Most cases in domestic animals are caused by dietary deficiency of either vitamin D or phosphorus, but occasional inherited forms are reported in pigs, sheep, cats, and dogs. There is variation between species in susceptibility to dietary vitamin D and phosphorus deficiency and in the ability to manufacture vitamin D in their skin. A number of mouse models have been discovered or created to study human skeletal diseases and skeletal homeostasis. With the discovery that vitamin D is involved in not only calcium and phosphorus homeostasis but also in the immune system and cancer, there is great potential for new and existing animal models to generate valuable information about vitamin D and its many functions. This review presents an overview of vitamin D metabolism and rickets in domestic and laboratory animals and makes comparisons where appropriate with the disease in humans. Keywords bone, rickets, vitamin D, phosphorus, genetic diseasesRickets is a classic metabolic bone disease of humans and animals, first described in the first and second centuries. 158,165 With the discovery that vitamin D could prevent rickets, the prevalence of this disease in developed countries plummeted; however, it still occurs. In fact, the prevalence of rickets and vitamin D insufficiency is increasing in people of all ages in the developed world, due in part to decreased sunlight exposure and widespread sunscreen usage. 88 The disease is well recognized in animals, but published reports are uncommon and sometimes confusing.The pathogenesis of rickets involves impaired mineralization of physeal and epiphyseal cartilage during endochondral ossification and of newly formed osteoid. Most cases in domestic animals are caused by dietary deficiency of either vitamin D or phosphorus, but occasional inherited forms are reported. 109,200 Osteomalacia is caused by a failure of newly formed osteoid to mineralize, but it occurs in adults after closure of growth plates. 109In this article, we review vitamin D metabolism and rickets, with reference to the disease in domestic animals but presenting comparison with the disease in humans where appropriate. Biology of Vitamin D Activation of Vitamin DVitamin D is available from two sources: isomerization of 7-dehydrocholesterol (7-DHC) in the skin to vitamin D 3 following exposure to ultraviolet light or from ingestion of vitamin D 2 or D 3 in the diet. Only a few foods, including cod liver oil and fatty fish such as salmon and sardines, naturally contain high concentrations of vitamin D 3 .49 Vitamin D 2 i...

Fibroblast Growth Factor 23

“…Substantial work is required to determine if the phosphatonin pathways of veterinary species are similar to those in humans; certainly, we know that there are differences in vitamin D metabolism, 42 and so it stands to reason that given evolutionary adaptation, differences may also occur in the phosphatonin system.…”

“…3 Rickets and osteomalacia are syndromes of deficient calcium and phosphorus deposition in osteoid during bone synthesis. 42 Failure of normal mineralization in the physeal or articular cartilage of children leads to rickets, characterized by thickening and flaring of physes, bowing of long bones, bone and joint pain, delayed growth, delayed standing or walking, frequent falling, and even seizures due to hypocalcemia. 188,206 Osteomalacia is observed in adults and leads to more occult signs such as bone pain, gait instability, muscle weakness, and pathological fractures.…”

“…41 Most cases of inherited rickets described in domestic animals, however, involve defects in vitamin D metabolism or function, particularly mutations in the vitamin D receptor. 42 The existence of a phosphatonin system in dogs comparable to that in humans was suggested by an early study in which a 6-week-old puppy developed phosphaturia after being injected with an extract from a tumor that caused TIO in a human patient. 8 This result suggests that a phosphatonin bone-renal axis probably occurs in the dog.…”

Investigation of the bone metabolism in dogs with leishmaniasis

“…It has been shown in the investigations that vitamin D is closely related to calcium and phosphor homeostasis, and plays a significant role in the bone model formation (Dittmer and Thompson 2011). In the study of Driel et al (2006) conducted in order to investigate the autocrine/paracrine function of 1α, 25-OH-D 3 , it was determined that 1α-hy-droxylase is expressed in the human osteoblasts, and also there are megalin and cubilin protein receptors bound to vitamin D. It was observed that osteoblasts produced 1α, 25-(OH)2D 3 , and ALP and osteocalcin expressions increased mildly with the addition of 25-OH-D 3 as a substrate to the osteoblast cell cultures while it did not have any effect on Ca and parathyroid hormone regulation.…”

“…The main activation stage in the vitamin D metabolism takes place in the kidneys and is catalyzed by 25-hydroxycalciferol--1α-hydroxylase. 1,25 dihydroxycholecalciferol (1,25 dihydroxyvitamin D) formed as a result of this hydroxylation is the most active form of vitamin D and it is responsible for all the effects of vitamin D (Gow et al 2011, Dittmer andThompson 2011).…”