Lapis ISSN 2398-2969

Hypovitaminosis D

Synonym(s): Vitamin D deficiency

Contributor(s): Sarah Pellett, Lesa Thompson

Introduction

  • Vitamin D maintains serum calcium levels within the normal range by its effects on intestinal absorption of calcium, mobilization of calcium to and from bone, and by regulating renal excretion of calcium.
  • Rabbits have a unique calcium metabolism which differs from other mammals.
  • If diets are sufficient in calcium, then calcium absorption in rabbits is not dependent on vitamin D3.
  • The main mechanism for calcium absorption in rabbits is passive diffusion from the gastrointestinal tract. The concentration gradient between the intestinal lumen and blood allows this process to occur and is directly related to dietary calcium concentration.
  • Phosphorus absorption is regulated by vitamin D.
  • Parathyroid hormone (PTH) and vitamin D3 mediate calcium preservation and excretion by the kidney.
  • Variable levels of vitamin D are present in hay.
  • Vitamin D is synthesized in the skin in the presence of UVB light.
  • If calcium-deficient diets are fed, vitamin D will increase calcium absorption by active transport.  Active transport requires a carrier protein which is synthesized in the intestinal mucosa in response to 1,25-dihydroxyvitamin D3.
  • Cause: inadequate dietary intake of exogenous vitamin D precursors and/or insufficient exposure to natural sunlight Nutrition: dietary requirements.
  • Signs: clinical signs associated with metabolic bone disease or dental disease.
  • Diagnosis: clinical examination, plasma biochemistry, 1,25-dihydroxycholecalciferol assay, diagnostic imaging.
  • Treatment: supportive care and address husbandry.
  • Prognosis: poor to guarded, depending on severity and duration.

Pathogenesis

Etiology

  • Published requirements for vitamin D3 are 800-1200 IU/kg of body weight.  
  • Hypovitaminosis D can arise from:
    • Inadequate dietary intake of exogenous vitamin D precursors.
    • Lack of or insufficient exposure to natural sunlight (UVB), essential for conversion of endogenous precursors.

Predisposing factors

General

  • Rabbits kept in hutches without access to sunlight.
  • House rabbits without access to sunlight.
  • Selective feeders on a poor (muesli-based) diet without access to hay.

Pathophysiology

  • 7-dehydrocholesterol (an endogenous vitamin D precursor) is converted to pre-vitamin D3 in skin that is exposed to ultraviolet light. It is then converted to cholecalciferol (vitamin D3) before it is bound to plasma protein and transported to the liver.
  • Plants contain ergosterol (a vitamin D precursor) which is converted to ergocalciferol (vitamin D2) by sunlight; this occurs in hay as it dries in the sunlight.  Vitamin D2 is ingested and is transported from the gastrointestinal tract to the liver.
  • Both vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) are hydroxylated to form 25-hydroxycholecalciferol. This is converted by parathyroid hormone (PTH) in response to low serum calcium to the active vitamin D metabolite (1,25-dihydroxycholecalciferol) in the kidney.
  • In most species, low amounts of vitamin D -> reduction of calcium absorption from the intestine and renal conservation of calcium -> decrease in blood calcium levels -> stimulation of PTH from parathyroid glands -> bone resorption. This results in calcium release and restoration of blood calcium levels to normal range.
  • In the rabbit, if the diet is sufficient in calcium then hypovitaminosis D will not prevent intestinal absorption of calcium. However, if the diet is deficient in calcium then vitamin D is essential for the active transport of calcium from the intestines.
  • In the rabbit, vitamin D is essential for phosphorus metabolism and deficiency results in a decrease in intestinal absorption of phosphorus -> hypophosphatemia.

Timecourse

  • Approximately 5 months for serum concentrations of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol to become undetectable in rabbits fed a vitamin D-deficient diet and with no access to UVB.
  • 1,25-dihydroxycholecalciferol in serum was below the limit of detection (<2.5pmol/l) in rabbits the spring after they were confined in a hutch throughout the winter period. By comparison, rabbits with unrestricted access to sunlight throughout winter had significantly higher 1,25-dihydroxycholecalciferol concentrations.

Diagnosis

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Treatment

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Prevention

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Proença L M & Mayer J (2014) Prescription diets for rabbits. Vet Clin North Am Exotic Anim Pract 17 (3), 485-502 PubMed.
  • Harcourt-Brown F M & Baker S J (2001) Parathyroid hormone, haematological and biochemical parameters in relation to dental disease and husbandry in pet rabbits. J Small Anim Pract 42 (3), 130-136 PubMed.
  • Fairham J & Harcourt-Brown F M (1999) Preliminary investigation of the vitamin D status of pet rabbits. Vet Rec 145 (16), 452-454 PubMed.
  • Rohde C M, Manatt M, Clagett-Dame M et al (1999) Vitamin A antagonises the action of vitamin D in rats. J Nutr 129 (12), 2246-2250 PubMed.
  • Harcourt-Brown F M (1996) Calcium deficiency, diet and dental disease in pet rabbits. Vet Rec 139 (23), 567-571 PubMed.
  • Brommage R, Miller S C, Langman C B et al (1988) The effect of chronic vitamin D deficiency on the skeleton in the adult rabbit. Bone 9 (3), 131-139 PubMed.
  • Bourdeau J E, Shwer-Dymerski D A, Stern P H et al (1986) Calcium and phosphorus metabolism in chronically vitamin D-deficient laboratory rabbits. Min Elec Metab 12 (3), 176-185 PubMed.
  • Nyomba B L, Bouillon R & De Moor P (1984) Influence of vitamin D status on insulin secretion and glucose tolerance in the rabbit. Endocrinol 115 (1), 191-197 PubMed.
  • Curry O B, Basten J F, Francis M J et al (1974) Calcium uptake by sarcoplasmic reticulum of muscle from vitamin D deficient rabbits. Nature 249 (452), 83-84 PubMed.
  • Kato J (1966) Effects of the administration of vitamin D2, D3, parathyroid hormone and calcium on hypocalcification of rabbit dentine and on changes in blood constituents caused by experimental rickets. Gunma J Med Sci 15 (3), 174-193 PubMed.

Other sources of information

  • Varga M (2014) Rabbit Basic Science.In: Textbook of Rabbit Medicine. 2nd edn. Butterworth Heinemann Elsevier, Edinburgh. pp 103-108.
  • Varga M (2014) Dental Disease. In: Textbook of Rabbit Medicine.  2nd edn.  Butterworth Heinemann Elsevier, Edinburgh. pp 203-248.
  • Prebble J (2014) Nutrition and feeding. In: BSAVA Manual of Rabbit MedicineEds: A Meredith & B Lord. BSAVA, Gloucester. pp 205-213.
  • Raymond J L (2013) Pathology of the Rabbit. Presented at the 56th Annual Pathology of Laboratory Animals course.
  • Klaphake E & Paul-Murphy J (2012) Disorders of the Reproductive and Urinary Systems. In: Ferrets, Rabbits and Rodents: Clinical Medicine and Surgery. 3rd edn. Eds: Quesenberry K E & Carpenter J W. W B Saunders Co, Philadelphia. pp 223-229.
  • Harris I (1994) The laboratory rabbit. ANZCCART fact sheets. ANZCCART News 7 (4).


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