Treat Lapis Hypervitaminosis D
ISSN 2398-2969      

Hypervitaminosis D

C  lapis
Contributor(s):

Sarah Pellett

Lesa Thompson

Anna Meredith

Synonym(s): Vitamin D toxicity

Introduction

Pathogenesis

Etiology

  • Incorrectly formulated diets.
  • Overzealous supplementation with oral or injectable preparations.
  • Published requirements for vitamin D3 are 800-1000 IU/kg of diet; excess levels of vitamin D3 (>2000-3000 IU/kg) are associated with disease.

Predisposing factors

General

  • Access to incorrectly formulated diet.
  • Vitamin D has been added to excess.
  • Incorrect and unnecessary supplementation.
  • Access to rodenticide (vitamin D) preparations.

Pathophysiology

  • The exact pathophysiology of the soft tissue mineralization in rabbits is unknown. In arterial smooth muscle cells, excess vitamin D upregulates the 1,25-dihydroxyvitamin D3 receptor, resulting in toxicity via increased calcium uptake.
  • High vitamin D levels may also contribute to dental disease as reported in other exotic mammal species.
  • Cholecalciferol is metabolized to 25-hydroxycholecalciferol in the liver. 25-hydroxycholecalciferol is then metabolized to several metabolites within the kidney, one being calcitriol, which in most species is the potent metabolite enhancing calcium absorption from the gastrointestinal tract and calcium resorption from bones.
  • 25-hydroxycholecalciferol is the active metabolite in cholecalciferol toxicity -> results in hypercalcemia and hyperphosphatemia -> metastatic and dystropic mineralization of soft tissues.
  • Cardiovascular insufficiency causes ascites and lung edema. Experimental hypervitaminosis D in rabbits resulting in renal and pulmonary calcifications has been shown be have limited reversibility.
There are limited studies on reference values for serum 25(OH) vitamin D levels in rabbits, and levels for optimal health have not yet been established. In pet rabbits Mäkitaipale et al (2019) showed that the serum 25-hydroxyvitamin D concentrations among 140 rabbits varied between 5 and 68 ng/ml, with the large variation likely due to the differences in diet and housing. Other studies have reported ranges of 14.0-81.0 nmol/L (5.6-32.5 ng/ml) in nine rabbits participating in an artificial UVB light study, and  133.3 to >775.5 nmol/L (53 to >310 ng/ml) in 28 breeding rabbits fed on a diet high in vitamin D. Fairham and Harcourt-Brown (1999) measured 1.25(OH) vitamin D in 13 pet rabbits and one wild rabbit, and found that levels ranged from undetectable to 65 pmol/litre (28.9 ng/ml). The concentration in the wild rabbit was 58 pmol/litre (25.8 ng/ml).

Timecourse

  • Clinical signs of toxicity may take weeks to several years to become apparent in rabbits.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Mäkitaipale J, Sievänen H, Sankari S & Laitinen-Vapaavuori O (2019) Diet is a main source of vitamin D in Finnish pet rabbits (Oryctolagus cuniculus). J Anim Physiol Anim Nutr (Berl) 103 (5), 1564-1570 PubMed. Proença L M & Mayer J (2014) Prescription diets for rabbits. Vet Clin North Am Exotic Anim Pract 17 (3), 485-502 PubMed.
  • Jekl V & Redrobe S (2013) Rabbit dental disease and calcium metabolism–the science behind divided opinions. JSAP 54 (9), 481-490 PubMed.
  • Jekl V, Gumpenberger M, Jeklova E et al (2011) Impact of pelleted diet of different mineral composition on the crown size of mandibular cheek teeth and mandibular relative density in degus (Octodon degus)​. Vet Rec 168 (24), 641 PubMed.
  • Lebas F (2010) Vitamins in rabbit nutrition: Literature review and recommendations. World Rabbit Sci 8 (4), 185-192 ResearchGate.
  • Zanuzzi C N, Barbeito C G, Ortíz M L et al (2010) Glycoconjugate histochemistry in the small and large intestine of normal and Solanum glaucophyllum-intoxicated rabbits. Res Vet Sci 89 (2), 214-222 PubMed.
  • Fisher P G (2006) Exotic mammal renal disease: causes and clinical presentation. Vet Clin North Am Exot Anim Pract 9 (1), 33-67 PubMed.
  • Rajasree S, Umashankar P R, Lal A V et al (2002) 1,25-dihydroxyvitamin D 3 receptor is upregulated in aortic smooth muscle cells during hypervitaminosis D. Life Sci 70 (15), 1777-1788 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.
  • Kampheus J (1991) Calcium metabolism of rabbits as an aetiological factor for urolithiasis. J Nutr 121 (11 Suppl), S95-596 PubMed.
  • Hänichen T & Hermanns W (1990) [The question of reversibility of tissue calcification in enzootic calcinosis of cattle and in experimental hypervitaminosis D]. Deutsche Tierarztliche Wochenschrift 97 (11), 479-482 PubMed.
  • Zimmerman T E, Giddens W E Jr., DiGiacomo R F et al (1990) Soft tissue mineralisation in rabbits fed a diet containing excess vitamin D. Lab Anim Sci 40 (2), 212-215 PubMed.
  • Warren H B, Lausen N C C, Segre G V et al (1989) Regulation of calciotropic hormones in vivo in the New Zealand White rabbit. Endocrinology 125 (5), 2683–2690 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.

Other sources of information

  • Orcutt C (2014) Cardiovascular Disease. In: BSAVA Manual of Rabbit Medicine. Eds: Meredith A & Lord B. BSAVA, Gloucester. pp 205-213.
  • Prebble J (2014) Nutrition and Feeding. In: BSAVA Manual of Rabbit Medicine.  Eds: Meredith A & Lord B. BSAVA, Gloucester. pp 205-213.
  • Raymond J L (2013) Pathology of the Rabbit. Presented at the 56th Annual Pathology of Laboratory Animals Course. Website: http://www.cldavis.org/cgi-bin/download.cgi?pid=1071 Last Accessed 18th February 2016.
  • Klaphake E & Paul-Murphy J (2012) Disorders of the Reproductive and Urinary System. 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 Fact Sheets. ANZCCART News 7 (4).

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