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Small Mammal Medicine: Rabbit:
Calcium Homeostasis in the Rabbit

Author: Sharon Redrobe, BSc (Hons), BVetMed CertLAS, DZooMed MRCVS
RCVS Specialist in Zoo and Wildlife Medicine; University of Nottingham School of Veterinary Medicine and Twymcross Zoo, Sutton Bonington & Warwickshire, United Kingdom

Date: March 15, 2010

Key words: Rabbit, calcium, parathyroid hormone, vitamin D, calcitriol, calcitonin, urolithiasis, urine, crystal

Key Points

  • Most mammals maintain blood calcium levels within a narrow range by controlling the absorption of calcium from the diet according to need.
  • Rabbits possess unique calcium metabolism. Blood calcium levels vary substantially with the calcium content of the diet. Rabbits absorb nearly all calcium ingested and excrete the excess by means of the kidneys.
  • Calcium precipitates in the alkaline urine of the rabbit and is excreted as insoluble crystalline salts in thick, cloudy, white urine or “bladder sludge”.
  • “Bladder sludge” in rabbits is principally composed of calcium phosphate or calcium carbonate crystals.
  • A massive aggregation of crystals may form a concretion or urolith within the urinary bladder over a matter of weeks.
  • Recommend low-calcium, grass-hay based diets for maintenance diets in adult rabbits.

Introduction

Calcium is the most abundant mineral in the body, and the majority of total body calcium is found within bones and teeth. Most mammals make only one or two sets of teeth in a lifetime, however rabbit (Oryctolagus cuniculus) teeth continually grow throughout their lifetime. This continual tooth eruption plays an important role in the rabbit’s long-term calcium needs.

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Hormonal regulation of calcium

Two hormones work together to keep blood calcium levels optimally balanced in most mammals: parathyroid hormone (PTH) and calcitonin (Table 1). When blood calcium levels approach the low end of the normal range, the parathyroid gland secretes PTH. PTH then stimulates the activity of alpha-hydroxylase within the renal tubules, which in turn increases the synthesis of the active form of vitamin D, 1,25-dihydroxycholecalciferol or calcitriol. Increased vitamin D synthesis promotes intestinal absorption of calcium and phosphorous for 24 to 48 hours.

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Table 1: Hormones involved in regulation of blood calcium levels in mammals

Effect Calcitonin Parathyroid hormone (PTH) Vitamin D
Net Effect on blood levels Ca

P

Ca

P

Ca

P

BONE (+) osteoblasts (+) osteoclasts* (+) osteoclasts
KIDNEY ↓Ca/P resorption ↑Ca absorption

↓P resorption

(+) Vit D synthesis

↑Ca/P resorption

INTESTINES ↑Ca absorption

* Small amounts of vitamin D are needed for PTH to have an effect on bone.

The thyroid gland produces calcitonin (Table 1) in response to elevations in blood calcium. Calcitonin promotes calcium withdrawal from the blood, increasing the absorption of calcium in bone.

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Calcium metabolism in rabbits

Calcium metabolism is unique in the rabbit. Unlike other mammals, blood calcium levels fluctuate widely. Intestinal absorption of calcium is virtually complete, making serum calcium levels proportional to dietary calcium intake. Both ionized and total serum calcium concentrations are elevated in the rabbit compared with those in other species (ionized calcium, 3.4 + 0.26 mEq/L; total calcium, 12.92 + 1.0 mg/dL). In most mammals, hypercalcemia is abnormal and may lead to renal damage or soft tissue calcification. Rabbits seem to tolerate relative hypercalcemia, although in rare instances persistently elevated blood calcium levels can result in soft tissue calcification even in the rabbit.

Because high dietary calcium levels produce high blood calcium levels in the rabbit, this suggests that calcitonin does not lower blood calcium. Since rabbits on a high calcium diet absorb and subsequently excrete large amounts of calcium, vitamin D metabolism has also been suggested to be unique. Calcium is readily absorbed from the gut in rabbits and may not require the action of vitamin D at all unless dietary calcium levels are restricted.

Changes in PTH occur at relatively high serum calcium levels in the rabbit. This suggests that the rabbit parathyroid gland is also reset to respond to changes in ionized calcium within the physiological range for that species. In other species, this relative insensitivity of the rabbit parathyroid gland to extracellular calcium would be analogous to primary hyperparathyroidism.

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Dietary calcium levels

An ideal pet rabbit diet is high in fiber (20-25%), low in fat (1%-3%), with a moderate protein level (12%-13%). Many commercial rabbit pellets are formulated from alfalfa meal, which contains calcium carbonate, a highly absorbable form of calcium. Alfalfa-based pellets are high in calcium, containing approximately 1.5% calcium.

For optimal health, an adult maintenance diet should contain sufficient, but not excessive, calcium (0.5%-1%) and the Ca:P ratio should be balanced between 1.2:1 to 2 :1. A suitable diet must also contain vitamin D, which may be added to pellets or provided in dried vegetation such as hay. Commercial low-calcium diets that use timothy meal produce a pellet containing 0.4-0.8% calcium (i.e. Bunny Basics/T, Oxbow Hay Company).

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Calcium and dental disease

Many pet rabbits suffer from dental abnormalities. The role of dietary calcium and vitamin D in the pathogenesis of dental disease remains controversial, and there are conflicting reports in veterinary medical literature. Dietary calcium has also been suggested to modulate periodontal disease in humans. Low dietary intake of calcium may result in more severe periodontal disease.

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Calcium metabolism and urolithiasis

Most mammals efficiently excrete excess calcium in bile and intestinal secretions, however rabbits filter excess calcium through their kidneys

and excrete it in urine. Similar patterns of urinary calcium excretion have been demonstrated in pikas (Ochotona spp.) and jackrabbits (Lepus spp.). When rats and rabbits are fed the same high-calcium diet, rats excrete 93% of ingested calcium in feces while rabbits excrete 60% of excess calcium in the urine. A 2-kg rabbit can excrete more urinary calcium than an adult human.

Rabbits on a high-calcium diet maintain the same urine volume but the calcium concentration in the urine increases. The rate of tubular calcium reabsorption in rabbits ranges from 40% to 94%, and is generally much lower than the 97% value in humans and dogs. Once the rabbit kidney has reached it relatively limited capacity for reabsorption, calcium precipitates within the urine. Calcium is excreted as insoluble crystalline salts in thick, cloudy, white urine or “bladder sludge” or “sand”. The alkaline pH of rabbit urine increases the likelihood of calcium precipitation.

“Bladder sludge” in rabbits is principally composed of calcium phosphate or calcium carbonate crystals. Calcium oxalate is seen less commonly since rabbits do not readily absorb calcium-bound oxalate. Heavy bladder sludge may promote hematuria and stranguria, and a massive aggregation of crystals may also progress within a few weeks to form a concretion or urolith within the urinary bladder. Discrete stones within the ureters and kidney are rare. This correlation between dietary calcium and bladder sludge or urolithiasis is the primary reason many small mammal veterinarians recommend low-calcium diets based on grass hays.

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Summary

Calcium metabolism is unique in the rabbit. Most mammals use vitamin D or calcitriol, parathyroid hormone, and calcitonin to maintain a consistent serum calcium level. In mammals other than rabbits, calcium absorption from the intestine is primarily controlled by vitamin D and PTH. Rabbits, have adopted a unique strategy in which most dietary calcium is absorbed and excess calcium is excreted by means of the kidneys. Therefore blood calcium levels vary substantially with the dietary calcium content. Urinary excretion of calcium varies with blood calcium levels as well, and rabbits are at increased risk of bladder sludge and urolithiasis on alfalfa-based, high-calcium diets.

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References

Eckermann-Ross C. Hormonal regulation and calcium metabolism in the rabbit. Vet Clin North Am Exot Anim Pract 11(1):139-152, 2008.

Harcourt-Brown FM, Baker SJ. Parathyroid hormone, haematological and biochemical parameters in relation to dental disease and husbandry in rabbits. J Small Anim Pract 42(3):130-136, 2001

Harcourt-Brown FM. Calcium deficiency, diet and dental disease in pet rabbits. Vet Rec 139(23):567-571, 1996

Kiliaridis S, Engström C, Lindskog-Stokland B, et al. Craniofacial bone remodeling in growing rats fed a low-calcium and vitamin-D-deficient diet and the influence of masticatory muscle function. Acta Odontol Scand 54:320-326, 1996

Nishida M, Grossi SG, Dunford RG, et al. Calcium and the risk for periodontal disease. J Periodontol 71(7):1057-1066, 2000

Norris SA, Pettifor JM, Gray DA, Buffenstein R. Calcium metabolism and bone mass in female rabbits during skeletal maturation: effects of dietary calcium intake. Bone 29(1):62-69, 2001

Redrobe S. Calcium metabolism in rabbits. J Exotic Pet Med 11(2):94-101, 2006.

Shell LG, Saunders G. Arteriosclerosis in a rabbit. J Am Vet Med Assoc 194 (5):679-680, 1989.

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