A novel CYP27B1 mutation causes a feline vitamin D-dependent rickets type IA

A 12-week-old domestic cat presented at a local veterinary clinic with hypocalcemia and skeletal abnormalities suggestive of rickets. Osteomalacia (rickets) is a disease caused by impaired bone mineralization leading to an increased prevalence of fractures and deformity. Described in a variety of species, rickets is most commonly caused by vitamin D or calcium deficiencies owing to both environmental and or genetic abnormalities. Vitamin D-dependent rickets type 1A (VDDR-1A) is a result of the enzymatic pathway defect caused by mutations in the 25-hydroxyvitamin D(3)-1-alpha-hydroxylase gene [cytochrome P27 B1 (CYP27B1)]. Calcitriol, the active form of vitamin D(3), regulates calcium homeostasis, which requires sufficient dietary calcium availability and correct hormonal function for proper bone growth and maintenance. Patient calcitriol concentrations were low while calcidiol levels were normal suggestive of VDDR-1A. The entire DNA coding sequencing of CYP27B1 was evaluated. The affected cat was wild type for previously identified VDDR-1A causative mutations. However, six novel mutations were identified, one of which was a nonsense mutation at G637T in exon 4. The exon 4 G637T nonsense mutation results in a premature protein truncation, changing a glutamic acid to a stop codon, E213X, likely causing the clinical presentation of rickets. The previously documented genetic mutation resulting in feline VDDR-1A rickets, as well as the case presented in this research, result from novel exon 4 CYP27B1 mutations, thus exon 4 should be the initial focus of future sequencing efforts.     

Management and prevention of vitamin D deficiency rickets in captive-born juvenile chimpanzees (Pan troglodytes).

Vitamin D deficiency rickets was diagnosed in three juvenile chimpanzees (Pan troglodytes) raised indoors under skylights and consuming only breast milk. Two cases detected early had mild but characteristic radiographic changes. More advanced disease presented with florid x-ray features of rickets and pathologic fractures, as well as hypocalcemia, hypophosphatemia, and low serum 25-hydroxyvitamin D levels. Treatment by a single injection of vitamin D2 in sesame oil (slow release) followed by daily oral supplementation with vitamin D2 corrected the condition. On the basis of experience with these cases and comparison with rickets in humans, a prevention protocol for mother-reared, inside-housed, chimpanzee juveniles was developed. Injection with slow release vitamin D2 (5,000 IU i.m. once) at 4 mo of age, followed by oral supplementation of 400 IU vitamin D2 daily until weaning, prevents rickets in juvenile chimpanzees raised indoors.     

Vitamin D-dependent rickets type 2 in a four-month-old cat

Vitamin D-dependent rickets type 2 in a four-month-old cat A 4-month-old male domestic shorthair cat was examined because of lethargy, vomiting, diarrhea, muscle tremors, and mydriasis. Laboratory evaluation revealed hypocalcemia, hyperphosphatemia, and high intact parathormone and calcitriol concentrations. Findings were compatible with a diagnosis of vitamin D-dependent rickets type 2. Treatment consisted of oral administration of calcium and calcitriol supplements. During the subsequent 18 months, the cat remained clinically normal. Treatment with oral calcium supplements was eventually discontinued, and the cat was able to maintain serum calcium concentrations within reference limits.     

Vitamin D-dependent non-type 1, non-type 2 rickets in a 3-month-old Cornish Rex kitten

CASE PRESENTATION AND ASSESSMENT: A 3-month-old female Cornish Rex kitten was found to have non-painful swelling of the carpal and tarsal regions when presented for routine neutering. The kitten was smaller in stature and less active than its siblings and, according to the owner, had a bunny-hopping gait, was reluctant to climb stairs and strained during defecation. Radiography of the affected limbs and a subsequent radiographic survey of the entire skeleton demonstrated features consistent with rickets. The three littermates were clinically and radiographically normal. As a nutritionally complete diet was being fed, it seemed most likely that the kitten had an inborn error related to vitamin D metabolism. Serum biochemistry demonstrated reduced total alkaline phosphatase activity and increased concentrations of parathyroid hormone. Concentrations of 1,25- and 25-hydroxycholecalciferol were markedly reduced, confirming the diagnosis of rickets. TREATMENT: The kitten was treated with calcitriol, administered orally once daily, and improved rapidly both clinically and radiologically. Serial laboratory studies suggested that the error in vitamin D metabolism was transient, and, at the time of writing, as an adult, the cat appears to require no ongoing replacement calcitriol therapy. CLINICAL RELEVANCE: This case emphasises the value of examining a full 'calcium profile' via a human or veterinary reference laboratory, and a favourable prognosis in some kittens with rickets makes such investigations worthwhile. Even when finances preclude detailed investigation, trial therapy using a nutritionally complete diet and physiological doses of calcitriol or cholecalciferol is inexpensive and can produce a good response.     

Vitamin D-dependent rickets type II in a cat

A cat with clinical signs Indicating rickets was diagnosed as having a defect of vitamin D receptors. Clinical signs had been seen from four months of age. Treatment with calcium supplementation and various forms of vitamin D did not alter plasma calcium levels or reverse skeletal lesions of lateral antebrachial bowing, lumbar spinal lordosis and costochondral beading. Analgesics were effective for relieving skeletal pain during the bone growth phase and were withdrawn when the animal reached skeletal maturity. Therapy for hip osteoarthritis was given from five years of age until the cat was euthanased at nine years of age as a result of refractory hip pain.     

Normal vitamin D receptor function with increased expression of 25-hydroxyvitamin D(3)-24-hydroxylase in Corriedale sheep with inherited rickets

A likely inherited disease with gross and microscopic features of rickets has been recognised in Corriedale sheep in New Zealand, and a defect in end-organ responsiveness to vitamin D has been proposed as a likely mechanism. The aim of the present study was to characterize the mode of inheritance and determine the disease mechanism. Breeding trials showed that the mode of inheritance was autosomal recessive. Serum chemistry testing using different methodology and studies in cultured skin fibroblasts did not support our previous hypothesis of a defect in end-organ responsiveness. The studies revealed normal serum 1,25-dihydroxyvitamin D concentrations, normal vitamin D receptor function, and the presence of 24-hydroxylase mRNA in cells from affected sheep, even without induction by 1,25-dihydroxyvitamin D₃. In addition, osteocalcin mRNA expression was similar in both affected and control sheep. It was concluded that increased expression of 25-hydroxyvitamin D₃-24-hydroxylase, the enzyme that breaks down vitamin D, may be involved in the pathogenesis of inherited rickets in Corriedale sheep, but its role requires further clarification.     

Chronic ingestion of high concentrations of cholecalciferol in cats

OBJECTIVE: To determine whether ingestion of 63 times the recommended amount of vitamin D3 (cholecalciferol) results in renal calcification or damage in cats. ANIMALS: 20 four-month-old kittens, 17 queens, and 20 kittens born to these queens. PROCEDURE: 4-month-old kittens and queens were given a purified diet with 846 microg of cholecalciferol/kg of diet (high vitamin D3 diet) or 118 microg of cholecalciferol/kg of diet (control diet) for 18 months. Kittens born to queens were weaned onto the same diet given to dams. RESULTS: There were no apparent adverse effects of the high vitamin D3 diet. Plasma cholecalciferol and 25-hydroxycholecalciferol (25-OHD3) concentrations of queens and 4-month-old kittens given the high vitamin D3 diet significantly increased with time. At 6 months, plasma cholecalciferol concentrations in these kittens and queens were 140.0+/-7.3 nmol/L and 423.6+/-26.6 nmol/L, respectively (10 times initial values). Corresponding 25-OHD3 concentration in queens was 587.5+/-59.4 nmol/L (2.5-fold increase over initial values). At 3 months of age, kittens born to queens given the high vitamin D3 diet had an increase in serum BUN and calcium concentrations and a decrease in RBC and serum total protein, albumin, and hemoglobin concentrations. By 18 months, these kittens had an increase in plasma cholecalciferol (276.0+/-22.2 nmol/L) and 25-OHD3 (1,071.9+/-115.3 nmol/L) concentrations. However, all indices of renal function and the appearance of renal tissue on histologic evaluation were normal. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that cats are resistant to cholecalciferol toxicosis when the diet is otherwise complete and balanced.     

Rickets in turkey poults

Fifteen outbreaks of rickets were diagnosed in turkey poults in Saskatchewan between 1978 and 1981. No relationship to farm, source of poults, or source of feed was apparent. Most outbreaks started when the poults were between 10 and 14 days of age, and they had recovered by 28 days of age. Losses varied from 1% to 14% of poults started. Skeletal lesions were characteristic of a vitamin D or calcium deficiency. On the basis of chemical analyses, adequate levels of calcium and phosphorus and proper amounts of vitamin premixes were present in the feed, but in five outbreaks biological feed tests implicated feed as a causative factor. The severity of rickets in poults fed defective feeds was markedly reduced by providing the poults with extra vitamin D in the drinking water or by injection. Two premixes used in different feeds contained adequate available vitamin D on the basis of biological testing. In some of the outbreaks, the rickets may have resulted from inadequate distribution of vitamin D in the feed, destruction of vitamin D during feed processing, or some unknown factor in the feed interfering with vitamin D utilization.     

The effect of dietary vitamin D supplementation on sodium-dependent phosphate uptake and expression of NaPi-IIb in the small intestine of weanling pigs

Two experiments were conducted to investigate the effects of 1,25(OH)₂D₃ to stimulate Na⁺-dependent phosphate uptake in Caco-2 cells, and the effects of dietary vitamin D supplementation to vitamin D-deficient nursery pigs on Na⁺-dependent nutrient uptake and mRNA expression of NaPi-IIb cotransporter and calbindin D9k in the jejunum. In Exp. 1, 250,000 Caco-2 cells were seeded on Costar 12 mm Snapwell inserts with a 0.40 µm polycarbonate filter and a seeding density of 0.25 × 10⁶ and studied at 15 d postconfluence. Cells were treated with 10 nM of either 1,25(OH)₂D₃ or vehicle for 48 h and then mounted in modified Ussing chambers for transepithelial measurements. In Exp. 2, pigs (n = 32) were removed from sows at 3 d of age, placed on a vitamin D-deficient milk replacer diet and housed in a room devoid of sunlight and UV light in the range of 280 to 300 nm. On day 28, serum 25(OH)D₃ concentrations were measured to verify low vitamin D status. Pigs (BW 10.10 ± 0.38 kg) were then individually housed day 28 postweaning and allotted to 1 of 2 dietary treatments. Dietary treatments consisted of corn-soybean-based diets with vitamin D supplementations of 0 or 1,500 IU/kg diet for 12 d. Blood samples were taken from the brachiocephalic vein on the initial (day 0) and final day (day 10, 11, or 12) of the study for analysis of serum 25(OH)D₃, P, and Ca. Pigs were euthanized and jejunal segments were harvested and used in modified Ussing chambers and for RNA isolation and subsequent quantitative RT-PCR analysis. In Exp. 1, treating Caco-2 cells with 10 nM 1,25(OH)₂D₃ resulted in a 52% increase (P < 0.005) in Na⁺-dependent phosphate uptake compared with cells treated with a vehicle. In Exp. 2, Na⁺-dependent phosphate and glucose transport did not differ (P > 0.10) among treatment groups. Additionally, NaPi-IIb and calbindin D9k mRNA expression were not different (P > 0.10) between treatment groups. No differences (P > 0.10) were detected in final serum P or 25(OH)D₃ concentrations between treatments. However, serum Ca linearly increased (P < 0.05) as the concentration of supplemental vitamin D increased in the diet. Overall, while 1,25(OH)₂D₃ stimulated Na⁺-dependent phosphate uptake in Caco-2 cells, supplementing diets with 1,500 IU/kg vitamin D₃ from cholecalciferol did not increase jejunal Na⁺-dependent phosphate uptake or NaPi-IIb mRNA expression over that of pigs fed diets with no supplemental cholecalciferol.     

Vitamin D doses for alpacas (Lama pacos)

OBJECTIVE: To assess the effectiveness of cholecalciferol (D3) doses for maintaining adequate vitamin D status in crias and adult female alpacas at pasture. DESIGN: A field experiment during winter and early spring in a herd on a farm in South Australia. ANIMALS AND PROCEDURE: Crias, usually less than 6 months of age and female alpacas, aged 2 to 6 years, were given a single subcutaneous dose of 0, 1000 or 2000 IU D3/kg body weight. Plasma concentrations of 25-hydroxycholecalciferol (25-OH D3), phosphorus, calcium and vitamins A and E and alkaline phosphatase activity were measured at intervals over a period of 16 weeks after treatment. RESULTS: Crias not given a vitamin D supplement had reduced growth rate during winter and one animal showed clinical signs of rickets. Vitamin D treatment had no effect on the body weight of mature females. Vitamin D supplements increased the 25-OH D3 and phosphorus concentrations in plasma of both crias and adult females; alkaline phosphatase activity was not affected by treatment. CONCLUSION: It is suggested that for alpacas in southern Australia a subcutaneous dose of 1000 IU D3/kg body weight to crias in late autumn and again in mid winter and to adult females in mid winter should prevent vitamin D inadequacy.     

Seasonal changes in serum calcium, phosphorus, and vitamin D concentrations in llamas and alpacas

OBJECTIVE: To evaluate the interaction of season and age on serum calcium, phosphorus, and vitamin D3 concentrations in llamas and alpacas. ANIMALS: 23 clinically normal llamas and 7 alpacas. PROCEDURES: Animals were assigned to 1 of the 3 following groups on the basis of age at the start of the study: adult (age, > or = 24 months; n = 8), yearling (> 12 but < 20 months; 5), and neonate (< 6 months; 17). Twelve serum samples were obtained at monthly intervals. Calcium, phosphorus, and vitamin D3 concentrations were measured, and the calcium-to-phosphorus concentration (Ca:P) ratio calculated. Effect of season and age on each of these variables was determined. RESULTS: Vitamin D3 concentrations varied significantly as a function of season; the highest and lowest concentrations were detected September through October and February through March, respectively. The seasonal decrease in vitamin D3 concentration was significantly greater in neonates and yearlings, compared with adults. Serum phosphorus concentration decreased as a function of age, with the most significant seasonal change detected in the neonate group. The Ca:P ratio in neonates varied between 1.1 and 1.3 except during winter months when it increased to > or = 2.0. CONCLUSIONS AND CLINICAL RELEVANCE: Mean vitamin D3 concentration varied by > 6 fold in neonatal and yearling llamas and alpacas and > 3 fold in adult animals as a function of season. These results support the hypothesis that seasonal alterations in vitamin D3 concentrations are a key factor in the development of hypophosphatemic rickets in llamas and alpacas.     

Pathology of vitamin D deficiency in growing turkeys

Turkey poults were fed a vitamin D-deficient diet and examined for clinical signs and structural changes of bone and parathyroid glands. Vitamin D-deficient poults developed ricketic changes during days 10 to 14. Control poults (deficient diet plus vitamin D) did not develop rickets. In deficient poults, lengths of proliferating-prehypertrophied zones of growth plates increased significantly in the proximal tibiotarsus but were only slightly elongated in the distal tibiotarsus. Unmineralized hypertrophic chondrocyte zones increased in length rapidly in conjunction with a decrease in the length of mineralized hypertrophic degenerative zones; this occurred more rapidly in proximal than in distal tibiotarsus. Other ricketic changes included decreases in bone ash, total femoral bone ash (calcium, phosphorus, magnesium), bone length, and body weight. Plasma alkaline phosphatase was increased, calcium was normal, and phosphorus was normal or elevated. Parathyroids were hyperplastic and had foci of degeneration. Vitamin D3 metabolites 25OHD3, 1,25(OH)2D3, and 24,25(OH)2D3 were rapidly depleted. Increase in bone ash Ca/P ratios in deficient poults suggests that phosphorus may be selectively released from ricketic bone. Low 25OHD3 and 1,25(OH)2D3 of control poults early in the experiment suggests that 1,400 IU of vitamin D3/kg of feed may not be an adequate level of vitamin D3 for growing turkey poults.     

Extrahepatic biliary atresia in a border collie

Progressive lameness and leg pain were the predominant clinical signs in a 17-week-old male border collie presented for examination. On clinical investigation, extrahepatic cholestasis in association with rickets due to inadequate vitamin D resorption was diagnosed. The dog was treated parenterally with vitamin D and a cholecystoduodenostomy was performed. At 25 days postsurgery the lameness had resolved and bone structure was radiographically normal. However, at six weeks postsurgery, the dog's condition deteriorated rapidly and euthanasia was finally performed at eight weeks postsurgery. At postmortem examination, Toxocara canis nematodes were found to have invaded the biliary system via the anastomosis between the gallbladder and duodenum, causing biliary and hepatic toxocariasis. The cause of the primary extrahepatic cholestasis was atresia of the common bile duct at the hepatic end. The liver tissue showed microscopic lesions of chronic extrahepatic cholestasis as well as acute inflammation associated with the nematode invasion. There was no postmortem evidence of bone lesions. Extrahepatic biliary atresia is extremely rare in animals and has not been described before in dogs. In contrast, it represents the most common cause of congenital cholestasis in children, occurring in approximately one per 10,000 to 15,000 live births.     

Exacerbative effect of vitamin A on malabsorption syndrome in chicks

The interaction between malabsorption syndrome (MAS) and dietary vitamins A and D was studied in broiler chicks reared in floor pens for 4 weeks. The chicks were naturally infected with MAS, whereas hatchmates fed the same diets but in a separate facility (battery brooder) did not exhibit signs of MAS and, therefore, were considered controls. MAS significantly reduced body weights, bone ash, serum calcium and phosphorus concentrations, and liver lipids and increased the incidence of skeletal abnormalities (tibial dyschondroplasia and rickets). Rather than ameliorating the effects of MAS, vitamin A caused a further reduction in body weight and bone ash. A possible nutrient interaction between vitamin A and vitamin D or vitamin E in birds with MAS may account for the exacerbative effect of vitamin A.     

A probable case of hypoparathyroidism in a cat

Idiopathic hypoparathyroidism was suspected in a young female cat. The relevant historical and clinical findings were: anorexia, intermittent muscle tremors, hindlimb ataxia, behavioural changes and cataracts. Salient laboratory findings were: hypocalcaemia, hyperphosphataemia and normal renal function (normal serum urea and creatinine concentrations with hypersthenuria). No evidence of intestinal malabsorption, pancreatitis or nutritional secondary hyperparathyroidism was found. Treatment with oral synthetic vitamin D (1,25 dihydroxycholecalciferol) and intravenous and oral calcium supplements was successful in correcting the hypocalcaemia and abolishing the clinical signs.     

Serum concentrations of 1,25-dihydroxycholecalciferol and 25-hydroxycholecalciferol in clinically normal dogs and dogs with acute and chronic renal failure

OBJECTIVE: To compare serum concentrations of 1,25-dihydroxycholecalciferol (1,25-[OH]2D3) and 25-hydroxycholecalciferol (25-[OH]D3) in healthy control dogs and dogs with naturally occurring acute renal failure (ARF) and chronic renal failure (CRF). ANIMALS: 24 control dogs, 10 dogs with ARF, and 40 dogs with CRF. PROCEDURE: Serum concentrations of 1,25-(OH)2D3 were measured by use of a quantitative radioimmunoassay, and serum concentrations of 25-(OH)D3 were measured by use of a protein-binding assay. RESULTS: Mean +/- SD serum concentration of 1,25-(OH)2D3 was 153 +/- 50 pmol/L in control dogs, 75 +/- 25 pmol/L in dogs with ARF, and 93 +/- 67 pmol/L in dogs with CRF. The concentration of 1,25-(OH)2D3 did not differ significantly between dogs with ARF and those with CRF and was in the reference range in most dogs; however, the concentration was significantly lower in dogs with ARF or CRF, compared with the concentration in control dogs. Mean +/- SD concentration of 25-(OH)D3 was 267 +/- 97 nmol/L in control dogs, 130 +/- 82 nmol/L in dogs with ARF, and 84 +/- 60 nmol/L in dogs with CRF. The concentration of 25-(OH)D3 was significantly lower in dogs with ARF or CRF, compared with the concentration in control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The concentration of 1,25-(OH)2D3 was within the reference range in most dogs with renal failure. Increased serum concentrations of parathyroid hormone indicated a relative deficiency of 1,25-(OH)2D3. A decrease in the serum concentration of 25-(OH)D3 in dogs with CRF appeared to be attributable to reduced intake and increased urinary loss.     

An outbreak of rickets in Corriedale sheep: evidence for a genetic aetiology

CASE HISTORY: A skeletal disease characterised by lameness, limb deformities and reduced growth rate occurred over two successive years in lambs born on a commercial sheep farm in Marlborough. A genetic aetiology was considered likely following exclusion of other known causes of rickets and because of the progressive nature of the disease, even after affected animals were transferred to another property. CLINICAL FINDINGS: Affected lambs appeared normal at birth but developed clinical signs during the first 2 months of life. The most severely affected animals either died or were euthanised within the first year of life, but some survived to breeding age. Serum biochemistry revealed hypocalcaemia, hypophosphataemia and increased concentrations of 1,25 dihydroxyvitamin D. The mean serum 25 hydroxyvitamin D concentration was similar to that of control lambs. PATHOLOGICAL FINDINGS: Gross lesions included enlarged costochondral junctions, bilateral irregularity of articular surfaces on humeral heads due to collapse of subchondral bone, thickened cortices in long bones and irregular thickening of physeal cartilages. Microscopically, tongues of hypertrophic chondrocytes extended from physes into metaphyseal regions; metaphyseal trabeculae were thick, disorganised and often lined by wide osteoid seams. Osteoclastic activity was excessive both in cortical and trabecular bone. DIAGNOSIS: Inherited rickets in Corriedale sheep. CLINICAL RELEVANCE AND CONCLUSIONS: This disease is likely to be present in several Corriedale sheep flocks in New Zealand and may have been misdiagnosed as arthritis or other diseases causing lameness and/or poor growth. A defect in end-organ responsiveness to 1,25 dihydroxyvitamin D is the likely mechanism. This disease of sheep may be a useful model for studying vitamin D metabolism and the treatment of inherited forms of rickets in human beings.     

Rickets in a Thoroughbred-cross foal: case report and review of the literature

Rickets is a metabolic bone disease associated with failure of endochondral ossification and impaired osteoid mineralization in growing animals. As a consequence, affected individuals can develop gross and microscopic bone malformations. The most common causes of rickets in domestic species include vitamin D and phosphorus deficiency. Rickets has been described in multiple species; however, comprehensive postmortem characterizations with confirmatory histopathology in equids have not been published. A 6-mo-old, Thoroughbred-cross foal was diagnosed with rickets based on gross autopsy findings and microscopic examination of the ribs and long bones. Grossly, all costochondral junctions of the ribs were enlarged with a “rachitic rosary” appearance, and there were multiple fracture calluses in the rib bodies. Epiphyses and metaphyses of the long bones appeared widened on sagittal section, and their physes were irregularly thickened. Histologically, there were poorly organized columns of hypertrophic chondrocytes within the physes of affected bones, islands of chondrocytes embedded within the primary and secondary spongiosa, and faintly eosinophilic seams of poorly mineralized osteoid within the bone trabeculae. Areas of focally increased osteoclastic activity were observed in some of the sections, perhaps pointing to a more complex metabolic bone disease in a growing animal. Low serum concentrations of calcium and 25-hydroxyvitamin D were detected in an antemortem sample. The pathogenesis of these imbalances was not definitively established, but lack of sunlight exposure, low concentration of vitamin D precursors in the diet (perhaps secondary to malnutrition), or both, were suspected; a genetic basis cannot be ruled out.     

Plasma and milk concentrations of vitamin D3 and 25-hydroxy vitamin D3 following intravenous injection of vitamin D3 or 25-hydroxy vitamin D3.

Plasma levels of vitamin D3 or 25-hydroxyvitamin D3 in ewes after administration of a single massive intravenous dose of vitamin D3 (2 X 10(6) IU) or 25-hydroxy vitamin D3 (5 mg) were determined at zero, one, two, three, five, ten and 20 days postinjection. In six ewes injected with vitamin D3 conversion of vitamin D3 to 25-hydroxy vitamin D3 resulted in a six-fold increase in the plasma 25-hydroxy vitamin D3 level within one day. Elevated levels were maintained until day 10 but by day 20 a substantial decline in the plasma 25-hydroxy vitamin D3 level had occurred. Peak levels of vitamin D3 were reached one day after injection and then continuously declined until day 20. Administration of 25-hydroxy vitamin D3 increased plasma concentrations of 25-hydroxy vitamin D3 to fivefold higher levels than those observed when vitamin D3 was injected, with approximately threefold higher levels of 25-hydroxy vitamin D3 maintained for five days. On day 10 and day 20 ewes which were injected with 25-hydroxy vitamin D3 still maintained plasma levels of 25-hydroxy vitamin D3 which were twice as high as those of ewes injected with vitamin D3. In six ewes injected with vitamin D3, a sharp increase in vitamin D3 level in milk occurred within one day and more than a tenfold elevation of milk vitamin D3 concentrations were maintained for ten days. By 20 days the milk vitamin D3 level had returned to preinjection levels. These observations suggest that indirect supplementation of the suckling ruminant with vitamin D3 may be achieved through maternal injection and subsequent mammary transfer.     

Hepatotoxicity of stanozolol in cats

OBJECTIVE: To determine hepatotoxicity of stanozolol in cats and to identify clinicopathologic and histopathologic abnormalities in cats with stanozolol-induced hepatotoxicosis. DESIGN: Clinical trial and case series. ANIMALS: 12 healthy cats, 6 cats with chronic renal failure, and 3 cats with gingivitis and stomatitis. PROCEDURES: Healthy cats and cats with renal failure were treated with stanozolol (25 mg, i.m., on the first day, then 2 mg, p.o., q 12 h) for 4 weeks. Cats with gingivitis were treated with stanozolol at a dosage of 1 mg, p.o., every 24 hours. RESULTS: Most healthy cats and cats with renal failure developed marked inappetence, groomed less, and were less active within 7 to 10 days after initiation of stanozolol administration. Serum alanine transaminase (ALT) activity was significantly increased in 14 of 18 cats after stanozolol administration, but serum alkaline phosphatase activity was mildly increased in only 3. Four cats with serum ALT activity > 1,000 U/L after only 2 weeks of stanozolol administration had coagulopathies; administration of vitamin K resolved the coagulopathy in 3 of the 4 within 48 hours. All 18 cats survived, and hepatic enzyme activities were normal in all cats tested more than 4 weeks after stanozolol administration was discontinued. Two of the 3 cats with gingivitis developed evidence of severe hepatic failure 2 to 3 months after initiation of stanozolol treatment; both cats developed coagulopathies. Histologic evaluation of hepatic biopsy specimens from 5 cats revealed diffuse hepatic lipidosis and cholestasis without evidence of hepatocellular necrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that stanozolol is hepatotoxic in cats.