Early manifestation of hypophosphatemic rickets in goslings: a potential role of insufficient muscular adenosine triphosphate in motility impairment of early P-deficient geese.

We aimed to determine the onset time of hypophosphatemic rickets and investigate the mechanism of motility impairment through adenosine triphosphate (ATP) production in goslings. Two hundred and sixteen 1-day-old male Jiangnan white geese were randomly divided into 3 groups, with 6 replicates and 12 geese per replicate. Birds were fed on 3 diets: a control diet (nonphytic phosphorus, NPP, 0.38%), a P-deficient diet (PD; NPP, 0.08%), and a high P diet (HP; NPP, 0.80%) for 14 d. Subsequently, all birds were shifted to the control diet for an additional 14 d. The cumulative incidence of lameness increased significantly (P < 0.01) starting on d 4, reaching over 80% on d 7 and 100% on d 12 in the PD group. Drinking and eating frequency decreased from d 4 and d 5, respectively, in the PD group compared to the other groups (most P < 0.01). The PD group exhibited shorter and narrower beaks, higher (worse) curvature scores of the beak and costochondral junctions, swelling caput costae, and dirtier feathers since d 4, in contrast to the control and HP groups (most P < 0.01). The HP had bigger (P < 0.05) beak and sternum sizes than the control groups on d 4 to 11. Leg muscle ATP levels were lower (P < 0.01 or 0.05) on d 4 to 11; in contrast, adenosine diphosphate (d 7-11) was higher in PD compared to the control (P < 0.05). Leg muscle ATP level had positive linear (R2 > 0.40) correlations (r > 0.60) with eating and drinking frequencies on d 7 and 11 (P < 0.01). Bone stiffness, feather cleanliness, and ATP levels recovered (P > 0.05) to the control level, whereas bone size did not recover (P < 0.05) in PD and HP after eating the control diet for 2 wk. The onset time of hypophosphatemic rickets was around 4 d in goslings, and insufficient leg muscle ATP was related to the impaired motility observed in early P-deficient geese.

Feline precision medicine using whole-exome sequencing identifies a novel frameshift mutation for vitamin D-dependent rickets type 2.

OBJECTIVES: A 14-week-old female domestic longhair kitten presented with shifting lameness and disproportionately smaller size compared with a co-housed littermate. METHODS: Hematology and serum biochemical testing were conducted to investigate causes for delayed growth, and radiographs of the appendicular skeleton were obtained. RESULTS: The afflicted kitten had marked hypocalcemia, mild hypophosphatemia and substantial elevations in alkaline phosphatase activity, as well as pathognomonic radiographic findings consistent with rickets. Skeletal changes and hypocalcemia prompted testing of concentrations of parathyroid hormone (PTH) and vitamin D metabolites. Endocrine testing demonstrated significant increases in serum concentrations of PTH and 1,25-dihydroxycholecalciferol (calcitriol), supporting a diagnosis of vitamin D-dependent rickets type 2. Provision of analgesia, supraphysiologic doses of calcitriol and calcium carbonate supplementation achieved normalization of the serum calcium concentration and restoration of normal growth, although some skeletal abnormalities persisted. Once skeletally mature, ongoing calcitriol supplementation was not required. Whole-exome sequencing (WES) was conducted to identify the underlying DNA variant. A cytosine deletion at cat chromosome position B4:76777621 in VDR (ENSFCAT00000029466:c.106delC) was identified and predicted to cause a stop codon in exon 2 (p.Arg36Glufs*18), disrupting >90% of the receptor. The variant was unique and homozygous in this patient and absent in the sibling and approximately 400 other cats for which whole-genome and whole-exome data were available. CONCLUSIONS AND RELEVANCE: A unique, heritable form of rickets was diagnosed in a domestic longhair cat. WES identified a novel frameshift mutation affecting the gene coding for the vitamin D3 receptor, determining the likely causal genetic variant. Precision medicine techniques, including whole-exome and whole-genome sequencing, can be a standard of care in cats to identify disease etiologies, and to target therapeutics and personalize treatment.

Rickets in white-eared opossums (Didelphis albiventris) / Raquitismo em gambás-de-orelha-branca (Didelphis albiventris)

Two young opossums were necropsied and diagnosed with rickets. This study aims to describe the clinical-pathological aspects of rickets in Didelphis albiventris. Macroscopically, the opossums presented kyphosis and scoliosis, lateral deviation of the limbs in varus, locomotion difficulty, and enlargement with softening of costochondral junctions (rickety rosary). Samples of bones and joints were processed for hematoxylin and eosin staining and Masson's trichrome. Microscopically, we observed thickening of the epiphyseal plate, characterized by irregular and multifocal proliferation of serialized and hypertrophic cartilage zones, which formed circular groups of large, dysplastic chondrocytes towards the spongy zone, often surrounded by non-mineralized osteoid tissue. In the cortical bone, there were pale eosinophilic zones around the Havers channels consistent with non-mineralized osteoid. The staining of Masson's trichrome evidenced the accumulation of osteoid tissue in cortical and trabecular bones. It is possible that a mixed cause of absorption deficiency of vitamin D3 associated with an unbalanced Ca:P diet based on lactose-free milk and fruits may have triggered the disease.(AU)

Dois gambás jovens foram necropsiados e diagnosticados com raquitismo. O objetivo do trabalho é descrever os aspectos clínico-patológicos de raquitismo em Didelphis albiventris. Macroscopicamente os gambás apresentaram cifose e escoliose, desvio lateral dos membros em varus, dificuldade de locomoção e alargamento com amolecimento das junções costocondrais (rosário raquítico). Amostras dos ossos e articulações foram processadas para coloração de hematoxilina e eosina e Tricrômico de Masson. Microscopicamente havia espessamento da placa epifisária, caracterizada pela proliferação irregular e multifocal das zonas de cartilagem seriada e hipertrófica, que formavam grupos circulares de condrócitos grandes, displásicos em direção a zona esponjosa frequentemente cercados por tecido osteoide não mineralizado. No osso cortical haviam zonas eosinofílicas pálidas ao redor dos canais de Havers consistentes com osteoide não mineralizado. A coloração de Tricrômico de Masson evidenciou o acúmulo de tecido osteoide no nosso cortical e trabecular. Acredita-se que uma causa mista de déficit de absorção de vitamina D3 associada a uma dieta desbalanceada em Ca:P a base de leite sem lactose e frutas tenha desencadeado a doença.(AU)

Normal physiological functions in two animal species with highly different vitamin d status compared to that of humans / Funciones fisiológicas normales en dos especies animales con estatus de vitamina d muy diferentes del actual en seres humanos

Mole rats live in permanent darkness, in networks of underground tunnels (which extend up to 1 km in the subsoil), excavated with their incisors, in warm and semi-arid areas of South Africa. Mole rats have an unusually impoverished vitamin D3 status with undetectable and low plasma concentrations of 25- hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3, respectively. They express 25-hydroxylase in the liver and 1-hydroxylase and 24-hydroxylase in their kidneys. The presence of specific receptors (VDR) was confirmed in the intestine, kidney, Harderʼs glands and skin. In spite of their poor vitamin D3 status, the apparent fractional intestinal absorption of calcium, magnesium and phosphate was high, always greater than 90%. Oral supplementation with cholecalciferol to mole rats did not improve the efficiency of gastrointestinal absorption of these minerals. Mole ratsdo not display the typical lesion of rickets: hypertrophic and radiolucent growth cartilages. Histological studies reported normal parameters of trabecular and cortical bone quality. Marmosets (monkeys of the New World) are not hypercalcaemic, eventhough they exhibit much higher levels of 25-hydroxyvitamin D3, 1α,25-dihydroxyvitamin D3 and parathyroid hormonethan that of rhesus monkeys and humans. Fed a high vitamin D3 intake (110 IU/day/100 g of body weight), a fraction of the experimental group was found to display osteomalacic changes in their bones: distinct increases in osteoid surface, relative osteoid volume, and active osteoclastic bone resorption. These findings suggest that some marmosets appears to suffer vitamin D-dependent rickets, type II. The maximum binding capacity of the VDR or the dissociation constant of VDR1α,25(OH)2D3 complex of mole rats and New World monkeys are distinctly different of VDR isolated from human cells. Health status of those species appears to be adaptations to the mutations of their VDR. Though rare, as mutations may occur at any time in any patient, the overall message of this review to clinicians may be: recent clinical studies strongly suggests that the normality of physiological functions might be a better indicator of the health status than the serum levels of vitamin D metabolites. (AU)

Las ratas topo viven en la oscuridad permanente, en redes de túneles subterráneos excavadas con sus incisivos (que se extienden hasta 1 km en el subsuelo), en áreas cálidas y semiáridas de Sudáfrica. Las ratas topo tienen un estatus de vitamina D3 inusualmente empobrecido con concentraciones plasmáticas indetectables de 25-hidroxivitamina D3 y bajas de 1α, 25-dihidroxivitamina D3. Poseen 25-hidroxilasa en el hígado y 1-hidroxilasa y 24-hidroxilasa en sus riñones. La presencia de receptores específicos (VDR) ha sido confirmada en el intestino, el riñón, las glándulas de Harder y la piel. A pesar de su pobre estatus de vitamina D3,la absorción fraccional intestinal aparente de calcio, magnesio y fosfato fue alta, siempre superior al 90%. La suplementación oral con colecalciferol a las ratas topo no mejoró la eficacia de la absorción gastrointestinal de estos minerales. No muestran la lesión típica del raquitismo: cartílagos de crecimiento hipertróficos y radiolúcidos. Varios estudios histológicos confirman los hallazgos radiológicos y se informan parámetros normales de la calidad ósea trabecular y cortical. Los titíes (monos del Nuevo Mundo) exhiben calcemias normales con niveles más elevados de 25-hidroxivitamina D3, 1α,25-dihidroxivitamina D3 y hormona paratiroidea que los monos rhesus y los seres humanos. Un tercio de un grupo de titíes alimentados con una alta ingesta de vitamina D3 (110 I/día/100 g de peso corporal) exhibió cambios osteomalácicos en sus huesos: aumento en la superficie osteoide, volumen osteoide y activa reabsorción osteoclástica. Estos hallazgos sugieren que una fracción de la población de titíes padece raquitismo dependiente de vitamina D, tipo II. Debido a mutaciones ocurridas hace millones de años, las máximas capacidades de ligamiento del VDR o los valores de la constante de disociación del complejo VDR-1α,25(OH)2D3 de las ratas topo o monos del Nuevo Mundo son muy diferentes de los verificables en receptores aislados de células humanas actuales. El mensaje de esta revisión a los médicos clínicos podría ser: varios estudios clínicos recientes indican que la normalidad de las funciones fisiológicas de un paciente es un mejor indicador de su salud que los niveles séricos de los metabolitos de la vitamina D. (AU)

Detection of enteric viruses in pancreas and spleen of broilers with runting-stunting syndrome (RSS) / Detecção de vírus entéricos em pâncreas e baço de frangos com a síndrome de nanismo e raquitismo (RSS)

Enteric disease is a multifactorial problem in chickens, which causes gastrointestinal alterations, elevated feed conversions and impairment. In the last years, several enteric viruses were implicated in enteric disease; case reports have shown their presence alone or in concomitant infections during outbreaks and have suggested that they might be determining factors in the aetiology of enteric disease. This study shows high detection rates of enteric viruses in the pancreas and spleen in samples from an outbreak of enteritis and malabsorption in 16 chicken flocks (n=80 broilers). Avian nephritis virus (ANV) was the most ubiquitous virus, present in 75% of the flocks followed by avian rotavirus group A (ART-A) with 68.75%, and by chicken astrovirus (CAstV) and chicken parvovirus (ChPV) in 43.75% of samples. Viruses were present in the pancreas of positive flocks at extremely high rates: 100% for ART-A, 91.7% for ANV, 100% for CAstV and 57.14% for ChPV. By contrast, only 16.7% and 57.14% of intestine samples were positive for ANV and CAstV, respectively. Avian reovirus (AReo) and avian adenovirus group 1 (FAdV-1) were not detected. These results suggest that high viral detection rates in pancreas samples may be a result of viremia during enteric disease, with subsequent damage of the exocrine pancreas, leading to runting-stunting syndrome (RSS).(AU)

A doença entérica é um problema multifatorial em galinhas que causa alterações gastrointestinais, conversão alimentar elevada e deficiência de crescimento. Nos últimos anos, os vírus entéricos foram associados à doença entérica; casos reportados mostraram a infecção de um único vírus e também infecções concomitantes durante os surtos sugerindo a presença de múltiplos fatores etiológicos nas doenças entéricas. Este estudo mostra uma alta taxa de detecção dos vírus entéricos em amostras de pâncreas e baço de um surto de enterite e má-absorção em 16 lotes de frangos (n=80 frangos). O vírus de nefrite aviária (ANV) foi o vírus mais detectado, estando presente em 75% dos lotes seguido pelo rotavírus aviário grupo A (ART-A) em 68,75% dos casos, e pelo astrovirus (CAstV) e parvovírus aviários (ChPV), ambos em 43,75% das amostras. Os vírus estavam presentes no pâncreas dos lotes positivos em percentuais elevados: 100% para ART-A e CAstV; 91,7% para ANV, e em 57,14% para ChPV. Em contraste, somente 16,7% e 57,14%, em amostras de intestino, foram positivos para ANV e CAstV, respectivamente. Reovírus aviário (AReo) e o adenovírus do grupo 1 (FAdV-1) não foram detectados. Estes resultados sugerem que os elevados percentuais de vírus detectados em amostras de pâncreas podem estar associados à viremia durante a doença entérica, com subsequente lesão no pâncreas exócrino das aves levando ao desenvolvimento da síndrome de nanismo e raquitismo.(AU)

Vitamin D and the immune system: beyond rickets.

In addition to its essential role in calcium homeostasis and bone metabolism, vitamin D has a diverse range of biological actions, including induction of cell differentiation, inhibition of cell growth, immunomodulation and control of hormonal systems. Vitamin D plays an immunoregulatory role in both the innate and adaptive immune systems. The active metabolite of the vitamin D endocrine system, 1,25-dihydroxyvitamin D (calcitriol), exerts pleiotropic effects through its interaction with the vitamin D receptor. Low vitamin D status in humans has been implicated in the etiology of neoplasia, autoimmune disease, cardiovascular disorders and infectious diseases. This review focuses on vitamin D and its effects on immune function, particularly in humans, with the aim to encourage further exploration in the veterinary field.

Amelogenesis imperfecta and other biomineralization defects in Fam20a and Fam20c null mice.

The FAM20 family of secreted proteins consists of three members (FAM20A, FAM20B, and FAM20C) recently linked to developmental disorders suggesting roles for FAM20 proteins in modulating biomineralization processes. The authors report here findings in knockout mice having null mutations affecting each of the three FAM20 proteins. Both Fam20a and Fam20c null mice survived to adulthood and showed biomineralization defects. Fam20b (-/-) embryos showed severe stunting and increased mortality at E13.5, although early lethality precluded detailed investigations. Physiologic calcification or biomineralization of extracellular matrices is a normal process in the development and functioning of various tissues (eg, bones and teeth). The lesions that developed in teeth, bones, or blood vessels after functional deletion of either Fam20a or Fam20c support a significant role for their encoded proteins in modulating biomineralization processes. Severe amelogenesis imperfecta (AI) was present in both Fam20a and Fam20c null mice. In addition, Fam20a (-/-) mice developed disseminated calcifications of muscular arteries and intrapulmonary calcifications, similar to those of fetuin-A deficient mice, although they were normocalcemic and normophosphatemic, with normal dentin and bone. Fam20a gene expression was detected in ameloblasts, odontoblasts, and the parathyroid gland, with local and systemic effects suggesting both local and/or systemic effects for FAM20A. In contrast, Fam20c (-/-) mice lacked ectopic calcifications but were severely hypophosphatemic and developed notable lesions in both dentin and bone to accompany the AI. The bone and dentin lesions, plus the marked hypophosphatemia and elevated serum alkaline phosphatase and FGF23 levels, are indicative of autosomal recessive hypophosphatemic rickets/osteomalacia in Fam20c (-/-) mice.

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.

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

UNLABELLED: 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 metabolism and rickets in domestic animals: a review.

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.

Diffuse osteopenia and myelopathy in a puppy fed a diet composed of an organic premix and raw ground beef.

CASE DESCRIPTION: An 8-month-old Shetland Sheepdog was evaluated because of the sudden onset of signs of neck pain, collapse, and inability to rise. A cursory diet history indicated that the dog had been fed a raw meat-based diet. CLINICAL FINDINGS: Initial evaluation of the dog revealed small physical stature, thin body condition, and signs of cranial cervical myelopathy. Radiographically, diffuse osteopenia of all skeletal regions was identified; polyostotic deformities associated with fracture remodeling were observed in weight-bearing bones, along with an apparent floating dental arcade. Hypocalcemia and hypophosphatemia were detected via serum biochemical analyses. The dog's diet was imbalanced in macronutrients and macrominerals. TREATMENT AND OUTCOME: The dog received supportive care and treatment of medical complications; neurologic abnormalities improved rapidly without intervention. Dietary changes were implemented during hospitalization, and a long-term feeding regimen was established. Following discharge from the hospital, exercise restriction was continued at home. Serial follow-up evaluations, including quantitative bone density measurements, revealed that dietary changes were effective. After 7 months, the dog was clinically normal. CLINICAL RELEVANCE: In the dog of this report, vitamin D-dependent rickets type I and suspected nutritional secondary hyperparathyroidism developed following intake of a nutritionally incomplete and unbalanced diet. The raw meat-based, home-prepared diet fed to the dog was not feed-trial tested for any life stage by the Association of American Feed Control Officials, and its gross nutrient imbalance induced severe metabolic, orthopedic, and neurologic abnormalities. Inadvertent malnutrition can be avoided through proper diet assessment and by matching nutrient profiles with patients' nutritional needs.

Expression of matrix metalloproteinases during vascularization and ossification of normal and impaired avian growth plate.

Enzymes of the matrix metalloproteinase (MMP) family regulate angiogenesis and are involved in the endochondral ossification process. Tibial dyschondroplasia (TD) and rickets are 2 disorders associated with impairments in this process, mainly in the vascularization of the avian growth plate. In this paper, we induced TD and rickets and studied the expression patterns of 4 members of the MMP family known to be important for endochondral ossification, MMP-2, 3, 9, and 13, in normal and impaired avian growth plates. The expression of MMP-3, 9, and 13 was reduced in the lesions and lined up parallel to the expulsion of blood vessels, which was extended up to the border of the lesion, but did not penetrate into it. Matrix metallopro-teinase-2 was not expressed in the TD lesion but was overexpressed in the rachitic lesion. We also studied the differentiation stage of the chondrocytes populating the lesions and found that the rachitic lesions were populated with proliferative chondrocytes, whereas the TD lesions were filled with chondrocytes that presented both proliferative and hypertrophic markers. These results suggest that MMP-3, 9, and 13 play a role in the vascularization and ossification processes, whereas MMP-2 is related to chondrocyte differentiation and may be involved in cartilage remodeling in the avian growth plate.

Immunolocalization of vascularization factors in normal, tibial dyschondroplasia and rachitic cartilage.

Tibial dyschondroplasia is a skeletal abnormality characterized by an avascular plug of cartilage in the metaphysis of the long bones of rapidly growing birds. An avascular, thickened growth plate also occurs in vitamin D/calcium-deficient rickets. This research was conducted to evaluate tibial dyschondroplasia and rachitic tissue for factors shown to be important in normal growth plate vascularization. Immunohistochemical analysis demonstrated the presence of vascular endothelial growth factor, its receptor Flk-1, and matrix metalloproteinases MMP-9 and MMP-13 to be present in all tissues examined. In most cases, immunostaining was intracellular, except near blood vessels where the matrix was also stained. The results suggest that, for the four proteins examined, disruption of their expression is not a key factor in the development of these avascular cartilage lesions in avians. The relationship of these observations to the pathology of tibial dyschondroplasia is discussed.

The effect of maternal dietary vitamin D3 supplementation on performance and tibial dyschondroplasia of broiler chicks.

A series of experiments was conducted to investigate the effects of maternal dietary vitamin D3 supplementation at 4 different times during the laying cycle, on the performance and bone quality of broiler chicks fed a diet that induced tibial dyschondroplasia (TD) or an adequate diet. Ross x Ross broiler breeder hens were fed a corn-soy diet with various levels of vitamin D3 from 24 to 66 wk of age. Eggs were collected at 39, 44, 53, and 64 wk of age and hatched. Chicks from hens fed 250 IU of D3/kg (low maternal D3 or LMD3) and 2,000 IU of D3/ kg (high maternal D3 or HMD3) levels were placed in battery brooders and fed the diets from 0 to 16 d. At 16 d, the chicks were weighed and killed; the left tibias were used for bone ash determinations, and the right tibias were used to score the incidence and severity of TD (0, 1, 2, or 3, where 3 is the most severe). Body weight gain and feed intake were significantly lower for the LMD3 chicks at wk 44 and 64, although there was no difference in weight at hatch. For the first 2 hatches (wk 39 and 44), the LMD3 and HMD3 chicks demonstrated high average TD scores (2.03 and 1.57 vs. 2.05 and 1.75 for the LMD3 vs. HMD3 chicks, respectively) and high average incidences of severe TD (50 and 35% vs. 45 and 34% for LMD3 vs. HMD3 levels, respectively). However, results from the last 2 hatches (wk 53 and 64) showed that HMD3 chicks, compared with LMD3 chicks, had reduced average TD scores (1.39 and 1.47 vs. 1.01 and 0.44 for LMD3 vs. HMD3 levels, respectively) and severe TD incidence (36 and 40% vs. 17 and 8% for the LMD3 vs. HMD3 levels, respectively). In this experiment, as egg production declined toward the end of the laying cycle, hens fed the HMD3 might have been able to deposit sufficient quantities of vitamin D3 in the egg to maintain excellent body weight gain at 16 d of age and reduce the incidence and severity of TD. Hens fed the LMD3 diet were unable to produce similar improvements.

Vitamin D-dependent rickets type 2 with characteristic radiographic changes in a 4-month-old kitten.

This report describes the presenting signs, biochemical abnormalities, and radiographic changes in a 4-month-old kitten with vitamin D-dependent rickets type 2. Details of therapy are described and possible reasons for treatment failure are discussed.

Studies on rickets and osteomalacia in Bactrian camels (Camelus bactrianus).

Epidemiological studies have indicated incidences of 32.9% and 27.8% for rickets and osteomalacia, respectively, in Bactrian camels (Camelus bactrianus), but there is an increased incidence under drought conditions, sometimes reaching 75%. We have found that concentrations of phosphorus and copper in forage and soil samples in a drought affected area were significantly lower than in a control area or normal reference values (P < 0.01) ; the mean Ca:P ratio in the forages was 50:1. The phosphorus content of blood and hair from affected camels was significantly less than that in controls (P < 0.01) and concentrations of copper in the liver and kidney were significantly lower in affected camels than control animals (P < 0.01); the concentrations of triiodothyronine (T(3)), thyroxine (T(4)) and parathyroid hormone (PTH) in the serum from affected animals were significantly higher than those from healthy controls (P < 0.01); serum inorganic phosphorus and ceruloplasmin levels were lower than those in the controls (P < 0.01 or P < 0.05); the concentrations of serum alpha-globulin and beta-globulin were significantly higher in the affected camels than in the healthy controls (P < 0.01). The pathological changes seen in camels affected with rickets included porous, brittle, light, osteoporotic bones that were susceptible to fractures and had less resistance to cutting and sawing. Wrist joints were enlarged with an apparent bowing of the long bones in forelimb and with typical broadening of the epiphyses. In adult female camels, many enlarged scars were often seen in ribs indicating earlier fractures. The disease could be cured with supplementary bone meal, phosphate or mineral mixtures and in field investigations clinical signs disappeared within 15 days. Over the same period, the concentrations of phosphorus and alkaline phosphatase in blood returned to normal. The disease may be effectively prevented by use of mineral blocks (block salt licks) or dosing orally with copper, selenium and cobalt soluble glass boluses. We conclude that rickets and osteomalacia are mainly caused by phosphorus and copper deficiencies in the pasture.

Effects of u.v. irradiation of very young chickens on growth and bone development.

Six experiments were conducted to study the effects of exposure of young chickens to u.v. radiation. Chickens were fed a cholecalciferol (D3)-deficient diet and exposed to u.v. radiation from fluorescent lights giving total radiance (285-365 nm) at 0.15 m of 99.9 mJ/s per m(2). In Expt 1, chickens had increased body weight, bone ash and plasma Ca and decreased incidence of rickets and tibial dyschondroplasia (TD) when exposed to fluorescent light radiation 24 h per d, 24 h every 2 d, or 24 h every 3 d starting with exposure on day 1 after hatching. However, when not exposed on day 1, but on days 4, 7, 10, 13 and 16, the bone ash was reduced, and the incidence of TD and rickets was increased, compared with chickens exposed on day 1 after hatching. When chickens were exposed at 1 d of age to radiation from two lamps, each of which gave a radiance (285-365 nm) at 0.26 m of 856 mJ/s per m(2), both the length of time of radiation and location of the lamps (above or below the chicken) influenced the response as measured by body weight, bone ash, plasma Ca and incidence of rickets. When chickens that received a TD-inducing diet were exposed to 30 min u.v. radiation from below at 1 d of age they developed significantly less TD than did those not exposed when fed either 27.5 or 55.0 microg D3/kg diet.

Metabolic disease in animals.

Rickets is a metabolic bone disorder characterized by osteopenic changes resulting from the failure of calcification of the osteoid matrix and absent mineralization of hypertrophic cartilage cells at the epiphyseal growth plates in growing primates, herbivores, swine, carnivores, and birds. The causes of rickets include inadequate dietary provision of calcium, phosphorus, and vitamin D. Osteomalacia in reptiles, simian bone disease in nonhuman primates, and osteodystrophia fibrosa (secondary hyperparathyroidism) or "bran disease" in herbivores are caused by a diet that has a much higher content of phosphorus than calcium, combined with inadequate exposure to direct sunlight. Medullary bone consists of interconnected spicules of bone resembling embryonic bone and is established in relation to the shell formation cycle of laying birds. Hypertrophic osteodystrophy develops in large-breed growing dogs, chickens, and guinea pigs and is possibly caused by vitamin C deficiency. Tibial dyschondroplasia is a defect in endochondral ossification characterized by a widened proximal tibial physis that is not penetrated by metaphyseal vascular sprouts, commonly found in growing broiler chickens, turkeys, and exotic birds.

Pathophysiological effects of low dietary phosphorus in pigs.

SUMMARY: The homeostasis of inorganic phosphate (P(i)) is regulated by parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25(OH)(2)D), and P(i)itself in the intestine, kidney, and bone in all the mammalian species studied. Determinations of the serum concentrations of PTH, 1,25(OH)(2)D and osteocalcin were done in 82 southern Romanian Landrace pigs originating from three herds with dietary P(i)deficiency. Serum P(i)concentrations were negatively correlated with those of 1,25(OH)(2)D. In lactating animals and sucklings, the linear relationships between P(i)and 1,25(OH)(2)D were not present. Serum P(i)concentrations were positively correlated with those of PTH. In lactating animals and young pigs, the linear relationships between P(i)and PTH were not evident. PTH and 1,25(OH)(2)D concentrations were negatively correlated. The serum concentrations of 1,25(OH)(2)D and osteocalcin were positively correlated. Milk P(i)concentrations ranging from 3.10 to 7.49 mmol/L were correlated positively with urinary P(i)concentrations ranging from 0.26 to 11.37 mmol/L. In conclusion, similarly to other species, P(i)homeostasis is achieved in pigs by feedback mechanisms between P(i), PTH and 1,25(OH)(2)D and osteocalcin production is induced by 1,25(OH)(2)D. The effect of lactation on P(i)homeostasis remains to be explored.