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Osteomalacia outbreaks often occur in cattle grazing native pastures in regions with endemic phosphorous (P) deficiency. This study evaluated the responses of two groups of cows, initially with clinical signs of chronic P deficiency, to P supplements (100 g P/kg) offered ad libitum for 13 weeks as a loose mineral mix (LMM group) or the same mineral mix offered as blocks (BMM group). Half of the cows in each group were categorized as 'with' or 'without' severe osteopenia according to a test that depended on the resistance to penetration of a needle through the left lateral process of the L4-L5 lumbar vertebra. The groups grazed two paddocks that were switched each 3 weeks. The liveweight, supplement intakes, and the P-concentrations in soil, forage, blood, and external cortical bone (ECB) of the ribs were measured. The bicarbonate-extractable P in soil was 3.5 mg/kg. The mean of total P in forage (0.95 g/kg/DM), inorganic P in serum (iP, 0.96 mmol/L), and total P in the ECB of the ribs (85 mg/mL) at the beginning of the experiment were all low and consistent with severe chronic P deficiency. The P supplementation allowed clinical recovery in 18/20 cows with their serum and ECB P and calcium approaching normal values and in the two remaining cows the only sign was abnormal gait. Cows consumed more of the LMM than BMM supplement (means 8.3 and 6.6 g P/day, respectively). After 13 weeks cows initially classified as 'with severe osteopenia' and supplemented with LMM had higher (P < 0.05) final liveweight (difference = 21.6 kg), iP (difference = 0.74 mmol/L), bone Ca (difference = 65.7 mg/mL) and bone P (difference = 26.5 mg/mL) concentrations and lower (P < 0.01) final serum Ca/iP ratio (difference = -0.65) than cows with severe osteopenia but supplemented with BMM. The treatment of severe P deficiency cows grazing P deficient sub-tropical grasslands by P supplementation for 13 weeks was more effective with LMM than BMM., Competing Interests: Declaration of Competing Interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper., (Published by Elsevier Ltd.)

We investigated 2 outbreaks of osteomalacia as a result of phosphorus (P) deficiency in herds of lactating beef cows grazing subtropical native pastures in Uruguay. Cows exhibited pica, difficulty to stand and walk, rib fractures, and body weight loss even with adequate forage availability. Osteopenia and severe osteomalacia were observed on gross and histologic examination. The concentrations of bicarbonate-extractable P in soil (4.0, 4.1 mg P/kg), total P in pasture (0.9, 1.1 g P/kg), inorganic P in serum (1.0, 0.71 mmol P/L), and P in bone (73 mg P/mL) were all low. Although injectable and mineral salt supplements provided additional P in both outbreaks, these supplementary amounts were insufficient to prevent P deficiency. The P ingested by the cows from the pasture and supplements would have provided 20-55% of their daily P requirements of ~21 g P/d. Osteomalacia occurred in cattle at the 2 ranches as a result of severe P deficiency in the soil and forage, and inadequate P supplementation. Following diagnosis, control of P deficiency in beef cattle requires estimation of the amount of pasture P ingested and provision of sufficient additional supplementary P to meet the animals' requirements.

A 9-yr-old female black-footed African penguin ( Spheniscus demersus ) was presented for necropsy after a history of reproductive abnormalities, paresis of limbs, weakness, and sudden death. Postmortem examination revealed soft keel, collapsed rib cage with beading of the ribs, and bilateral parathyroid enlargement. Classic histologic lesions of fibrous osteodystrophy with osteomalacia were observed in the ribs, vertebrae, and to a lesser extent in the femur and tibiotarsus associated with hyperplasia of parathyroid glands. This represents the first report of nutritional secondary hyperparathyroidism in birds of the order Spheniciformes , most likely caused by low levels of calcium supplementation during egg laying. The reproductive abnormalities observed in this penguin and others from the same group (asynchronous egg-laying cycles, abnormal breeding behavior) were most likely exacerbated by the lack of an adequate photoperiod mimicking the natural daylight pattern.

Four captive, lesser hedgehog tenrecs ( Echinops telfairi ) were euthanized for soft bones that prevented normal mastication and/or ambulation. Antemortem radiographs (available in 2 cases) revealed osteopenia. Antemortem bloodwork (available in 2 cases) revealed hypophosphatemia. Dietary history (available in 2 cases) indicated the animals were eating only insects. Histologically, all examined bones had wide osteoid seams that caused expansion of the cortices. Osteoid deposition was exuberant and it partially filled marrow cavities (hyperostosis). Nondecalcified sections of bone (available in 2 cases) revealed that osteoid was poorly mineralized, consistent with osteomalacia. Insects are poor dietary sources of vitamin D, and dietary vitamin D deficiency is considered the most likely cause for metabolic bone disease in these animals.

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.

Two case reports demonstrate the consequences of a deficient calcium supply in dogs. The first case describes an adult dog with a history of food allergy. The dog had been fed with an unbalanced elimination diet (no minerals and vitamins supplemented) over many years and was referred with the diagnosis of osteomalacia (rubber jaw) for optimization of his ration. The second case refers to a puppy which was fed a homemade diet without supplementing the missing minerals and vitamins and suffered a femur fracture after moderate physical impact. In both cases, the computer-aided ration calculation showed a suboptimal to severely deficient supply for several minerals and vitamins, in particular calcium whereas serum calcium levels were normal. Both dogs recovered after being fed a complete and balanced diet. In conclusion, a survey of the feeding using ration calculation is essential especially in the case of potential nutrition-related skeletal disorders. Serum calcium levels cannot be used as a tool to diagnose nutritional calcium deficiency.

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.

Metabolic diseases of cows represent the leading internal pathology in Lithuania in terms of incidence and economic impact. This paper summarizes the mineral metabolic state of milk cows, and details the influence of feeding on serum levels of calcium, nonorganic phosphorus, magnesium, potassium, sodium, glucose, total protein, and urea quantity, and correlationd among them, in healthy dry or post-calving cows as well as in cows with osteomalacia and milk fever after calving. There was less pronounced hypocalcaemia and there were only minor changes in phosphorus, magnesium, potassium and sodium in the serum of healthy dry and post-calving cows that had silage and mineral-vitamin supplements, compared to cows that did not have supplements and silage. There was a fall in calcium and phosphorus (to 1.89 +/- 0.12 mmol/L and 0.71 +/- 0.06 mmol/L, respectively) in the blood of cows sick with milk fever after calving, while levels of magnesium and potassium were increased. The correlation between calcium and phosphorus was r = 0.6993, p < 0.001 in the serum of sick cows. There was a fall in calcium, phosphorus and magnesium (to 1.86 +/- 0.46 mmol/L, 0.75 +/- 0.37 mmol/L, and 0.60 +/- 0.19 mmol/L, respectively) and an increase in sodium level (to 158.90 +/- 19.30 mmol/L) in the blood of cows with osteomalacia in comparison with healthy cows.

An interaction between blood levels of parathyroid hormone, calcitonin, 1.25-dihydroxycholecalciferol and levels of calcium, phosphorus and magnesium was examined in 85 cows, which included healthy cows and cows with ostemalacia, mastitis and paresis. Levels of parathyroid hormone (PTH) and calcitonin were determined in vitro using IMMULITE analyser (Diagnostic Products Corporation, USA), by means of immunometric assay. Levels of vitamin D were measured using the enzyme linked immunosorbent assay (ELISA). Levels of calcium, phosphorus and magnesium were determined using the automated Eos-Bravo analyser (Hospitex Diagnostics, Italy) with HOSPITEX reagents. The lowest blood levels of calcium (1.38 +/- 0.18 mmol/L) and phosphorus (0.65 +/- 0.12 mmol/L) were found in cows with parturient paresis. Decreased blood levels of phosphorus and magnesium were also determined in cows with osteomalacia. For cows with parturient paresis, which received a mineral supplement, the average serum level of calcium was by 20.7% higher than the level found in those which did not receive a supplement, and the level of phosphorus was by 23.6% higher, however, these levels remained low. The blood level of parathyroid hormone ranged from 3.47 to 5.20 pmol/L in healthy cows and from 3.95 to 15.21 pmol/L in sick cows. The highest and statistically significant increase in blood PTH level (up to 18.31 +/- 1.88 pmol/L) was found in cows with parturient paresis. The blood level of PTH correlated inversely with the level of calcium in cows with osteomaliacia (r = -0.89) and in cows with parturient paresis (r = -0.49 and r = -0.61, respectively). The serum level of calcitonin ranged from 1.46 pmol/L to 2.40 pmol/L in healthy and sick cows and the difference was not statistically significant. Lower serum levels of vitamin D were found in heifers-in-calf and in cows with mastitis. A clear correlation between levels of calcitonin, vitamin D and macronutrients was not found.

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., (Copyright 2000 Baillière Tindall.)

The major welfare concern during the handling of laying hens is that of broken bones. With particular reference to the United Kingdom, this paper reviews the work that has been done to quantify the problem, to examine the causes, and to investigate factors that affect it. The number of freshly broken bones found in live birds prior to slaughter and the number of old healed breaks found at slaughter are unacceptably high. End-of-lay hens from battery cages have especially fragile bones and these are easily broken during the rough handling that is received during depopulation. Birds from more extensive laying systems have stronger bones and suffer fewer breaks during depopulation but have a greater prevalence of old healed breaks. The old breaks occur as a result of collisions due to poor design within these housing systems. The number of fresh breaks can be reduced by increasing bone strength and handling birds with more care. The numbers of old breaks can be reduced by better design of housing systems and the physical environment within them.

Metabolic bone disease was diagnosed in an 11-month-old female common marmoset (Callithrix jacchus). It was depressed, reluctant to move, and was cachectic and small for its age. Laboratory findings included anaemia, azotaemia and an inverse calcium to phosphorus ratio. The radiological findings showed simultaneous signs of osteomalacia and soft-tissue calcification. There was decreased bone density with lytic areas in the pelvis and femur, and severe bilateral nephrocalcinosis. Postmortem examination revealed marked focal dystrophic calcification of the epi- and myocardium. Calcium and vitamin D3 deficiency (nutritional secondary hyperparathyroidism) was the most likely cause of the osteomalacia.

Data from an animal health service in the Punjab of Pakistan showed that 39 adult female buffaloes with haemoglobinuria were 21 times more likely to have serum inorganic phosphorus (serum P) levels < 0.97 mmol/l than 24 controls sampled during the period of case occurrence (December 1984-March 1985). Age > 7 years or early lactation (1-60 days post partum) were unrelated to the disease. Similarly, symptoms of osteomalacia in 19 multiparous buffaloes were associated with low P (OR = 14.3) but not with age. Subsequently, a serum survey was carried out from February 1985 to July 1987 to investigate serum P variations with season and host factors. Data from 139 farms (426 adult female buffaloes, 468 lactations) indicated strong farm and seasonal effects on serum P. Serum P declined during the study period and was lowest during December-March 1985/1986 and again 1986/1987. Calving season, parity > 1, high pregnancy > 6 months, or daily milk production were not related to serum P in the final model. Seasonal effects were interpreted as soil borne and related to feed changes from maize to berseem in December.

Captive lizards fed a variety of vegetarian and carnivorous diets frequently develop severe nutritional osteodystrophy. Five hatchling iguanas which were captive for 5 months and fed a diet low in calcium and phosphorus developed clinical signs and lesions typical of nutritional osteodystrophy in captive lizards. They had tetany with severe osteoporosis, pathologic fractures, and cartilaginous diaphyseal enlargements of long bones which either were associated with fractures or with intact bones. Hatchling and juvenile iguanas fed a similar diet low in calcium (0.1%) and phosphorus (0.2%) under experimental conditions developed hypocalcemia, tetany, osteoporosis with but adequate in phosphorus (1.1%) developed progressive hypocalcemia and severe osteopososis with pathologic fractures. Control iguanas fed a diet with adequate calcium (2.7%) and phosphours (1.1%) had well mineralized bones with wide cortices and thick metaphyseal trabeculae. Iguanas fed low calcium experimental diets whether low or adequate in phosphorus developed hypocalcemia with compensatory secondary hyperparathyroidism resulting in severe osteodystrophy similar to that reported in captive lizards.

Morphometric and bone density studies were performed on bones from 10 healthy adult dogs and 9 dogs that had exhibited signs of intestinal malabsorption for variable periods of time. The dogs with malabsorption syndrome had a marked decrease in the amount of trabecular bone in lumbar vertebrae (P less than 0.001). Evaluation of undecalcified rib cross sections revealed these dogs had a decrease in trabecular thickness (P less than 0.01) and cortical area (P less than 0.01). There was a decrease in the proportion of the trabecular surface covered with osteoblasts (P less than 0.01) and an increase in resting resorption surface (P less than 0.01) and trabecular specific surface (P less than 0.01). Three of the dogs with malabsorption syndrome and all control dogs were labeled with oxytetracycline prior to sacrifice. The dogs with malabsorption syndrome had a decreased number or complete absence of labeled bone formation sites when compared to controls. No difference was found in bone mineral density in the malabsorption cases as a group, although 1 of the dogs that had an increase in percent osteoid volume and percent osteoid-covered surface had lower ash/ml in trabecular bone samples from lumbar vertebrae. Parathyroid gland weights were available for 6 of the 9 dogs, and these were not significantly different from controls. The findings indicate that decreased bone formation, probably due to the poor nutritional status associated with malabsorption, was an important factor in the development of osteopenia.

Turkey, broiler breeder, and layer cases submitted for necropsy in 1986 to the University of Georgia were categorized by diagnosis, grouped by clinical features, season, age, and presenting history, and evaluated for statistically significant patterns. The most commonly diagnosed diseases were: fowl cholera in turkeys, 64 cases (34.4% of cases; 26.2% of diagnoses); staphylococcal arthritis/synovitis (SA/S) in broiler breeders, 35 cases (20.7%; 17.7%); and osteomalacia in layers, 17 cases (21.0%; 15.6%). In turkeys, fowl cholera, colibacillosis, and aspergillosis were significantly more common in the fourth, second, and third quarters of the year, respectively; enteritis and viral enteritis were more common in early grow-out, and osteomyelitis, SA/S, and synovitis were greatest in late grow-out. Overall, musculoskeletal problems in turkeys were more common in the third quarter and were less common in the first and fourth quarters. Erysipelas occurred most frequently in turkeys 50 to 112 days of age. In both broiler breeders and layers, SA/S was more common in the second quarter, and a history of musculoskeletal problems was less common in both post-peak-production broiler breeders and layers. Fowl pox was more common in the fourth quarter and in late-production broiler breeders. In layers, osteomalacia and Marek's disease were more common in the first and fourth quarters, respectively.

--Weights and mean nuclear surfaces of external epithelial bodies were examined in 53 clinically intact young fattening bulls, 49 clinically intact dairy cows, 55 young fattening bulls slaughtered on account of emergency mainly for osteolamacia and rickets, and 50 cows that had died of various diseases. --Absolute parenchymal levels were found to increase along with growing age. --In young fattening bulls, epithelial bodies lost weight and nuclear surface along with severity of pathological bone changes. --Epithelial bodies in cows and young fattening bulls feeding primarily on silage were more active than those of animals feeding to a larger extent on meadow hay or kept grazing. --No signs of increased activity of epithelial bodies were recordable from animals with osteomalacia or those close to parturition. --All results so far derived from the above studies seem to suggest that, with the present regime of cattle feeding, calcium deficit or phosphate excess are not involved in the development of skeletal diseases. The findings so far obtained in the context of epithelial bodies have confirmed the contrary to the effect that calcium excess and phosphate deficit have remained to be the major causes of skeletal diseases.

When chicks were fed excessive CaCo3, some of them manifested the toes and legs bent in an abnormal direction and final inability to walk in proportion to the dose of calcium. However, chicks fed CaHPO4 containing the same dose of Ca, instead of CaCO3, showed no abnormality of the legs. The leg abnormality of chicks fed excessive CaCO3 resembled the symptom of chicks fed a vitamin D-deficient diet, but there slight differences in serum Ca level and in the findings of the legs by roentgenography between both chick groups. In the radiograph of chicks fed excessive CaCO3, definite radiolucent area were found in all the bone joints related with poor mineralization. Furthermore, a slight elevation of Ca concentration, a decrease in inorganic phosphorous concentration and a remarkable increase in alkaline phosphatase activity were found in the sera of the chicks fed excessive CaCO3. In these chicks were observed the hypertrophic cartilage at the end of bones and an increase in osteoid seams at the diaphysis in the non-decalcified bone section. The findings described above suggested that an excessive Ca supply to chicks might cause a disturbance in P metabolism and produce hypophosphatemic rickets.

Seventy samples of bone bioptates from 70 cows were examined by the biochemical analysis and radiographically. By biochemical examination of bone bioptates taken from the tuber coxae we demonstrated the osteoporotic process in 87% of examined dairy cows, the osteomalacic process in 57% and the combined form, i.e. osteoporosis/osteomalacia in 51.4% of examined dairy cows. According to the distribution of findings in relation to the phases of reproduction cycle, the frequency of pathological findings was found to be highest in cows after calving. The examination of ash for the content of osteotrophic minerals, calcium and phosphorus, has demonstrated the physiological relation in 5.7% of dairy cows only, widened ratio in 87.2% and reduced one in 7.1% of dairy cows. By a comparison of the biochemical finding with the radiographic one we have revealed the difference, by 23% lower, in identification of pathological cases by the radiographic method. The method of radiographic examination of bone bioptates can be used as screening in the diagnostics of metabolic osteopathies.

The clinical signs of osteomalacia in year old crocodiles were kyphoscoliosis, "glassy teath", "rubber jaws" and extreme weakness. Treatment with high oral doses of calcium led to slow improvement. After six months the surviving animal could walk again, but the vertebral column remained deformed after two years.