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The common marmoset (Callithrix jacchus) is a New World primate that is used in biomedical research due to its small size and relative ease of handling compared with larger primates. Although bone disease in common marmosets is well recognized, there are very few detailed descriptions in the literature that cover the range of lesions seen in these animals. For all animals used to model human disease, it is important to be aware of background lesions that may affect the interpretation of study findings. This retrospective study details bone diseases encountered in marmoset breeding colonies at 2 different institutions. Affected marmosets at Johns Hopkins University had lesions compatible with diagnoses of rickets, fibrous osteodystrophy and osteopenia. Affected marmosets at the Wisconsin National Primate Research Center exhibited severe lesions of osteoclastic bone resorption and remodeling that had an unusual distribution and were not easily categorized into a known disease entity. The purpose of this report is to document these naturally occurring skeletal lesions of common marmosets and suggest an approach to evaluating skeletal disease in prospective studies of these animals that will allow the most accurate diagnoses., (© The Author(s) 2015.)

Rickets can be attributed to nutritional, genetic, hormonal, or toxic disturbances and is classified as a metabolic bone disease. Rickets is most often associated with inappropriate dietary levels of calcium, phosphorus, and/or vitamin D. During a 27-month period (January 2010 through March 2012), the Iowa State University Veterinary Diagnostic Laboratory investigated causes of sudden, unexpected death and lameness in growing pigs throughout the Midwestern United States. Clinical observations from 17 growing pig cases included weakness, lameness, reluctance to move, muscle fasciculations and/or tremors, tetany, and death. Ribs were weak, soft, and bent prior to breaking; rachitic lesions were apparent at costochondral junctions in multiple cases. Acute and/or chronic bone fractures were also noted in multiple bones. Failure of endochondral ossification, expanded physes, infractions, thin trabeculae, and increased osteoclasts were noted microscopically. Decreased bone ash and serum 25(OH)D(3), combined with clinical and microscopic evaluation, confirmed a diagnosis of vitamin D-dependent rickets in all cases. In 3 cases, disease was linked to a specific nutrient supplier that ultimately resulted in a voluntary feed recall; however, most cases in the current investigation were not associated with a particular feed company. The present report describes vitamin D-associated rickets and its importance as a potential cause of weakness, lameness, muscle fasciculations, recumbency or sudden unexpected death in swine, and describes appropriate samples and tests for disease diagnosis.

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.

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.

Rickets was diagnosed in 11 rheas from four flocks in Ohio. At necropsy, had pliable bones with prominent valgus or varus deformation of the femoral bone and/or the tibiotarsal bone, marked thickening of the metaphyseal plates, and frequent fractures. Histopathologically, bones of rachitic birds showed marked retention of cartilage core within the growth plate, mainly because of a significant lengthening of the hypertrophied zone of the growth plate in relationship to the remaining zones. Feed analysis showed that rachitic birds were fed diets having higher calcium/phosphorus (Ca/P) ratios (1.38-4.32) than that of the diet fed to nonrachitic birds from a different flock (0.65 Ca/P ratio). Serum analysis of blood from clinically rachitic birds from the affected flocks revealed a marked hypophosphatemia (3.0-4.7 mg/dl), mild hypocalcemia, and normal 25-(OH)-vitamin D concentrations as compared with values in nonrachitic birds, which had serum phosphorus concentrations of 8.5-8.7 mg/dl. These findings suggest that rickets in growing rheas was associated with marked hypophosphatemia and improper Ca/P ratios.

The effects of Vitamin D deficiency rickets on the formation of mineralized dental tissues were studied in a breed of pigs which had moderate and marked hypocalcemia because of an inherited defect in the renal production of the biologically-active Vitamin D metabolites. Affected piglets developed classical symptoms of rickets which were fatal unless Vitamin D supplements were given. The dissected mandibles of homozygous (rickets) and heterozygous (normal) pigs were photographed and radiographed. Compared with those of normal pigs, the mandibles of homozygous pigs demonstrated slowed development/eruption of permanent teeth, under-mineralized bone, underdeveloped dentin (enlarged pulp chambers), interglobular dentin, and enamel hypoplasia. Enamel defects in rachitic pig teeth were difficult to observe radiographically, but could be detected visually and by SDS-PAGE analysis of the enamel protein components of developing and maturing enamel. There was significant retention of amelogenins in the enamel maturation zones of developing molars taken from rachitic pigs, but there was no obvious difference in the patterns of amelogenin processing.

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.