JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1171672): 11-month-old female black spider monkey (Ateles fusciceps robustus)
HISTORY: This monkey had a misshapen skull and long bones.
HISTOPATHOLOGIC DESCRIPTION: Slide A: Tooth with alveolar bone, mandible (per contributor): Cortical (compact) bone is thinned or absent and there is diffuse loss of alveolar and mandibular bony trabeculae (osteopenia). Remaining thin, irregular trabeculae of woven bone are lined by rare osteoblasts and increased numbers of osteoclasts within Howship’s lacunae (active resorption) with distinct resting and reversal lines. Osteoclasts are also free within the fibrous stroma. Trabeculae are surrounded and widely separated by haphazardly arranged spindle cells (fibroblasts) admixed with dense, well-vascularized fibrous connective tissue that replaces normal hematopoietic elements and adipose tissue and extends to the adjacent periosteal surface.
MORPHOLOGIC DIAGNOSIS: Alveolar and mandibular bone (per contributor): Fibrous osteodystrophy, diffuse, severe, black spider monkey (Ateles fusciceps robustus), nonhuman primate.
HISTOPATHOLOGIC DESCRIPTION: Slide B: Long bone: Diffusely, cortical compact bone, and metaphyseal and diaphyseal cancellous bone is thin to absent and widely separated by increased amounts of loose fibrous connective tissue and fibroblasts that multifocally replace myeloid adipocytes and hematopoietic cells. Multifocally, there are variably sized clusters of osteoclasts within Howship's lacunae (bone resorption). Focally, the physis is expanded up to twice normal by a thickened zone of hypertrophy. Small blood vessels in this area form irregular channels into the cartilaginous matrix. There are retained fragmented cores of cartilage in the primary spongiosa, which are often surrounded by variable amounts of homogeneous eosinophilic matrix (osteoid). There is an overall decrease in the number of osteoblasts. Within the epiphyseal growth plate, there are additional areas of retained unmineralized cartilage. There is a focal 1 x 1.5 mm diameter subchondral cyst in the epiphysis.
MORPHOLOGIC DIAGNOSIS: Long bone: Fibrous osteodystrophy, diffuse, marked with focal physeal osteochondrodysplasia (rachitic).
ETIOLOGIC DIAGNOSIS: Nutritional secondary hyperparathyroidism
CAUSE: Dietary vitamin D3 deficiency and/or dietary calcium/phosphorus imbalance
SYNONYMS: Simian bone disease; cage paralysis
· Simian bone disease is a historic disease from laboratory and zoo settings, and remains an infrequent problem in pet monkeys
· Fibrous osteodystrophy (FOD) in non-human primates is a form of nutritional hyperparathyroidism; fibrous osteodystrophy in New World primates has historically been associated with commercial diets containing vitamin D2 as the sole source of vitamin D (deficient in vitamin D3)
· FOD is characterized by extensive bone resorption, fibrous tissue proliferation and poorly mineralized immature bone; most often occurs in response to primary or secondary hyperparathryroidism (see also M-M10)
· FOD also occurs more often in horses, pigs, dogs and cats, ferrets, and reptiles; rarely occurs in goats; there is unsubstantiated evidence of the disease occurring in sheep and cattle
· Rickets (M-M08) is a disease of young growing animals in which there is inadequate mineralization of the developing cartilaginous and osseous matrix; the disease is caused by deficiencies of vitamin D or phosphorous; fibrous osteodystrophy results in animals effected with Rickets when there is concurrent low calcium levels (due to decreased absorption)
· Secondary hyperparathyroidism associated with marmoset wasting syndrome (malabsorption due to inflammatory gastrointestinal disease) has been reported in a group of common marmosets with bone lesions (FOD, rickets, and osteopenia)
· The common denominator is the stimulation of excess parathyroid hormone (PTH) production caused by low plasma ionized calcium levels, due to several different potential dietary imbalances: 1) low calcium diet; 2) excessive phosphorous with normal or low calcium; or 3) inadequate amounts of vitamin D3
· In the classic disease of New World primates, dietary vitamin D3 is required to prevent hypocalcemia; a dietary deficiency in vitamin D3, even in the presence of a normal amount of vitamin D2, will result in inadequate levels of 1,25
hydroxycholecalciferol (calcitriol), the active form of vitamin D
· The apparent vitamin D2-resistance and absolute requirement of vitamin D3 in New World primates, particularly marmosets (not Old World primates) may be associated with differences in binding characteristics of transport proteins or to a high degree of stereospecificity of receptors in target cells for cholecalciferol
· Deficiency in active metabolites of vitamin D → decreased intestinal calcium and phosphorus absorption (with subsequent decreased serum levels) and decreased bone matrix synthesis and mineralization → hypocalcemia → stimulates parathyroid glands to secrete PTH → increased mobilization of calcium and phosphorus from bone → increased levels of PTH (with normal renal function) → decreased renal tubular resorption of phosphate and increased resorption of calcium → restores normal blood calcium levels
· Concurrent gastrointestinal disease may play a role in development of bone disease thru decreased absorption of vitamin D and/or calcium
· In response to elevated PTH, bone marrow stromal cells differentiate into fibroblasts
· Elevated plasma phosphorus levels depress calcium levels and may also stimulate the release of PTH
TYPICAL CLINICAL FINDINGS:
· Affected monkeys reluctant to move and are inactive, and have thin, dull hair coats; normal resistance to handling is diminished
· There is difficulty with mastication; distortion of limbs and facial bones may be present (often maxilla and mandible)
· May show non-weight bearing lameness of one or more extremities; pathologic fractures are common
· Maintain a stiff, hunchback posture as a result of lordosis, scoliosis, and kyphosis of the spine
· Radiographically, generalized skeletal demineralization (decreased radiodensity) and bowing deformities of long bones are evident
· Serum levels of calcium and phosphorous are often in the low normal ranges
· Elevated alkaline phosphatase level is probably the most reliable indicator in animals with overt bone disease
TYPICAL GROSS FINDINGS:
· Skeletal system:
· Distortion or bowing of the distal aspects of long bo6nes
· On sectioning, cortical bone is thin with prominent trabeculae and a widened marrow cavity
· Fractures and healed fractures with abundant fibrous callus
· Predilection cancellous bones of the skull
· Large fibrous jaw bones (both maxilla and mandible) with separation and loss of teeth and marked thickening of the maxilla and calvarium
· Parathyroid glands are diffusely enlarged
TYPICAL LIGHT MICROSCOPIC FINDINGS:
· Adult animals: Widespread increased osteoclastic resorption and replacement by fibrous connective tissue
· Increased osteoid seams with marked resorption of existing spongy or cortical bone and high numbers of osteoclasts within Howship's lacunae; osteoclastic
resorption begins on the endocortical bone surface, but any vascular spaces within the bone can undergo marked enlargement by osteoclastic resorption and replacement by fibrous tissue
· Invasion of Haversian spaces and the marrow canal by fibrous tissue
· Formation of cysts within the fibrous marrow, most often in mandible, maxilla or long bones; also known as “brown tumors” due to blood and hemosiderin within lesion, and arise from expansion of cortical bone secondary to endocortical bone resorption and the increased intraosseous pressure from vascular congestion
· No lesions are expected in the growth plate or articular-epiphyseal cartilage complex
· Young animals: Persistence of irregular, distorted cartilage masses; osteoid is deposited more abundantly in young animals, and osteoid is resistant to osteoclastic resorption, therefore osteoclast activity may be less pronounced in fibrous osteodystrophy associated with rickets
Microscopically (fibrous osteodystrophy):
· Neoplasia: Fibrosarcoma, giant cell sarcoma
· Horses: “big head”, “bran disease”- diets in which Ca:P ratio is 1:3 or greater; usually from diets consisting largely of grain, corn, and grain by-products such as bran; bilateral facial swelling (see also M-M10); horses are very sensitive to high phosphorus levels
· Swine: Young growing animals; often results from unsupplemented grain rations;
· Dogs/Cats: Diets composed entirely of meat
· Other species: Goats, cattle, camelids, birds, reptiles, dolphins, marsupials
· Humans: Osteitis fibrosa cystica
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