Cranial and vertebral osteosarcoma commonly has T2 signal heterogeneity, contrast enhancement, and osteolysis on MRI: A case series of 35 dogs.

Magnetic resonance imaging (MRI) is commonly used to evaluate the central nervous system (CNS) in dogs; however, published studies describing the MRI appearance of cranial and vertebral osteosarcoma are scarce. In this multicenter, retrospective, case series study, MRI studies of 35 dogs with cranial or vertebral osteosarcoma were prospectively scored by consensus of two veterinary radiologists. Recorded characteristics were location, signal intensity (compared to gray matter), homogeneity, contrast enhancement, margin delineation, local invasion, osteolysis, osteosclerosis, zone of transition, periosteal proliferation, pathological fracture, meningeal/CNS involvement, and presence of metastatic disease. Locations included the parietal bone (n = 1), occipital bone (n = 2), or cervical (n = 5), thoracic (n = 17), lumbar (n = 7), or sacral vertebrae (n = 3). Common features included signal heterogeneity in T2-weighted (T2W) images (n = 35), contrast enhancement (in all 34 dogs with postcontrast MRI), osteolysis (n = 34), compression of the CNS or cauda equina (n = 33), an associated soft tissue mass (n = 33), a long zone of transition (n = 30), osteosclerosis (n = 28), signal isointensity to normal-appearing gray matter in T1-weighted images (T1W, n = 26), and T2W hyperintensity of adjacent brain or spinal cord (n = 23). Other findings included periosteal proliferation (n = 18), meningeal contrast enhancement (n = 17), T1W and T2W hypointense foci in the soft tissue mass (n = 14), invasion into adjacent bones (n = 10), pathological vertebral fractures (n = 7), regional lymphadenopathy (n = 6), skip metastases (n = 2), lung nodule (n = 1), diaphragmatic nodule (n = 1), and brain invasion (n = 1). Contrast enhancement was typically strong and heterogeneous. Magnetic resonance imaging features of cranial and vertebral osteosarcoma were analogous to those previously reported for other imaging modalities. Osteosarcoma should be a differential diagnosis for compressive, contrast-enhancing, osteolytic lesions of the cranium or vertebrae.

Linking gene expression and phenotypic changes in the developmental and evolutionary origins of osteosclerosis in the ribs of bowhead whales (Balaena mysticetus).

Bowhead whales are among the longest-lived mammals with an extreme lifespan of about 211 years. During the first 25 years of their lives, rib bones increase in mineral density and the medulla transitions from compact to trabecular bone. Molecular drivers associated with these phenotypic changes in bone remain unknown. This study assessed expression levels of osteogenic genes from samples of rib bones of bowheads. Samples were harvested from prenatal to 86-year-old whales, representing the first third of the bowhead lifespan. Fetal to 2-year-old bowheads showed expression levels consistent with the rapid deposition of the bone extracellular matrix. Sexually mature animals showed expression levels associated with low rates of osteogenesis and increased osteoclastogenesis. After the first 25 years of life, declines in osteogenesis corresponded with increased expression of EZH2, an epigenetic regulator of osteogenesis. These findings suggest EZH2 may be at least one epigenetic modifier that contributes to the age-related changes in the rib bone phenotype along with the transition from compact to trabecular bone. Ancient cetaceans and their fossil relatives also display these phenotypes, suggesting EZH2 may have shaped the skeleton of whales in evolutionary history.

Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs.

BACKGROUND: Erythrocytic pyruvate kinase (PK) deficiency, first documented in Basenjis, is the most common inherited erythroenzymopathy in dogs. OBJECTIVES: To report 3 new breed-specific PK-LR gene mutations and a retrospective survey of PK mutations in as mall and selected group of Beagles and West Highland White Terriers (WHWT). ANIMALS: Labrador Retrievers (2 siblings, 5 unrelated), Pugs (2 siblings, 1 unrelated), Beagles (39 anemic, 29 other),WHWTs (22 anemic, 226 nonanemic), Cairn Terrier (n = 1). METHODS: Exons of the PK-LR gene were sequenced from genomic DNA of young dogs (<2 years) with persistent highly regenerative hemolytic anemia. RESULTS: A nonsense mutation (c.799C>T) resulting in a premature stop codon was identified in anemic Labrador Retriever siblings that had osteosclerosis, high serum ferritin concentrations, and severe hepatic secondary hemochromatosis. Anemic Pug and Beagle revealed 2 different missense mutations (c.848T>C, c.994G>A, respectively) resulting in intolerable amino acid changes to protein structure and enzyme function. Breed-specific mutation tests were developed. Among the biased group of 248 WHWTs, 9% and 35% were homozygous (affected) and heterozygous, respectively, for the previously described mutation (mutant allele frequency 0.26). A PK-deficient Cairn Terrier had the same insertion mutation as the affected WHWTs. Of the selected group of 68 Beagles, 35% were PK-deficient and 3% were carriers (0.37). CONCLUSIONS AND CLINICAL IMPORTANCE: Erythrocytic PK deficiency is caused by different mutations in different dog breeds and causes chronic severe hemolytic anemia, hemosiderosis, and secondary hemochromatosis because of chronic hemolysis and, an as yet unexplained osteosclerosis. The newly developed breed-specific mutation assays simplify the diagnosis of PK deficiency.

Generalized osteosclerosis in a cat.

A 12-year-old, neutered male, domestic long-hair cat was evaluated for a 6-month history of inspiratory stertor and epiphora. In computed tomography of the skull and pelvis, and radiographs of the thorax, right femur and stifle there was generalized osteosclerosis, with obliteration of the nasal turbinates and nasolacrimal duct obstruction. The cat also had a large fibrosarcoma involving the right pelvic limb. Osteosclerosis is a rare disorder that is poorly understood but has been described in several species. Various manifestations, potential causes, and radiologic findings of osteosclerosis are discussed.

Genetic test for pyruvate kinase deficiency of Basenjis.

Pyruvate kinase (PK) deficiency is an autosomal, recessive, inherited disease of Basenjis that causes chronic, regenerative, hemolytic anemia. Diagnostic methods currently used to identify carrier animals rely on measurement of erythrocyte PK activity and frequently give equivocal results. A genetic test incorporating polymerase chain reaction amplification of genomic DNA and restriction fragment length polymorphism has been developed to determine the PK genotype of Basenjis. To determine whether results of this genetic test compared with results of standard tests for PK deficiency, erythrocyte PK activity, hematocrit, and reticulocyte counts were determined in, and the genetic test was performed on, 24 dogs. The genetic test accurately identified the 11 dogs whose PK genotype was known prior to this study, and results were consistent with results of measuring erythrocyte PK activity in the remaining 13 dogs. The genetic test may be of value in determining PK genotype of Basenjis.

Determination of erythrocyte pyruvate kinase deficiency in Basenjis with chronic hemolytic anemia.

Erythrocyte pyruvate kinase (PK) deficiency was first described in Basenjis 20 years ago. Although the approach to diagnosis had not been well established, a screening program to detect heterozygotes was thought to have eliminated PK deficiency from the Basenjis of the United States. Four not closely related Basenjis with severe chronic hemolytic anemia, from various parts of the United States, were studied. Their PCV ranged from 16 to 25% and their reticulocyte count was always above 15%. A progressive osteosclerosis was seen in all of the Basenjis and hepatic failure developed in 2 of them. The erythrocyte intermediary metabolite patterns indicated a glycolytic defect at the PK step. Erythrocyte PK activities were markedly increased in the anemic Basenjis, compared with those of a control group, but the enzyme in these Basenjis had abnormal kinetic properties and was thermolabile. An antibody against R-type PK, the regular erythrocyte PK form, did not neutralize the PK activity of affected Basenjis, and results of electrophoretic studies suggested the expression of M2-type PK, a leukocyte and fetal erythroid PK-type. Clinically healthy heterozygous Basenjis had half-normal R-type PK activity and did not express the M2-type in their erythrocytes. We conclude that severe chronic hemolytic anemia, caused by erythrocyte PK deficiency, and associated osteosclerosis still develop in Basenjis. A definitive diagnosis cannot be reached by simply measuring erythrocyte PK activity; rather, diagnosis requires measurement of glycolytic substrate accumulation and enzyme stability and immunologic or electrophoretic studies of erythrocyte PK.

Subchondral lucency of the third carpal bone in Standardbred racehorses: 13 cases (1982-1988).

Thirteen Standardbreds had subchondral lucency of the third carpal bone (C3), described as single or multiple central areas of C3 bone loss in the radial fossa. Sclerosis of the radial fossa was also detected. The mean age of 9 stallions, 3 mares, and 1 gelding was 4.1 years (range, 3 to 7 years). All horses had an acute moderate to severe lameness referable to the middle carpal joint. A dorsoproximal dorsodistal (skyline) radiographic projection was most useful and identified mild (3 horses), moderate (6 horses), and severe (4 horses) subchondral lucency and sclerosis of the radial fossa. The margin of C3 was intact dorsal to the lucent areas in all horses. In 12 horses, arthroscopic surgical evaluation and curettage of the lesion were performed. Of the 9 horses monitored long enough to allow racing, 8 horses (89%) returned to racing, although only 6 (75%) raced at the same degree of competition. Subchondral lucency of C3 resulted from chronic damage to C3 with subsequent osteochondral collapse or acute C3 proximal surface osteochondral fracture.

Osteosclerosis in F344/DuCrj rats.

Osteosclerosis was observed in the tibia and sternum in F344/DuCrj rats of both sexes at 6, 18 and 30 months of age. The lesion first seen was a proliferation of osteogenic tissues on the marrow surface of the cortical bone and bone trabeculae, resulting in replacement of the marrow cavity by lamellar bone. Most of the affected rats had associated degenerative osteoarthrosis and regressive changes of the growth plate. Osteosclerosis was considered to be an aging change, lesions were observed at 6 months and increased in frequency with age.

Osteosclerosis, a recessive skeletal mutation on chromosome 19 in the mouse.

Osteosclerosis (oc) is an osteopetrotic mutation in the mouse inherited as an autosomal recessive on chromosome 19. Affected animals (oc/oc) exhibit the characteristic radiologic and histologic hallmarks of osteopetrosis including a generalized increase in skeletal density and absence of marrow cavities. Most die within three weeks after birth. Osteoclasts are cytologically abnormal by light microscopy in that they do not have cytoplasmic vacuoles. Presumptive evidence of rickets in this mutation includes thick cartilagenous growth plates and excessive osteoid. Extensive extramedullary hemopoiesis occurs in the liver and spleen of mutants. This unique constellation of features suggests that the oc mutation is a valuable model in which to investigate the pathogenesis of osteopetrosis.

Panosteitis in a cocker spaniel dog.

A 12-month-old, desexed female Cocker Spaniel had intermittent bilateral foreleg lameness which was due to panosteitis of the radius and ulna. The disease was in the active 'middle' state. Endosteal and periosteal new bone formation was demonstrated by histological examination and accounted for the diffuse osteosclerotic appearance of the radial and ulnar diaphyses seen on radiographs.

Renal secondary hyperparathyroidism in aged Sprague-Dawley rats.

Fourteen aged Sprague-Dawley rats had typical renal secondary hyperparathyroidism. The renal disease was severe glomerulosclerosis with tubular dilation. The parathyroid glands were enlarged and had hyperplasia of chief cells. Bone lesions were generalized osteodystrophia fibrosa and osteosclerosis. All rats had osteodystrophia fibrosa and it was severe in 10 rats. Only four rats had osteosclerosis and it was moderate. Metastatic calcification was seen in various soft tissues in 13 rats.

Pyruvate kinase deficiency anemia with terminal myelofibrosis and osteosclerosis in a beagle.

A 15-month-old male Beagle with chronic hemolytic anemia was found to have erythrocytic pyruvate kinase deficiency and, terminally, myelofibrosis and osteosclerosis. The dog's erythron was studied by procedures that enabled close comparison with congenital hemolytic anemia (pyruvate kinase deficiency) of Basenji dogs. The affected dog's sire, dam, and one littermate--each clinically and hematologically normal--were found to have 50% reduction in erythrocytic pyruvate kinase (PK) activity.