Neoplastic cells were isolated from 2 sibling Great Dane/Labrador Retriever mixed-breed dogs in which telangiectatic type osteosarcomas arose concurrently. Cells from various sites in the same osteosarcoma appeared similar in culture, but there were differences between the 2 osteosarcomas in growth characteristics and appearance of cells. Cells from 1 osteosarcoma had a small, but significant (P less than 0.05), cyclic adenosine monophosphate response to parathyroid hormone stimulation, indicating a low order of osteoblastic differentiation. Cells from the other osteosarcoma had no response to parathyroid hormone stimulation. Cells from both osteosarcomas and a concentrated cell-free filtrate from the osteosarcoma with osteoblastic differentiation were injected into nude mice, but osteosarcomas were not induced. Results of ultrastructural examination of osteosarcoma samples for viral particles were negative and supernatant fluids from cultured cells were considered negative for viral reverse transcriptase activity.

We compared the frequency and severity of osteochondrosis lesions in young Thoroughbred horses with cervical stenotic myelopathy (CSM) vs that in clinically normal Thoroughbreds of the same age. All lesions of the cervical vertebrae and appendicular skeleton were classified histologically as osteochondrosis or nonosteochondrosis and were measured for severity. Minimal sagittal diameter was significantly smaller in horses with CSM from C2 through C6; no difference was detected at C7. Severity of cervical vertebral osteochondrosis was greater in the horses with CSM, however frequency was not different. Frequency and severity of nonosteochondrosis lesions were not different in cervical vertebrae or appendicular skeleton. Frequency and severity of appendicular skeleton osteochondrosis lesions were both greater in horses with CSM. Osteochondrosis and nonosteochondrosis lesions were more severe on facets at sites of compression than on facets at noncompressed sites in horses with CSM. However, compression was also observed at sites with no articular facet lesions. The association of widespread osteochondrosis and spinal canal narrowing with CSM suggests CSM may represent a systemic failure in the development or maturation of cartilage and bone.

Lumbar and thoracic vertebrae of the extinct horse, Equus occidentalis, were examined for gross and radiographic evidence of overriding spinous processes. Of 2,661 vertebrae examined, 580 had intact spinous processes. Thirty-six intact spinous processes, which appeared grossly similar to overriding spinous processes in the modern domestic horse, E caballus caballus, were radiographed. Of these 36 vertebrae, 2 had radiographic signs compatible with a radiographic diagnosis of overriding spinous processes, ie, radiographically observed lysis and/or sclerosis. Seemingly, weight bearing or other stresses imposed by human beings may not have induced the signs of overriding spinous processes.

The effects of intra-articular administration of methylprednisolone acetate (MPA) on the healing of full-thickness osteochondral defects and on normal cartilage were evaluated in 8 horses. In group-1 horses (n = 4), a 1-cm-diameter, full-thickness defect was created bilaterally in the articular cartilage on the dorsal distal surface of the radial carpal bone. Cartilage defects were not created in group-2 horses (n = 4). One middle carpal joint was randomly selected in each horse (groups 1 and 2), and treated with an intra-articular injection of 100 mg Of MPA, once a week for 4 treatments. Injections began 1 week after surgery in group-1 horses. The contralateral middle carpal joint received intra-articular injections of an equivalent volume of 0.9% sodium chloride solution (SCS), and served as a control. Horses were evaluated for 16 weeks, then were euthanatized, and the middle carpal joints were examined and photographed. Synovial and articular cartilage specimens were obtained for histologic and histochemical evaluation. Gross morphometric evaluation of the healing defects in group-1 horses revealed that 48.6% of the defect in control joints and 0% of the defect in MPA-treated joints was resurfaced with a smooth, white tissue, histologically confirmed as fibrocartilage. This replacement tissue was a firmly attached fibrocartilage in control joints and a thin fibrous tissue in MPA-treated joints. The articular cartilage in joints treated with MPA had morphologic changes, including chondrocyte cluster formation, loss of palisading architecture, and cellular necrosis in both groups of horses. Histochemical (safranin-0) staining intensity was reduced significantly (P < 0.05) in all layers of articular cartilage in MPA-treated joints in groups 1 and 2. In the replacement tissue, intense safranin-O staining was found only in the chondrocyte clusters deep in the tissue of control joints, confirming fibrocartilage repair. Intra-articular administration of MPA in this dosing regimen thus induced degenerative changes in normal articular cartilage and resulted in histomorphologic changes in the repair of full-thickness articular osteochondral defects in horses.

Osteoporosis is defined as a decrease in bone mass that leads to an increased risk of fracture. The therapeutic effect of 1alpha,25 dihydroxycholecalciferol, the hormonal form of vitamin D3 that mediates calcium translation in intestine and bone, on the healing process of fracture has still been controversial. These studies were designed to understand the healing process of normal fibular fracture, the osteoporotic changes after ovariectomy, and the theraqeutic effects of 1alpha,25 dihydroxycholecalciferol on the osteoporotic fracture in rats. The simple transverse fractures of rat fibulae were produced with a rotating diamond saw. The changes of the biochemical and mechanical indices of rats were investigated. The mechanical study based on bending test revealed the healing of the fibular fracture in the 5th week after simple transverse fracture. The osteoporosis impaired more the healing of osteoporotic fibular fracture than normal non-osteoporotic fibular fracture. The healing process of osteoporotic fracture was facilitated by the treatment with 1alpha,25 dihydroxycholecalciferol, however was delayed more than the healing process of normal fracture. The bone strength based on the bending test also confirmed this tendency. The bone strengths in the 5th week after fracture of normal bone, osteoporotic bone, and 1alpha,25 dihydroxycholecalciferol-treated osteoporotic bone were 75%, 41% and 67%, respectively, in comparison with those of intact bone. In conclusion, 1alpha,25 dihydroxycholecalciferol was effective in promoting the osteroporotic fracture healing.

Periosteal autograft were used for repair of large osteochondral defects in 10 horses aged 2 to 3 years old. In each horse, osteochondral defects measuring 1.0 X 1.0 cm2 were induced bilaterally on the distal articular surface of each radial carpal bone. Control and experimental defects were drilled. Periosteum was harvested from the proximal portion of the tibia and was glued into the principal defects, using a fibrin adhesive. Control defects were glued, but were not grafted. Sixteen weeks after the grafting procedure, the quality of the repair tissue of control and grafted defects was assessed biochemically. Total collagen content and the proportion of type-II collagen were determined. Galactosamine and glucosamine contents also were determined. From these measurements, contents of chondroitin and keratan sulfate and total glycosaminoglycan, and galactosamine-to-glucosamine ratio were calculated. All biochemical variables were compared with those of normal equine articular cartilage taken from the same site in another group of clinically normal horses. Total collagen content was determined on the basis of 4-hydroxyproline content, using a colorimetric method. The proportions of collagen types I and II in the repair tissue were assessed by electrophoresis of their cyanogen bromide-cleaved peptides on sodium dodecyl sulfate slab gels. Peptide ratios were computed and compared with those of standard mixtures of type-I and type-II collagens. Galactosamine and glucosamine contents were determined by use of ion chromatography. In general, the biochemical composition of repair tissue of grafted and nongrafted defects was similar, but clearly differed from that of normal articular cartilage. Total glycosaminoglycan content, galactosamine and glucosamine contents, and galactosamine-to-glucosamine ratio of grafted and nongrafted defects were all significantly (P < 0.05) less than corresponding values in normal equine articular cartilage. By contrast, total collagen content of neocartilaginous tissues of grafted and nongrafted defects was greater than that of normal articular cartilage, although the difference was not significant. The proportion of type-I and type-II collagens in repair tissue in grafted and nongrafted defects was 70 and 30%, respectively. The fibrous nature of the repair tissue reported in a companion morphologic and histochemical study was substantiated by the biochemical results. We concluded that use of periosteal autograft did not improve the healing of osteochondral defects.

The third carpal bone (C3) was collected from both forelimbs of 27 Thoroughbreds. On the basis of age, training, and history, specimens were assigned to 1 of 5 groups: yearling, untrained horses (group 1, n = 4); 2- to 3-year-old, untrained horses (group 2, n = 7); trained 2-year-old horses (group 3, n = 6); trained 3-year-old horses (group 4, n = 6); and 3-year-old, trained horses with carpal pathologic features (group 5, n = 4). A transverse section of subchondral bone 5-mm thick was cut in a precise fashion 10 mm below the proximal articular surface of all specimens. After high-detail radiography was done, indentation testing was performed on the proximal surface of the section at points 5 mm apart. The stiffness of the subchondral cancellous bone was determined from the slope of the load vs displacement curve. Topographic plots of stiffness measurements were compared with radiographs of each specimen. Point determinations were averaged to derive measures for the radial and intermediate facets, and for regions 5, 10, 15, and 20 mm from the dorsal margin of C3. Area fraction (1-p; p = porosity) was measured for the radial and intermediate facets, using an automated image analysis system. Significant (P < 0.05) increases in stiffness and area fraction were found in the C3 from trained horses (groups 3 to 5), compared with untrained horses (groups 1 to 2). Stiffness and area fraction of the radial facet of pathologic C3 were significantly higher than the same variables measured in C. from any other group. A typical profile of regional subchondral stiffness was identified in C3 from normal horses, with maximal stiffness measured 10 mm from the dorsal articular margin. A different pattern was found in pathologic C3, with significantly greater stiffness 15 and 20 mm from the dorsal articular margin when compared with normal horses. A highly significant (P < 0.0001) direct linear correlation between stiffness and area fraction at the radial facet was found. Topographic and radiographic analysis demonstrated good correlation between stiffness and radiographic density of the bone sections. The observed patterns of normal and pathologic C3 were contrasted. In particular, a large gradient in sub-chondral stiffness was identified in pathologic C3 at the dorsomedial aspect of the bone.

The use of periosteal autografts to resurface osteochondral defects was investigated in 10 horses (2 to 3 years old), and the repair tissue was characterized morphologically. Middle carpal joint arthrotomies were made, and osteochondral defects were induced bilaterally on the distal articular surface of each radial carpal bone. Each defect measured approximatively 1 cm2 and extended 3 mm into the subchondral bone plate. Residual subchondral bone plate of control and principal defects was perforated by drilling. A sterile fibrin adhesive was made by mixing a fibrinogen component and a thrombin component. A periosteal autograft was harvested from the proximal portion of the tibia and was glued onto the recipient osseous surface, with its cambium facing the joint cavity. Control defects were glued, but not grafted. Horses were walked 1 hour daily on a walker, starting at postoperative week 7 and continuing for 9 weeks. Sixteen weeks after the grafting procedure was done, carpal radiography was performed, after which horses were euthanatized. Quality of repair tissue of control and grafted defects was evaluated and compared grossly, histologically, and histochemically. Using a reticule, the proportions of various repair tissue types filling each defect were quantitated. Seven weeks after the grafting procedure was done, bilateral arthroscopy revealed synovial adhesions and marginal pannus formation in control and grafted defects. None of the autograft was found floating unattached within the respective middle carpal joints. At 16 weeks, the gross appearance of most grafted and nongrafted defects was similar, and repair was dominated by a fibrous pannus. In 4 grafted defects, bone had formed either concentrically within the defect or eccentrically in the fibrous adhesions between the defect and the joint margin. Histologically, all grafted and nongrafted defects were repaired similarly by infiltration of a mixture of fibrous tissue, fibrocartilage, and bone. Fibrous tissue was the predominant tissue in most defects and its mean proportion was 56 and 59% in the grafted and nongrafted defects, respectively. Fibrocartilaginous tissue in the deeper layers approximated 20%, and woven bone at the base of the defect was 20% in all defects. Histochemically, difference in staining for proteoglycans was not observed between grafted and nongrafted defects. Little remaining original periosteal graft tissue was evident at the defect sites. The only distinguishing feature of grafted defects was the presence of islands of bone formation either at the defect site (n = 2 horses), or in somewhat dorsally displaced tissue that was incorporated in fibrous adhesions (n = 2 horses). It was concluded that use of periosteal autograft did not improve the healing of osteochondral defects of the distal portion of the radial carpal bone. The repair tissue produced in grafted and nongrafted defects was similar and was principally fibrous in nature.

Six mature Holstein bulls were given an 8-day course of phenylbutazone (PBZ) orally (loading dose, 12 mg of PBZ/kg of body weight and 7 maintenance doses of 6 mg of PBZ/kg, q 24 h). Plasma concentration-vs-time data were analyzed, using nonlinear regression modeling. The harmonic mean +/- pseudo-SD of the biologic half-life of PBZ was 61.8 +/- 12.8 hours. The arithmetic mean +/- SEM of the total body clearance and apparent volume of distribution were 0.0021 +/- 0.0001 L/h/kg and 0.201 +/- 0.009 L/kg, respectively. The predicted mean minimal plasma concentration of PBZ with this dosage regimen was 75.06 +/- 4.05 microgram/ml. The predicted minimal plasma drug concentration was compared with the observed minimal plasma drug concentration in another group of bulls treated with PBZ for at least 60 days. Sixteen mature Holstein bulls were given approximately 6 mg of PBZ/kg, PO, daily for various musculoskeletal disorders. The mean observed minimal plasma concentration of PBZ in the 16 bulls was 76.10 +/- 2.04 microgram/ml, whereas the mean predicted minimal plasma concentration was 74.69 +/- 3.10 microgram/ml. Dosages of 4 to 6 mg of PBZ/kg, q 24 h, or 10 to 14 mg of PBZ/kg, q 48 h, provided therapeutic plasma concentrations of PBZ with minimal steady-state concentrations between 50 and 70 microgram/ml.