Objective—To evaluate the temporal pattern of
prostaglandin (PG) E2 concentrations in synovial fluid
after transection of the cranial cruciate ligament
(CCL) in dogs and to correlate PGE2 concentrations
with ground reaction forces and subjective clinical
variables for lameness or pain.
Animals—19 purpose-bred adult male Walker
Procedure—Force plate measurements, subjective
clinical analysis of pain or lameness, and samples of
synovial fluid were obtained before (baseline) and at
various time points after arthroscopic transection of
the right CCL. Concentrations of PGE2 were measured
in synovial fluid samples, and the PGE2 concentrations
were correlated with ground reaction
forces and clinical variables.
Results—The PGE2 concentration increased significantly
above the baseline value throughout the entire
study, peaking 14 days after transection. Peak vertical
force and vertical impulse significantly decreased by
day 14 after transection, followed by an increase over
time without returning to baseline values. All clinical
variables (eg, lameness, degree of weight bearing,
joint extension, cumulative pain score, effusion score,
and total protein content of synovial fluid, except for
WBC count in synovial fluid) increased significantly
above baseline values. Significant negative correlations
were detected between PGE2 concentrations
and peak vertical force (r, –0.5720) and vertical
impulse (r, –0.4618), and significant positive correlations
were detected between PGE2 concentrations
and the subjective lameness score (r, 0.5016) and
effusion score (r, 0.6817).
Conclusions and Clinical Relevance—Assessment
of the acute inflammatory process by measurement
of PGE2 concentrations in synovial fluid may be correlated
with the amount of pain or lameness in dogs.
(Am J Vet Res 2004;65:1269–1275)
Objective—To determine whether decreases in peak
vertical force of the hind limb after transection of the
cranial cruciate ligament (CrCL) would be indicative of
medial meniscal damage in dogs.
Animals—39 purpose-bred adult male Walker
Procedure—The right CrCL was transected arthroscopically.
Force plate measurements of the right
hind limb were made prior to and 2, 4, 10, and 18
weeks after transection of the CrCL. Only dogs with
≥ 10% decreases in peak vertical force after week 2
were considered to have potential meniscal damage.
Dogs that did not have ≥ 10% decreases in peak vertical
force at any time point after week 2 were
assigned to group 1. Group 2 dogs had ≥ 10%
decreases in peak vertical force from weeks 2 to 4
only. Group 3 and 4 dogs had ≥ 10% decreases in
peak vertical force from weeks 4 to 10 only or from
weeks 10 to 18 only, respectively. Damage to menisci
and articular cartilage was graded at week 18, and
grades for groups 2 to 4 were compared with those
of group 1.
Results—The percentage change in peak vertical
force and impulse area was significantly different in
groups 2 (n = 4), 3 (4), and 4 (4) at the end of each
measurement period (weeks 4, 10, and 18, respectively)
than in group 1 (27). The meniscal grade for
groups 2 to 4 was significantly higher than for group
1. A ≥ 10% decrease in peak vertical force had sensitivity
of 52% and accuracy of 72% for identifying
dogs with moderate to severe medial meniscal damage.
Conclusions and Clinical Relevance—In dogs with
transected or ruptured CrCLs, force plate analysis can
detect acute exacerbation of lameness, which may be
the result of secondary meniscal damage, and provide
an objective noninvasive technique that delineates
the temporal pattern of medial meniscal injury.
( Am J Vet Res 2005;66:156–163)
Objective—To compare articular cartilage from horses
with naturally developing osteochondrosis (OC)
with normal articular cartilage and healing cartilage
obtained from horses with experimentally induced
Sample Population—109 specimens of articular cartilage
from 78 horses.
Procedure—Morphologic characteristics, proteoglycan
(PG), and type II collagen were analyzed in articular cartilage
of OC specimens (group 1), matched healing cartilage
obtained 40 days after experimentally induced
osteochondral fractures (group 2), and matched normal
cartilage from the same sites (group 3).
Results—79 specimens of OC cartilage were
obtained from horses. Ex vivo PG synthesis was significantly
greater in the femoral cartilage, compared
with synthesis in the tibial cartilage, and significantly
greater for groups 1 and 2, compared with group 3.
For groups 1 and 2, femoral fragments had significantly
greater PG content, compared with PG content
in tibial fragments. Keratan sulfate content was significantly
less in group 3, compared with groups 1 and
2. Cartilage from the OC specimens had loss of structural
architecture. The OC tissue bed stained positive
for chondroitin sulfate and type II collagen, but the
fracture bed did not.
Conclusions and Clinical Relevance—Our analyses
could not distinguish articular cartilage from horses
with OC and a healing fracture. Both resembled an
anabolic, reparative process. Immunohistochemical
analysis suggested a chondromyxoid tissue in the OC
bed that was morphologically similar to fibrous tissue
but phenotypically resembled hyaline cartilage. Thus,
tissue in the OC bed may be degenerative cartilage,
whereas tissue in the fracture bed may be reparative
fibrous callus. (Am J Vet Res 2005;66:1881–1890)
Objective—To assess clinical, radiographic, histologic, and biochemical effects of sodium pentosan polysulfate (NaPPS) administered IM for treatment of experimentally induced osteoarthritis in horses.
Procedures—Osteoarthritis was induced arthroscopically in 1 middle carpal joint of all horses. Nine horses received NaPPS (3 mg/kg, IM) on study days 15, 22, 29, and 36. Nine control horses received the same volume of saline (0.9% NaCl) solution IM on study days 15, 22, 29, and 36. Clinical, radiographic, gross, histologic, histochemical, and biochemical findings as well as findings of synovial fluid analysis were evaluated.
Results—No adverse treatment-related events were detected. Induced osteoarthritis caused a substantial increase in lameness, response to flexion, joint effusion, radiographic findings, synovial membrane inflammation, and articular cartilage fibrillation. Articular cartilage fibrillation was substantially reduced by NaPPS treatment, and concentrations of chondroitin sulfate 846 epitope were significantly increased in the synovial fluid of osteoarthritic and nonosteoarthritic joints of treated horses.
Conclusions and Clinical Relevance—Results indicated that NaPPS has some beneficial disease-modifying effects and may be a therapeutic option for osteoarthritis in horses.
OBJECTIVE To evaluate the efficacy of IV administration of a product containing hyaluronan, sodium chondroitin sulfate, and N-acetyl-d-glucosamine for prevention or treatment of osteoarthritis in horses.
ANIMALS 32 healthy 2- to 5-year-old horses.
PROCEDURES The study involved 2 portions. To evaluate prophylactic efficacy of the test product, horses received 5 mL of the product (n = 8) or saline (0.9% NaCl) solution (8; placebo) IV every fifth day, starting on day 0 (when osteoarthritis was induced in the middle carpal joint of 1 forelimb) and ending on day 70. To evaluate treatment efficacy, horses received either the product or placebo (n = 8/treatment) on days 16, 23, 30, 37, and 44 after osteoarthritis induction. Clinical, diagnostic imaging, synovial fluid, gross anatomic, and histologic evaluations and other tests were performed. Results of each study portion were compared between treatment groups.
RESULTS Limb flexion and radiographic findings were significantly worse for horses that received the test product in the prophylactic efficacy portion than for placebo-treated horses or product-treated horses in the treatment efficacy portion. In the prophylactic efficacy portion, significantly less articular cartilage erosion was identified in product-treated versus placebo-treated horses. In the treatment efficacy portion, joints of product-treated horses had a greater degree of bone edema identified via MRI than did joints of placebo-treated horses but fewer microscopic articular cartilage abnormalities.
CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that caution should be used when administering the evaluated product IV to horses, particularly when administering it prophylactically, as it may have no benefit or may even cause harm.
Objective—To investigate the influence of early conditioning exercise on the development of gross cartilage defects and swelling behavior of cartilage extracellular matrix (ECM) in the midcarpal joint of horses.
Procedures—6 horses underwent early conditioning exercise from birth to 18 months of age (CONDEX group), and 6 horses were used as control animals (PASTEX group). The horses were euthanized at 18 months of age, and the midcarpal joints were harvested. Gross defects of the cartilage surface were classified and mapped. Opposing surfaces of the third and radial carpal bones were used to quantify swelling behavior of the cartilage ECM.
Results—A wide range of gross defects was detected in the cartilage on the opposing surfaces of the bones of the midcarpal joint; however, there was no significant difference between the CONDEX and PASTEX groups. Similarly, no significant difference in swelling behavior of the cartilage ECM was evident between the CONDEX and PASTEX groups.
Conclusions and Clinical Relevance—In the study reported here, we did not detect negative influences of early conditioning exercise on the prevalence of gross defects in cartilage of the midcarpal joint or the quality of the cartilage ECM as defined by swelling behavior. These results suggested that early conditioning exercise may be used without negative consequences for the midcarpal joint and the cartilage ECM of the third and radial carpal bones.
Objective—To describe and measure histologic features of midcarpal joint cartilage defects in Thoroughbreds and evaluate the influence of early conditioning exercise on defect development.
Sample—24 midcarpal joints from twelve 18-month-old Thoroughbreds.
Procedures—Midcarpal joints from 12 horses (6 exercised spontaneously at pasture only and 6 given additional conditioning exercise beginning at a mean age of 3 weeks were evaluated. Gross cartilage defects were assessed histologically. Third and radial carpal bones were categorized with regard to the presence or absence of calcified cartilage (CC) abnormalities at the dorsoproximal and dorsodistal articular surfaces, respectively; histomorphometric assessment and statistical analysis were conducted for the third carpal bone.
Results—Number and severity of defects did not appear different between exercise groups. Nine third or radial carpal bones had thickened CC with microcracks, matrix and osteochondral junction changes, and increased vascularity, without histologic changes in the hyaline cartilage. Third carpal bones with CC abnormalities had significantly thicker CC (452 vs 228 μm) than did those without CC abnormalities in the evaluated region. However, in the same region, there were no significant differences in hyaline cartilage thickness (681 vs 603 μm), vascular channel area in the subchondral bone (624,894 vs 490,320 μm2), or number of vascular channels (15.9 vs 18.0).
Conclusions and Clinical Relevance—Early exercise did not appear to influence the distribution or severity of cartilage defects in the midcarpal joint. Calcified cartilage abnormalities beneath the undisrupted hyaline cartilage in the dorsoproximal aspect of the third carpal bone may represent the first changes in the pathogenesis of midcarpal osteochondral disease.
Objective—To investigate histomorphometric changes in the cartilage and subchondral bone of the third carpal bone associated with conditioning exercise in young Thoroughbreds.
Animals—Nine 18-month-old Thoroughbreds.
Procedures—Both third carpal bones of 9 horses (4 exercised spontaneously at pasture only and 5 given additional conditioning exercise beginning at a mean age of 3 weeks) were evaluated. Histomorphometric variables (hyaline and calcified cartilage thickness and collagen orientation; vascular channel area, number, and orientation; and osteochondral junction rugosity) of the third carpal bone, sampled at 4 dorsopalmar sites in the radial facet, were compared between the exercised and nonexercised groups.
Results—The vascular channel area measured at the 4 dorsopalmar sites was larger in the exercised group than in the control group, but none of the variables were significantly different between groups. Both groups had significant site-specific variations in all measured variables. Most importantly, the vascular channel area was highest in the most dorsal aspect.
Conclusions and Clinical Relevance—Results suggested that the mild exercise imposed in both groups during the developmental period appeared to be associated with an increase in the vascular channel area beneath the calcified cartilage layer in the third carpal bone. This increased vascular channel area could also be associated with high stress in the dorsal aspect of the radial facet, a region that is known to be vulnerable to osteochondral fragmentation.
Objective—To develop an antibody that specifically
recognizes collagenase-cleaved type-II collagen in
equine articular cartilage.
Sample Population—Cartilage specimens from
horses euthanatized for problems unrelated to the
Procedure—A peptide was synthesized representing
the carboxy- (C-) terminus (neoepitope) of the equine
type-II collagen fragment created by mammalian collagenases.
This peptide was used to produce a polyclonal
antibody, characterized by western analysis for
reactivity to native and collagenase-cleaved equine
collagens. The antibody was evaluated as an antineoepitope
antibody by ELISA, using peptides ± an
amino acid at the C-terminus of the immunizing peptide.
Collagen cleavage was assayed from equine
articular cartilage cultured with interleukin-1 (IL-1), ± a
synthetic MMP inhibitor, BAY 12-9566. Cartilage
specimens from osteoarthritic and nonarthritic joints
were compared for antibody staining.
Results—An antibody, 234CEQ, recognized only collagenase-
generated 3/4-length fragments of equine
type-II collagen. This was a true antineoepitope antibody,
as altering the C-terminus of the immunizing
peptide significantly decreased competition for binding
in an inhibition ELISA. The IL-1-induced release of
type-II collagen fragments from articular cartilage was
prevented with the MMP inhibitor. Cartilage from an
osteoarthritic joint of a horse had increased staining
with the 234CEQ antibody, compared with normal
Conclusions and Clinical Relevance—We generated
an antineoepitope antibody recognizing collagenase-
cleaved type-II collagen of horses. This antibody
detects increases in type-II collagen cleavage in diseased
equine articular cartilage. The 234CEQ antibody
has the potential to aid in the early diagnosis of
arthritis and to monitor treatment responses. (Am J
Vet Res 2001;62:1031–1039)
Objective—To determine whether serum concentrations
of biomarkers of skeletal metabolism can,
in conjunction with radiographic evaluation, indicate
severity of osteochondrosis in developing
Animals—43 Dutch Warmblood foals with varying
severity of osteochondrosis.
Procedure—24 foals were monitored for 5 months
and 19 foals were monitored for 11 months. Monthly
radiographs of femoropatellar-femorotibial and tibiotarsal
joints were graded for osteochondral abnormalities.
Serial blood samples were assayed for 8 cartilage
and bone biomarkers. At the end of the monitoring
period, foals were examined for macroscopic
Results—Temporal relationships were evident
between certain serum biomarkers and osteochondrosis
severity in foals during their first year.
Biomarkers of collagen degradation (collagenasegenerated
neoepitopes of type-II collagen fragments,
type-I and -II collagen fragments [COL2-3/4Cshort],
and cross-linked telopeptide fragments
of type-I collagen) and bone mineralization (osteocalcin)
were positive indicators of osteochondrosis
severity at 5 months of age. In foals with lesions at
11 months of age, osteochondrosis severity correlated
negatively with COL2-3/4Cshort and osteocalcin
and positively with C-propeptide of type-II procollagen
(CPII), a collagen synthesis marker.
Radiographic grading of osteochondrosis lesions
significantly correlated with macroscopic osteochondrosis
severity score at both ages and was
strongest when combined with osteocalcin at 5
months and CPII at 11 months.
Conclusions and Clinical Relevance—The ability of
serum biomarkers to indicate osteochondrosis severity
appears to depend on stage of disease and is
strengthened with radiography. In older foals with
more permanent lesions, osteochondrosis severity is
significantly related to biomarker concentrations of
decreased bone formation and increased cartilage synthesis.
(Am J Vet Res 2004;65:143–150)