Differential gene expression analysis reveals pathways important in early post-traumatic osteoarthritis in an equine model.

BACKGROUND: Post-traumatic osteoarthritis (PTOA) is a common and significant problem in equine athletes. It is a disease of the entire joint, with the synovium thought to be a key player in disease onset and progression due to its role in inflammation. The development of effective tools for early diagnosis and treatment of PTOA remains an elusive goal. Altered gene expression represents the earliest discernable disease-related change, and can provide valuable information about disease pathogenesis and identify potential therapeutic targets. However, there is limited work examining global gene expression changes in early disease. In this study, we quantified gene expression changes in the synovium of osteoarthritis-affected joints using an equine metacarpophalangeal joint (MCPJ) chip model of early PTOA. Synovial samples were collected arthroscopically from the MCPJ of 11 adult horses before (preOA) and after (OA) surgical induction of osteoarthritis and from sham-operated joints. After sequencing synovial RNA, Salmon was used to quasi-map reads and quantify transcript abundances. Differential expression analysis with the limma-trend method used a fold-change cutoff of log2(1.1). Functional annotation was performed with PANTHER at FDR < 0.05. Pathway and network analyses were performed in Reactome and STRING, respectively. RESULTS: RNA was sequenced from 28 samples (6 preOA, 11 OA, 11 sham). "Sham" and "preOA" were not different and were grouped. Three hundred ninety-seven genes were upregulated and 365 downregulated in OA synovium compared to unaffected. Gene ontology (GO) terms related to extracellular matrix (ECM) organization, angiogenesis, and cell signaling were overrepresented. There were 17 enriched pathways, involved in ECM turnover, protein metabolism, and growth factor signaling. Network analysis revealed clusters of differentially expressed genes involved in ECM organization, endothelial regulation, and cellular metabolism. CONCLUSIONS: Enriched pathways and overrepresented GO terms reflected a state of high metabolic activity and tissue turnover in OA-affected tissue, suggesting that the synovium may retain the capacity to support healing and homeostasis in early disease. Limitations of this study include small sample size and capture of one point post-injury. Differentially expressed genes within key pathways may represent potential diagnostic markers or therapeutic targets for PTOA. Mechanistic validation of these findings is an important next step.

Partial ceratohyoidectomy as surgical treatment for horses with temporohyoid osteoarthropathy: 10 cases (2010-2021).

OBJECTIVE: To describe outcomes of horses with temporohyoid osteoarthropathy (THO) treated with partial ceratohyoidectomy. ANIMALS: 10 client-owned horses. PROCEDURES: Medical records from 2 institutions were examined for records of horses with THO treated with partial ceratohyoidectomy between 2010 and 2021. History, signalment, clinical signs, diagnostics, medications, and surgery-related details were recorded. Horses with a minimum of 6 months follow-up were recruited for neurologic and imaging examinations in the hospital or field where radiography of the basihyoid-ceratohyoid articulation were performed along with CT, when available. RESULTS: 10 horses with THO were included (9 unilateral; 1 bilateral). Nine planned partial ceratohyoidectomies were performed in 8 horses, whereas 2 horses had preoperatively planned complete ceratohyoidectomies transitioned to partial ceratohyoidectomies during surgery due to intraoperative complications. Postoperative complications occurred mostly in transitioned surgeries (obstructed airway, tongue mobility issues, and incisional hemorrhage), whereas only 1 horse with a planned ceratohyoidectomy had postoperative complication of rhabdomyolysis. All complications resolved before hospital discharge. Neurologic signs improved in all 10 horses, with 2 showing complete resolution. Nine horses were available for radiographic follow-up, 6 of which also had head CT scans. A space between the ceratohyoid and basihyoid bones was measurable on radiography in all 9 horses, and was confirmed on CT. Three horses demonstrated proliferation of either ceratohyoid or basihyoid bones. The 9 horses with unilateral disease returned to previous work, and the horse with bilateral disease was retired. CLINICAL RELEVANCE: Partial ceratohyoidectomy is a surgical option for treatment of THO that provides similar clinical outcomes to published reports on ceratohyoidectomy.

Targeting Soluble Epoxide Hydrolase and Cyclooxygenases Enhance Joint Pain Control, Stimulate Collagen Synthesis, and Protect Chondrocytes From Cytokine-Induced Apoptosis.

Objective: To determine the symptomatic and disease-modifying capabilities of sEH and COX inhibitors during joint inflammation. Methods: Using a blinded, randomized, crossover experimental design, 6 adult healthy horses were injected with lipopolysaccharide (LPS; 3 µg) from E. coli in a radiocarpal joint and concurrently received the non-selective cyclooxygenase (COX) inhibitor phenylbutazone (2 mg/kg), the sEH inhibitor t-TUCB (1 mg/kg) or both (2 mg/kg phenylbutazone and 0.1, 0.3, and 1 mg/kg t-TUCB) intravenously. There were at least 30 days washout between treatments. Joint pain (assessed via inertial sensors and peak vertical forces), synovial fluid concentrations of prostanoids (PGE2, TxB2), cytokines (IL-1ß, IL-6, TNF-α) and biomarkers of collagen synthesis (CPII) and degradation (C2C) were measured at pre-determined intervals over a 48-h period. The anti-apoptotic effect of COX and sEH inhibitors was determined via ELISA technique in primary equine chondrocytes incubated with TNF-α (10 ng/ml) for 24 h. Apoptosis was also determined in chondrocytes incubated with sEH-generated metabolites. Results: Combined COX and sEH inhibition produced significantly better control of joint pain, prostanoid responses, and collagen synthesis-degradation balance compared to each compound separately. When administered separately, pain control was superior with COX vs. sEH inhibition. Cytokine responses were not different during COX and/or sEH inhibition. In cultured chondrocytes, sEH inhibition alone or combined with COX inhibition, but not COX inhibition alone had significant anti-apoptotic effects. However, sEH-generated metabolites caused concentration-dependent apoptosis. Conclusions: Combined COX and sEH inhibition optimize pain control, attenuate loss of articular cartilage matrix during joint inflammation and cytokine-induced chondrocyte apoptosis.

Associations of horse age, joint type, and osteochondral injury with serum and synovial fluid concentrations of type II collagen biomarkers in Thoroughbreds.

OBJECTIVE: To determine the effects of horse age, osteochondral injury, and joint type on a synthesis biomarker and 3 degradative biomarkers of type II collagen in Thoroughbreds. ANIMALS: Healthy rested adult (3- to 12-year-old) Thoroughbreds (n = 19), yearling (1- to 2-year-old) Thoroughbreds (40), and Thoroughbred racehorses (2 to 7 years old) undergoing arthroscopic surgery for removal of osteochondral fragments that resulted from training or racing (41). PROCEDURES: Samples of blood and metacarpophalangeal, metatarsophalangeal, or carpal joint synovial fluid (SF) were collected from all horses. Commercially available assays were used to analyze SF and serum concentrations of type II collagen biomarkers of synthesis (carboxy propeptide of type II collagen [CPII]) and degradation (cross-linked C-telopeptide fragments of type II collagen [CTX II], neoepitope generated by collagenase cleavage of type I and II collagen [C1,2C], and neoepitope generated by collagenase cleavage of type II collagen [C2C]). RESULTS: Osteochondral injury affected concentrations of CPII, CTX II, C1,2C, and C2C in SF, serum, or both, compared with concentrations in healthy adult horses. Compared with adult horses, yearling horses had increased SF or serum concentrations of degradative biomarkers (CTX II, C1,2C, and C2C). Concentrations were higher in carpal than metacarpophalangeal or metatarsophalangeal joints for all biomarkers in osteochondral-injured horses. Variable differences in SF concentrations between joint types were detected in healthy adult and yearling horses. CONCLUSIONS AND CLINICAL RELEVANCE: Horse age, osteochondral injury, and joint type all significantly affected type II collagen biomarker concentrations in SF and serum of Thoroughbreds.

Effect of exercise and osteochondral injury on synovial fluid and serum concentrations of carboxy-terminal telopeptide fragments of type II collagen in racehorses.

OBJECTIVE: To investigate the effects of exercise and osteochondral injury on concentrations of carboxy-terminal telopeptide fragments of type II collagen (CTX-II) in synovial fluid (SF) and serum of Thoroughbred racehorses and to compare findings with radiographic and arthroscopic scores of joint injury severity. ANIMALS: 78 Thoroughbreds with (n = 38) and without (40) osteochondral injury. PROCEDURES: Serum and metacarpophalangeal or carpal joint SF samples were collected from noninjured horses before and at the end of 5 to 6 months of race training (pre- and postexercise samples, respectively) and from horses with osteochondral injury (1 joint assessed/horse). Synovial fluid and serum CTX-II concentrations were determined by use of an ELISA. Radiographic and arthroscopic scores of joint injury severity were determined for the injured horses. RESULTS: The CTX-II concentrations in SF and SF:serum CTX-II ratio were significantly higher for horses with joint injuries, compared with pre- and postexercise findings in noninjured horses. Serum CTX-II concentrations in postexercise and injured-horse samples were significantly lower than values in pre-exercise samples. On the basis of serum and SF CTX-II concentrations and SF:serum CTX-II ratio, 64% to 93% of serum and SF samples were correctly classified into their appropriate group (pre-exercise, postexercise, or injured-joint samples). In horses with joint injuries, arthroscopic scores were positively correlated with radiographic scores, but neither score correlated with SF or serum CTX-II concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that serum and SF CTX-II concentrations and SF:serum CTX-II ratio may be used to detect cartilage degradation in horses with joint injury.

Evaluation of diffusion of triamcinolone acetonide from the distal interphalangeal joint into the navicular bursa in horses.

OBJECTIVE: To determine whether triamcinolone acetonide diffuses from the distal interphalangeal joint (DIPJ) to the navicular bursa, diffusion is direct or systemic, and addition of sodium hyaluronan has an effect on diffusion in horses. ANIMALS: 11 adult horses without forelimb lameness. PROCEDURES: 1 randomly chosen forelimb DIPJ of each horse received an injection of 10 mg of triamcinolone acetonide plus 20 mg of sodium hyaluronan (group 1), and the contralateral forelimb DIPJ received an injection of 10 mg of triamcinolone acetonide plus 2 mL of lactated Ringer's solution (group 2). Synovial fluid samples were taken from both forelimb navicular bursae and 1 hind limb navicular bursa (systemic control group) at 6 hours. Triamcinolone acetonide concentrations in synovial fluid were quantified by use of high-performance liquid chromatography plus tandem mass spectrometry. Data were logarithmically transformed, and contrast analysis was performed on the 3 groups. RESULTS: Triamcinolone acetonide was detected in navicular bursal samples in all groups. Groups 1 and 2 had significantly greater concentrations of triamcinolone acetonide than the systemic control group. There was no significant difference between groups 1 and 2. CONCLUSIONS AND CLINICAL RELEVANCE: Triamcinolone acetonide diffused directly from the DIPJ into the navicular bursa in clinically normal horses, and diffusion was not affected by addition of hyaluronan. Injection into the DIPJ with triamcinolone acetonide or a triamcinolone acetonide-hyaluronan combination can potentially be used for treatment of navicular syndrome, but further studies are needed to determine whether triamcinolone acetonide diffuses similarly in horses with navicular syndrome.

Prevalence of various presale radiographic findings and association of findings with sales price in Thoroughbred yearlings sold in Kentucky.

OBJECTIVE: To estimate prevalences of various presale radiographic findings and of presale arthroscopy in horses offered for sale at the 2006 Keeneland September yearling sale and to compare sales prices between yearlings with and without various presale radiographic findings or a history of arthroscopy. ANIMALS: 397 Thoroughbred yearlings. DESIGN: Cross-sectional study. PROCEDURES: Presale radiographs and health records were examined to estimate prevalences of various radiographic findings and presale arthroscopy. Sales price records were used to compare sales prices between yearlings with and without various presale radiographic findings or a history of arthroscopy. RESULTS: In the forelimbs, the most common radiographic findings were vascular channels in the proximal sesamoid bones (23%), enthesophytes or osteophytes in the radiocarpal joint (22%), and osteochondritis lesions involving the sagittal ridge of the third metacarpal bone (20%). In the hind limbs, the most common radiographic findings were enthesophytes or osteophytes involving the proximal sesamoid bones (39%), abnormalities of the distodorsal aspect of the third metatarsal bone (36%), enthesophytes or osteophytes involving the distal intertarsal joint (27%), and osteochondritis lesions involving the stifle joint (8%). Thirteen percent of horses had a history of presale arthroscopy. Median sales price was significantly lower in horses with fragments of the proximal phalanx than in horses without. Median sales price was significantly higher in horses with a history of presale arthroscopy than in horses without. CONCLUSIONS AND CLINICAL RELEVANCE: Results revealed significant associations between a diagnosis of fragments of the proximal phalanx, presale arthroscopy, and sales price in Thoroughbred yearlings.

Systemic and local effects of lidocaine or mepivacaine when used for intravenous regional anaesthesia of the distal limb in standing sedated horses.

BACKGROUND: Local anaesthetics are being combined clinically with amikacin in intravenous regional limb perfusion (IVRLP), with limited knowledge on the analgesia provided and its onset and duration of action after tourniquet application and release. OBJECTIVE: To evaluate the systemic clinical effect, limb withdrawal to nociceptive stimulation, and plasma and synovial fluid concentrations after IVRLP with lidocaine or mepivacaine in standing sedated horses. STUDY DESIGN: Prospective, controlled, randomised, cross-over study. METHODS: Six healthy adult horses were sedated and received IVRLP with lidocaine, mepivacaine or saline (negative control), or perineural anaesthesia of the medial and lateral palmar and palmar metacarpal nerves (positive control) in one forelimb with a 3-week washout period between trials. Electrical and mechanical stimuli were used to test nociceptive threshold of the limb before and after IVRLP/perineural anaesthesia. For lidocaine and mepivacaine trials, blood was collected from the jugular vein and synovial fluid from the radiocarpal joint before, during and out to 24 hours after IVRLP. Drug concentrations were measured using high-performance liquid chromatography. RESULTS: Nociceptive thresholds for lidocaine, mepivacaine and perineural anaesthesia trials were significantly increased compared with saline and baseline values at 10, 20 and 30 minutes, with no differences between anaesthetic trials. During this time, horses had lower heart rates than IVRLP with saline. After tourniquet release at 30 minutes, nociceptive thresholds for lidocaine and mepivacaine trials gradually returned to baselines, whereas perineural anaesthesia trial remained unchanged out to an hour. Plasma lidocaine and mepivacaine concentrations were ≤50 ng/mL while the tourniquet was in place, significantly increasing 10 minutes after tourniquet release. Maximal lidocaine and mepivacaine concentrations in synovial fluid were reached 25 minutes after IVRLP injection. MAIN LIMITATIONS: Amikacin was not included in the perfusate. CONCLUSION: Similar to perineural anaesthesia, IVRLP with lidocaine or mepivacaine provides anti-nociception to the distal limb in standing sedated horses while a tourniquet is applied with concentrations remaining below toxic levels in plasma and synovial fluid.

High-mobility group box chromosomal protein 1 as a potential inflammatory biomarker of joint injury in Thoroughbreds.

OBJECTIVE: To investigate effects of osteochondral injury on high-mobility group box chromosomal protein 1 (HMGB-1) concentrations in synovial fluid (SF) from Thoroughbreds and to compare these results with radiographic and arthroscopic scores of severity of joint injury. ANIMALS: 40 clinically normal rested Thoroughbreds (group 1) and 45 Thoroughbreds with osteochondral injury as a result of racing. PROCEDURES: SF was obtained from the metacarpophalangeal (MCP) joints, metatarsophalangeal (MTP) joints, middle carpal joints, and radiocarpal joints. For group 2, radiographic and arthroscopic scores were determined. Concentrations of SF HMGB-1 were determined by use of an ELISA. RESULTS: SF HMGB-1 concentrations in osteochondral-injured MCP-MTP joints were significantly higher than in normal MCP-MTP joints. Similarly, SF HMGB-1 concentrations in osteochondral-injured carpal joints were significantly higher than in normal carpal joints. Radiographic and arthroscopic scores were not correlated with SF HMGB-1 concentrations. Synovial fluid HMGB-1 concentrations > or = 11 ng/mL for MCP-MTP joints and > or = 9 ng/mL for carpal joints discriminated osteochondral-injured joints from normal joints. Horses with HMGB-1 concentrations > or = 11 ng/mL for MCP-MTP joints were twice as likely to have an osteochondral injury, and horses with HMGB-1 concentrations > or = 9 ng/mL for carpal joints were 4 times as likely to have an osteochondral injury. CONCLUSIONS AND CLINICAL RELEVANCE: Osteochondral injury was associated with a significant increase in SF HMGB-1 concentrations in MCP-MTP and carpal joints, compared with results for clinically normal Thoroughbreds. Analysis of SF HMGB-1 concentrations may be useful for evaluation of joint injury in horses.

Palmar/plantar approach for radiographic-guided injection of the equine distal interphalangeal joint collateral ligament insertion.

There are limited radiographic-guided injection techniques of the insertion of the distal interphalangeal joint (DIPJ) collateral ligaments. The objective of this study was to develop and evaluate a palmar/plantar radiographic-guided injection of the collateral ligament insertion in cadavers. Fifty limbs were used to develop the technique and 24 additional limbs were used to evaluate accuracy. An 18 G, 9 cm spinal needle was placed in the depression between the palmar digital neurovascular bundle and arch of the ungular cartilage with dorsodistal advancement towards the distal phalanx collateral fossa. Radiographs verified ideal needle location on the proximal border of the distal phalanx at the collateral fossa. Dye was injected. Hoof walls were partially removed and collateral ligaments were dissected with needles in place to determine needle and dye location. Accuracy of needle placement into the insertion of the DIPJ collateral ligament was 41/48 (85 per cent), with lower accuracy of dye within the ligament (34/48; 71 per cent). Dye entered the DIPJ in 2/48 injections, but dye entered periligamentous structures in 22/48 (46 per cent) injections. A palmar/plantar radiographic-guided injection of the insertion of the DIPJ collateral ligament had high accuracy rate with low injection rate of the DIPJ in cadavers.

Comparison of two indirect techniques for local delivery of a high dose of an antimicrobial in the distal portion of forelimbs of horses.

OBJECTIVE: To compare isolated limb retrograde venous injection (ILRVI) and isolated limb infusion (ILI) for delivery of amikacin to the synovial fluid of the distal interphalangeal and metacarpophalangeal joints and to evaluate the efficacy of use of an Esmarch tourniquet in standing horses. ANIMALS: 6 healthy adult horses. PROCEDURES: Horses were randomly assigned in a crossover design. In ILRVI, the injection consisted of 1 g of amikacin diluted to a total volume of 60 mL administered during a 3-minute period. In ILI, the infusion consisted of 1 g of amikacin diluted to 40 mL administered during a 3-minute period followed by administration of boluses of diluent (82 mL total) to maintain vascular pressure. During ILI, the infusate and blood were circulated from the venous to the arterial circulation in 5-mL aliquots. Synovial fluid and serum samples were obtained to determine maximum amikacin concentrations and tourniquet leakage, respectively. RESULTS: Both techniques yielded synovial concentrations of amikacin > 10 times the minimum inhibitory concentration (MIC) for 90% of isolates (80 microg/mL) and > 10 times the MIC breakpoint (160 microg/mL) of amikacin-susceptible bacteria reported to cause septic arthritis in horses. These values were attained for both joints for both techniques. Esmarch tourniquets prevented detectable loss of amikacin to the systemic circulation for both techniques. CONCLUSIONS AND CLINICAL RELEVANCE: Both techniques reliably achieved synovial fluid concentrations of amikacin consistent with concentration-dependent killing for bacteria commonly encountered in horses with septic arthritis. Esmarch tourniquets were effective for both delivery techniques in standing horses.

Lameness, athletic performance, and financial returns in yearling Thoroughbreds bought for the purpose of resale for profit.

OBJECTIVE: To characterize lameness during training and compare exercise variables and financial returns among yearling Thoroughbreds that were bought for the purpose of resale for profit. ANIMALS: 40 yearling Thoroughbreds. DESIGN: Prospective study. PROCEDURES: Horses purchased at yearling sales (summer 2004) were trained prior to resale at 2-year-olds in training sales (spring 2005). Horses were monitored daily for diagnosis and treatment of lameness during training. Selected variables, including sex, age, purchase price, lameness, distance (No. of furlongs) galloped during training, and financial returns, were compared among horses that had performance speeds (assessed at 2-year-olds in training sales) classified as fast, average, or slow. RESULTS: 37 of 40 horses became lame during training, most commonly because of joint injury. Eighteen of the lame horses had hind limb injuries only; 5 horses had injuries in forelimbs and hind limbs. The frequency of new cases of lameness increased as the date of the 2-year-olds in training sales approached. At the sales, 4, 21, and 15 horses were classified as fast, average, or slow, respectively; median financial return was slightly (but significantly) different among horses classified as fast ($14,000), average ($0), or slow (-$8,000). CONCLUSIONS AND CLINICAL RELEVANCE: Incidence of lameness during training in yearling horses purchased for the purpose of resale for profit was high. Lameness more commonly affected hind limbs than forelimbs and was attributable to joint injury in most horses. Financial returns differed between horses classified as fast and average or slow at the 2-year-olds in training sales.

Low- Versus High-Intensity Plyometric Exercise During Rehabilitation After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Plyometric exercise is used during rehabilitation after anterior cruciate ligament (ACL) reconstruction to facilitate the return to sports participation. However, clinical outcomes have not been examined, and high loads on the lower extremity could be detrimental to knee articular cartilage. PURPOSE: To compare the immediate effect of low- and high-intensity plyometric exercise during rehabilitation after ACL reconstruction on knee function, articular cartilage metabolism, and other clinically relevant measures. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: Twenty-four patients who underwent unilateral ACL reconstruction (mean, 14.3 weeks after surgery; range, 12.1-17.7 weeks) were assigned to 8 weeks (16 visits) of low- or high-intensity plyometric exercise consisting of running, jumping, and agility activities. Groups were distinguished by the expected magnitude of vertical ground-reaction forces. Testing was conducted before and after the intervention. Primary outcomes were self-reported knee function (International Knee Documentation Committee [IKDC] subjective knee form) and a biomarker of articular cartilage degradation (urine concentrations of crosslinked C-telopeptide fragments of type II collagen [uCTX-II]). Secondary outcomes included additional biomarkers of articular cartilage metabolism (urinary concentrations of the neoepitope of type II collagen cleavage at the C-terminal three-quarter-length fragment [uC2C], serum concentrations of the C-terminal propeptide of newly formed type II collagen [sCPII]) and inflammation (tumor necrosis factor-α), functional performance (maximal vertical jump and single-legged hop), knee impairments (anterior knee laxity, average knee pain intensity, normalized quadriceps strength, quadriceps symmetry index), and psychosocial status (kinesiophobia, knee activity self-efficacy, pain catastrophizing). The change in each measure was compared between groups. Values before and after the intervention were compared with the groups combined. RESULTS: The groups did not significantly differ in the change of any primary or secondary outcome measure. Of interest, sCPII concentrations tended to change in opposite directions (mean ± SD: low-intensity group, 28.7 ± 185.5 ng/mL; high-intensity group, -200.6 ± 255.0 ng/mL; P = .097; Cohen d = 1.03). Across groups, significant changes after the intervention were increased the IKDC score, vertical jump height, normalized quadriceps strength, quadriceps symmetry index, and knee activity self-efficacy and decreased average knee pain intensity. CONCLUSION: No significant differences were detected between the low- and high-intensity plyometric exercise groups. Across both groups, plyometric exercise induced positive changes in knee function, knee impairments, and psychosocial status that would support the return to sports participation after ACL reconstruction. The effect of plyometric exercise intensity on articular cartilage requires further evaluation. REGISTRATION NUMBER: Clinicaltrials.gov NCT01851655.

Evaluation of changes in vertical ground reaction forces as indicators of meniscal damage after transection of the cranial cruciate ligament in dogs.

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 Hounds. 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 > or =10% decreases in peak vertical force after week 2 were considered to have potential meniscal damage. Dogs that did not have > or =10% decreases in peak vertical force at any time point after week 2 were assigned to group 1. Group 2 dogs had > or =10% decreases in peak vertical force from weeks 2 to 4 only. Group 3 and 4 dogs had > or =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 > or =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.

Effects of zoledronate on markers of bone metabolism and subchondral bone mineral density in dogs with experimentally induced cruciate-deficient osteoarthritis.

OBJECTIVE: To evaluate effects of zoledronate on markers of bone metabolism in dogs after transection of the cranial cruciate ligament (CrCL). ANIMALS: 21 adult dogs. PROCEDURE: Unilateral CrCL transection was performed arthroscopically. Dogs were allocated to 3 groups (control group, low-dose zoledronate [10 microg/kg, SC, q 90 d for 12 months], and high-dose zoledronate [25 microg/kg, SC, q 90 d for 12 months]). Serum osteocalcin (OC), serum bone-specific alkaline phosphatase (BAP), and urine pyridinoline and deoxypyridinoline concentrations were measured at 0, 1, 3, 6, 9, and 12 months after surgery. Bone mineral density (BMD) was determined in the distal portion of the femur and proximal portion of the tibia via computed tomography at each time point. Data were analyzed by a repeated-measures ANOVA. RESULTS: oledronate inhibited OC in the high-dose group at 9 and 12 months and at 12 months in the low-dose group, compared with the control group. High-dose zoledronate decreased BAP concentrations 3 and 9 months after surgery. In the control group, BMD was decreased in the femoral condyle and caudal tibial plateau. Zoledronate prevented significant BMD decreases starting 1 month after transection, compared with control dogs. In the caudomedial aspect of the tibial plateau, both zoledronate groups had significant increases in BMD after 3 months, compared with control dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Zoledronate may reduce subchondral bone loss and effect markers of bone metabolism in dogs with experimentally induced instability of the stifle joint and subsequent development of osteoarthritis.

Correlation of prostaglandin E2 concentrations in synovial fluid with ground reaction forces and clinical variables for pain or inflammation in dogs with osteoarthritis induced by transection of the cranial cruciate ligament.

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 Hounds. 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.

Concentrations of stromal cell-derived factor-1 in serum, plasma, and synovial fluid of horses with osteochondral injury.

OBJECTIVE: To determine whether stromal cell-derived factor-1 (SDF-1) concentrations in serum, plasma, and synovial fluid differed among untrained, race-trained, and osteochondral-injured Thoroughbred racehorses. ANIMALS: 22 racehorses without osteochondral injury and 37 racehorses with osteochondral injury. PROCEDURES: Horses without osteochondral injury were examined before and after 5 to 6 months of race training. Horses with osteochondral injury were undergoing arthroscopic surgery for removal of osteochondral fragments from carpal or metacarpophalangeal or metatarsophalangeal joints (fetlock joints). Serum, plasma, and fetlock or carpal synovial fluid samples were obtained and analyzed for SDF-1 concentration by use of an ELISA. RESULTS: In horses with fetlock or carpal joint injury, mean synovial fluid SDF-1 concentrations were significantly higher, serum SDF-1 concentrations were significantly lower, and synovial fluid-to-serum SDF-1 ratios were significantly higher than in untrained and trained horses. Synovial fluid SDF-1 concentrations were not significantly different between trained and untrained horses. Plasma SDF-1 concentrations were not different among the 3 groups. Results obtained with serum, compared with synovial fluid and plasma, had better sensitivity for differentiating between osteochondral-injured horses and uninjured horses. In horses with fetlock joint osteochondral injury, serum SDF-1 concentrations were correlated with radiographic and arthroscopic inflammation scores, but not arthroscopic cartilage scores. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that serum SDF-1 concentrations were more sensitive than plasma and synovial fluid concentrations for detection of osteochondral injury in the fetlock or carpal joint of racehorses. Analysis of serum and synovial SDF-1 concentrations in horses with experimentally induced joint injury may help define the onset and progression of post-traumatic osteoarthritis and aid in the evaluation of anti-inflammatory treatments.

Impact of walking surface on the range of motion of equine distal limb joints for rehabilitation purposes.

The aim of this study was to evaluate the effect of three footing surfaces on the flexion/extension, and range of motion (ROM) of the carpus, tarsus and fetlocks in the horse. The percentage of stride spent in the stance phase of sound horses at the walk was also measured. Nine sound horses were walked on hard ground (HD), soft ground (SF) and a land treadmill (LT), and five complete gait cycles were recorded by a digital video camera. Retro-reflective markers were placed on the skin at four anatomical locations on the left fore and hind limbs, and data were analyzed using two-dimensional (2D) motion-analysis software. Maximal flexion/extension angles and range of motion were calculated for each joint, and the percentage of the stride spent in stance phase was determined for each stride. Maximal flexion of the tarsus and hind fetlock was greater on LT and SF compared to HD, while maximal flexion of the carpus was greater on LT compared to HD and SF. Maximal extension of the carpus was greater on HD compared to SF and LT, maximal extension of the tarsus was greater on HD and SF compared to LT, and maximal extension of the forelimb and hind limb fetlocks was greater on LT compared to HD and SF. The greatest overall ROM of the carpus and fetlocks was achieved on LT, while the greatest overall ROM of the tarsus was achieved on SF. The stance percentage of the stride for the hind limb was significantly different between all surfaces. In conclusion, walking surface influences flexion/extension of the carpus, tarsus and fetlocks in healthy horses, which should be considered when walking equine rehabilitation cases.

Chondroprotective effects of zoledronic acid on articular cartilage in dogs with experimentally induced osteoarthritis.

OBJECTIVE: To assess effects of zoledronic acid on biomarkers, radiographic scores, and gross articular cartilage changes in dogs with induced osteoarthritis. ANIMALS: 21 purpose-bred hound-type dogs. PROCEDURES: The left stifle joint of each dog was examined arthroscopically to determine initial articular cartilage status, which was followed by cranial cruciate ligament (CrCL) transection to induce osteoarthritis. Dogs were assigned to 3 groups (control group, low dose [10 µg of zoledronic acid/kg], or high dose [25 µg of zoledronic acid/kg). Treatments were administered SC every 3 months for 1 year beginning the day after CrCL transection. Serum and synovial fluid samples and radiographs were obtained 0, 1, 3, 6, 9, and 12 months after transection. At 12 months, each joint was scored for cartilage defects. Serum and synovial fluid biomarkers of bone and cartilage turnover (bone-specific alkaline phosphatase, type I and II collagen, carboxy-propeptide of type II collagen, and chondroitin sulfate 846) were analyzed with ELISAs. RESULTS: The high-dose group had fewer total articular defects and lower severity scores in CrCL-transected stifle joints than did the control group. In addition, the high-dose group had significantly less change in collagenase cleavage of type I or II collagen in the synovial fluid at 1 and 3 months after CrCL transection than did the control group and also had greater changes in bone-specific alkaline phosphatase in synovial fluid at 3 months after CrCL transection than did the control group. CONCLUSIONS AND CLINICAL RELEVANCE: Zoledronic acid had a chondroprotective effect in dogs with a transected CrCL.