Comparison between standard ultrasonography, angle contrast ultrasonography, and magnetic resonance imaging characteristics of the normal equine proximal suspensory ligament.

Previous studies have proposed that standard ultrasonography may not adequately represent the pertinent anatomic characteristics of the equine proximal suspensory ligament. The purpose of the study was to compare the use of standard ultrasonography, angle contrast ultrasonography, MRI, and histology for identification of the anatomic characteristics of the normal equine suspensory ligament in the forelimb. Horses free from forelimb lameness with no palpable abnormalities in the region of the suspensory ligament were included in the study. The proximal suspensory ligaments in 20 forelimbs were examined using the standard ultrasound technique, angle contrast ultrasound technique, and MRI, followed by histologic evaluation. Total transverse (cross-sectional) area of the proximal suspensory ligament was estimated using the standard ultrasound and the angle contrast ultrasound techniques, MRI, and histologic sections for the following parameters: total area of the ligament, ligament fibers, muscle, and fat. The proximal suspensory ligament lobe size and tissue distribution were compared and subjectively graded (0-4) for asymmetry. Subjectively, angle contrast ultrasound technique improved differentiation of fibers from the remaining tissue types and allowed identification of the peripheral ligament margin. There was no significant difference in asymmetry scores between modalities. The asymmetry scores of the right and left forelimbs were significantly different with both ultrasound and MRI, based on the level of measurement. The angle contrast ultrasound technique has limitations compared to MRI. However, it provides additional diagnostic information that is not available with the standard ultrasound technique.

Clinical and Histologic Manifestations of a Novel Rectus Femoris Myotendinous Junction Injury in Rats.

Background: Animal models of muscle injury have primarily relied on methods which do not mimic the chronic scarring that typically occurs adjacent to the myotendinous junction (MTJ). The goal of this study was three-fold: (i) to create a strain-induced in vivo model of rectus femoris MTJ injury in rats; (ii) to document clinical manifestations of injury using longitudinal tracking of individual animals via voluntary and compulsory (treadmill) mobility analyses and (iii) to validate and assess the model for persistent scarring through serial histologic assessment and development of a semi-quantitative grading scheme to characterize injury response over time. Methods: Strain-induced MTJ injury was generated in male Sprague Dawley rats via needle tension directed along the transverse axis between the rectus femoris muscle and distal tendon that attaches to the patella. Animals received mobility assessments (gait analysis using a DigiGait Treadmill System and weight bearing using a Tekscan Rodent Walkway System) at days 0, 1, 3, 6, 13, 20, and 27 of the experimental protocol. Rats were euthanized at 1, 3, 7, 14, and 28 days post-injury (n = 6 rats per time-point) and hindlimbs were processed for histology. Results: Significant changes in locomotor parameters included injured and contralateral limb paw area, max dA/dt (limb deceleration/breaking time), stride time, stance time, force time impulse, and fore/hind symmetry, and injured limb maximum force. The most significant and consistent histologic finding was a pathologic fibrotic adhesive lesion at the muscle and tendon interface along the proximal aspect of the patella just distal to the injury site. This lesion was composed of reactive fibroblasts, disorganized collagen fibers, vascular profiles, and a myxomatous ground substance stroma. Conclusions: This work is the first to characterize the clinical and pathologic development of a chronic model of rectus femoris MTJ injury, which resulted in altered mobility likely caused by a strain-induced fibrotic scar along the anterior patella. Notably, both the functional and pathologic changes recapitulated the course of injury progression similar to what is described in humans. This work provides a unique model to study MTJ injury mechanisms for the identification of enhanced treatment options for patients who suffer from activity-related muscle conditions.

Statistical evaluation of biomedical studies.

The aim of this chapter is to familiarize the reader with the basic information and common statistical analyses used in medical research. The chapter will aid in deciding what type of analyses best fit the study data and how each analysis differs. The chapter was written to be user-friendly from a medical research and statistical consultant perspective.

The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the horse.

OBJECTIVE: Equine models of osteoarthritis (OA) have been used to investigate pathogenic pathways of OA and evaluate therapeutic candidates for naturally occurring equine OA which is a significant clinical disease in the horse. This review focuses on the macroscopic and microscopic criteria for assessing naturally occurring OA in the equine metacarpophalangeal joint as well as the osteochondral fragment-exercise model of OA in the equine middle carpal joint. METHODS: A review was conducted of all published OA studies using horses and the most common macroscopic and microscopic scoring systems were summarized. Recommendations regarding methods of OA assessment in the horse have been made based on published studies. RESULTS: A modified Mankin scoring system is recommended for semi-quantitative histological assessment of OA in horses due to its already widespread use and similarity to other scoring systems. Recommendations are also provided for histological scoring of synovitis and macroscopic lesions of OA as well as changes in the calcified cartilage and subchondral bone of naturally occurring OA. CONCLUSIONS: The proposed system for assessment of equine articular tissues provides a useful method to quantify OA change. It is believed that addition of quantitative tracing onto plastic and macroscopic measurement as recently described would be an improvement for overall assessment of articular cartilage change.

Effect of self-assembling peptide, chondrogenic factors, and bone marrow-derived stromal cells on osteochondral repair.

OBJECTIVE: The goal of this study was to test the ability of an injectable self-assembling peptide (KLD) hydrogel with or without chondrogenic factors (CF) and allogeneic bone marrow stromal cells (BMSCs) to stimulate cartilage regeneration in a full-thickness, critically-sized, rabbit cartilage defect model in vivo. We used CF treatments to test the hypotheses that CF would stimulate chondrogenesis and matrix production by cells migrating into acellular KLD (KLD+CF) or by BMSCs delivered in KLD (KLD+CF+BMSCs). DESIGN: Three groups were tested against contralateral untreated controls: KLD, KLD+CF, and KLD+CF+BMSCs, n=6-7. Transforming growth factor-ß1 (TGF-ß1), dexamethasone, and insulin-like growth factor-1 (IGF-1) were used as CF pre-mixed with KLD and BMSCs before injection. Evaluations included gross, histological, immunohistochemical and radiographic analyses. RESULTS: KLD without CF or BMSCs showed the greatest repair after 12 weeks with significantly higher Safranin-O, collagen II immunostaining, and cumulative histology scores than untreated contralateral controls. KLD+CF resulted in significantly higher aggrecan immunostaining than untreated contralateral controls. Including allogeneic BMSCs+CF markedly reduced the quality of repair and increased osteophyte formation compared to KLD-alone. CONCLUSIONS: These data show that KLD can fill full-thickness osteochondral defects in situ and improve cartilage repair as shown by Safranin-O, collagen II immunostaining, and cumulative histology. In this small animal model, the full-thickness critically-sized defect provided access to the marrow, similar in concept to abrasion arthroplasty or spongialization in large animal models, and suggests that combining KLD with these techniques may improve current practice.

Clinical update on the use of mesenchymal stem cells in equine orthopaedics.

Stem cells have received much attention in recent times because of their potential to improve healing of othropaedic problems. This manuscript presents the genesis, issues and current state of stem cell treatment in equine medicine. Current literature supports the use of mesenchymal stem cells (MSCs) for treatment of orthopaedic problems.

Serum biomarker levels for musculoskeletal disease in two- and three-year-old racing Thoroughbred horses: A prospective study of 130 horses.

REASON FOR PERFORMING STUDY: Biomarkers have shown some in vivo promise for the detection of musculoskeletal injuries, but further study to assess biomarker levels in clinical orthopaedic disease is required. OBJECTIVE: To assess 7 serum biomarkers for the detection of musculoskeletal injuries. METHODS: Two- and 3-year-old racehorses were entered into the study (n = 238). Exit criteria were lack of training for >30 days, or completion of 10 study months. Data from horses with solitary musculoskeletal injuries and completion of >2 months were analysed. Musculoskeletal injury was considered intra-articular fragmentation (IAF), tendon or ligamentous injury (TL), stress fractures (SF) and dorsal metacarpal disease (DMD). Monthly lameness examination and serum collection were performed. Serum was analysed for glycosaminoglycan (GAG), type I and II collagen degradation (C1, 2C), type II collagen synthesis (CPII), type II collagen degradation (Col CEQ), aggrecan synthesis (CS846), osteocalcin (OC) as a marker of bone formation and (C-terminal telopeptide of type I collagen) CTX as a marker of bone degradation. RESULTS: Of the 238 horses 59 injured and 71 uninjured control horses met the analysis criteria. Based on injury no significant differences in the proportions were observed for age, gender or lesion type, although a higher proportion of injuries occurred at the beginning of the study. Of injured horses, 16 (27%) sustained an IAF, 17 (29%) a TL injury, 7 (12%) SF and 19 (32%) were diagnosed with DMD. There were significant changes seen in biomarkers based on the injury incurred when longitudinal samples were assessed. Furthermore, based on the serum biomarkers collected prior to injury, horses could be correctly classified as injured or uninjured 73.8% of the time. CONCLUSIONS: A unique biomarker pattern occurred before each injury and this was beneficial in classifying horses as injured or uninjured. POTENTIAL RELEVANCE: Biomarkers have the potential to be used as a screening aid prior to musculoskeletal injury.

Concurrent or sequential development of medial meniscal and subchondral cystic lesions within the medial femorotibial joint in horses (1996-2006).

UNLABELLED: Summary Reasons for performing study: Medial meniscal injuries and subchondral cystic lesions (SCL) are known to occur independently within the medial femorotibial (MFT) joint in horses. However, there are no reports of a potential clinical relationship between these 2 types of lesions. OBJECTIVES: To: 1) document the concurrent presence or sequential development of medial meniscal and SCL of the medial femoral condyle within the MFT joint; and 2) determine the prognosis with both types of lesions. METHODS: Retrospective case series of horses with both a medial meniscal and SCL of the medial femoral condyle identified concurrently or sequentially by radiography, arthroscopy or post mortem examination. Case records and radiographs were reviewed, and a telephone survey of referring veterinarians, owners and trainers was conducted. RESULTS: Twenty-one horses (9.1% of all horses undergoing MFT joint arthroscopy) were identified to have both a medial meniscal injury and SCL of the medial femoral condyle. Thirteen horses had both abnormalities identified concurrently, 6 developed a meniscal lesion subsequent to SCL debridement, and 2 developed a SCL subsequent to a medial meniscal injury. Only 4/19 horses were classified as successful and returned to their intended use. The severity of the meniscal injury was significantly associated with the severity of lameness but not with outcome. CONCLUSIONS: A low percentage of horses may develop both a meniscal injury and SCL of the medial femoral condyle within the MFT joint and have a poor prognosis. POTENTIAL RELEVANCE: Trauma to the MFT joint may lead to both meniscal and subchondral bone damage of the medial femoral condyle that may be recognised concurrently or sequentially.

Effects of exercise vs experimental osteoarthritis on imaging outcomes.

OBJECTIVE: To identify changes in imaging outcomes in a controlled model of osteoarthritis (OA) vs exercise. METHOD: Sixteen 2-year-old horses were randomly assigned to an exercise control (n=8) or an exercise OA (n=8) group. All horses had middle carpal joints arthroscopically explored and an osteochondral fragment was induced in one middle carpal joint of the OA group. All horses were treadmill exercised for the duration of the study (91 days). Clinical, radiographic, nuclear scintigraphic, computed tomographic and magnetic resonance imaging (MRI) examinations were performed and outcomes of these were compared between groups. Imaging results were correlated to clinical, biomarker and gross pathologic results. RESULTS: The OA group had significant increases in clinical outcomes and most imaging parameters. Specifically, the OA group showed significant increases in radiographic lysis and nuclear scintigraphic uptake. There was very little change in subchondral bone density, but a significant change in subchondral bone edema. Radiographic lysis, radial carpal bone edema and nuclear scintigraphy were strongly correlated with clinical changes and radial carpal bone edema was strongly correlated with changes in Type I and Type II collagen found in the synovial fluid. CONCLUSIONS: OA induced significant changes in imaging parameters beyond the adaptation seen with exercise. Bone edema detected with MRI was closely correlated with collagen biomarkers detected in the synovial fluid.

Changes in synovial fluid and serum biomarkers with exercise and early osteoarthritis in horses.

OBJECTIVE: To discriminate between changes in biomarkers with exercise compared to changes in biomarkers with osteoarthritis (OA) in exercising horses. METHOD: Sixteen, 2-year-old horses were randomly assigned either to an exercise-alone (n=8) or OA-affected (also exercised) (n=8) group. All horses had both mid-carpal joints arthroscoped and OA induced in one mid-carpal joint in the OA-affected joints of OA-affected horses. Two weeks after surgery all horses commenced a strenuous exercise program on a high-speed treadmill. Clinical outcomes and synovial fluid and serum biomarkers, were evaluated weekly. Synovial and serum biomarkers evaluated were epitope CS846 (CS846), epitope CPII (CPII), glycosaminoglycans (GAGs), epitope Col CEQ (Col CEQ) (a marker of type II collagen degradation), type I and II collagen degradation fragments (C1,2C), osteocalcin, C-terminal of bone type I collagen (CTX1), type I collagen (Col I) and (synovial fluid only of cartilage) prostaglandin E2 (PGE2) levels. Horses were euthanized at day 91 and their joints assessed grossly, histopathologically, and histochemically. RESULTS: Exercise induced a significant increase in synovial fluid CS846, CPII, GAG, Col CEQ, C1,2C, osteocalcin and Col I concentrations. There was a significant increase in synovial fluid CS846, CPII, Col CEQ, C1,2C, osteocalcin, Col I and PGE2 concentrations in OA-affected joints compared to exercise-alone joints. The concentration of serum CS846, CPII, GAG, osteocalcin, C1,2C and Col I increased with exercise. For each of these biomarkers there was also a statistically significant increase in serum biomarker levels in OA-affected horses compared to exercise-alone horses. CONCLUSIONS: Six synovial fluid and serum biomarkers were useful in separating early experimental OA from exercise alone but synovial fluid CTX1 and serum Col CEQ and CTX1 were not.

Arthroscopic injection of corticosteroids into the fibrous tissue of subchondral cystic lesions of the medial femoral condyle in horses: a retrospective study of 52 cases (2001-2006).

REASONS FOR PERFORMING STUDY: There are no published results of subchondral cystic lesions (SCLs) in the medial femoral condyle (MFC) treated with arthroscopic injection of corticosteroids into the lining of the cyst. OBJECTIVES: 1) To determine the success rate for treatment of SCLs in the MFC with arthroscopic injection of the fibrous tissue of the cyst with corticosteroids. 2) To identify any factors that may predict outcome. HYPOTHESES: Injection of the fibrous tissue of SCLs of the MFC with corticosteroids utilising arthroscopic guidance yields a similar or higher chance for intended performance than does arthroscopic debridement as previously reported; this technique will be effective for treating SCLs in older horses. METHODS: Horses with clinical and radiographic evidence of a SCL in the MFC were injected with corticosteroids under arthroscopic guidance, and case records and radiographs were reviewed retrospectively. A telephone survey of referring veterinarians, owners and trainers was conducted. RESULTS: Thirty-five of 52 (67%) cases were classified as successful involving 73 SCLs of which 56 (77%) were classified as successful. There was no significant association between age group (age3 years) and outcome, or cyst configuration and outcome. Significantly more unilateral SCLs (28/31 [90%] SCLs) were classified as successful than bilateral (28/42: 67%). There were significant differences in outcome based on the surgeon operating the case and an association between pre-existing radiographic findings of osteophytes and negative outcome. CONCLUSIONS: Injection of SCLs utilising arthroscopic guidance is an effective alternative method of surgical treatment of SCL. POTENTIAL RELEVANCE: This technique offers a similar chance of success as has been reported with debridement and may allow for a shorter period of convalescence. If unsuccessful, the option remains to debride the cyst in a second surgery.

Assessment of a novel equine tarsocrural experimental joint disease model using recombinant interleukin-1ß and arthroscopic articular sampling of the medial malleolus of the tibia on the standing sedated horse.

Joint disease and osteoarthritis are common problems in the horse and numerous experimental studies have been developed to determine the safety and efficacy of new therapies. Synovitis, a critical component of joint disease, has been experimentally induced using recombinant interleukin-1 beta (reIL-1ß) to investigate new joint therapies in a controlled environment, although the use of reIL-1ß has not been reported in the equine tarsocrural joint. A common consequence of performing controlled experiments is that articular tissue collection typically requires general anesthesia or euthanasia. This report describes a minimally invasive surgical biopsy technique to harvest joint tissues from the tarsocrural joint in standing horses. The aims of the study were to assess subjective and objective pain parameters following reIL-1ß induced synovitis in the tarsocrural joint and to describe the surgical technique including the location and quantity of tissues obtained with this method. Experimental synovitis was induced using reIL-1ß in one equine tarsocrural joint of each horse using a randomised controlled design. The minimally invasive surgical technique provided sufficient amounts of articular cartilage from the medial malleolus of the tibia and synovium to perform viability, biochemical and histological assessments without necessitating general anesthesia. The minimally invasive technique also allowed for lameness assessment that could have been influenced by more invasive methods of tissue collection. No incisional or lameness complications were detected after use. The synovitis model and surgical technique provided ample tissue for laboratory evaluation and avoided general anesthesia or sacrifice of the horse.

Growth factor and receptor mRNA expression in the intestine of horses with large colon volvulus: a pilot study.

REASONS FOR PERFORMING STUDY: Growth factors (GF) are important for maintenance and repair of intestinal mucosal structure and function, but there have been no studies investigating growth factor (GF) or growth factor receptor (GF-R) mRNA expression in the intestine of horses with large colon volvulus (LCV). OBJECTIVES: (1) To determine mRNA expression for epidermal growth factor (EGF), EGF receptor (EGF-R), insulin-like growth factor-I (IGF), IGF receptor (IGF-R), vascular endothelial growth factor (VEGF) and VEGF receptor (VEGF-R) in the intestine of horses with an LCV compared to normal intestine. (2) To measure the correlation between histological intestinal injury and mRNA expression. METHODS: In 5 horses, samples were collected from the mid-jejunum (small intestine, SI), pelvic flexure (PF) and right dorsal colon (RDC) prior to creation of the LCV (NORM), 1 h following creation of the LCV (ISCH) and 1 h following correction of the LCV (REPER). In 2 clinical cases of LCV, samples were collected from the PF and RDC. Samples were assessed histologically for the amount of intestinal injury. The mRNA expressions of growth factors and receptors were determined using qRT-PCR. RESULTS: VEGF and VEGF-R mRNA expression was greater in horses with an LCV compared to NORM. Expression of IGF-R mRNA increased in the SI during ISCH and REPER. CONCLUSION AND POTENTIAL RELEVANCE: The increase compared to NORM in VEGF and VEGF-R mRNA expression in horses with LCV may be important in early intestinal healing and may also explain, in part, the increase in vascular permeability in horses with a LCV. Expression of IGF and IGF-R in the SI warrants further investigation and may be important for understanding post operative complications in horses with SI lesions.

A comparative study of articular cartilage thickness in the stifle of animal species used in human pre-clinical studies compared to articular cartilage thickness in the human knee.

Histological measurements of the thickness of non-calcified and calcified cartilage, as well as the subchondral bone plate in five locations on the femoral trochlea and medial femoral condyles of species were used in preclinical studies of articular cartilage and compared to those of the human knee. Cadaver specimens were obtained of six human knees, as well as six equine, six goat, six dog, six sheep and six rabbit stifle joints (the animal equivalent of the human knee). Specimens were taken from the lateral trochlear ridge, medial trochlear ridge and medial femoral condyle. After histopathological processing, the thickness of non-calcified and calcified cartilage layers, as well as the subchondral bone plate, was measured. Average articular cartilage thickness over five locations were 2.2-2.5 mm for human, 0.3 mm for rabbit, 0.4-0.5 mm for sheep, 0.6-1.3 mm for dog, 0.7-1.5 mm for goat and 1.5-2 mm for horse. The horse provides the closest approximation to humans in terms of articular cartilage thickness, and this approximation is considered relevant in pre-clinical studies of cartilage healing.

Comparison of intra-articular drilling and diode laser treatment for arthrodesis of the distal tarsal joints in normal horses.

REASONS FOR PERFORMING STUDY: Anecdotal reports suggest that laser-facilitated arthrodesis of the distal tarsal joints improves the prognosis compared with intra-articular drilling but no objective comparisons have been performed. OBJECTIVES: To evaluate intra-articular drilling and laser-facilitated arthrodesis using in situ and in vivo techniques. METHODS: Fourteen cadaver limbs were evaluated in situ for chondrocyte viability after both surgical techniques. In vivo, one randomly selected limb was subjected to laser-facilitated arthrodesis and the other underwent intra-articular drilling in 6 normal horses. Clinical examinations were performed at 1, 3 and 5 months. Two horses were subjected to euthanasia at 1, 3 and 5 months. RESULTS: Significantly more chondrocyte death was observed with laser-facilitated arthrodesis compared to drilling, but the overall degree suggested only a focal effect. In vivo, both groups demonstrated minimal post operative morbidity. There was more evidence of arthrodesis seen at all time points with intra-articular drilling. CONCLUSIONS: This study demonstrated that changes associated with ultimate arthrodesis occur earlier after intra-articular drilling of the distal tarsal joints than laser-facilitated arthrodesis, although clinically affected horses may respond differently. POTENTIAL RELEVANCE: Intra-articular drilling may provide earlier arthrodesis of the distal tarsal joints, but not necessarily a better long-term result.

Effects of glucosamine hydrochloride and chondroitin sulphate, alone and in combination, on normal and interleukin-1 conditioned equine articular cartilage explant metabolism.

REASONS FOR PERFORMING STUDY: Clinical trials in human and veterinary literature have documented the benefits of oral nutraceutical joint supplements containing glucosamine (GU) and chondroitin sulphate (CS) to treat mild to moderate osteoarthritis, but the effects of these components have not yet been conclusively determined. OBJECTIVES: To assess varying dosages of GU and CS on normal and interleukin-1alpha (IL-1) conditioned equine cartilage explants and rationalise the use of these products. HYPOTHESIS: Treatment would not be detrimental to cartilage metabolism and higher dosages and the combination of GU and CS would be more beneficial than lower dosages and. GU or CS alone. METHODS: Articular cartilage explants collected from the femoral trochlea and condyles were cultured in normal and IL-1 conditioned media. Treatment groups included 0, 12.5, 25,125 and 250 microg/ml concentrations of GU alone, CS alone, or GU+CS in combination. Glycosaminoglycan (GAG) synthesis and total GAG content in the explants and media were analysed. RESULTS: There were no detrimental effects of GU, CS or GU+CS on cartilage metabolism. High dosages of GU+CS reduced total GAG release into the media (degradation). CONCLUSIONS: Our results suggests that GU+CS may prevent cartilage GAG degradation. POTENTIAL RELEVANCE: The combination of GU and CS may be more effective in preventing or treating osteoarthritis in horses than either product alone.

Comparison of subjective lameness evaluation, force platforms and an inertial-sensor system to identify mild lameness in an equine osteoarthritis model.

When mild lameness exists, agreement between clinicians is often controversial due to its subjective nature. The goal of the study was to compare subjective and objective methods to identify the presence of mild lameness using an established model of osteoarthritis (OA) in which OA was induced by creating a unilateral carpal osteochondral fragment (OCF) in the middle carpal joint of 16 horses. Subjective lameness evaluations (blinded and unblinded), force platforms (FP), and an inertial-sensor system (ISS) were used to detect forelimb lameness at four time points. Limbs identified as lame by each method were compared as well as compared with the OCF limb at each time point. Spearman correlations were calculated between all outcome parameters. Independent of time, blinded subjective evaluation (54%) and the ISS (60%) identified a higher percentage of horses as lame in the OCF limb compared to FP (40%). Blinded subjective evaluation and the ISS agreed which forelimb was lame more often (50%) compared with blinded subjective evaluation and the FP (38%). Induction of mild lameness within the OCF limb was supported by an increase in the frequency of horses considered lame by both subjective evaluations the ISS and a decrease (3.6%) in mean (among all horses) peak vertical force from baseline to post OCF induction. The percentage of horses identified as lame in the OCF limb, independent of time, was highest with the ISS (60%) followed by blinded subjective evaluation (51%) and the FP (42%). It was concluded that the best agreement was between subjective evaluation and the inertial-sensor system.

A dose titration of triamcinolone acetonide on insulin-like growth factor-1 and interleukin-1-conditioned equine cartilage explants.

REASONS FOR PERFORMING STUDY: Previous in vitro pilot studies have defined a potentially beneficial effect of insulin-like growth factor-1 (IGF-1) and triamcinolone acetonide (TA) on interleukin-1 (IL-1)-conditioned equine cartilage. Furthermore, an optimal dose for IGF-1 treatment alone has been documented previously using the same test system as in the current project. OBJECTIVES: To perform a dose titration of TA on IL-1-conditioned equine articular cartilage explants in the presence of an optimised IGF-1 dose, in order to optimise a triamcinolone concentration for use in combination with IGF-1 for future investigations. METHODS: Cartilage explants were harvested from the distal femur of a normal horse. The effect of a clinically relevant TA dose range was evaluated in the presence of IL-1 and IGF-1 through measurement of proteoglycan (PG) matrix metabolism (synthesis and degradation). RESULTS: TA and IGF-1 in combination inhibited the IL-1-induced release of PG matrix components (glycosaminoglycan or GAG) from the articular cartilage, as well as producing a significant increase in GAG synthesis. CONCLUSIONS: This experiment provided proof of principle that a combination treatment appears to be able to combat the IL-1-induced matrix depletion, while enhancing anabolic metabolism within the articular cartilage. POTENTIAL RELEVANCE: The use of IGF-1 in conjunction with TA in vivo has the potential to provide beneficial anabolic effects not seen with TA alone.

Effects of osteochondral fragmentation and intra-articular triamcinolone acetonide treatment on subchondral bone in the equine carpus.

To determine the effects of osteochondral fragmentation and intra-articular corticosteroid treatment on dynamics of bone remodelling and fragility, 12 horses each had a unilateral, 8 mm osteochondral fragment created in the distal aspect of one radiocarpal bone. Six of the horses were treated in the fragmented joint, and the other 6 were treated in the nonfragmented joint with 12 mg of triamcinolone acetonide (TA) 14 and 28 days after surgery. All horses were exercised on a high-speed treadmill starting 15 days, and ending 72 days after surgery. Horses treated with TA in the fragmented joints were significantly less lame than those treated in the nonfragmented joints. Third carpal bones from joints with fragments showed significantly more vascularity, single labelled surface, total labelled surface and mineralising surface in subchondral and subjacent trabecular bone. Trends were also seen towards higher vascular canal volume and osteochondral junction remodelling sites in third carpal bones from fragmented joints. No significant differences were seen in microdamage density or size between fragmented and nonfragmented joints. No significant influence of TA treatment was seen on any parameter measured. The results from this study show that osteochondral fragmentation induces significant changes in remodelling of opposing bones, and that the administration of corticosteroids into joints with fragmentation does not significantly alter bone remodelling or fragility.

Effects of dosage titration of methylprednisolone acetate and triamcinolone acetonide on interleukin-1-conditioned equine articular cartilage explants in vitro.

REASONS FOR PERFORMING STUDY: Osteoarthritis is a frequent sequela of joint disease, especially with severe injuries or if attempts at therapy are unsuccessful. Negative and positive effects of corticosteroid treatment of articular cartilage have been demonstrated by in vitro and in vivo studies. OBJECTIVES: To assess the metabolic effects of varying dosages of methylprednisolone acetate (MPA) and triamcinolone acetonide (TA) on interleukin-1alpha (IL-1) conditioned equine cartilage explants. Our hypothesis was that lower dosages of corticosteroids would be less detrimental to cartilage metabolism than higher dosages. TA would be less detrimental to cartilage metabolism than MPA. METHODS: Treatment groups included articular cartilage explants with no IL-1 (control), IL-1 alone, and IL-1 plus 10, 5, 1 and 0.5 mg/ml MPA or 1.2, 0.6, 0.12 and 0.06 mg/ml TA. Explants were labelled with 35SO4 prior to the beginning and end of the experiment to assess glycosaminoglycan (GAG) degradation and synthesis, respectively. Total GAG content in media and explants and total cartilage DNA were also analysed. RESULTS: MPA and TA reduced GAG synthesis compared to control and IL-1 alone. The highest dosage of MPA (10 mg/ml) reduced GAG synthesis less than lower dosages of MPA and all dosages of TA. Compared to IL-1 alone, all dosages of TA and lower dosages of MPA increased GAG degradation. MPA at 10 mg/ml reduced GAG degradation. Both MPA and TA increased media GAG content compared to control and IL-1 explants. Total cartilage GAGs were unchanged with MPA, but reduced with TA, compared with IL-1 alone. Total cartilage DNA was decreased with MPA and increased with TA compared to IL-1 and control explants. CONCLUSIONS: MPA and TA did not counteract the negative effects of IL-1 and did not maintain cartilage metabolism at control levels. Lower dosages of MPA and TA were not less detrimental to cartilage metabolism than higher dosages. TA did not appear to be less harmful than MPA on cartilage metabolism. The results of this study differ from the findings of comparable in vivo studies. POTENTIAL RELEVANCE: The low numbers of horses used in this study limits extrapolation of these findings to the equine population; however, this study also questions the clinical relevance of this in vitro model.