Objective—To compare biomechanical strength, interface quality, and effects of bone healing in bone-implant interfaces that were untreated or treated with calcium phosphate cement (Ca-cement), magnesium phosphate cement (Mg-cement), or polymethylmethacrylate (PMMA) in horses.
Animals—6 adult horses.
Procedures—4 screw holes were created (day 0) in each third metacarpal and third metatarsal bone of 6 horses. In each bone, a unicortical screw was placed in each hole following application of Ca-cement, Mg-cement, PMMA, or no treatment (24 screw holes/treatment). Screws were inserted to 2.82 N m torque. Horses were euthanized and bones were harvested at day 5 (16 screw holes/treatment) or day 182 (8 screw holes/treatment). Radiography, biomechanical testing, histomorphometry, and micro–computed tomography were performed to characterize the bone-implant interfaces.
Results—Use of Mg-cement increased the peak torque to failure at bone-implant interfaces, compared with the effects of no treatment and Ca-cement, and increased interface toughness, compared with the effects of no treatment, Ca-cement, and PMMA. Histologically, there was 44% less Ca-cement and 69% less Mg-cement at the interfaces at day 182, compared with amounts present at day 5. Within screw threads, Ca-cement increased mineral density, compared with PMMA or no treatment. In the bone adjacent to the screw, Mg-cement increased mineral density, compared with PMMA or no treatment. One untreated and 1 Ca-cement–treated screw backed out after day 5.
Conclusions and Clinical Relevance—In horses, Mg-cement promoted bone-implant bonding and adjacent bone osteogenesis, which may reduce the risk of screw loosening.
Objective—To evaluate inflammatory responses induced via intra-articular recombinant human interleukin (IL)-1β treatment in horses receiving a dietary nutraceutical (DN; composed of mussel, shark cartilage, abalone, and Biota orientalis lipid extract) and assess the clinical effects of long-term DN administration.
Animals—22 healthy horses.
Procedures—12 horses were fed 0, 15, 45, or 75 mg of DN (3 horses/treatment) daily for 84 days. General health and clinicopathologic variables were monitored at intervals. Ten other horses received 0 or 15 g of DN/d (5 horses/treatment) for 29 days (beginning day −14). One intercarpal joint in each horse was injected twice with IL-1β (10 and 100 ng on days 0 and 1, respectively), and the contralateral joint was similarly injected with saline (0.9% NaCl) solution. Synovial fluid prostaglandin E2 (PGE2), sulfated glycosaminoglycan (GAG), nitric oxide (NO), and protein concentrations and leukocyte counts were analyzed before and at intervals after injections.
Results—Administration of the DN (up to 75 g/d) to horses for 84 days did not induce any adverse effects. In the other experiment, synovial fluid PGE2, GAG, and protein concentrations and leukocyte count increased after intra-articular injections of IL-1β (compared with effects of saline solution injections) in horses that received no DN; NO concentration was not affected. In horses that were fed the DN, intra-articular IL-1β injections did not induce significant increases in synovial fluid PGE2 and GAG concentrations.
Conclusions and Clinical Relevance—Results suggested that administration of the DN may be useful in preventing inflammation associated with arthritis and degenerative joint disease in horses.
Objective—To determine the validity, reliability, and sensitivity of a published chronic pain index by completion of a questionnaire in Finnish by owners of dogs with chronic signs of pain caused by osteoarthritis.
Animals—61 client-owned dogs with osteoarthritis.
Procedures—Validity, internal consistency, and repeatability testing of the questionnaire were evaluated by completion of questions in Finnish by owners of 61 dogs; the questionnaire was named the Helsinki chronic pain index (HCPI). Sensitivity testing of the questionnaire was determined from data of 2 smaller groups of dogs treated with carprofen (n = 17) or placebo (17). Owners completed the questionnaire 5 times during a 16-week period. Psychometric properties of the HCPI were evaluated.
Results—Principal component analysis yielded only a single stable component, indicating that the HCPI was best explained as an 11-item single construct index of chronic pain. Changes in the HCPI correlated well with change in quality of life and with change in the mobility visual analogue scale (r = 0.72 and r = 0.67, respectively), indicating a high predictive validity. Internal consistency (Cronbach A value = 0.82) and test-retest reliability (intraclass correlation coefficient = 0.84 for items and 0.92 for the HCPI) were high. Changes in scores (from baseline to treatment and back to no treatment) between the carprofen treatment group and placebo control group were significant, indicating high sensitivity.
Conclusions and Clinical Relevance—The Finnish version of the HCPI provided a valid, reliable, and responsive tool for assessment of response to treatment in dogs with osteoarthritis.
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 assess the clinical, biochemical, and histologic effects of extracorporeal shock wave therapy (ESWT) in the treatment of horses with experimentally induced osteoarthritis (OA).
Animals—Twenty-four 2- to 3-year-old horses without evidence of lameness.
Procedures—OA was induced arthroscopically in 1 middle carpal joint of each horse. Fourteen days after induction of OA, horses were treated with a sham ESWT probe (placebo; n = 8), polysulfated glycosaminoglycan (PSGAG) administered IM every 4 days for 28 days as a positive control treatment (8), or ESWT administered on days 14 and 28 with a focused shock wave unit (8). Evaluations included clinical assessments of degree of lameness every 2 weeks and weekly synovial fluid analyses. Horses were euthanized 70 days after induction of OA, and gross pathologic and histologic examinations of cartilage and synovial membrane specimens were performed at necropsy. A generalized linear mixed model was used to compare outcomes among treatment groups.
Results—No adverse treatment-related events were detected in any horse. The degree of lameness in horses treated with ESWT improved significantly, compared with the degree of lameness in placebo- or PSGAG-treated horses. No disease-modifying effects were evident in results for synovial fluid, synovial membranes, or cartilage from the ESWT- or PSGAG-treated horses.
Conclusions and Clinical Relevance—Although a disease-modifying effect of ESWT was not detected, the significant clinical effect of ESWT suggested that this modality should be considered for treatment of horses with OA in combination with another modality that does affect the disease process.
Objective—To assess clinical, biochemical, and histologic effects of polysulfated glycosaminoglycan (PSGAG) or sodium hyaluronan administered intra-articularly in treatment of horses with experimentally induced osteoarthritis.
Procedures—Osteoarthritis was induced arthroscopically in 1 middle carpal joint of all horses. Eight horses received hyaluronan (20 mg) and amikacin (125 mg) intra-articularly on study days 14, 21, and 28. Eight horses received PSGAG (250 mg) and amikacin (125 mg) intra-articularly on study days 14, 21, and 28. Eight control horses received 2 mL of saline (0.9% NaCl) solution and amikacin (125 mg) intra-articularly on study days 14, 21, and 28. Clinical, radiographic, synovial fluid analysis, gross, histologic, histochemical, and biochemical findings were evaluated.
Results—No adverse treatment-related events were detected. Induced osteoarthritis caused a substantial change in lameness, response to flexion, joint effusion, and radiographic findings, and of these, synovial fluid effusion was reduced with PSGAG, compared with control horses. No changes in clinical signs were seen with PSGAG or hyaluronan, compared with control horses. Histologically, the degree of synovial membrane vascularity and subintimal fibrosis was significantly reduced with PSGAG treatment, compared with controls. Histologically, significantly less fibrillation was seen with hyaluronan treatment, compared with controls.
Conclusions and Clinical Relevance—Results indicated that PSGAG and hyaluronan had beneficial disease-modifying effects and are viable therapeutic options for osteoarthritis in horses.
Objective—To assess the clinical, biochemical, and histologic effects of topically administered diclofenac liposomal cream (DLC) in the treatment of horses with experimentally induced osteoarthritis.
Procedures—Osteoarthritis was induced arthroscopically in 1 middle carpal joint of all horses. Eight horses treated with DLC were given 7.3 g twice daily via topical application. Eight horses treated with phenylbutazone were given 2 g orally once daily. Eight control horses received no treatment. Evaluations included clinical, radiographic, magnetic reso-nance imaging, synovial fluid, gross, and histologic examinations as well as histochemical and biochemical analyses.
Results—No adverse treatment-related events were detected. Horses that were treated with DLC or phenylbutazone had significant clinical improvement of lameness, unlike the control horses. Treatment with DLC induced significant improvement in staining and total articular glycosaminoglycan content, compared with no treatment. Treatment with phen-ylbutazone induced significant reduction in synovial fluid prostaglandin E2 concentration, compared with DLC and no treatment. Treatment with DLC induced significantly less radial carpal bone sclerosis and overall gross cartilage erosion, compared with phenylbutazone.
Conclusions and Clinical Relevance—Results indicated that DLC had both clinical sign–modifying and disease-modifying effects. Only clinical sign–modifying effects were detected in association with phenylbutazone administration. Treatment with DLC had significant beneficial effects, compared with phenylbutazone, and no detrimental effects. Results suggested that DLC is a viable therapeutic option for horses with osteoarthritis.
Objective—To test the hypothesis that simulated digests of Biota orientalis (BO) and a dietary nutraceutical (DN; composed of mussel, shark cartilage, abalone, and BO seed lipid extract) inhibit prostaglandin E2 (PGE2), nitric oxide (NO), and glycosaminoglycan (GAG) production in interleukin (IL)-1–stimulated cartilage explants.
Sample Population—Cartilage tissue from 12 pigs.
Procedures—Articular cartilage explants were conditioned with a simulated digest of BO (BOsim) or DN (DNsim) at concentrations of 0, 0.06, or 0.18 mg/mL or indomethacin (INDOsim; 0 or 0.02 mg/mL) for 72 hours. Control explants received digest vehicle only. Explants were or were not stimulated with recombinant human-IL-1β (10 or 0 ng/mL) during the final 48 hours of culture. Concentrations of PGE2, GAG, and NO in media samples (mPGE2,mGAG, and mNO concentrations, respectively) were analyzed, and explant tissue was stained fluorochromatically to determine chondrocyte viability. Treatment effects during the final 48-hour culture period were analyzed.
Results—IL-1 increased mPGE2, mGAG, and mNO concentrations in control explants without adversely affecting cell viability. Treatment with INDOsim blocked PGE2 production and increased mNO concentration in IL-1–stimulated and unstimulated explants and increased mGAG concentration in unstimulated explants. Treatment with DNsim (0.06 and 0.18 mg/mL) reduced mPGE2 concentration in IL-1–stimulated and unstimulated explants, reduced mNO concentration in IL-1–stimulated explants, and increased mNO concentration in unstimulated explants. Treatment with 0.18 mg of DNsim/mL increased cell viability in the presence of IL-1. In IL-1–stimulated explants, BOsim (0.06 and 0.18 mg/mL) reduced mPGE2 concentration, but 0.18 mg of BOsim/mL increased cell viability.
Conclusions and Clinical Relevance—Effects of IL-1 on cartilage explants in vitro were modulated by DNsim and BOsim.
Objective—To determine the quantity (concentration) and quality (molecular weight) of synovial fluid hyaluronan with respect to presence and severity of osteoarthritis in stifle joints of dogs.
Animals—21 purpose-bred dogs and 6 clinically affected large-breed dogs (cranial cruciate ligament [CrCL] disease with secondary osteoarthritis).
Procedures—Research dogs underwent arthroscopic surgery in 1 stifle joint to induce osteoarthritis via CrCL transection (CrCLt; n = 5 stifle joints), femoral condylar articular cartilage groove creation (GR; 6), or meniscal release (MR; 5); 5 had sham surgery (SH) performed. Contralateral stifle joints (n = 21) were used as unoperated control joints. Synovial fluid was obtained from research dogs at time 0 and 12 weeks after surgery and from clinically affected dogs prior to surgery. All dogs were assessed for lameness, radiographic signs of osteoarthritis, and pathologic findings on arthroscopy as well as for quantity and quality of hyaluronan.
Results—Clinically affected dogs had significantly greater degrees of pathologic findings, compared with dogs with surgically induced osteoarthritis (ie, those with CrCLt, GR, and MR stifle joints), and with respect to lameness scores, radiographic signs of osteoarthritis, pathologic findings on arthroscopy, and synovial fluid hyaluronan concentration. Synovial fluid from stifle joints of dogs with surgically induced osteoarthritis had hyaluronan bands at 35 kd on western blots that synovial fluid from SH and clinically affected stifle joints did not.
Conclusions and Clinical Relevance—Synovial fluid hyaluronan quantity and quality were altered in stifle joints of dogs with osteoarthritis, compared with control stifle joints. A specific hyaluronan protein fragment may be associated with early pathologic changes in affected joints.
Objective—To evaluate the effect of intra-articular injection of gelatin hydrogel microspheres containing basic fibroblast growth factor (bFGF) on experimentally induced defects in third metacarpal bones (MC3s) of horses, in vivo.
Animals—6 healthy adult Thoroughbreds.
Procedures—Horses were anesthetized, and a hole (diameter, 4.5 mm) was drilled into the medial condyle of both MC3s of each horse. One milliliter (100 μg) of a solution of gelatin hydrogel microspheres (2 mg) containing bFGF was injected into the joint capsule of the right metacarpophalangeal joint of each horse (bFGF joint). One milliliter of saline (0.9% NaCl) solution was injected into the left metacarpophalangeal joint (control joint). Radiography was performed 1 day and 4, 8, 12, and 16 weeks after surgery to evaluate bone defect refilling. Sixteen weeks after surgery, multidetector-row computed tomography (MDRCT) was performed to determine the degree of refilling at the bone defect site.
Results—Radiography revealed healing of bone defects at 4 to 12 weeks after surgery in bFGF joints and at 8 to 16 weeks after surgery in control joints. In addition, MDRCT revealed a higher degree of healing in bFGF versus control joints. Mean ± SD MDRCT score for bFGF joints (411.7 ± 135.6 Hounsfield units) was significantly higher than that for control joints (240.8 ± 133.1 Hounsfield units).
Conclusions and Clinical Relevance—Treatment of horses with gelatin hydrogel microspheres that contained bFGF enhanced bone regeneration and healing of experimentally induced defects. This treatment strategy may be useful for treating horses with fractures.