Spencer A. Johnston

Osteoarthritis: Joint Anatomy, Physiology, and Pathobiology

Normal cartilage is a complex material consisting of a solid matrix composed primarily of collagen and proteoglycan, which is saturated with water. It is not a homogenous material. The interaction of the physical and biochemical structures of cartilage is necessary to allow the normal function of providing nearly frictionless motion, wear resistance, joint congruence, and transmission of load to subchondral bone. Chondrocytes are responsible for synthesizing and maintaining this material. Osteoarthritis occurs when there is disruption of normal cartilage structure and homeostasis. Osteoarthritis results from a complex interaction of biochemical and biomechanical factors that occur concurrently and serve to perpetuate degradative change. The progressive pathologic change that occurs in osteoarthritis has been characterized, not only for articular cartilage but also for periarticular tissues. The occurrence of mechanical and biochemical changes is well established, but the role of each in the etiopathogenesis of osteoarthritis is not rigidly defined. It is likely that there are multiple etiologies sharing common pathways of physical and chemical disruption. (see Fig. 1). The changes associated with osteoarthritis ultimately have an impact on the patient through decreased ability to use the joint or the production of pain, or both. Unfortunately, once these changes are severe enough to be recognized clinically, they are likely to be irreversible with current treatments. Nevertheless, understanding the basic mechanisms involved in the development and progression of osteoarthritis provides a basis for establishing a reasonable expectation for the patient and a rational plan for medical and surgical treatment of this condition.

Conservative and medical management of hip dysplasia.

Hip dysplasia has been managed conservatively and medically since the initial description of this disease in 1935. However, little factual information is known about the benefits of the various forms of conservative and medical management. Nonsteroidal anti-inflammatory drugs have been a mainstay of treatment, with the only real debate being which NSAID to use. Only with the recent anecdotal reports of polysulfated glycosaminoglycan has there been any change in medical management of CHD, and this method of treatment warrants further investigation. Conservative and medical management definitely have a role in the treatment of CHD. It must be remembered, however that CHD is primarily a disease of biomechanical alterations and joint laxity, with the cartilage effects being secondary. With a great enough degree of laxity, coxofemoral incongruency, articular damage, or osteoarthritic change, conservative and medical management will not be effective. At that stage, surgical management must be considered.

Efficacy of ABT-116, an antagonist of transient receptor potential vanilloid type 1, in providing analgesia for dogs with chemically induced synovitis

OBJECTIVE To investigate the ability of ABT-116 (a proprietary antagonist of transient receptor potential vanilloid type 1) administered at 2 doses to attenuate lameness in dogs with experimentally induced urate synovitis. ANIMALS 8 purpose-bred mixed-breed dogs. PROCEDURES In a 4-way crossover study, dogs orally received each of low-dose ABT-116 treatment (LDA; 10 mg/kg), high-dose ABT-116 treatment (HDA; 30 mg/kg), firocoxib (5 mg/kg), and no treatment (nontreatment) once a day for 2 days, in a randomly assigned order. Synovitis was induced on the second day of each treatment period by intra-articular injection of either stifle joint with sodium urate, alternating between joints for each treatment period, beginning with the left stifle joint. Ground reaction forces, clinical lameness scores, and rectal temperature were assessed before the injection (baseline) and at various points afterward. RESULTS Lameness scores at the 2-, 6-, and 12-hour assessment points were higher than baseline scores for HDA and nontreatment, whereas scores at the 2- and 6-hour points were higher than baseline scores for LDA. For firocoxib, there was no difference from baseline scores in lameness scores at any point. Compared with baseline values, peak vertical force and vertical impulse were lower at 2 and 6 hours for HDA and nontreatment and at 2 hours for LDA. No changes in these values were evident for firocoxib. The HDA or LDA resulted in higher rectal temperatures than did treatment with firocoxib or nothing, but those temperatures did not differ among treatments. CONCLUSIONS AND CLINICAL RELEVANCE HDA had no apparent effect on sodium urate-induced lameness; LDA did attenuate the lameness but not as completely as firocoxib treatment. High rectal temperature is an adverse effect of oral ABT-116 administration that may be of clinical concern.

In vitro effects of meloxicam on metabolism in articular chondrocytes from dogs with naturally occurring osteoarthritis

OBJECTIVE To assess effects of in vitro meloxicam exposure on metabolism in articular chondrocytes from dogs with naturally occurring osteoarthritis. SAMPLE Femoral head cartilage from 16 dogs undergoing total hip replacement. PROCEDURES Articular cartilage samples were obtained. Tissue sulfated glycosaminoglycan (SGAG), collagen, and DNA concentrations were measured. Collagen, SGAG, chondroitin sulfate 846, NO, prostaglandin E2 (PGE2), and matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, and MMP-13 concentrations in culture medium were analyzed. Aggrecan, collagen II, MMP-2, MMP-3, MMP-9, MMP-13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4, ADAMTS-5, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, TIMP-3, interleukin-1β, tumor necrosis factor-α, cyclooxygenase-1, cyclooxygenase-2, and inducible nitric oxide synthase gene expression were evaluated. Comparisons between tissues cultured without (control) and with meloxicam at concentrations of 0.3, 3.0, and 30.0 μg/mL for up to 30 days were performed by means of repeated-measures analysis. RESULTS Meloxicam had no effect on chondrocyte SGAG, collagen, or DNA concentrations. Expression of ADAMTS-5 was significantly decreased in all groups on all days, compared with the day 0 value. On day 3, culture medium PGE2 concentrations were significantly lower in all meloxicam-treated groups, compared with values for controls, and values remained low. Culture medium MMP-3 concentrations were significantly lower on day 30 than on day 3 in all meloxicam-treated groups. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that in vitro meloxicam treatment of osteoarthritic canine cartilage for up to 30 days did not induce matrix degradation or stimulate MMP production. Meloxicam lowered PGE2 release from this tissue, and effects on tissue chondrocyte content and matrix composition were neutral.

Radiographic Quantitative Assessment of Caudal Proximal Tibial Angulation in 100 Dogs with Cranial Cruciate Ligament Rupture

Objective To evaluate inter- and intraobserver variability in the measurement of distal tibial axis/proximal tibial axis angle (DPA) from lateral radiographs of canine tibia in dogs with cranial cruciate ligament rupture (CCLR). Study Design Retrospective clinical study. Animals Dogs (n=100) with cranial cruciate ligament rupture. Methods Medical records of dogs diagnosed with CCLR were reviewed. In addition to signalment and TPA measurements, measured DPA (mDPA) was calculated for each lateral view of the tibia in each animal, twice, by 3 blinded observers. Subjective scoring of DPA (sDPA) was also recorded, twice, by 3 additional blinded observers from lateral views of the proximal half of the tibia in each dog. Inter- and intraobserver variability was measured by intraclass correlation coefficient (ICC) for each measurement. Correlation between mDPA and sDPA was also determined. Results Median tibial plateau angle (TPA) of the subject population was 27.9° (range 18.8–41.3°; IQR: 25.5–30.75°). Mean ± SD mDPA was 6.50 ± 2.81° (confidence intervals [CI]: 5.94–7.06°; range 0–13.33°). There was no correlation between age and weight of dogs and the mDPA (P=.58 and .12). There was a moderate correlation between mDPA and TPA (r2=0.49, P<.0001). There was a moderate correlation between sDPA and mDPA (r2=0.27, P<.0001). Good inter- and intraobserver agreement was found in the measurement of mDPA. Conclusion mDPA is a reproducible measurement of caudal angulation of proximal tibia. Furthermore, mDPA of dogs with cranial cruciate ligament disease in this report are in concordance with previous reports.OBJECTIVE To evaluate inter- and intraobserver variability in the measurement of distal tibial axis/proximal tibial axis angle (DPA) from lateral radiographs of canine tibia in dogs with cranial cruciate ligament rupture (CCLR). STUDY DESIGN Retrospective clinical study. ANIMALS Dogs (n=100) with cranial cruciate ligament rupture. METHODS Medical records of dogs diagnosed with CCLR were reviewed. In addition to signalment and TPA measurements, measured DPA (mDPA) was calculated for each lateral view of the tibia in each animal, twice, by 3 blinded observers. Subjective scoring of DPA (sDPA) was also recorded, twice, by 3 additional blinded observers from lateral views of the proximal half of the tibia in each dog. Inter- and intraobserver variability was measured by intraclass correlation coefficient (ICC) for each measurement. Correlation between mDPA and sDPA was also determined. RESULTS Median tibial plateau angle (TPA) of the subject population was 27.9° (range 18.8-41.3°; IQR: 25.5-30.75°). Mean ± SD mDPA was 6.50 ± 2.81° (confidence intervals [CI]: 5.94-7.06°; range 0-13.33°). There was no correlation between age and weight of dogs and the mDPA (P=.58 and .12). There was a moderate correlation between mDPA and TPA (r(2)=0.49, P<.0001). There was a moderate correlation between sDPA and mDPA (r(2)=0.27, P<.0001). Good inter- and intraobserver agreement was found in the measurement of mDPA. CONCLUSION mDPA is a reproducible measurement of caudal angulation of proximal tibia. Furthermore, mDPA of dogs with cranial cruciate ligament disease in this report are in concordance with previous reports.

Radiographic Quantitative Assessment of Caudal Proximal Tibial Angulation in 100 Dogs with Cranial Cruciate Ligament Rupture: Caudal Proximal Tibial Angulation in Dogs with Cranial Cruciate Ligament Rupture

Objective To evaluate inter- and intraobserver variability in the measurement of distal tibial axis/proximal tibial axis angle (DPA) from lateral radiographs of canine tibia in dogs with cranial cruciate ligament rupture (CCLR). Study Design Retrospective clinical study. Animals Dogs (n=100) with cranial cruciate ligament rupture. Methods Medical records of dogs diagnosed with CCLR were reviewed. In addition to signalment and TPA measurements, measured DPA (mDPA) was calculated for each lateral view of the tibia in each animal, twice, by 3 blinded observers. Subjective scoring of DPA (sDPA) was also recorded, twice, by 3 additional blinded observers from lateral views of the proximal half of the tibia in each dog. Inter- and intraobserver variability was measured by intraclass correlation coefficient (ICC) for each measurement. Correlation between mDPA and sDPA was also determined. Results Median tibial plateau angle (TPA) of the subject population was 27.9° (range 18.8–41.3°; IQR: 25.5–30.75°). Mean ± SD mDPA was 6.50 ± 2.81° (confidence intervals [CI]: 5.94–7.06°; range 0–13.33°). There was no correlation between age and weight of dogs and the mDPA (P=.58 and .12). There was a moderate correlation between mDPA and TPA (r2=0.49, P<.0001). There was a moderate correlation between sDPA and mDPA (r2=0.27, P<.0001). Good inter- and intraobserver agreement was found in the measurement of mDPA. Conclusion mDPA is a reproducible measurement of caudal angulation of proximal tibia. Furthermore, mDPA of dogs with cranial cruciate ligament disease in this report are in concordance with previous reports.OBJECTIVE To evaluate inter- and intraobserver variability in the measurement of distal tibial axis/proximal tibial axis angle (DPA) from lateral radiographs of canine tibia in dogs with cranial cruciate ligament rupture (CCLR). STUDY DESIGN Retrospective clinical study. ANIMALS Dogs (n=100) with cranial cruciate ligament rupture. METHODS Medical records of dogs diagnosed with CCLR were reviewed. In addition to signalment and TPA measurements, measured DPA (mDPA) was calculated for each lateral view of the tibia in each animal, twice, by 3 blinded observers. Subjective scoring of DPA (sDPA) was also recorded, twice, by 3 additional blinded observers from lateral views of the proximal half of the tibia in each dog. Inter- and intraobserver variability was measured by intraclass correlation coefficient (ICC) for each measurement. Correlation between mDPA and sDPA was also determined. RESULTS Median tibial plateau angle (TPA) of the subject population was 27.9° (range 18.8-41.3°; IQR: 25.5-30.75°). Mean ± SD mDPA was 6.50 ± 2.81° (confidence intervals [CI]: 5.94-7.06°; range 0-13.33°). There was no correlation between age and weight of dogs and the mDPA (P=.58 and .12). There was a moderate correlation between mDPA and TPA (r(2)=0.49, P<.0001). There was a moderate correlation between sDPA and mDPA (r(2)=0.27, P<.0001). Good inter- and intraobserver agreement was found in the measurement of mDPA. CONCLUSION mDPA is a reproducible measurement of caudal angulation of proximal tibia. Furthermore, mDPA of dogs with cranial cruciate ligament disease in this report are in concordance with previous reports.