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 nducible 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.
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.
Objective—To compare ground reaction forces (GRFs) measured by use of a pressure-sensitive walk-way (PSW) and a force plate (FP) and evaluate weekly variation in the GRFs and static vertical forces in dogs.
Animals—34 clinically normal dogs and 5 research dogs with lameness.
Procedure—GRF data were collected from 5 lame and 14 clinically normal dogs by use of an FP and a PSW. Peak vertical force (PVF), vertical impulse (VI), and velocity measurements (determined by use of photocells and PSW data) were compared between groups. Peak vertical force, VI, stride length, ground phase time (ie, contact time), and static body weight distribution data were collected on 2 occasions, 1 week apart, in 20 different clinically normal dogs by use of a PSW; week-to-week variation in values was evaluated.
Results—Measurements of velocity derived by use of the photocells were not different from those derived by use of the PSW. For any 1 limb, values derived by use of the PSW were significantly lower than values derived with the FP. For values obtained by use of either technique, there were no differences between left and right limbs except for values of PVF measured via PSW in forelimbs. Values of PVF, VI, contact time, stride length, and static weight distribution generated by the PSW did not vary from week to week.
Conclusions and Clinical Relevance—Values for GRFs varied between the FP and PSW. However, data derived by use of PSW were consistent and could be used to evaluate kinetic variables over time in the same dog.
Objective—To investigate the ability of perzinfotel (an N-methyl-d-aspartate receptor antagonist) and a proprietary phospholipase A2 (PLA2) inhibitor to attenuate lameness in dogs with sodium urate (SU)–induced synovitis.
Animals—8 adult dogs.
Procedures—A blinded 4-way crossover study was performed. Dogs received perzinfotel (10 mg/kg), a proprietary PLA2 inhibitor (10 mg/kg), carprofen (4.4 mg/kg; positive control treatment), or no treatment (negative control treatment). On the fourth day after initiation of treatment, synovitis was induced via intra-articular injection of SU 1 hour before administration of the last treatment dose. Ground reaction forces were measured and clinical lameness evaluations were performed before (baseline [time 0]) and 2, 4, 6, 8, 12, and 25 hours after SU injection. There was a 21-day washout period between subsequent treatments. Data were analyzed via repeated-measures ANOVAs.
Results—Peak vertical force (PVF) and vertical impulse (VI) values for negative control and perzinfotel treatments were significantly lower at 2 and 4 hours, compared with baseline values. Values for PVF and VI for the PLA2 inhibitor and positive control treatments did not differ from baseline values at any time points. Between-treatment comparisons revealed significantly higher PVF and VI values for the positive control treatment than for the negative control and perzinfotel treatments at 2 and 4 hours. Values for VI were higher for PLA2 inhibitor treatment than for negative control treatment at 2 hours.
Conclusions and Clinical Relevance—Perzinfotel did not significantly alter SU–induced lameness. The proprietary PLA2 inhibitor attenuated lameness but not as completely as did carprofen.
Objective—To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs.
Animals—8 client-owned dogs with clinical signs of osteoarthritis.
Procedures—Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.1 mg/kg, PO, q 24 h) for 10 days each, with an interval of at least 14 days between treatments. On days 0 and 10, blood was collected for platelet aggregation assays, thrombelastography, and measurement of lipopolysaccharide-stimulated prostaglandin E2, platelet thromboxane B2 (TXB2), and free serum TXB2 and 6-keto-prostaglandin F (PGF)-1α concentrations.
Results—Platelet aggregation decreased after treatment with aspirin and carprofen, whereas significant changes from baseline were not detected for the other drugs tested. Thrombelastograms obtained after treatment with carprofen revealed decreased maximum amplitude and α-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E2 decreased after treatment with carprofen or deracoxib, and platelet TXB2 production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1α did not change significantly after treatment with any of the drugs, although the ratio of free TXB2 to 6-keto-PGF-1α decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib.
Conclusions and Clinical Relevance—At the dosages tested, treatment with meloxicam affected platelet function minimally in dogs with osteoarthritis. Treatment with carprofen decreased clot strength and platelet aggregation. Clot strength was increased after treatment with deracoxib.
Objective—To evaluate the quality of information
regarding osteoarthritis (OA) in dogs currently available
on the World Wide Web.
Procedure—5 search engines were searched with
the keywords "dog," "degenerative joint disease,"
"canine," and "osteoarthritis," and the first 50 sites
listed by each search engine were analyzed. Unique
Web site addresses were distributed to 3 diplomates
of the American College of Veterinary Surgeons, who
provided a standardized evaluation of each site.
Results—30 unique Web sites were evaluated.
Twenty (66%) provided information consistent with
conventional knowledge as outlined in textbooks and
peer-reviewed literature, 8 (27%) provided experimental
or anecdotal information in addition to conventional
knowledge, and 2 (7%) provided misleading information.
Mean scores for overall usefulness of the information
provided in regard to clinical features of and
treatment for OA were 1.3 and 1.5, respectively (1 =
information of minimal use; 5 = very useful information).
Twenty-three (77%) sites encouraged pet owners
to seek the advice of a veterinarian. Twenty-three
(77%) sites were given overall quality scores < 2, and
7 (23%) were given scores between 2 and 3 (1 = site
was counterproductive; 5 = site was very valuable).
Conclusions and Clinical Relevance—Results suggest
that the quality of information currently available
on the Web that addresses OA in dogs is questionable.
Although most of the sites conveyed some conventional
information with reasonable accuracy, the
information was incomplete, of minimal use, and
often considered counterproductive. (J Am Vet Med
Objective—To determine pharmacokinetics of meloxicam in healthy green iguanas following PO and IV administration and assess potential toxicity.
Animals—21 healthy green iguanas (Iguana iguana).
Procedures—To assess pharmacokinetics, 13 iguanas were administered a single dose (0.2 mg/kg) of meloxicam PO and, 14 days later, the same dose IV. To assess potential toxicity, 4 iguanas were given meloxicam at a dosage of 1 or 5 mg/kg, PO, every 24 hours for 12 days, and results of histologic examination were compared with results for another 4 iguanas given a single dose of meloxicam (0.2 mg/kg).
Results—There were no significant differences between PO and IV administration with regard to terminal half-life (mean ± SD, 12.96 ± 8.05 hours and 9.93 ± 4.92 hours, respectively), mean area under the curve to the last measured concentration (5.08 ± 1.62 μg•h/mL and 5.83 ± 2.49 μg•h/mL), volume of distribution (745 ± 475 mL/kg and 487 ± 266 mL/kg), or clearance (40.17 ± 10.35 mL/kg/h and 37.17 ± 16.08 mL/kg/h). Maximum plasma concentration was significantly greater following IV (0.63 ± 0.17 μg/mL) versus PO (0.19 ± 0.07 μg/mL) administration. Time from administration to maximum plasma concentration and mean residence time were significantly longer following PO versus IV administration. Daily administration of high doses (1 or 5 mg/kg) for 12 days did not induce any histologic changes in gastric, hepatic, or renal tissues.
Conclusions and Clinical Relevance—Results suggested that administration of meloxicam at a dose of 0.2 mg/kg IV or PO in green iguanas would result in plasma concentrations > 0.1 μg/mL for approximately 24 hours. (Am J Vet Res 2010;71:1277–1283)