Biomedical subjects

R J Todhunter

Publications and source records attributed to R J Todhunter.

At least 19 recordsLinked to original sources

PubMed2006

Technical note: Use of marker-based relationships with multiple-trait derivative-free restricted maximal likelihood.

The widespread use of the set of multiple-trait derivative-free REML programs for prediction of breeding values and estimation of variance components has led to significant improvement in traits of economic importance. The initial version of this software package, however, was generally limited to pedigree-based relationships. With continued advances in genomic research and the increased availability of genotyping, relationships based on molecular markers are obtainable and desirable. The addition of a new program to the set of multiple-trait derivative-free REML programs is described that allows users the flexibility to calculate relationships using standard pedigree files or an arbitrary relationship matrix based on genetic marker information. The strategy behind this modification and its design is described. An application is illustrated in a QTL association study for canine hip dysplasia.

Animals↗

PubMed2005

Analysis of allele fidelity, polymorphic information content, and density of microsatellites in a genome-wide screening for hip dysplasia in a crossbreed pedigree.

Recent advances in genomics resources and tools are facilitating quantitative trait locus mapping. We developed a crossbreed pedigree for mapping quantitative trait loci for hip dysplasia in dogs by crossing dysplastic Labrador Retrievers and normal Greyhounds. We show that one advantage to using a crossbreed pedigree is the increased marker informativeness in the backcross/F2 population relative to the founder populations. We also discuss three factors that affect the detection power in the context of this crossbreed pedigree: being able to detect and correct genotyping errors, increasing marker density for chromosomes with a sparse coverage, and adding individuals to the mapping population as soon as they become available.

Alleles↗

PubMed2005

Genes in canine articular cartilage that respond to mechanical injury: gene expression studies with Affymetrix canine GeneChip.

The Affymetrix canine GeneChip with 23,836 probe sets was used to look for cartilage genes that are significantly altered in response to mechanical impact. The model using canine articular cartilage explants loaded in vitro has been described previously (Chen et al., J Orthop Res 19:703-711, 2001). It is our hypothesis that genes that are activated or repressed in articular cartilage after impact injury initiate cartilage degeneration, leading to osteoarthritis in dogs. Gene expression of known cartilage genes was generally consistent with cartilage biology. A total of 528 genes were significantly (P < .01) up- or down- regulated in response to mechanical damage. After applying the strict Bonferroni correction, 172 remained significantly affected. One of these genes, MIG-6/gene 33, was chosen for verification by real- time quantitative reverse transcriptase polymerase chain reaction (RT-PCR). A 3.8- fold increase in expression was confirmed, consistent with the microarray chip data. Deficiencies in the current annotation of the canine chip are discussed. Gene expression studies with the Affymetrix canine GeneChip are potentially valuable, but await more complete annotation.

Animals↗

PubMed2005

In vitro biomechanical comparison of limited contat dynamic compression plate and locking compression plate.

The locking compression plate (LCP) supports biological osteosynthesis by functioning as an internal fixator, rather than as a full or limited contact bone plate which must be adequately contoured and affixed directly to the bone for stable internal fixation of the fracture. In order to help justify the use of the LCP in our veterinary patients, in vitro biomechanical testing was performed comparing the LCP to the conventional limited contact dynamic compression plate (LC-DCP) in canine femurs. We hypothesized that the LCP construct would be at least as stiff under bending and torsional loads as the LC-DCP. The LCP and LC-DCP were applied over a 20-mm osteotomy gap to contralateroal bones within each pair of 14 femora. Non-destructive four-point bending and torsion, and cyclical testing in torsion were performed. The constructs were then loaded to failure in torsion. In medial-lateral and lateral-medial structural bending, significant differences were not found between the LCP and LC-DCP, however, at the gap, the LCP construct was stiffer than the LC-DCP in lateral-medial bending. Significant differences in behaviour over time were not noted between the plate designs during cyclical testing. When loading the constructs to failure in internal rotation, the LC-DCP failed at a significantly lower twist angle (P = .0024) than the LCP. Based on the similar performance with loading, the locking compression plate is a good alternative implant for unstable diaphyseal femoral fracture repair in dogs.

Animals↗

PubMed2001

Comparison of three radiographic methods for diagnosis of hip dysplasia in eight-month-old dogs.

OBJECTIVE: To compare the accuracy of the extended-hip radiographic (EHR) score, the distraction index (DI), and the dorsolateral subluxation (DLS) score for identifying hip dysplasia in dogs at 8 months of age. DESIGN: Cohort study ANIMALS: 129 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbreds. PROCEDURE: Radiography was performed when dogs were 8 months of age. Dogs were euthanatized at 8 to 36 months of age; hip dysplasia was diagnosed at the time of necropsy on the basis of results of a gross examination of the articular cartilage of the hip joints for signs of osteoarthritis. RESULTS: The EHR score, DI, and DLS score at 8 months of age were all significantly correlated with degree of cartilage degeneration at necropsy. Sensitivity and specificity of using EHR score at 8 months of age to diagnose hip dysplasia (scores > 3 were considered abnormal) were 38 and 96%, respectively; sensitivity and specificity of using DI (values > 0.7 were considered abnormal) were 50 and 89%; and sensitivity and specificity of using DLS score (scores < 55% were considered abnormal) were 83 and 84%. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that specificities of the 3 methods for diagnosing hip dysplasia in dogs at 8 months of age were similar. However, the DLS score had higher sensitivity, indicating that there were fewer false-negative results.

Animals↗

PubMed2001

Corticosteroids alter the differentiated phenotype of articular chondrocytes.

Experimental evidence suggests that recommended dosages of some corticosteroids used clinically as antiinflammatory agents for treating arthropathies damage articular cartilage, but low dosages may be chondroprotective. The purpose of this study was to evaluate how different concentrations of methylprednisolone affect chondrocyte function and viability. Articular cartilage and chondrocytes were obtained from young adult horses, 1.5-3.5 years of age. Corticosteroid-induced changes in collagen expression were studied at the transcriptional level by Northern blot analyses and at the translational level by measuring [3H]-proline incorporation into [3H]-hydroxyproline. Fibronectin mRNA splicing patterns were evaluated with ribonuclease protection assays. Cytotoxicity was studied using erythrosin B dye exclusion. Steady-state levels of type II procollagen mRNA decreased without concurrent changes in type I procollagen expression as the medium methylprednisolone concentrations were increased from 1 x 10(1) to 1 x 10(8) pg/ml, dropping below 10% of control values by 1 x 10(5) pg/ml. Cytotoxicity occurred as methylprednisolone levels were increased further from 1 x 10(8) to 1 x 10(9) pg/ml. Changes in total collagen (protein) synthesis were less pronounced, but also demonstrated significant suppression between 1 x 10(4) and 1 x 10(8) pg/ml. Corticosteroid-induced changes in fibronectin isoform levels were evaluated in articular cartilage samples without in vitro culture. The cartilage-specific (V + C)(-) isoform was suppressed in both normal and inflamed joints by a single intraarticular injection (0.1 mg/kg) of methylprednisolone. Combined, these data indicate that methylprednisolone suppresses matrix protein markers of chondrocytic differentiation. Decreased and altered chondrocyte expression of matrix proteins likely contributes to the pathogenesis of corticosteroid-induced cartilage degeneration.

Animals↗

PubMed2001

Repeatability of dorsolateral subluxation scores in dogs and correlation with macroscopic appearance of hip osteoarthritis.

OBJECTIVE: To determine whether dorsolateral subluxation (DLS) scores in young dogs could be used to reliably predict which dogs would develop evidence of hip osteoarthritis and whether DLS scores measured at various ages correlated with each other. ANIMALS: 129 Labrador Retrievers, Greyhounds, and Labrador Retriever-Greyhound crossbreds. PROCEDURES: DLS scores were measured on radiographs taken at 4, 8, and 12 months of age and at necropsy (8 to 36 months of age). At necropsy, the hip joints were examined macroscopically and a score assigned for degree of cartilage degeneration. RESULTS: DLS scores at 4 (n = 35, r(s) = -0.62), 8 (n = 106, r(s) = -0.54), and 12 (n = 15, r(s) = -0.87) months of age were significantly correlated with cartilage degeneration scores, and DLS scores at 8 months of age were significantly correlated with scores obtained at the time of necropsy (n = 39, r(s) = 0.87). The DLS scores at 4 months of age were significantly different from scores at 8 months of age, but scores did not differ significantly thereafter. Likelihood ratios for cartilage lesions for low (< 45%), intermediate (> or = 45 but < or = 55%), and high (> 55%) DLS scores at 8 months of age were 8.0, 2.6, and 0.2, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that DLS score at 8 months of age was a reasonable, albeit imperfect, predictor of the condition of the hip joint cartilage at necropsy. Thus, the DLS method might be useful for early identification of dogs with hip dysplasia.

Animals↗

PubMed2000

Comparison of the trotting gaits of Labrador Retrievers and Greyhounds.

OBJECTIVE: To compare the trotting gaits of Labrador Retrievers and Greyhounds to determine whether differences in locomotion are attributable to differences in their manner of moving or to body size and shape differences between these 2 breeds. ANIMALS: 8 healthy 5-month-old Greyhounds and 5 healthy Labrador Retrievers between 6 and 18 months old. PROCEDURE: A series of 4 force platforms was used to record independent ground reaction forces on the forelimbs and hind limbs during trotting. Values of stride parameters were compared between breeds before and after normalization for size differences. Standard values of absolute and normalized stride period and stride length were determined from linear regressions of these parameters on relative (normalized) velocity. Forces were normalized to body weight and compared at the same relative velocity. RESULTS: Greyhounds used fewer, longer strides than the Labrador Retrievers to travel at the same absolute speed. After normalization for body size differences, most measurable differences between breeds were eliminated. Subtle differences that did persist related to proportion of the stride that the forefoot was in contact with the ground, timing of initial hind foot contact relative to initial forefoot contact, and distribution of vertical force between the forelimbs and hind limbs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that apparent differences in the trotting gait between Labrador Retrievers and Greyhounds are mainly attributable to differences in size, and that dogs of these 2 breeds move in a dynamically similar manner at the trot.

Animals↗

PubMed1999

Site-specific variation in femoral head cartilage composition in dogs at high and low risk for development of osteoarthritis: insights into cartilage degeneration.

OBJECTIVE: To determine which characteristics of cartilage lesion pathology are detected in dogs at high risk to develop osteoarthritis prior to diagnosis by standard radiographs or macroscopic cartilage abnormality on necropsy. METHODS: Fourteen disease-free dogs were assigned to risk groups based on hip distraction index. For seven dogs, three dimensional images of hip joints from computed tomography were available. At necropsy, ligamentum capitis femoris volumes were measured and articular cartilage was harvested and analyzed for percent water, swelling, glycosaminoglycan, and fibronectin. Comparisons were made with nine dogs with macroscopic cartilage lesions (OA group). RESULTS: Ligament volumes were greater in the high distraction index group (P=0.000). Water content was elevated in the lesion area in both low and high risk dogs (P=0.000); no additional increase was noted in the high risk group. Glycosaminoglycan content was slightly elevated in the surrounding area in both groups (P< 0.02) but loss was noted histologically in the lesion area of the high risk group. Fibronectin was increased in the lesion area and in the high risk group (P=0.000). The magnitude of this increase was greatest in the lesion area (P=0.000) in explants. Computed tomography indicated dorsal acetabular rim impingement on the lesion area in high risk dogs. CONCLUSIONS: Water content and swelling suggest matrix structure is weaker at the site of lesion predilection in all dogs regardless of risk status. Computed tomography imaging is consistent with site specific initiation of lesions by mechanical factors.

Animals↗

PubMed1999

Acceleration and balance in trotting dogs.

During quadrupedal trotting, diagonal pairs of limbs are set down in unison and exert forces on the ground simultaneously. Ground-reaction forces on individual limbs of trotting dogs were measured separately using a series of four force platforms. Vertical and fore-aft impulses were determined for each limb from the force/time recordings. When mean fore-aft acceleration of the body was zero in a given trotting step (steady state), the fraction of vertical impulse on the forelimb was equal to the fraction of body weight supported by the forelimbs during standing (approximately 60 %). When dogs accelerated or decelerated during a trotting step, the vertical impulse was redistributed to the hindlimb or forelimb, respectively. This redistribution of the vertical impulse is due to a moment exerted about the pitch axis of the body by fore-aft accelerating and decelerating forces. Vertical forces exerted by the forelimb and hindlimb resist this pitching moment, providing stability during fore-aft acceleration and deceleration.

Animals↗

PubMed1999

Prognostic factors affecting survival of 507 horses with joint disease: (1983 to 1990).

Between July 1, 1983 and December 31, 1990, risk factors were determined for all horses with joint disease presented to a referral center, of being discharged, of ever becoming sound, or of being alive at 3 mo follow-up. Logistic multiple-regression models were done separately for foals (< or = 4 mo), yearlings (> 4-24 mo) and racing or nonracing adult horses (> 24 mo). The breakdown in this study was 53 foals, 87 yearlings, 141 nonracing adults, and 226 racing adults. Thirty-one foals (58%), 68 yearlings (78%), 119 non-racing adults (84%), and 213 racing adults (94%) were discharged. Foals with a less severe lameness, duration of illness of > 1 d, and infectious arthritis had increased odds of discharge. At follow-up, 12 of 18 (67%) were alive, 10 (56%) of which were sound. Yearlings with osteochondrosis had higher odds of discharge; at follow-up, 38 of 49 (78%) were alive, 32 (65%) of which were sound. For non-racing adults, horses with less severe lameness, without a miscellaneous diagnosis, or intended for pleasure use had increased odds of discharge. At follow-up, 55 of 78 (70%) were alive and 33 of 58 (57%) with soundness data became sound. Risk factors for higher odds of being alive at follow-up were carpal lameness, arthroscopic surgery, a prognosis other than poor, became sound, above-median hospitalization costs, and duration of follow-up. The 161 racing adults (76% of discharges), with follow-up, were more likely to have had osteoarthritis, higher hospital costs, hospitalization > 1 d, and arthroscopy. Sixty-four (60%) of these became sound; the odds increased if the horse was not severely lame at admission or was hospitalized for > 1 d. Risk factors and prognosis differed by age-use group among horses seen at our hospital.

Animals↗

PubMed1999

Comparison of measurements of dorsolateral subluxation of the femoral head and maximal passive laxity for evaluation of the coxofemoral joint in dogs.

OBJECTIVE: To determine whether dorsolateral subluxation (DLS) of the femoral head reflects osseous conformation of the coxofemoral (hip) joint and represents a property distinct from maximum passive laxity of the hip joint in dogs. ANIMALS: 14 Labrador Retrievers, 16 Greyhounds, 58 Greyhound-Labrador Retriever mixed-breed dogs, and 1 Rottweiler. PROCEDURES: DLS of the femoral head (DLS score) and passive laxity of the hip joint (distraction index) were determined radiographically in 3 groups of dogs: not treated (167 joints of 84 dogs); before and after injecting 2 ml of hyaluronan into 25 hip joints of 13 dogs; and before and after unilateral triple pelvic osteotomy in 5 dogs. Results of the 2 methods were compared for each group. RESULTS: In untreated dogs, the correlation coefficient (r) of DLS score versus distraction index was -0.73 and -0.69 for 84 left and 83 right hip joints, respectively. Mean coefficient of determination (r2) for both hips was 0.5. Mean DLS score did not differ before and after intra-articular injection of hyaluronan into either hip joint, whereas mean distraction index increased significantly after intra-articular injection. Unilateral triple pelvic osteotomy resulted in a significant increase in DLS score, compared with values obtained before surgery. However, distraction index before and after surgery did not differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE: The DLS test assesses the congruity of the acetabulum and the femoral head in a canine hip joint and thus represents a characteristic distinct from maximum passive laxity. The DLS score and the distraction index evaluate different components of hip joint stability.

Animals↗

PubMed1998

Acute synovitis and intra-articular methylprednisolone acetate in ponies.

OBJECTIVE: To determine how acute synovitis, with and without intra-articular methylprednisolone acetate (MPA), affect synthesis of proteoglycan, total protein, and collagen in articular cartilage and total protein synthesis in synovial membrane. DESIGN: Synovitis was induced in 10 ponies by the injection of 0.5 ng lipopolysaccharide (LPS) into the left radiocarpal and midcarpal joints every 2 days for a total of four treatments. Synovitis was documented by clinical examination and synovial fluid analyses. Two days before euthanasia, MPA (0.1 mg/kg) was injected with the last dose of LPS into both the left and right radiocarpal and midcarpal joints of five of these ponies. Proteoglycan synthesis in articular cartilage explants from these joints was measured by incorporation of sodium [35S]sulfate. The size of the proteoglycan monomers and their aggregation with hyaluronan was assessed by size-exclusion chromatography. Protein synthesis in articular cartilage was measured by incorporation of [3H]proline and collagen synthesis by conversion of [3H]proline into [3H]hydroxyproline. Protein synthesis was measured in synovial membrane explants by incorporation of [35S]methionine. RESULTS: Ponies developed carpal effusion and mild lameness accompanied by increased total nucleated cell count and total solids in synovial fluid in response to the LPS injections. Moderate to severe synovial membrane proliferation and inflammation were observed histopathologically in joints injected with LPS but no consistent light-microscopical changes were observed in the articular cartilage from these joints. Intra-articular MPA alone was associated with decreased proteoglycan synthesis and increased protein and collagen synthesis in the cartilage explants. Total protein synthesis by synovial membrane was also increased by MPA alone. In contrast, no differences in protein or proteoglycan synthesis were observed in explants from the joints with synovitis, with or without intra-articular MPA. Treatment with MPA, LPS, and LPS/MPA did not alter proteoglycan aggregate size, but LPS-induced synovitis resulted in an increase in the second largest population of monomers. MPA increased the synthesis of small proteoglycan monomers. CONCLUSION: Based on the methods used, acute synovitis prevented changes induced by intra-articular MPA alone. Results suggested that the effect of intra-articular MPA on joint metabolism was different between inflamed and normal joints. Experimental studies must consider the effect of inflammation, as well as the potential to introduce in vitro culture artifacts when investigating the effect of intra-articular corticosteroids on chondrocyte function.

Acute Disease↗

PubMed1998

Effect of synovitis and corticosteroids on transcription of cartilage matrix proteins.

OBJECTIVE: To determine whether steady-state levels of type-II procollagen, aggrecan core protein, or fibronectin mRNA in articular chondrocytes are altered by synovitis or administration of methylprednisolone acetate (MPA). SAMPLE POPULATION: Articular cartilage specimens collected from 10 ponies, 2.5 to 3.5 years old and 200 to 300 kg. PROCEDURE: 4 experimental groups were compared, using the cartilage specimens: control, MPA-treated, lipopolysaccharide-induced synovitis, and lipopolysaccharide-induced synovitis with MPA treatment. RNA was isolated from articular cartilage and compared by northern blot analysis, using equine-specific cDNA probes. RESULTS: Synovitis increased steady-state levels of type-II procollagen mRNA fivefold and of aggrecan mRNA twofold. Administration of a single intra-articular injection of MPA (0.1 mg/kg of body weight) decreased type-II procollagen transcripts in normal cartilage sixfold, without significant effect on aggrecan or total fibronectin mRNA values. MPA treatment of inflamed joints decreased type-II procollagen and aggrecan mRNA to levels that were not significantly different from those in untreated control specimens. CONCLUSIONS: Articular chondrocytes increase type-II procollagen and aggrecan synthesis in response to synovitis. MPA alters chondrocyte function in normal and inflamed cartilage, suggesting that potential changes in cartilage matrix protein synthesis should be considered when evaluating the therapeutic value of intra-articular administration of corticosteroids. CLINICAL RELEVANCE: Knowledge of how synovitis and corticosteroids (independently and in combination) affect synthesis of cartilage matrix proteins is relevant to understanding pathogenesis of traumatic osteoarthritis and improving therapeutic strategies.

Aggrecans↗

PubMed1997

Onset of epiphyseal mineralization and growth plate closure in radiographically normal and dysplastic Labrador retrievers.

OBJECTIVE: To determine whether onset of mineralization of the femoral and proximal tibial epiphyses and age at closure of the femoral and acetabular triradiate growth plates was different for Labrador Retrievers that were radiographically normal or that had canine hip dysplasia (CHD). DESIGN: Cohort study. ANIMALS: 36 Labrador Retriever puppies. PROCEDURE: Puppies were radiographed every other day from the time they were 8 to 10 days old until ossification of the femoral heads was apparent. Radiographs were then obtained weekly until puppies were 1 month old and then monthly until puppies were 8 to 12 months old. Age at which mineralization was first observed in the proximal and distal femoral and proximal tibial epiphyses and at which the femoral capital, triradiate acetabular, and distal femoral growth plates were no longer radiographically visible were recorded. Fifteen dogs were euthanatized and necropsied to determine whether dogs had CHD. RESULTS: There were 26 radiographically normal left and right hip joints and 10 dysplastic left and right hip joints. Onset of mineralization of the proximal femoral epiphyses and of the right proximal tibial epiphysis was significantly later in dysplastic than in radiographically normal puppies. The left femoral capital growth plates closed significantly later in dysplastic than in radiographically normal joints, but other differences in growth plate closure were not detected. CLINICAL IMPLICATIONS: Endochondral ossification may be abnormal in dogs with CHD. The disease appears to affect multiple joints, even though it is most evident clinically in the hip joint.

Aging↗

PubMed1997

Variations in composition of cartilage from the shoulder joints of young adult dogs at risk for developing canine hip dysplasia.

OBJECTIVE: To determine whether the composition of cartilage from the shoulder joints of dogs varied with the risk of developing canine hip dysplasia (CHD). DESIGN: Observational study. ANIMALS: 12 skeletally mature (approx 1 year old) Labrador Retrievers. PROCEDURE: Dogs were classified as having a low, moderate, or high risk of developing CHD on the basis of distraction indices. Cartilage was harvested from the craniolateral and weight-bearing regions of the humeral heads, and wet weight per unit area and dry, glycosaminoglycan, and fibronectin contents were determined. RESULTS: Glycosaminoglycan and dry contents did not vary among risk groups. For cartilage from the craniolateral region of the humeral head, wet weight per unit area and fibronectin content increased as risk of developing CHD increased. Wet weight and fibronectin content of cartilage from the weight-bearing region of the humeral head did not vary among risk groups. CLINICAL IMPLICATIONS: Dogs that have a high risk of developing CHD are also more likely to develop osteoarthritis of the shoulder joint. The observed increases in wet weight per unit area and fibronectin content in cartilage from the craniolateral region of the humeral head in dogs at a high risk of developing CHD may be early sings of incipient osteoarthritis.

Animals↗

PubMed1997

Concentrations of keratan sulfate in plasma and synovial fluid from clinically normal horses and horses with joint disease.

OBJECTIVE: To determine whether keratan sulfate concentrations in plasma or synovial fluid from clinically normal horses were different from concentrations in horses with joint disease and whether concentrations varied with type of joint disease. DESIGN: Case-control study. ANIMALS: 67 clinically normal horses, 10 clinically normal foals, and 160 horses with joint disease. PROCEDURE: ELISA was used to measure keratan sulfate concentrations. RESULTS: Mean plasma keratan sulfate concentration (mean +/- SEM, 580 +/- 124 ng/ml) in foals peaked at 10 weeks of age. Mean plasma keratan sulfate concentration in clinically normal horses was 200 ng/ml (95% confidence interval, 157 to 251 ng/ml). Horses with osteochondral (chip) fractures, other closed intraarticular fractures, inflammatory arthritis (synovitis), infectious arthritis, or osteochondrosis had significantly higher plasma keratan sulfate concentrations than did clinically normal horses, but horses with osteoarthritis did not. Breed, gender, and type of joint disease affected keratan sulfate concentration in synovial fluid. Standard-breds with chip fractures of the metacarpophalangeal/ metatarsophalangeal joints had significantly higher keratan sulfate concentrations in synovial fluid than did Thoroughbreds. Keratan sulfate concentrations in synovial fluid from osteoarthritic carpal joints were lower than concentrations in normal carpal joints and tarsocrural joints with inflammatory joint disease. CLINICAL IMPLICATIONS: Keratan sulfate concentration alone was not a specific marker of joint disease but was affected by various joint diseases.

Aging↗

PubMed1997

Slow-acting, disease-modifying osteoarthritis agents.

There is evidence to suggest that tetracyclines have benefit beyond their antimicrobial activity. The ability to inhibit metalloproteinase activity may provide a disease-modifying effect in OA, and available data suggest that further investigation is warranted. Controlled, double-blind, prospective clinical studies have not been completed. The canine cruciate ligament transection model studies are frequently cited as the most convincing in vivo evidence of a benefit of oral tetracycline therapy for the treatment of OA. Until more evidence becomes available, the use of tetracyclines as therapeutic agents for OA should be considered investigational.

Administration, Oral↗