Effects of continuous oral administration of phenylbutazone on biomarkers of cartilage and bone metabolism in horses.
OBJECTIVE
To evaluate the effects of continuous oral administration of phenylbutazone on serum and synovial fluid biomarkers of skeletal matrix metabolism in horses.


METHODS
11 adult female horses without clinical or radiographic evidence of joint disease.


METHODS
Horses were randomly assigned to control or treatment groups. Phenylbutazone was administered orally twice daily at a dose of 4.4 mg/kg for 3 days to the treatment group and subsequently at a dose of 2.2 mg/kg for 7 days. Serum and radiocarpal synovial fluid samples were obtained at baseline and thereafter at regular intervals for 4 weeks. Biomarkers of cartilage aggrecan synthesis (chondroitin sulfate 846) and type II collagen synthesis (procollagen type II C-propeptide) and degradation (collagen type II cleavage) were assayed. Biomarkers of bone synthesis (osteocalcin) and resorption (C-terminal telopeptide of type I collagen) were also measured.


RESULTS
No significant differences were found between control and treatment groups or temporally for the biomarkers chondroitin sulfate 846, procollagen type II C-propeptide, collagen type II cleavage, and C-terminal telopeptide of type I collagen in serum or synovial fluid. A significant increase in osteocalcin concentration occurred in synovial fluid during treatment in the treated group. No treatment effect was detected for serum osteocalcin concentration.


CONCLUSIONS
Results suggested that continuous phenylbutazone administration at recommended doses altered some biomarkers in healthy equine joints after short periods of administration. Increased osteocalcin concentration may indicate an undetermined anabolic effect of phenylbutazone administration on periarticular bone or transient induction of osteogenesis in articular chondrocytes or a mesenchymal subpopulation of synoviocytes.
Fradette
Marie-Eve
ME
Département de Sciences Cliniques, Université de Montréal, St-Hyacinthe, QC J2S 7C6, Canada.
Céleste
Christophe
C
Richard
Hèléne
H
Beauchamp
Guy
G
Laverty
Sheila
S
D000284:Administration, Oral; D053674:Aggrecans / Q000096:biosynthesis; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism*; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006736:Horses / Q000378:metabolism*; D010653:Phenylbutazone / Q000008:administration & dosage* / Q000494:pharmacology*; D005723:gamma-Glutamyltransferase / Q000097:blood
D053674:Aggrecans; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D024043:Collagen Type II; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D010653:Phenylbutazone