Effects of oral treatment with chondroitin sulfate and glucosamine in an experimental model of metacarpophalangeal osteoarthritis in horses

Abstract

Background: Combined chondroitin sulfate (CS) and glucosamine (GlcN) has been widely used in oral formulations to prevent and treat osteoarthritis. CS is effective for controlling pain in osteoarthritic patients, whereas GlcN can stimulate glycosaminoglycan synthesis, thus reducing extracellular matrix degradation. Although several studies have been published on this topic, the effectiveness of treatment with oral CS and GlcN remains uncertain. The objective of this study was to analyze the progression of experimentally induced osteoarthritis in horses and verify the effectiveness of an oral compound based on CS and GlcN to treat and/or modulate this disease. The study analyzed the metacarpophalangeal joint of the left thoracic limb of 16 horses divided into two groups, with eight horses treated with CS and GlcN in the treated group (GT) and eight untreated horses in the control group (GC). Chondral lesions were induced through arthroscopy, which was defined as time-point zero (T0). Physical, ultrasonographic, and radiographic examinations and synovial fluid biomarkers measurements were performed on days 0, 30, 60, 90, and 120. At the end of the experiment (T4), arthroscopy was performed again to macroscopically evaluate the joints and collect material for microscopic analysis.

Results: Significant differences were observed between groups in some evaluated parameters, such as visual lameness assessment, synovial concentrations of prostaglandin E2, and ultrasound examination. However, the GT still presented slightly improved results for joint flexion angle, analysis of lameness using sensors, and histopathological analysis of chondral repair tissue, however, without the statistical significance (p>0.05).

Conclusions: The treatment was considered effective in the clinical modulation of experimental osteoarthritis, with improvement of some parameters in the GT. However, this type of treatment may not be entirely effective to change the catabolic process in articular cartilage and the progressive induced chondral damage.

Keywords: Equine; Glycosaminoglycan; Joint; Lameness; Osteoarthritis.

Fig. 1

Lameness assessment: Boxplot graphs were applied when data were not normally distributed, and the best measure of central tendency was the median. The scores were obtained after the lameness evaluation using the American Association of Equine Practitioners lameness scale (AAEP) and analysis using the motion sensor (Lameness Locator), at times T0 to T4, for the control group (GC) and treated group (GT). The boxes represent data variability. The bottom of the box corresponds to the point of 25% of the sample, the top of the box corresponds to the point of 75% of the sample, and the line inside corresponds to the median (point that divides the sample by 50%, in the center of distribution). *Presence of outliers, there was statistical difference between groups at T4 (p < 0.05)

Fig. 2

Ultrasonographic images of GC (C and D) and GT (A and B): the images show osteochondral irregularities on the condyles (arrow in A), enlarged and heterogeneous plica (arrow in B), osteophytes and fragmentation in the first phalanx (arrow in C), and synovitis with increased synovial vascularization (color Doppler in D)

Fig. 3

Arthroscopic images: the images at T4 show fibrocartilage formation at the lesion site (arrow in A), osteophytes and fragmentations in the first phalanx (arrow in B), increased vascularization and villous hypertrophy in synovitis (arrows in C and D), hemorrhage points and necrosis (arrows in E), and erosions (arrow in F)

Fig. 4

Microscopic analysis of the tissues at T4: Boxplot graphs were applied when data were not normally distributed, and the best measure of central tendency was the median. The graph shows the scores of the control group (GC) and treated group (GT) at T4 for synovial membrane and cartilage. The higher the score, the worse was the tissue condition. The boxes represent data variability. The bottom of the box corresponds to the point of 25% of the sample, the top of the box corresponds to the point of 75% of the sample, and the line inside corresponds to the median (point that divides the sample by 50%, in the center of distribution). *Presence of outliers. There was no statistically significant difference between the groups

Fig. 5

Osteoarthritis induction by arthroscopy and macroscopic joint examination. A Schematic demonstration of the location of the grooves (#) made in the cartilage tissue of the third metacarpal condyles to induce osteoarthritis at T0 [21]. B Arthroscopic image showing the position of the arthroscopic drill to make the grooves. C Arthroscopic image showing the final aspect of the lesions in the medial condyle at T0