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. 2016 Dec;3(1):17.
doi: 10.1186/s40634-016-0053-5. Epub 2016 Aug 15.

Functional Outcome Measures in a Surgical Model of Hip Osteoarthritis in Dogs

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Free PMC article

Functional Outcome Measures in a Surgical Model of Hip Osteoarthritis in Dogs

Dianne Little et al. J Exp Orthop. .
Free PMC article

Abstract

Background: The hip is one of the most common sites of osteoarthritis in the body, second only to the knee in prevalence. However, current animal models of hip osteoarthritis have not been assessed using many of the functional outcome measures used in orthopaedics, a characteristic that could increase their utility in the evaluation of therapeutic interventions. The canine hip shares similarities with the human hip, and functional outcome measures are well documented in veterinary medicine, providing a baseline for pre-clinical evaluation of therapeutic strategies for the treatment of hip osteoarthritis. The purpose of this study was to evaluate a surgical model of hip osteoarthritis in a large laboratory animal model and to evaluate functional and end-point outcome measures.

Methods: Seven dogs were subjected to partial surgical debridement of cartilage from one femoral head. Pre- and postoperative pain and functional scores, gait analysis, radiographs, accelerometry, goniometry and limb circumference were evaluated through a 20-week recovery period, followed by histological evaluation of cartilage and synovium.

Results: Animals developed histological and radiographic evidence of osteoarthritis, which was correlated with measurable functional impairment. For example, Mankin scores in operated limbs were positively correlated to radiographic scores but negatively correlated to range of motion, limb circumference and 20-week peak vertical force.

Conclusions: This study demonstrates that multiple relevant functional outcome measures can be used successfully in a large laboratory animal model of hip osteoarthritis. These measures could be used to evaluate relative efficacy of therapeutic interventions relevant to human clinical care.

Keywords: Articular cartilage repair; Collagen; Inflammation; Pain; Proteoglycan; Synovium; Tissue engineering.

Figures

Fig. 1
Fig. 1
(A) Distraction index of operated and control limbs as assessed by radiography. *Operated significantly less than control limb (p = 0.04). (B) Modified Lane radiographic scores of operated and control limbs. *Significantly greater score than control limb (p = 0.022). Bars sharing the same letters are not significantly different from each other (p < 0.05), n = 7. (C) Preoperative (a,c) and 20-week (b,d) radiographs of control (a,b) and operated (c,d) limbs. Range in radiographic appearance of preoperative femoral head phenotype from normal (e) to dysplastic (f). Open arrow heads indicate circumferential linear femoral head osteophytes, and closed arrow heads indicate caudal curvilinear femoral neck osteophytes
Fig. 2
Fig. 2
a Change in bodyweight compared to preoperative values. *Week 20 differs from weeks 1–5 (p = 0.03). +Week 19 differs from weeks 1 and 2 (p = 0.03). b Pre- and postoperative limb circumference in control and operated limbs. *Control and operated are different (p < 0.007). #Significantly different from preoperative within the same limb (p < 0.03). c Difference in total range of motion between control and operated limbs pre- and postoperatively. *Different from time 0 (p < 0.04). d Glasgow Composite Measure Pain Scale – Short Form. *Day 1 different from day 0 (p < 0.0001). #Weeks 6–21 different from day 1 (p < 0.02). e Canine Brief Pain Inventory. #Different from all other time points (p < 0.001). *Different from preoperative (p < 0.04)
Fig. 3
Fig. 3
a Mean total daytime (light phase) and nighttime (dark phase) activity counts for each 12-h time period over a 7-day recording period. *Significantly different from every other day data point (p < 0.02). #Different from time 0 day (p < 0.04). +Same as week 1 day (p > 0.05). b Mean number of daytime (light phase) rest periods and nighttime (dark phase) activity bouts for each 12-h cycle over a 7-day recording period. *p < 0.04, # < 0.05. c Mean total duration of daytime (light phase) rest periods and nighttime (dark phase) activity bouts over each 12-h cycle over a 7-day recording period. d Mean total activity count each hour over a 24-h cycle and 7-day recording period—one-way within-subjects analysis of variance with multiple dependent measures (time of day and postoperative time). *Different between preoperative and 20 weeks postoperatively within subject
Fig. 4
Fig. 4
a Duty factor for each limb preoperatively and at 20 weeks postoperatively. IL = ipsilateral forelimb (same side forelimb); CL = contralateral forelimb (diagonal forelimb). b Ratio of peak vertical force for operated limb compared to all other limbs preoperatively and at 20 weeks postoperatively. O:C = operated vs. control; O:CL = operated vs. contralateral forelimb; O:IL = operated vs. ipsilateral forelimb. c Ratio of impulse for operated limb compared to all other limbs preoperatively and at 20 weeks postoperatively. d Ratio of maximum peak pressure for operated limb compared to all other limbs preoperatively and at 20 weeks postoperatively. e Change in distribution of bodyweight to each limb at 20 weeks postoperatively compared to preoperatively, and between forelimbs (FL) and hind limbs (HL). *Different from preoperative; bars having different letters are significantly different
Fig. 5
Fig. 5
a Total modified Mankin scores for femoral head and acetabulum in control and operated hip joints, 20 weeks after surgery. *p = 0.03. b Safranin O/Fast Green images of the articular cartilage of zones 1 and 4 of the femoral head and acetabulum in control and operated hip joints. Scale bar = 100 μm. c Schematic of the mean modified Mankin scores by joint region in control and operated femoral head and acetabulum, with significant correlations between femoral head zone 2–4 modified Mankin score and acetabulum zone 1, 7 & 8 modified Mankin score identified for control limbs (solid lines --------), between operated limb femoral head zones 3–6 and corresponding acetabulum zone 8 (dotted lines ……), and between zones 3–5 on operated femoral head (dashed lines - - - - -). The region of debrided cartilage on operated femoral head is delineated by dashed lines/dots in zones 3–5. d Modified Mankin scores by femoral head and acetabulum regional zone for control and operated limbs. *Operated different from control
Fig. 6
Fig. 6
a Regional synovitis score for control and operated limbs. *p = 0.05 for control vs. operated. No individual region effect. b Representative histological images (H&E) of synovium from cranial, caudal, lateral and medial aspects of the hip joint in control and operated limbs. Scale bar = 100 μm

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