Clinico-therapeutic efficacy of Pentosan Polysulfate and Grapiprant for the management of osteoarthritis in dog

Introduction

The human-animal relationship has evolved since prehistoric times through domestication and co-evolution, significantly influencing human society and survival (Kacker and Srivastava, 2018). In India, rapid urbanization, increased disposable income, and the rise of nuclear families have contributed to a growing demand for companion animals, particularly dogs, which are now considered integral family members [19] . Osteoarthritis (OA) is the most common joint disorder in dogs, characterized by progressive degeneration of articular cartilage, inflammation, pain, stiffness, and reduced mobility (Elders, 2000; Noth et al., 2008). It affects approximately one in five dogs, imposing both clinical and economic burdens (Hielm-Bjorkman et al., 2003; Aragon et al., 2007; Anderson et al., 2018). The condition is more prevalent in overweight, obese, and neutered animals, as well as in large breeds such as Labrador Retrievers, German Shepherds, and Rottweilers (Bland, 2015; Anderson et al., 2020) [1,2,3,5,12,21] .

Osteoarthritis may be primary (age-related) or secondary to conditions such as hip dysplasia, elbow dysplasia, patellar luxation, and cranial cruciate ligament rupture. Its pathogenesis involves degradation of cartilage matrix components, synovial inflammation, osteophyte formation, and subchondral bone remodeling (Huang et al., 2010; Dubey et al., 2018) [18] . Clinical signs include lameness, stiffness, reluctance to move, and pain on joint manipulation. Diagnosis is based on clinical evaluation and imaging modalities such as radiography, CT, and MRI (Braun and Gold, 2012) [6,11] . Management of OA is primarily symptomatic and multimodal, involving NSAIDs, analgesics, nutraceuticals, physiotherapy, and surgical interventions in advanced cases (Cook and Payne, 1997). However, field conditions often limit effective diagnosis and treatment [10] . Pentosan Polysulfate Sodium (PPS) is a disease-modifying osteoarthritis drug with chondroprotective and antiinflammatory properties, promoting cartilage repair and inhibiting degradation (Ghosh, 1999; Wijekoon et al., 2018) [15] . Grapiprant, a selective EP4 receptor antagonist, provides targeted pain relief by inhibiting prostaglandin-mediated inflammation with fewer side effects compared to conventional NSAIDs (Nagahisa et al., 2016; Sartini et al., 2021) [20,25,31] . Nutraceuticals such as undenatured type-II collagen and omega-3 fatty acids further support joint health and improve clinical outcomes. Considering the need for effective and standardized treatment protocols, the present study was undertaken with the following objectives:

Objectives of the study 1. To compare the efficacy of Pentosan Polysulfate Sodium (PPS) and Grapiprant in osteoarthritis in dogs. 2. To study haemato-biochemical alterations associated with Pentosan Polysulfate Sodium (PPS) and Grapiprant therapy

Materials and methods

Study Location and Design

The study was conducted at the Department of Veterinary Surgery and Radiology, Veterinary Clinical Complex, PGIVAS, Akola. A total of 25 dogs with hind limb lameness or locomotor disability were screened, and 16 dogs with confirmed hip osteoarthritis were selected and randomly divided into two groups (n=8 each).

Treatment Protocol

Groups (n= no. of dogs) Therapeutic Drugs and Protocol

Group I (n=8) Inj. Pentosan Polysulfate Sodium @ 3 mg/kg BW by subcutaneous route at weekly intervals for four weeks.

Tab. Undenatured type-II Collagen and Omega 3 fatty acid according to body weight orally.

Group II (n=8) Tab. Grapiprant @ 2mg/kg BW OD orally for 7 days Tab. Undenatured type-II Collagen and Omega 3 fatty acid according to body weight orally.

Incidence Study

Incidence of osteoarthritis was calculated based on joint involvement, breed, age, and sex, and expressed as percentages.

Physiological Parameters

Rectal temperature, heart rate, and respiratory rate were recorded on day 0, 21, and 45 post-treatment. All clinical parameters were evaluated on day 0, 21, and 45.

Clinical Evaluation

Haematological Analysis

Blood samples collected in EDTA vials were analysed for haemoglobin (Hb), total erythrocyte count (TEC), total leucocyte count (TLC), and differential leucocyte count (DLC) using an automated haematology analyser.

Biochemical Analysis

Serum samples were analysed for calcium, phosphorus, alkaline phosphatase (ALP), and total protein using a semiautomatic analyser.

Radiographic Examination

Radiographs of the hip joint were taken under sedation and general anesthesia using ventrodorsal extended view.

Osteoarthritic changes such as osteophytes, joint space narrowing, and subchondral sclerosis were recorded.

Radiographic Scoring

Severity of osteoarthritis was graded on a scale of 1-4 (slight to severe) based on standard radiographic criteria.

Statistical Analysis

Data were analysed using ICAR-WASP version 2.0. A twoway factorial design and ANOVA were used to determine significant differences between groups and time intervals.

Results and Discussion

Study Overview:

Out of 25 dogs presented with hind limb lameness, 16 dogs diagnosed with hip osteoarthritis were included in the study. These animals were randomly divided into two groups (n=8 each) and subjected to two different therapeutic protocols along with nutraceutical supplementation. Clinical, physiological, hematological, biochemical, and radiographic parameters were evaluated at different intervals to assess treatment efficacy.

Incidence of Osteoarthritis 5.2.1 Overall Incidence:

The hip joint was the most commonly affected joint with 16 cases (64%), followed by stifle joint 4 cases (16%), elbow joint 3 cases (12%), and carpal joint 2 cases (8%). These findings are in accordance with Subin (2005), Singh (2019), Varghese (2019), and Bano et al. (2022), who also reported higher incidence of hip osteoarthritis in dogs [4,26,27,30] .

Breed-wise Incidence

Among the 16 dogs affected with hip osteoarthritis, Labrador Retrievers showed the highest incidence (7 cases; 43.75%), followed by German Shepherds (4 cases; 25%), Golden Retrievers (2 cases; 12.50%), and other breeds including Rottweiler, Dobermann, and Great Dane (1 case each; 6.25%). These findings are in accordance with Subin (2005), Singh (2019), and Anderson et al. (2020), who reported higher susceptibility in large breeds due to increased body weight and joint stress [2,26,27] .

Age-wise Incidence

Higher incidence was observed in dogs aged 5-10 years (9 cases; 56.25%), followed by dogs above 10 years (5 cases; 31.25%) and 1-5 years age group (2 cases; 12.50%). These findings are in agreement with Todhunter et al. (2003), Singh (2019), and Varghese (2019), indicating that osteoarthritis is a progressive age-related disorder [26,29,30] .

Gender-wise Incidence

Out of 16 cases, males (9 cases; 56.25%) were more commonly affected than females (7 cases; 43.75%). Similar observations have been reported by Subin (2005) and Suheb et al. (2021), possibly due to increased activity and body weight in male dogs [27,28] .

Physiological Parameters

Rectal temperature, heart rate, and respiration rate remained within normal physiological limits in all animals throughout the study period, with no significant variation between treatment groups or observation intervals. This suggests that osteoarthritis is primarily a localized musculoskeletal disorder without systemic physiological involvement. Similar findings were reported by Subin (2005), Singh (2019), Varghese (2019), and Patel et al. (2025) [22,26,27,30] . [9,22,28] . Lameness scores also showed significant improvement in all treated dogs, reflecting enhanced mobility and joint function. Greater clinical improvement observed in Group I may be attributed to the chondroprotective and cartilage-regenerating effects of pentosan polysulfate, as reported by Budsberg et al. (2007) and Bwalya et al. (2017) [7,8] .

Clinical Parameters

Weight-bearing ability improved in all animals, indicating restoration of functional limb use. Group I animals showed comparatively superior improvement, which may be due to improved joint lubrication and reduced cartilage degeneration. Similar findings were reported by Elmesiry et al. (2016) and Wijekoon et al. (2018) [13,31] . The improvement observed in Group II animals treated with Grapiprant may be attributed to selective EP4 receptor antagonism leading to effective analgesia, as described by Rausch-Derra et al. (2016) and Enomoto et al. (2024). Additionally, the administration of undenatured type-II collagen and omega-3 fatty acids in both groups may have contributed to reduction in inflammation and improvement in joint health, as reported by Roush et al. (2010) and Gupta et al. (2011) [14,16,23,24] .

Haematological Parameters

Haematological parameters including haemoglobin, total erythrocyte count, total leucocyte count, and differential leucocyte count remained within normal physiological limits in all 16 dogs and did not show significant variation throughout the study period. This indicates absence of systemic inflammatory or hematological changes, as osteoarthritis primarily affects joint structures. These findings are in accordance with Subin [4,22,26,27,28] .

Biochemical Parameters

Serum biochemical parameters including calcium, phosphorus, alkaline phosphatase, and total protein remained within normal limits in all animals and did not show significant variation between groups or observation intervals. This suggests that osteoarthritis does not significantly influence systemic metabolic functions. Similar findings have been reported by Subin (2005), Rausch-Derra et al. (2016), Singh (2019), and Varghese (2019) [23,26,27,30] .

Radiographic Findings

Radiographic evaluation of all 16 dogs revealed progressive improvement in joint condition over time in both treatment groups. Changes observed included reduction in osteophyte formation, improvement in joint space, and better joint congruency. The improvement was more pronounced in Group I animals treated with Pentosan Polysulfate Sodium, indicating its disease-modifying effects on cartilage and joint structures.

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