Distal tarsal joints osteoarthritis: Evidence behind bisphosphonates and NSAIDs to improve lameness

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Appraisal, application and reflection

There is no prospective clinical study comparing the effects of NSAIDs versus bisphosphonates on improvement of lameness related to bone spavin in horses. There are two generations of biosphosphonates. The early generation, contains nitrogen and includes tiludronate and clodronate, which are considered less potent. The latest generation comprises pamidronate and zoledronate and are highly potent.

There are more publications looking into bisphosphonates as a treatment for navicular disease (Denoix, J. M. et al., 2003; Dyson, S. J. et al., 2005; Mitchell, A. et al., 2019; and Whitfield, C.T. et al., 2016), but the work of Gough et al. (2010) appears to be the only publication found by the author on the use of bisphosphonates as a treatment for bone spavin in horses. A review of the efficacy of tiludronate in horses (Kamm, L. et al., 2008) mentions several smaller studies, namely a case series (Riccio, B. et al., 2002) and clinical observations (Dyson, S. J. et al., 2004) that were never officially published. None of these provide sufficient evidence that bisphosphonates are truly beneficial in cases of distal tarsal joints OA.

In both of the publications presented here, lameness is used as the principal outcome evaluated to determine if either firocoxib or tiludronate are effective in improving the lameness of the horses with distal tarsal joints OA. As lameness evaluation is a very subjective process and taken together with the fact both studies are “multicentric”, the accuracy of the outcome evaluation is questionable. Unlike more recent studies on the topic (Mitchell, A. et al. 2019 and Whitfield, C.T. et al. 2016), no inertial sensor system nor ground-mounted stationary force plate system was employed. Further publications with more objective lameness evaluations and other measured outcomes are needed. For example, in a similar study comparing the efficacy of phenylbutazone versus firocoxib in horses with naturally occurring osteoarthritis (Doucet, M. Y. et al., 2008), lameness was used as the outcome evaluated, as well as other more objective measures: reaction to manipulation/joint flexion, joint swelling, joint circumference and range of motion.

In the study by Orsini et al. (2012), the lamenesses were graded on the AAEP Lameness Scale (Grade 0–5) by a veterinary surgeon on days 0, 7 and 14, but were also graded by the horses’ caregivers on days 7 and 14. As there was no placebo or control group in this study, none of these individuals were blinded and all were aware the horse was under treatment with firocoxib. In the study by Gough et al. (2010), the lameness was graded on a scale of 0-10 by a veterinary surgeon on days 0, 60 and 120 in a randomised double-blind placebo control study. However, the authors state that horses not responsive to treatment at day 60 could receive the standard dose of tiludronate at that time, voiding the double-blind aspect of the study design. These breaches in study designs introduce biases, namely in the assessment of the lameness and this greatly impacts on the reliability of the results.

Interestingly, the author only found the study from Orsini et al. (2012) looking at firocoxib as an NSAID medication for distal tarsal joints OA and “none” using phenylbutazone. The study from Orsini et al. (2012) is in fact a clinical trial investigating the efficacy of firocoxib in management of musculoskeletal pain and lameness associated with osteoarthritis. While 197/390 (50.5%) of the horses had signs of musculoskeletal pain or lameness associated with one joint, 79/197 (40.1%) of these were thought to involve the tarsus (radiographs were not mandatory to confirm the diagnosis). The results are presented in such a way that it is not possible to determine how many of these horses affected with tarsal OA really improved because of firocoxib administration. The authors report 80% improvement of lameness overall after 14 days. In a very similar study (Doucet, M. Y. et al., 2008), published prior to the above mentioned, there was no difference in lameness scores between the firocoxib group (0.1 mg/kg, PO, SID for 14 days) and the phenylbutazone group (4.4 mg/kg, PO, SID for 14 days) for pain related to naturally occurring osteoarthritis (which was confirmed radiographically prior to entering the study). In the latter as in the former, there is no clear groups separating the effect of each NSAIDs on horses affected by tarsal OA compared to any other degenerative joint disease. However, the author chose not to present the work of Doucet here as all horses fell under one large category: naturally occurring OA.

Based on the current literature, there is insufficient evidence to advocate for the use of NSAIDs more than bisphosphonates or the contrary for the treatment of distal tarsal joints OA in horses. The longest follow-up period was 4 months in the study from Gough et al. (2010) and 2 weeks for Orsini et al. (2012). There is a need for a prospective double-blind clinical trial including one bisphosphonates group, one NSAID group and one control group with long-term follow-up of the horses lameness as well as other more objective outcomes.

For an overview of the efficacy and effects of bisphosphonates in horses with navicular disease, the reader can consult recent publications, including different administration routes: IM (Mitchell, A. et al. 2019), IV or intravenous regional limb perfusion (IV-RLP) (Whitfield, C.T. et al. 2016; Schoonover, M.J. et al. 2019).

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