OBJECTIVE To determine the single-dose pharmacokinetics of clodronate disodium (CLO) in juvenile sheep and the plasma protein binding (PPB) of CLO in juvenile sheep and horses. ANIMALS 11 juvenile crossbred sheep (252 ± 6 days) for the pharmacokinetic study. Three juvenile crossbred sheep (281 ± 4 days) and 3 juvenile Quarter Horses (599 ± 25 days) for PPB analysis. METHODS CLO concentrations were determined using liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental analysis from plasma samples obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, and 72 hours after CLO administered IM at 0.6 mg/kg. PPB was determined using equine and ovine plasma in a single-use rapid equilibrium dialysis system. RESULTS The mean and range for maximum plasma concentration (Cmax: 5,596; 2,396–8,613 ng/mL), time of maximal concentration (Tmax: 0.5; 0.5–1.0 h), and area under the curve (AUCall: 12,831; 7,590–17,593 h X ng/mL) were similar to those previously reported in horses. PPB in sheep and horses was moderate to high, with unbound fractions of 26.1 ± 5.1% in sheep and 18.7 ± 7.5% in horses, showing less than a 1.4-fold difference. CLINICAL RELEVANCE The pharmacokinetic parameters and PPB of CLO in juvenile sheep were similar to those previously reported in horses. The results suggest that juvenile sheep can be utilized as an animal model for studying the potential risks and/or benefits of bisphosphonate use in juvenile horses.

Osteoclasts are unique and vital bone cells involved in bone turnover. These cells are active throughout the individual’s life and play an intricate role in growth and remodeling. However, extra-label bisphosphonate use may impair osteoclast function, which could result in skeletal microdamage and impaired healing without commonly associated pain, affecting bone remodeling, fracture healing, and growth. These effects could be heightened when administered to growing and exercising animals. Bisphosphonates (BPs) are unevenly distributed in the skeleton; blood supply and bone turnover rate determine BPs uptake in bone. Currently, there is a critical gap in scientific knowledge surrounding the biological impacts of BP use in exercising animals under two years old. This may have significant welfare ramifications for growing and exercising equids. Therefore, future research should investigate the effects of these drugs on skeletally immature horses.

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Objective: To determine the effects of clodronate disodium (CLO) on control and recombinant equine interleukin-1β (IL-1β)-treated equine joint tissues. Study design: In vitro experimental study. Sample population: Cartilage explants, chondrocytes, and synoviocytes (n = 3 horses).Methods: Monolayer cultures of chondrocytes and synoviocytes from three horses were subjected to: control media (CON), 5 ng/ml CLO (C/low), 50 ng/ml CLO (C/med), 100 ng/ml CLO (C/high), with and without IL-1β, and 10 ng/ml IL-1β (IL) alone for 72 hours. Cartilage explants from three horses were subjected to CON, IL, C/low, and C/med with and without IL-1β for 72 hours. Culture media was analyzed for prostaglandin-E 2 (PGE 2 ), interleukin-6 (IL-6), and nitric oxide (NO). Explant media was analyzed for glycosaminoglycan (GAG) content and NO. At 72 hours, explant and monolayer culture viability were assessed, and explant GAG content was measured.Results: IL-1β treatment resulted in higher media concentrations of GAG, NO, PGE 2 , and IL-6 compared to the CON treatment (p < .05), demonstrating a catabolic effect of IL-1β on explants and monolayer cultures. CLO treatments did not increase media concentrations of GAG, NO, PGE 2 , or IL-6 compared to CON, indicating no cytotoxic effect. Nevertheless, CLO treatments administered to IL-1β-treated monolayer cultures and explants did not significantly reduce the inflammatory response regardless of concentration. Conclusion:CLO did not demonstrate cytotoxic nor cytoprotective effects in normal and IL-1β-stimulated chondrocytes, synoviocytes or explants in culture.Clinical significance: This study does not support the use of CLO as an antiinflammatory treatment. Further research is necessary to confirm any antiinflammatory effects of CLO on joint tissues.

The main factors influencing speed in athletes are stride length (SL) and stride rate (SR). However, conflict remains whether SL or SR is the key determinant of higher speeds. Quarter Horses (QH) generally reach higher speeds in their races than do Thoroughbreds (TB). However, the influence of SL and SR on this greater speed is unclear. Therefore, the main objective of this study was to compare SL and SR in QH and TB raced in short (sprint) and long (classic) distances. We hypothesized that QH have a higher SR in comparison to TB, and SR decreases as distance increases. Two race distances were analyzed for each breed: QH races of 100.6 and 402.3 m, and TB races of 1,207.0 m and 2,011.7 m. Data from twenty horses were obtained, consisting of five horses from each race distance (10 QH and 10 TB). Five individuals watched recordings of each race three times counting the number of strides taken by each winning horse. The SR was calculated using the average number of strides over a given race duration, and SL was determined by calculating the total number of strides over the distance covered. Speed was calculated by dividing the distance by the time of the winning horse. The PROC Mixed Procedure was used to identify statistical differences between breeds, and between distances within the same breed. Results showed that although the SL of the TB was longer in comparison with the QH (P &lt; 0.001), the average SR in QH was higher than in TB (2.88 vs 2.34 + 0.03 strides/s; P &lt; 0.001). Further, QH classic distance demonstrated a faster speed than TB at either distance (P &lt; 0.001). In conclusion, QH achieve a higher SR in comparison to TB (between 14-20% more than TB), confirming the importance of SR in achieving high racing speeds.