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Antibiotics are commonly given to horses to treat known bacterial infections or as prophylaxis against the development of infection. Diarrhea is a recognized adverse effect of antimicrobial administration in horses (antimicrobial associated diarrhea, AAD). In veterinary referral centers, AAD has a reported incidence of 22 to 94% (McGorum, 2010), while horses with AAD are 4.5 times more likely to die compared with horses with other types of colitis (Woods and Cohen, 1999). Although all antibiotics have potential to induce diarrhea, some have increased risk due to low oral absorption, biliary excretion, or enterohepatic recycling. The role of dysbiosis in the gut microbiota is a key feature in the pathogenesis of AAD. Disruption of commensal bacteria of the hindgut allows for pathogen overgrowth and alteration in microbial metabolic function. To date, 16S rRNA sequencing has been used to characterize the effects of penicillin, trimethoprim sulfa, doxycycline, erythromycin, ceftiofur, enrofloxacin, oxytetracycline and metronidazole on the fecal microbiome in healthy horses (Costa et al., 2015; Arnold et al., 2020; Liepman, 2022). Regardless of mechanism of action, antibiotics typically reduce diversity (species richness and evenness) and alter the bacterial community structure of the fecal microbiome, even when animals maintain normal health status and fecal character (Arnold et al., 2021). These effects typically require at least 30 days before the microbiome returns to baseline (Gomez et al, 2023). In horses with colitis, changes in the microbiome are often significant. Horses with AAD demonstrate the most severe disruption of the fecal microbiome compared with horses with Salmonella or undifferentiated colitis. These changes are evident from the phylum to species level, and include important phyla such as Bacteroidetes, Firmicutes, Fibrobacter and Verrucomicrobia (Arnold et al., 2020; Liepman, 2022; Costa et al., 2015). Alterations in the microbiota result in functional metabolic changes that are clinically manifested by diarrhea. Potential changes include alterations in the metabolism of bile acids, carbohydrates including short chain fatty acids, amino acids, lipids and proteins. There is also evidence that antimicrobials increase intestinal permeability via effects on tight junction proteins and by compromising the barrier function provided by the mucus layer between the enterocytes and gut lumen. Recent work comparing horses on antimicrobials that did and did not develop diarrhea confirm that horses with diarrhea have depletion of Verrocomicrobia and metabolites related to gastrointestinal barrier function (Arnold et al., 2021). [ABSTRACT FROM AUTHOR]

The non-nitrogenous bisphosphonate clodronate disodium (CD) inhibits bone resorption and is approved for horses ≥ 4 yr of age. Extra-label use in juvenile exercising horses is a concern due to potential interference with normal bone growth and development. The objective was to determine the effects of single and repeated doses of CD on bone optical density (radiographic bone aluminum equivalence; RBAE) and lameness score (LS) in juvenile, exercising horses. Quarter Horses [n = 32 (16 geldings, 16 fillies); 500 ± 13 d of age; body weight (BW) = 336 ± 26 kg]) were used to test the hypothesis that horses receiving CD would have greater RBAE and reduced LS, and additional doses of CD would accentuate these effects. In a 168-d trial, horses were housed in individual stalls, and fed 1% BW/d concentrate and ad libitum Coastal bermudagrass hay. Horses were exercised 5 d/wk following a phase-based progressive workload using a free stall exerciser; Phase I (d 0 to 84) mimicked sales preparation whereas Phase II (d 85 to 168) simulated early training. Horses were stratified by age, BW, sex, and initial RBAE into control (CON; n = 8), single dose CD (1X; d 84; n = 8), 2-doses CD (2X; d 0 and d 84; n = 8), and four-doses CD (4X; d 0, d 42, d 84, d 126; n = 8). On injection d (0, 42, 84, and 126), horses were administered either 1.8 mg/kg BW CD (OSPHOS) or isovolumetric saline. On d 0, 84, and 168, dorsalpalmar and lateral-medial radiographs of the left third metacarpus and metatarsus were captured. An aluminum step wedge was included in each image and raw images were analyzed (Quantity One Basic, BioRad) to determine total bone RBAE at 1 cm distal to the nutrient foramen. On d 0 and d 168, horses were evaluated by a veterinarian unaware of treatment group and assigned a LS according to the American Association of Equine Practitioners Lameness Scale. The RBAE and LS data were analyzed via PROC MIXED and PROC GENMOD, respectively, in SAS. For each view, RBAE increased from d 0 to d 84 and remained increased to d 168 (P ≤ 0.02), regardless of treatment, likely due to progressing exercise protocol. On d 0, 29 horses were LS 0, 1 horse was LS 1, and 2 horses were LS 2; LS did not differ among treatment groups (P = 0.61). On d 168, 5 horses were LS 0, 13 horses were LS 2, 11 horses were LS 3, and 1 horse was LS 4; LS did not differ among treatments (P = 0.16). Based on these results, the hypothesis that single or repeated CD administration would increase RBAE and decrease lameness in juvenile, exercised Quarter Horses was rejected. [ABSTRACT FROM AUTHOR]

Intra-articular corticosteroids (IAC) are administered to horses experiencing joint inflammation, at times with a concurrent articular antibiotic for prophylaxis. However, information regarding the biologic effects of IAC and potential for microbial contamination in IAC-administered joints is limited in young, exercising horses. The objective of this study was to evaluate the impact of IAC on traditional microbial culture, synovial fluid (SF) volume, and the presence of IAC; hypothesizing negative microbial culture, no change of SF volume, and detection of IAC in SF post-administration. To test this, 2-yr-old Quarter Horses {n = 24; body weight (BW) = 409 ± 6 kg; 825 ± 21 d of age; 12 fillies, 12 geldings) were stratified by BW, age, and sex, and randomly assigned to 1 of 3 treatment groups for a 56-d trial. Horses were housed individually in stalls with runs and fed concentrate offered at 0.75% BW/d split evenly every 12 h with ad libitum Coastal bermudagrass hay and water. Every 21 d, BW and body condition score (BCS) were recorded, and concentrate was adjusted accordingly. Horses were exercised 5 d/wk, up to 45 min/d in a progressive workload using a free-stall exerciser. Blood was collected postexercise during wk 1, 4, and 7 via jugular venipuncture and lactate (BL) was measured to monitor increasing workload. Intra-articular treatments consisted of 0 mg (CON; n = 8), 6 mg (CORT6; n = 8), or 12 mg (CORT12; n = 8) of triamcinolone acetonide (TA). On d 0, treatments were administered in one randomly selected radiocarpal joint per horse. Following aseptic preparation, SF from both radiocarpal joints was collected before administration (pre), and on d 7, 14, 28, and 56. Volume of SF was recorded, and standard microbial culture and detection of TA were performed by a commercial laboratory. Data were analyzed using PROC MIXED (BW, BCS, BL, SF volume) and PROC GLM (TA) of SAS. For SF volume, data from the contralateral radiocarpal joint were used as a covariate. Horses increased BW and BCS over time (P ≤ 0.01) across treatments. Post-exercise BL increased from wk 1 to 4 and remained increased through wk 7 (P < 0.01). Microbial culture for all horses and time points were negative. Concentration of TA was not evaluated on d 7 due to limited SF volume, but TA was detected on d 14 and concentration did not differ between CORT6 and CORT12 (P = 0.13). Recorded SF volume did not change from d 0 (pre) to 7 but increased to d 56, regardless of treatment (P < 0.01). These results indicate that, based on standard culture, TA administration did not result in positive microbial culture, or decrease SF volume in young horses undergoing regular exercise, however, TA was detectable to d 14. [ABSTRACT FROM AUTHOR]

Intra-articular lipopolysaccharide (LPS) is an established model for inducing robust, transient inflammation and increasing cartilage metabolism for up to 24 h following administration. Currently, there is limited information evaluating the long-term effects of this gram-negative endotoxin on the intra-articular environment of young horses. Therefore, the objective of this study was to determine the lasting effects of a single administration of intra-articular LPS on synovial biomarkers of inflammation and cartilage metabolism over 35 wk. Quarter Horse yearlings [n = 10; body weight (BW) = 409 ± 24 kg; 619 ± 16 d of age; fillies, (n = 7) and geldings (n = 3), originating from a single herd were used to test the hypothesis that intraarticular inflammation and cartilage metabolism would not be elevated at 35 wk post-injection. Each horse had one randomly selected radiocarpal joint injected with 0.8 mL of a 0.5 ng LPS solution derived from Escherichia coli O55:B5 (INFL; Sigma-Aldrich, St. Louis, MO) and the contralateral joint received sterile lactated Ringer’s solution (CON) as a control. Synovial fluid was obtained on 0 (before injection of LPS), 2, and 35 wk following arthrocentesis. Synovial fluid samples were analyzed in duplicate for carboxypropeptide of type II collagen (CPII), collagenase cleavage neopeptide (C2C), chondroitin sulfate 846 epitope (CS846), and prostaglandin E2 (PGE2 ) by commercial ELISA (IBEX Pharm, Montreal, Quebec, CA and Arbor Assays, Ann Arbor, MI). Biomarkers were analyzed using PROC MIXED of SAS v9.4 with repeated measures (time). The model included treatment (CON, INFL), time (week), and treatment × time interaction as fixed effects. Synovial biomarkers PGE2, CPII, and CS846 changed over time (P < 0.01) regardless of LPS administration, increasing from 0 to 2 wk and declining to below baseline concentrations at wk 35. There was a treatment × time interaction (P ≤ 0.01) in which INFL joints had decreased catabolic C2C concentrations compared with CON joints at wk 35. Therefore, LPS administration did not increase cartilage metabolism and inflammation levels at 2 or 35 wk post-LPS induction, indicating no negative effects compared with the contralateral controls. This study supports using intra-articular LPS in young horses without negative long-term effects. [ABSTRACT FROM AUTHOR]

Concerns over the extra-label use of bisphosphonates in skeletally immature horses has extended to include its likely re-release from bone into circulation in response to stressors. Therefore, the objective of this study was to be first to quantify the re-release of clodronate in response to controlled stressors. Yearling Quarter horses (n = 32) were stratified by age, body weight (BW), sex, and initial bone optical density into four treatment groups for a 168-d trial. Treatments consisted of control (CON; n = 8), single-dose (1X; d 84; n = 8), 2-dose (2X; d 0 and 84; n = 8), and four-dose groups (4X; d 0, 42, 84, and 126; n = 8). All horses received iso-volumetric intramuscular injections of either 1.8 mg/kg BW clodronate disodium (OSPHOSÒ) or saline (placebo) on d 0, 42, 84, and 126. Horses were housed in individual stalls (3.6 m × 7.2 m). Diets were formulated to meet nutrient requirements including concentrate offered every 12-h and ad libitum coastal bermudagrass (Cynodon dactylon) hay and water. Horses were exercised 5 d/ wk with a progressive workload, and maximum exercise intensity was reached on d 120, verified via heart rate and blood lactate. On d 120, blood samples were collected prior to the start of the exercise bout (pre), and 0-, 0.5-, 1-, 3-, 12-, and 24-h post exercise. Both tuber coxae of each horse were biopsied on d 168 with blood samples collected prior to (pre), and 0, 12, 24, 48, 72, 168, and 336 h post biopsy. Clodronate was quantified in plasma from exercise and biopsy samples using liquid chromatography tandem mass spectrometry. Exercise and biopsy serum were analyzed for cortisol, a marker of stress, while biopsy serum was analyzed for substance P, a pain marker. Data were analyzed using SAS PROC MIXED. Exercise did not result in clodronate re-release as there was no treatment x time interaction or time effect (P ≥ 0.44), but clodronate was dose-dependently greater in treated groups throughout the exercise collection period (P < 0.01). A treatment x time interaction (P ≤ 0.01) was observed for clodronate concentrations surrounding bone biopsy in which concentrations decreased at 168 h post biopsy before increasing at 336 h in 4X horses. Substance P increased over time (P < 0.01) following biopsy, regardless of treatment. Despite decreasing over time (P ≤ 0.01), there were similarly no treatment differences (P ≥ 0.46) nor treatment ´ time interactions (P ≥ 0.78) for cortisol following either exercise or bone insult. In conclusion, submaximal exercise did not result in re-release of clodronate; however, direct bone insult disrupted clodronate concentrations in horses receiving 4 administrations of bisphosphonate despite no treatment impact on stress or pain indicators. [ABSTRACT FROM AUTHOR]

Anthelmintics are commonly used in the equine industry to reduce parasite load, but there is a growing concern about anthelmintic resistance, especially in young horses where there is limited information available. Twenty-four, 2-yr-old Quarter Horses (825 ± 21 d of age, initial BW 409 ± 6 kg, 12 fillies and 12 geldings) originating from a single herd were used in a 42-d study to investigate the effectiveness of a commercial anthelmintic (fenbendazole) on fecal egg counts (FEC), hypothesizing that there would be a decrease in FEC following anthelmintic administration. Horses were housed individually (3.7m x 11m) and offered ad libitum Coastal Bermudagrass hay and water and fed a pelleted concentrate offered at 0.75% (as-fed) of their BW. During the 42-d study, BW was obtained and BCS were assigned in 21-d intervals. Fenbendazole was administered orally on d 0 and 14 dosed on BW per manufacturer label. Fresh fecal samples were collected on d 0 and 14, before anthelmintic administration, and on d 28 and 42. Fecal egg floats were conducted using the Modified Wisconsin Method, and eggs per gram (EPG) were determined in duplicate. A fecal egg count reduction test (FECRT) was calculated, beginning on d 14. Outliers were determined as values ± 2 standard deviations of the mean, and data were analyzed using PROC MIXED of SAS (v9.4) with the main effect of time. Horses increased in BW (P ≤ 0.01) over time, but BCS did not change (P = 0.25). Mean FEC increased over time (P ≤ 0.01), beginning on d 14, and remained increased to d 42 compared to baseline. However, there was a trend (P = 0.07) for mean FEC to be less on d 42 (189.70 ± 29 EPG) when compared with d 14 (251 ± 28 EPG). The calculated reduction of FEC were below the targeted 95% or greater and included d 14 (1.04%), d 28 (35%), and d 42 (41%). The increased shedding of eggs did not negatively impact BW or BCS. However, we reject the hypothesis since FEC increased following an-thelmintic treatment, indicating the need for consistent monitoring of anthelmintic efficacy in young horses. [ABSTRACT FROM AUTHOR]

Including Saccharomyces cerevisiae fermentation product (SCFP) into the diets of young, exercising horses may prolong their performance career by optimizing the intra-articular environment. Our objective was to evaluate the effect of dietary SCFP on joint inflammation in yearlings undergoing regular exercise, challenged with intra-articular lipopolysac-charide (LPS). Thirty Quarter Horse yearlings (374 ± 25 kg BW; 562 ± 16 d of age; 15 fillies and 15 geldings) were used in a 60-d study to test the hypothesis that dietary SCFP (TruEquine C, Diamond V Mills, Inc.) ameliorates joint inflammation following an acute inflammatory insult. Horses were stratified by BW, age, sex, and randomly assigned to dietary treatments (n = 10/treatment): Control (0), 46, or 92 mg/kg BW SCFP. Treatments were top-dressed onto a custom-formulated concentrate void of added microbials offered at 1% BW/d (as-fed) every 12 h. Horses were individually stalled (3.6 m x 7.3 m) and offered ad libitum Coastal bermudagrass hay. Using a free-stall exerciser, horses were exercised following a progressive workload regimen for 30 min/d, 5 d/wk. On d 46, all horses underwent an intra-articular LPS challenge where each horse had one radial carpal joint randomly assigned to receive either 0.8 mL of a 0.5 ng LPS solution or sterile lactated Ringer's solution (LRS) as a contralat-eral control. Synovial fluid samples were obtained pre-injection (h 0) and at 6, 12, 24, and 336 h post-injection and analyzed for prostaglandin E2 (PGE2), a proinflammatory prostaglandin via commercial ELISA, and for chemokine-concentration (signaling proteins that direct immune cells; CCL2, and CCL11) and cytokines (inflammatory mediators; TNFα and IL-10) using a multiplex platform via commercial laboratory. Non-normal data (PGE2, IL-10, and CCL2) were log transformed, and all markers were analyzed using MIXED procedure of SAS v9.4. Mean separation was achieved with orthogonal contrasts, and contralateral control carpi were used as a covariate across all hours. There was no effect of SCFP on synovial logPGE2 (P = 0.42), logCCL2 (P = 0.90), CCL11 (P = 0.26), or logIL-10 (P = 0.23). However, there was a treatment x hour interaction for CCL11 (P = 0.04) where the Control had increased concentrations compared with SCFP treatment groups at 6 h post-injection. Furthermore, logIL-10 also had a treatment x hour interaction (P = 0.05) where the 46mg/kg BW group had decreased concentrations at h 12 compared with the Control and 92mg/kg BW group. The main effect of treatment for TNFa (P = 0.04) revealed that the 92mg/kg BW group had less concentrations than the 46mg/kg BW group and tended to have less concentrations than the Control group across all hours. Results indicate that SCFP may help mitigate inflammation markers following an acute intra-articular inflammatory insult. [ABSTRACT FROM AUTHOR]

Bisphosphonates alter bone metabolism via inhibition of osteoclastic bone resorption. Although bisphosphonates are beneficial to treat bone disease, extra-label use in healthy juvenile horses may interfere with normal bone metabolism. The objective was to determine plasma pharmacokinetics of the bisphosphonate clodronate disodium (CD) following a single intramuscular dose to better define the time course of CD in juvenile horses. Ten yearling Quarter Horses (334 ± 18 kg, 504 ± 13 d of age) were used to test the hypothesis that juvenile horses would have faster clearance rate of CD compared with previously published data in adult horses. Horses were placed in individual stalls, jugular intravenous catheters were inserted, and an initial blood sample (0 h) was collected. Horses were administered CD intramuscularly at 1.8 mg/kg BW per label. Plasma samples were collected at 0.5, 1, 3, 6, 12, 24, 48, and 72 h post-administration. Plasma concentration of clodronate was determined by liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using a two-compartment model. Blood chemistry parameters [blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALKP), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and creatine kinase (CK)] were determined via a commercial laboratory. Included blood chemistry parameters were analyzed for an effect of time using PROC Mixed of SAS. Clodronate was detected in plasma up to 72 h post-administration. Maximum plasma concentration (43,971 ± 25,920 ng/mL) was reached at 0.5 h postadministration. Analysis revealed bicompartmental kinetics with distribution and terminal half-lives of 1.9 ± 0.4 h and 24.4 ± 4.3 h, respectively. Area under the curve to last sample was 22,755 ± 11,426 ng*h/mL and extrapolated to infinity was 26,778 ± 12,465 ng*h/mL. Blood chemistry parameters varied over time within normal ranges. Markers of renal function, BUN and creatinine, decreased from h 0 to h 72 (P < 0.01). Liver function markers ALKP and AST were not affected by CD treatment (P > 0.27). However, GGT and CK changed over time (P < 0.01), with GGT greater at 48 h than other time points, and CK increasing from 0.5 to 24 h before decreasing by 72 h but remaining above baseline. Plasma clodronate concentrations were greater in juvenile horses than previously reported in mature horses (Krueger et al., 2020, Equine Vet J.; Knych et al., 2022, Equine Vet J.). Further, the observed bicompartmental kinetics differed from the linear kinetics previously reported in mature horses whereby juvenile horses from the current study had greater exposure to CD over time as indicated by a longer terminal half-life. Moreover, the single intramuscular dose of CD (1.8 mg/kg BW) did not cause markers of kidney or liver function to deviate from normal ranges in juvenile Quarter Horses. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a prevalent and economically costly source of lameness in the athletic horse. Previous studies investigating OA pathology have focused on localized trauma to the articular cartilage of a joint, largely ignoring the systemic immune status of the animal. In this study, yearling Quarter Horses were used to evaluate systemic cytokine gene expression and circulating leukocytes following a localized intra-articular inflammatory insult of the endotoxin, lipopolysaccharide (LPS). Treatments for the 35-d experiment included an intra-articular injection of 0.25 ng (n = 7) or 0.50 ng (n = 6) of LPS obtained from Escherichia coli O55:B5 or sterile lactated Ringer's solution (n = 6; control) into the radial carpal joint. Blood and synovial fluid samples were collected at preinjection hour 0 and 2, 6, 12, and 24 h postinjection. Synovial fluid was obtained for a companion study. Total RNA was isolated from plasma leukocytes and real-time PCR was used to determine relative gene expression of the cytokines interleukin (IL)-1beta (β), IL-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Total leukocyte subpopulations and differentials were performed using a cell counter. Data were analyzed using the PROC MIXED procedure of SAS. Gene expression of all cytokines were unaffected by intra-articular treatment. However, IL-1β increased above baseline beginning at hour 6 and remained elevated to 24 h (P = 0.04). In contrast, IL-6 decreased from hours 6 to 12 and then increased to 24 h (P = 0.02). Levels of TNF-α increased at 6 and 12 h (P = 0.01) postinjection. Only IL-8 exceeded a 2-fold change in expression (P = 0.01), peaking at 12 h and indicating greater responsiveness to arthrocentesis when compared with other cytokines. No treatment effects on the leukocyte population were observed; however, total circulating leukocytes increased over time (P = 0.04), peaking at 6 h postinjection. Similarly, an increase over time was observed in monocytes (P = 0.02) and in platelets (P = 0.01) at 24 h postinjection. The results indicate that regardless of treatment, a mild immune response was elicited, which may be due to repeated arthrocentesis. Future experiments should consider the effects of arthrocentesis and potential systemic inflammatory response, even in control animals, when administering intra-articular LPS to young horses. [ABSTRACT FROM AUTHOR]

Anecdotal assertions that bisphosphonates, such as clodronate disodium (CD), exhibit anti-inflammatory properties has led to extra-label use, despite a lack of scientific evidence of its efficacy. The objective of this study was to determine the effects of CD on intra-articular inflammation, hypothesizing that intra-muscular administration of CD would reduce intra-articular inflammation following an acute inflammatory challenge by lipopolysaccharide (LPS). To test this, 32 yearling Quarter horses were stratified by age (500 ± 13 d), BW (336 ± 26 kg), sex (n = 16 female; n = 16 male) and initial bone optical density into 4 treatment groups. The 140-d study consisted of two phases: Phase 1 (d 0 to 83) and Phase 2 (d 84 to 140) emulated sale preparation and early performance training, respectively. Horses were housed individually (3.6 m × 7.3 m) and fed to meet requirements of growing horses undergoing moderate training. Treatments consisted of control (CON; n = 8; no CD), single-dose (1X; n = 8; d 84), two-doses (2X; n = 8; d 0, 84), and four-doses (4X; n = 8; d 0, 42, 84, 126) of CD. All horses received isovolumetric intramuscular injections of 1.8mg/kg BW clodronate disodium (OSPHOS) or saline (placebo) on d 0, 42, 84, and 126. Following treatment administration on d 126, radial carpal joints of each horse were injected with 0.8 mL of either 0.5 ng sterile LPS derived from Escherichia coli O55:B5 or sterile lactated Ringer's solution as a contralateral control. Synovial fluid was collected before LPS injection (h 0) and at 6, 12, 24, and 336 h post injection. Synovial fluid was analyzed using an ELISA for prostaglandin E2 (PGE2), an indicator of joint inflammation. Data were log transformed and analyzed using the MIXED procedure of SAS. There was an h × LPS interaction (P < 0.01) confirming an acute, transient inflammatory response with increased PGE2 at 6, 12, and 24 h compared with the contralateral control joint, and resolved (P = 0.62) by h 336 post-injection. There was a treatment × h × LPS interaction (P = 0.02) in which 1X, 2X and 4X CD groups had greater synovial PGE2 concentrations at 6 h post-injection in the LPS joint compared with CON. In summary, intra-articular LPS induced localized inflammation, and the PGE2 response was greater in all horses treated with CD. The results of this study reject the hypothesis, suggesting clodronate disodium administration does not reduce intra-articular inflammation following acute induced synovitis. [ABSTRACT FROM AUTHOR]

Off-label bisphosphonate use in juvenile horses is widespread despite little scientific understanding of biological and welfare impacts on skeletally immature, exercising horses. Therefore, the objective was to determine the effects of clodronate disodium on growth parameters of young horses. Thirty-two yearling Quarter horses (335 ± 4 kg, 500 ± 13 d of age) were stratified by age, BW, sex, and initial bone density by aluminum equivalence into four treatment groups for a 168-d trial. The experimental period was divided into two phases mimicking common management practices in horses undergoing sales preparation (Phase I: d 0 to 83) and early performance training (Phase II: d 84 to 168). Horses were housed in individual stalls (3.6 m × 7.2 m). Diets were formulated to meet nutrient requirements including concentrate offered every 12 h and ad libitum access to coastal bermudagrass (Cynodon dactylon) hay and water. Treatments consisted of control (CON; n = 8), single-dose (1X; n = 8), two-dose (2X; n = 8), and four-dose groups (4X; n = 8). All horses received iso-volumetric intramuscular injections of either 1.8 mg/kg BW clodronate disodium (OSPHOSÒ) or saline (placebo) on d 0, 42, 84, and 126. Physical measurements including BW, wither height (WH), hip height (HH), body length (BL), and heart girth (HG) circumference were recorded every 42 d, beginning on d 0. Data were analyzed using PROC MIXED procedure of SAS. There were no treatment differences (P = 0.62) or treatment' time interactions (P = 0.25) for BW, WH, HH, BL, and HG, but all measurements increased over time (P = 0.01). These results indicate that clodronate does not impact physical growth parameters in juvenile horses undergoing forced exercise. Further work is ongoing to determine tissue-specific effects of clodronate on bone growth and development in yearling Quarter horses. [ABSTRACT FROM AUTHOR]