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Bisphosphonates are commonly used to treat and prevent bone loss, but their effects in active, juvenile populations are unknown. This study examined the effects of intramuscular clodronate disodium (CLO) on bone turnover, serum bone biomarkers (SBB), bone mineral density (BMD), bone microstructure, biomechanical testing (BT), and cartilage glycosaminoglycan content (GAG) over 165 days. Forty juvenile sheep (253 ± 6 days of age) were divided into four groups: Control (saline), T0 (0.6 mg/kg CLO on day 0), T84 (0.6 mg/kg CLO on day 84), and T0+84 (0.6 mg/kg CLO on days 0 and 84). Sheep were exercised 4 days/week and underwent physical and lameness examinations every 14 days. Blood samples were collected for SBB every 28 days. Microstructure and BMD were calculated from tuber coxae (TC) biopsies (days 84 and 165) and bone healing was assessed by examining the prior biopsy site. BT and GAG were evaluated postmortem. Data, except lameness data, were analyzed using a mixed-effects model; lameness data were analyzed as ordinal data using a cumulative logistic model. CLO did not have any measurable effects on the skeleton of sheep. SBB showed changes over time (p ≤ 0.03), with increases in bone formation and decreases in some bone resorption markers. TC biopsies showed increasing bone volume fraction, trabecular spacing and thickness, and reduced trabecular number on day 165 versus day 84 (p ≤ 0.04). These changes may be attributed to exercise or growth. The absence of a treatment effect may be explained by the lower CLO dose used in large animals compared to humans. Further research is needed to examine whether low doses of bisphosphonates may be used in active juvenile populations for analgesia without evidence of bone changes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Plate let-rich plasma (PRP) and mesenchymal stromal or stem cells (MSCs) have been investigated as treatments for equine tendon and ligament injuries, but little consensus exists on the efficacy of these treatments. The study sought to evaluate the efficacy of PRP and MSC treatments by systematic review and meta-analysis. METHODS: A systematic review was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines. Inclusion criteria required an original, peer-reviewed study where horses were administered MSCs or PRP (or both), and a comparator group was described. Studies were assessed for risk of bias and study quality. Random effects meta-analysis with inverse variance weighting was used to calculate pooled estimates of the ORs for the primary outcomes of return to performance and reinjury. RESULTS: The search criteria identified 764 unique studies, and 21 studies met the inclusion criteria for the systematic review. Seventeen studies were further assessed for the primary outcomes of return to performance and reinjury rate within a meta-analysis. Meta-analyses revealed no increase in the likelihood of a return to performance with any of the biologic treatments. However, MSCs and MSCs administered concurrently with PRP provide a reduced risk of reinjury. CLINICAL RELEVANCE: The current study identified a decrease in reinjury rate in horses administered MSCs or a combination of MSCs and PRP for tendinopathy and desmopathy. However, results should be interpreted with consideration of the heterogeneity of findings, poor study quality, and high risk of bias in the majority of studies. [ABSTRACT FROM AUTHOR]

OBJECTIVE To establish an orthopedic, preclinical, ovine model of controlled exercise using an equine walker. ANIMALS 20 Dorset-Polypay sheep. PROCEDURES Sheep underwent 11 weeks of exercise, 4 days per week. Exercise duration and intensity increased until sheep performed 25 minutes at 1.3 m/s and 5 min at 2.0 m/s. Physical/lameness examinations were conducted every 14 days. Blood was collected every 28 days for analysis of serum bone biomarkers (SBB): bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), carboxy-telopeptide of type I collagen cross-links (CTX-I), tartrate-resistant acid phosphatase 5b (TRAP5b), and receptor activator of nuclear factor-kβ ligand (RANKL). RESULTS Sheep adapted easily to group exercise. Animals grew taller (P = .006) but had a 4% weight loss (P = .003). RANKL was reduced on days 28 and 84 compared to day 56 (P < .05), CTX-1 was reduced on days 28 and 84 compared to days 0 and 56 (P < .05), and TRAP5b was greater on day 28 compared to day 0 (P = .009). BALP and PINP did not change. CLINICAL RELEVANCE The described preclinical model of exercising sheep has distinct advantages including ease of handling, an established lameness scale, commercially available ovine SBB assays, and the ability to alter footing characteristics and complete circular exercise. Decreasing CTX-I and RANKL with no change in BALP and PINP suggests reduced bone resorption over the study period. Future studies may include a sedentary group or utilize adult animals to alleviate any influence of growth on SBB. [ABSTRACT FROM AUTHOR]

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 singleuse 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. [ABSTRACT FROM AUTHOR]

Objective: To establish an orthopedic, preclinical, ovine model of controlled exercise using an equine walker., Animals: 20 Dorset-Polypay sheep., Procedures: Sheep underwent 11 weeks of exercise, 4 days per week. Exercise duration and intensity increased until sheep performed 25 minutes at 1.3 m/s and 5 min at 2.0 m/s. Physical/lameness examinations were conducted every 14 days. Blood was collected every 28 days for analysis of serum bone biomarkers (SBB): bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), carboxy-telopeptide of type I collagen cross-links (CTX-I), tartrate-resistant acid phosphatase 5b (TRAP5b), and receptor activator of nuclear factor-kβ ligand (RANKL)., Results: Sheep adapted easily to group exercise. Animals grew taller (P = .006) but had a 4% weight loss (P = .003). RANKL was reduced on days 28 and 84 compared to day 56 (P < .05), CTX-1 was reduced on days 28 and 84 compared to days 0 and 56 (P < .05), and TRAP5b was greater on day 28 compared to day 0 (P = .009). BALP and PINP did not change., Clinical Relevance: The described preclinical model of exercising sheep has distinct advantages including ease of handling, an established lameness scale, commercially available ovine SBB assays, and the ability to alter footing characteristics and complete circular exercise. Decreasing CTX-I and RANKL with no change in BALP and PINP suggests reduced bone resorption over the study period. Future studies may include a sedentary group or utilize adult animals to alleviate any influence of growth on SBB.