Clodronate disodium does not produce measurable effects on bone metabolism in an exercising, juvenile, large animal model.

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.

Review of cellular therapies provides new insights into the potential treatment of diverse neurologic diseases in horses and dogs.

Neurological diseases and injuries in veterinary patients (horses, dogs, and cats) are complex, and effective treatment options are limited. Neuronal loss, damage to nerve conduction pathways, and inflammation and scarring associated with spinal cord injury pose major challenges in managing many neurological diseases. Furthermore, most of these neuropathologies lack definitive pharmacological treatments, driving interest and research into novel interventions. Our objective is to provide a narrative review of the current literature surrounding cellular therapies including neuronal and glial stem cells, neurotrophic factors, mesenchymal stem or stromal cells, and cells derived from induced pluripotent stem cells for the treatment of diverse neurological pathologies. Cellular therapies have the potential for cellular replacement, immune modulation, and paracrine signaling and the flexibility of being used alone or alongside surgical intervention. Mesenchymal stem or stromal cells are arguably the most researched cellular therapy and have been administered intrathecally, IV, intra-arterially, intranasally, and intraspinally with few adverse reactions. Limited clinical and experimental studies have suggested efficacy in diseases including acute spinal cord injury and intervertebral disc disease. Little is currently known about the safety and efficacy of neural stem cells, precursor cell administration, and induced pluripotent stem cell-derived treatments. Further research is necessary to determine the efficacy and long-term safety of cellular therapies. Future aims should include larger controlled clinical trials in companion animals for common neurologic conditions including acute spinal cord injury, intervertebral disc disease, peripheral nerve injury, degenerative neuropathies, and age-associated cognitive decline.

Stem cells and platelet-rich plasma for the treatment of naturally occurring equine tendon and ligament injuries: a systematic review and meta-analysis.

BACKGROUND: Platelet-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.

Literature review details and supports the application of platelet-rich plasma products in canine medicine, particularly as an orthobiologic agent for osteoarthritis.

Platelet-rich plasma (PRP) and other platelet-derived products represent a subset of regenerative medicine and have been researched in the veterinary community for the treatment of osteoarthritis, soft tissue wounds, tendinopathies, periodontitis, and fracture repairs. PRP is simple to produce, relatively affordable, safe, and can be delivered on site, making it an appealing therapeutic agent in veterinary medicine. As an orthobiologic for the treatment of osteoarthritis, it is one of few interventions with clinical study support that possess anabolic potential. Platelet product variability is wide ranging and often described in terms of cellular content or platelet enrichment. Growth factors associated with platelet activation and subsequent degranulation may mediate inflammation, modulate cellular immune response, and promote tissue repair. Product composition, dosage, and application likely influence treatment outcomes depending on the classification of the disease targeted. Sufficient canine data regarding the formulation and clinical application of canine PRP exist to warrant review. The aim of this narrative is to provide scientific background and clinical insight for veterinarians regarding platelet product content/formulation, mechanisms of action, considerations for use, and clinical application in dogs.

Lumbar vertebral bone density is decreased in horses with pituitary pars intermedia dysfunction.

BACKGROUND: Pathological fractures have been reported in equids with pituitary pars intermedia dysfunction (PPID) but their prevalence and pathogenesis is unknown. OBJECTIVES: To compare: (1) bone mineral density (BMD) in weight bearing and nonweight bearing bones in PPID+ equids and aged and young PPID- controls; and (2) biomechanical properties of the fourth lumbar vertebral body in PPID+ equids and aged PPID- equids. STUDY DESIGN: Case-control study: five PPID+ equids and six aged and four young PPID- control horses. METHODS: PPID status was based on clinical signs and necropsy examination of the pituitary gland (PG). The lumbar vertebral column, right front third metacarpus (MC3), left hind third metatarsus (MT3), and PG were removed after euthanasia. BMD was determined by quantitative computed tomography of regions of interest (ROI) in each bone and biomechanical testing was performed on the fourth lumbar vertebral body. Serum concentrations of parathormone (PTH), ionised Ca++ , 25-hydroxyvitamin D, and osteocalcin (OC) were also measured. Data were analysed using one-way ANOVA and correlation analyses. RESULTS: BMD of trabecular and cortical regions of interest (ROI) of the third, fourth (L4), and fifth lumbar vertebrae were significantly lower in PPID+ equids as compared with aged (p < 0. 001) and young (p < 0.01) PPID- controls. In contrast, no differences were found in BMD of trabecular or cortical ROIs of MC3 and MT3 between groups. No differences were detected in force at fracture, displacement at fracture, Young's modulus or strain of L4 between PPID+ and aged PPID- horses. No differences were found in serum PTH, ionised Ca++ , 25-hydroxyvitamin D, or OC concentrations between groups. MAIN LIMITATIONS: Limited number of equids studied and variation in test results. CONCLUSIONS: BMD of nonweight bearing bones can be decreased with PPID and could increase risk of developing pathological fractures.

Exercising sheep as a preclinical model for musculoskeletal research.

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-kß 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.