Dose-Finding Study for Intraarticular Treatment With Stanozolol in Horses

Rinnovati, Riccardo; Romagnoli, Noemi; Spadari, Alessandro

doi:10.1016/j.jevs.2015.08.009

Cited by 7 publications

(12 citation statements)

References 11 publications

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“…An anti-catabolic effect potentiates stanozolol's anabolic effect at the glucocorticoide receptor level, where it behaves as a competitive antagonist of the catabolic corticosteroids 19 . In vitro human studies and ovine and equine models have described that stanozolol was able to induce fibroblasts, to increase collagen production in a dose-dependent pathway through transforming growth factor-1β synthesis while decreasing nitric oxide production and stimulating the autocrine secretion of insulin-like growth factor-1, which induces osteoblast proliferation and collagen synthesis 20 – 23 . In humans, an increase of transforming growth factor-1β synthesis is related to a decrease in articular pain 24 .…”

Section: Introductionmentioning

confidence: 99%

“…In dogs, a 0.3 mg/kg dose has been described for intra-articular administration, in the management of knee OA, and oral use to treat tracheal collapse 26 , 27 . Before evaluating multiple administrations, as described in other animal models 21 , 23 , the assessment of a single administration of stanozolol is required to determine treatment safety its effect following intra-articular administration.…”

Section: Introductionmentioning

confidence: 99%

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Effect of a single intra-articular administration of stanozolol in a naturally occurring canine osteoarthritis model: a randomised trial

Alves

Santos²,

Jorge³

et al. 2022

Sci Rep

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Osteoarthritis (OA) is a disease with a high negative impact on patient’s quality of life and a high financial burden. It is a source of chronic pain and affects all mammals, including humans and dogs. As the dog is a common model for translation research of human OA, and exploring spontaneous dog OA can improve the health and well-being of both humans and dogs. To describe the effect of the intra-articular administration of stanozolol in a naturally occurring canine OA model, forty canine (N = 40) hip joints were randomly assigned to receive stanozolol or saline (control). On treatment day and at 8, 15, 30, 90, and 180 days post-treatment, several evaluations were conducted: weight distribution, joint range of motion, thigh girth, digital thermography, and radiographic signs. Also, synovial fluid C-reactive protein and interleukin-1 levels were evaluated. Results from four Clinical Metrology Instruments was also gathered. Results were compared with Repeated Measures ANOVA, with a Huynh–Feldt correction, paired-samples t-test, or Wilcoxon signed-rank test, with p < 0.05. OA was graded as mild (90%), moderate (5%), and severe (5%), including both sexes. They had a mean age of 6.5 ± 2.4 years and a bodyweight of 26.7 ± 5.2 kg. No differences were found between groups at treatment day in all considered evaluations. Weight distribution showed significant improvements with stanozolol from 15 days (p < 0.05) up to 180 days (p < 0.01). Lower values during thermographic evaluation in both views taken and improved joint extension at 90 (p = 0.02) and 180 days (p < 0.01) were observed. Pain and function scores improved up to 180 days. In the control group, radiographic signs progressed, in contrast with stanozolol. The use of stanozolol was safe and produced significant improvements in weight-bearing, pain score, and clinical evaluations in a naturally occurring canine OA model.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of a single intra-articular administration of stanozolol in a naturally occurring canine osteoarthritis model: a randomised trial

Alves

Santos²,

Jorge³

et al. 2022

Sci Rep

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“…Stanozolol is a synthetic derivative of testosterone, and its properties include anabolic/androgenic activity 40 . When administered IA, it is able to induce fibroblasts to increase collagen production, decrease nitric oxide production and induce osteoblast proliferation and collagen synthesis 41 – 44 . It also has a chondroprotective and cartilage regeneration effect, while reducing osteophyte formation and subchondral bone reaction 42 , 45 .…”

Section: Introductionmentioning

confidence: 99%

Intraarticular triamcinolone hexacetonide, stanozolol, Hylan G-F 20 and platelet concentrate in a naturally occurring canine osteoarthritis model

Alves

Santos²,

Jorge³

et al. 2021

Sci Rep

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Osteoarthritis (OA) is a disease transversal to all mammals, a source of chronic pain and disability, a huge burden to societies, with a significant toll in healthcare cost, while reducing productivity and quality of life. The dog is considered a useful model for the translational study of the disease, closely matching human OA, with the advantage of a faster disease progression while maintaining the same life stages. In a prospective, longitudinal, double-blinded, negative controlled study, one hundred (N = 100) hip joints were selected and randomly assigned to five groups: control group (CG, n = 20, receiving a saline injection), triamcinolone hexacetonide group (THG, n = 20), platelet concentrate group (PCG, n = 20), stanozolol group (SG, n = 20) and hylan G-F 20 group (HG). Evaluations were conducted on days 0 (T0, treatment day), 8, 15, 30, 60, 90, 120, 150 and 180 days post-treatment, consisting of weight distribution analysis and data from four Clinical Metrology Instruments (CMI). Kaplan–Meier estimators were generated and compared with the Breslow test. Cox proportional hazard regression analysis was used to investigate the influence of variables of interest on treatment survival. All results were analyzed with IBM SPSS Statistics version 20 and a significance level of p < 0.05 was set. Sample included joints of 100 pelvic limbs (of patients with a mean age of 6.5 ± 2.4 years and body weight of 26.7 ± 5.2 kg. Joints were graded as mild (n = 70), moderate (n = 20) and severe (n = 10) OA. No differences were found between groups at T0. Kaplan–Meier analysis showed that all treatments produced longer periods with better results in the various evaluations compared to CG. Patients in HG and PCG took longer to return to baseline values and scores. A higher impact on pain interference was observed in THG, with a 95% improvement over CG. PCG and HG experienced 57–81% improvements in functional evaluation and impairments due to OA, and may be a better options for these cases. This study documented the efficacy of several approaches to relieve OA clinical signs. These approaches varied in intensity and duration. HG and PCG where the groups were more significant improvements were observed throughout the follow-up periods, with lower variation in results.

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“…Each horse was exposed to 4 different treatment groups (4 wells per group): (1) media only (negative control) (2) media + IL-1β (Recombinant Equine IL-1β, R&D Systems, Abingdon, UK) (10 ng/ml) (positive control) (3) media + IL - 1β (10 ng/ml) + stanozolol (Sungate, ACME, Cavriago, Italy) (0.4 mg/ml) 4) media + stanozolol (0.4 mg/ml). The stanozolol concentration was extrapolated by using the clinically recommended dose of 5 mg per joint [ 20 ] and assuming the volume of a non-distended metacarpalphalangeal joint to be 12.5 ml [ 29 ]. After 24 h in culture conditions, cell viability was performed on one well per group.…”

Section: Methodsmentioning

confidence: 99%

“…Intra-articular administration of stanozolol has recently been postulated as a treatment for OA. Studies investigating the clinical effects of the intra-articular use of stanozolol in horses have shown promising results in the ability of this drug to effectively manage lameness associated with OA and have suggested that stanozolol has the potential to stimulate cartilage repair [ 19 , 20 ]. There is also anecdotal evidence of positive results obtained in equine clinical practice, including cases refractory to intra-articular glucocorticoids [ 21 ] and in the management of subchondral bone pain [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of stanozolol on normal and IL-1β-stimulated equine chondrocytes in vitro

et al. 2018

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BackgroundIntra-articular administration of stanozolol has shown promising results by improving the clinical management of lameness associated with naturally-occurring osteoarthritis (OA) in horses, and by decreasing osteophyte formation and subchondral bone reaction in sheep following surgically induced OA. However, there is limited evidence on the anti-inflammatory and modulatory properties of stanozolol on articular tissues. The objective of the current study was to evaluate the effects of stanozolol on chondrocyte viability and gene expression in normal equine chondrocytes and an inflammatory in vitro system of OA (interleukin-1β (IL-1β) treated chondrocytes).ResultsChondrocytes from normal metacarpophalangeal joints of skeletally mature horses were exposed to four treatment groups: (1) media only (2) media+IL-1β (3) media+IL-1β + stanozolol (4) media+stanozolol. Following exposure, chondrocyte viability and the expression of catabolic, anabolic and structural genes were determined. General linear models with Dunnet’s comparisons with Bonferroni’s adjustment were performed. Cell viability was similar in all groups. Stanozolol treatment reduced gene expression of MMP-13, MMP-1, IL-6 and COX-2 in both normal and IL-1β treated chondrocytes. Stanozolol treatment reduced ADAMTS4 gene expression in normal chondrocytes. Stanozolol reduced the expression of COL2A1.ConclusionsThe current study demonstrates stanozolol has chondroprotective effects through downregulation of genes for pro-inflammatory/catabolic cytokines and enzymes associated with OA. However, there is no evidence of increased cartilage stimulation through upregulation of the anabolic and structural genes tested.

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Dose-Finding Study for Intraarticular Treatment With Stanozolol in Horses

Cited by 7 publications

References 11 publications

Effect of a single intra-articular administration of stanozolol in a naturally occurring canine osteoarthritis model: a randomised trial

Effect of a single intra-articular administration of stanozolol in a naturally occurring canine osteoarthritis model: a randomised trial

Intraarticular triamcinolone hexacetonide, stanozolol, Hylan G-F 20 and platelet concentrate in a naturally occurring canine osteoarthritis model

Effects of stanozolol on normal and IL-1β-stimulated equine chondrocytes in vitro

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