Abstract: To assess the effects of clinically relevant doses of commonly employed intra-articular corticosteroids-specifically, triamcinolone acetonide (TCA), methylprednisolone acetate (MPA), and combination of betamethasone acetate and betamethasone sodium phosphate (BM)-on equine osteoclasts. Methods: In vitro controlled laboratory study. Methods: Three donor mares (13-19 years). Methods: Following differentiation from bone marrow aspirates, osteoclasts were cultured alone (pure osteoclast cultures; n = 18 wells per group) or on equine bone slices (osteoclast-bone cultures; n = 6 wells per group) and treated with TCA (36 μg/mL), MPA (48 μg/mL), or BM (4 μg/mL). Untreated wells were controls. Outcome parameters included number of osteoclasts, bone resorption area and media biomarker concentrations, specifically tartrate-resistant acid phosphatase isoform-5b (TRACP-5b) and C-terminal telopeptide of type I collagen (CTX-I), measured using enzyme-linked immunosorbent assay (ELISA). Results: In pure osteoclast cultures (n = 16 wells in control and BM groups; n = 17 wells in TCA and MPA groups), mature osteoclast numbers were lower following corticosteroid addition compared with controls (MPA, p < .001; TCA, p = .009; BM, p = .002), and lower in the MPA group than the TCA group (p = .015). There was no difference in TRACP-5b between groups. In osteoclast-bone cultures (n = 5 in control group; n = 6 wells in TCA, MPA and BM groups), CTX-I decreased with MPA treatment compared with controls (p = .001), TCA (p = .006), and BM (p = .007) groups. TRACP-5b decreased with TCA compared with controls (p = .001). No differences in bone resorption area were measured. Conclusions: Clinically relevant doses of commonly employed intra-articular corticosteroids-TCA, MPA, and BM-impacted equine osteoclast activity in vitro. Conclusions: Understanding that intra-articular corticosteroids may influence osteoclast activity, potentially affecting subchondral bone remodeling and repair, is important for guiding judicious use in equine joint management.
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Overview
This study investigated how clinically relevant doses of commonly used intra-articular corticosteroids affect the function of equine osteoclasts in vitro, revealing that these steroids impair osteoclast activity.
Background
Osteoclasts are specialized cells responsible for bone resorption, playing an essential role in bone remodeling and repair.
In equine joint management, intra-articular corticosteroids such as triamcinolone acetonide (TCA), methylprednisolone acetate (MPA), and combinations of betamethasone acetate and betamethasone sodium phosphate (BM) are commonly used to reduce inflammation.
It is important to understand how these corticosteroids impact osteoclast function, as this may influence subchondral bone health and the overall healing process of joint tissues.
Research Objective
To assess the effects of clinically relevant doses of TCA, MPA, and BM on the number, activity, and bone-resorbing function of equine osteoclasts cultured in vitro.
Methods
Bone marrow aspirates were obtained from three donor mares aged 13-19 years to isolate osteoclast precursors.
Osteoclast differentiation was induced and cells were cultured in two conditions:
Pure osteoclast cultures (without bone substrate)
Osteoclast-bone cultures (osteoclasts grown on equine bone slices to allow assessment of bone resorption)
Cells were treated with specific doses of corticosteroids consistent with clinical intra-articular use:
TCA at 36 μg/mL
MPA at 48 μg/mL
BM at 4 μg/mL
Control wells received no corticosteroid treatment.
Outcome measures included:
Number of mature osteoclasts
Bone resorption area on bone slices
Biomarkers in culture media:
Tartrate-resistant acid phosphatase isoform-5b (TRACP-5b), an enzyme marker of osteoclast activity and number
C-terminal telopeptide of type I collagen (CTX-I), a marker of bone collagen degradation reflecting bone resorption activity
Biomarkers were quantified using enzyme-linked immunosorbent assay (ELISA).
Key Results
Osteoclast Number (Pure Cultures):
All corticosteroid treatments significantly reduced the number of mature osteoclasts compared to controls:
MPA group had the greatest reduction (p < .001)
TCA group showed moderate reduction (p = .009)
BM group also had significant reduction (p = .002)
MPA caused a greater decrease in osteoclast number compared to TCA (p = .015)
No significant differences were observed between groups in TRACP-5b levels in pure cultures.
Osteoclast Activity on Bone Slices:
CTX-I levels (indicative of bone resorption) were significantly lower in MPA-treated cultures compared to:
Controls (p = .001)
TCA group (p = .006)
BM group (p = .007)
TRACP-5b concentration decreased significantly following TCA treatment compared to controls (p = .001).
No significant differences in the actual bone resorption area were detected across groups.
Conclusions and Implications
Clinically relevant doses of TCA, MPA, and BM corticosteroids impair equine osteoclast function in vitro, primarily by reducing the number of mature osteoclasts and altering bone resorption biomarkers.
The observed reduction in osteoclast number and activity could influence subchondral bone remodeling processes by slowing bone resorption, which may impact healing or repair in equine joints receiving intra-articular corticosteroid treatment.
Despite changes in biomarker levels, actual bone resorption area did not show significant differences, possibly due to the duration or sensitivity of the assay.
Understanding these effects is critical for veterinarians and researchers to guide the judicious use of intra-articular corticosteroids in managing equine joint diseases and minimizing potential adverse effects on bone health.
Cite This Article
APA
Malek G, Kamus L, Richard H, Beauchamp G, Laverty S.
(2026).
Clinically relevant intra-articular corticosteroid doses impair equine osteoclast function in vitro.
Vet Surg, 55(7), 1223-1236.
https://doi.org/10.1111/vsu.70132
Comparative Orthopaedic Research Laboratory, Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
Kamus, Louis
Comparative Orthopaedic Research Laboratory, Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
Richard, Hélène
Comparative Orthopaedic Research Laboratory, Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
Beauchamp, Guy
Comparative Orthopaedic Research Laboratory, Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
Laverty, Sheila
Comparative Orthopaedic Research Laboratory, Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada.
MeSH Terms
Animals
Horses
Osteoclasts / drug effects
Osteoclasts / physiology
Female
Methylprednisolone Acetate
Methylprednisolone / analogs & derivatives
Methylprednisolone / administration & dosage
Methylprednisolone / pharmacology
Betamethasone / analogs & derivatives
Betamethasone / administration & dosage
Betamethasone / pharmacology
Betamethasone / adverse effects
Triamcinolone Acetonide / administration & dosage
Triamcinolone Acetonide / pharmacology
Triamcinolone Acetonide / adverse effects
Injections, Intra-Articular / veterinary
Cells, Cultured
Tartrate-Resistant Acid Phosphatase
Adrenal Cortex Hormones / administration & dosage
Adrenal Cortex Hormones / pharmacology
Bone Resorption / veterinary
Grant Funding
Natural Sciences and Engineering Research Council of Canada
Quebec Cell, Tissue and Gene Therapy Network - ThéCell (a thematic network supported by the Fonds de recherche du Québec - Santé)
Université de Montréal, Fond du Centenaire, Fonds en Santé Équine
American College of Veterinary Surgeons Foundation, 2023 Surgery Resident Research Grant
Conflict of Interest Statement
The authors declare no conflicts of interest related to this study.
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