Journal of Musculoskeletal Trauma

Original Article

NSAID-induced suppression of type X collagen and VEGF expression in the early phase of rat femoral fracture healing: Maria Zafar, Rana Mohammad Zeeshan, Safia Tasawar, Muhammad Saad Ilyas, Amer Aziz, Uruj Zehra; Received November 18, 2025 Accepted March 4, 2026 Published online April 10, 2026; DOI: https://doi.org/10.12671/jmt.2025.00367 [Epub ahead of print]

Abstract PDF Supplementary Material: Background
The current literature presents conflicting evidence regarding the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on fracture healing. This experimental study aimed to evaluate and compare the histological and immunohistochemical changes during femoral fracture healing in rats treated with a nonselective cyclooxygenase (COX) inhibitor (diclofenac sodium) and a selective COX-2 inhibitor (celecoxib).
Methods
Thirty-six male Wistar (standard outbred) albino rats weighing 200–400 g underwent standardized mid-diaphyseal femoral fracture surgery. The animals were randomized into three groups (n=12 per group): group 1 received diclofenac sodium, group 2 received celecoxib, and group 3 served as the control group and received 1 mL of distilled water orally once daily. Six rats from each group were euthanized at the end of the 2nd and 7th weeks after fracture for sample collection. Histological examination was complemented by immunohistochemical analysis, and the expression of type X collagen and vascular endothelial growth factor (VEGF) was assessed using the immunoreactive score (IRS) method.
Results
Healing scores were significantly higher in the control group at both time points (2nd week, P=0.01; 7th week, P=0.03). At the 2nd week, rats treated with diclofenac sodium demonstrated significantly greater fibrosis (P=0.01), and by the 7th week, they exhibited impaired bone formation (P=0.003) along with increased bone defects (P=0.01). IRS values for type X collagen and VEGF were significantly higher in the control group than in both treatment groups during the 2nd week (P=0.01 and P=0.005, respectively).
Conclusions
These findings suggest that, in this rat model, NSAIDs, particularly nonselective COX inhibitors, may disrupt the early phases of bone repair by affecting hypertrophic chondrocyte differentiation and reducing angiogenic activity. Although these results indicate a potential risk to optimal healing, they are preclinical observations, and their relevance to clinical fracture management should be interpreted with caution. Level of evidence: V.

72 View
2 Download

First
Prev
Page of 1
Next
Last

Search