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Original Article | Volume 27 Issue 1 (, 2022) | Pages 164 - 166
Evaluation of Oxidative Stress Biomarkers and Drug Therapy in Fracture Healing Among Orthopedic Patients: A Prospective Biochemical and Pharmacological Study.
 ,
 ,
1
Assistant Professor, Department of Pharmacology, Santosh Medical College & Hospital, India.
2
Department of Biochemistry, Raipur Institute of Medical Sciences, Raipur, India.
3
Department of Orthopaedics, Shri Balaji Institute of Medical Sciences, Raipur, India.
Under a Creative Commons license
Open Access
Received
July 27, 2022
Revised
Aug. 15, 2022
Accepted
Aug. 30, 2022
Published
Sept. 3, 2022
Abstract

Background- Fracture healing is a complex biological process involving inflammation, cellular proliferation, and bone remodelling. Oxidative stress plays a crucial role in bone metabolism and may influence fracture healing outcomes. Reactive oxygen species (ROS) generated during tissue injury can affect osteoblast and osteoclast activities, thereby impacting bone regeneration. Pharmacological interventions such as calcium, vitamin D, analgesics, and anti-inflammatory drugs are commonly prescribed to facilitate recovery. Objective: To evaluate oxidative stress biomarkers and pharmacological management in orthopedic patients undergoing fracture healing and to determine their association with clinical recovery. Materials and Methods: A prospective observational study was conducted among patients with long-bone fractures admitted to the orthopedic department of a tertiary care hospital. Serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, and reduced glutathione (GSH) were assessed at baseline and during follow-up. Drug utilization patterns and clinical outcomes were evaluated. Results: Patients demonstrated significantly elevated MDA levels immediately following fracture, indicating increased oxidative stress. Antioxidant biomarkers such as SOD, catalase, and GSH gradually improved during the healing process. Calcium and vitamin D supplementation were the most commonly prescribed therapies. Patients exhibiting lower oxidative stress levels showed faster radiological and clinical healing. Conclusion: Oxidative stress biomarkers are valuable indicators of fracture healing progression. Appropriate pharmacological management combined with monitoring of oxidative stress parameters may improve therapeutic outcomes in orthopedic patients.

Keywords
INTRODUCTION

Fracture healing represents a coordinated biological process involving inflammatory, reparative, and remodeling phases. Successful bone regeneration requires balanced cellular activity and adequate biochemical signaling. Reactive oxygen species are generated following trauma and contribute to inflammatory responses at the fracture site.

 

Although physiological levels of ROS are necessary for cellular signaling, excessive oxidative stress can impair osteoblast differentiation, reduce bone mineralization, and delay fracture union. Several studies have demonstrated elevated lipid peroxidation products and altered antioxidant enzyme activities following skeletal injury.

 

Biochemical markers such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase, and reduced glutathione (GSH) are widely used to assess oxidative stress status. Understanding the relationship between these biomarkers and fracture healing may provide insights into therapeutic optimization.

 

The present study evaluates oxidative stress biomarkers and pharmacological interventions among orthopedic patients with fractures.

MATERIALS AND METHODS

Study Design Prospective observational study. Study Setting Department of Orthopedics in a tertiary care teaching hospital. Study Population Adult patients diagnosed with traumatic fractures requiring hospitalization. Inclusion Criteria • Age ≥18 years. • Radiologically confirmed fracture. • Patients willing to provide informed consent. Exclusion Criteria • Chronic inflammatory disorders. • Malignancy. • Chronic liver disease. • Chronic renal failure. • Long-term antioxidant supplementation. Sample Size A total of 120 patients were enrolled. Data Collection Demographic and clinical information was collected using structured case report forms. Biochemical Assessment Blood samples were collected at: • Day 1 (baseline) • Week 4 • Week 8 • Week 12 The following biomarkers were analyzed: • Malondialdehyde (MDA) • Superoxide dismutase (SOD) • Catalase • Reduced glutathione (GSH) Drug Utilization Assessment Prescribed medications were categorized as: • Analgesics • Non-steroidal anti-inflammatory drugs • Calcium supplements • Vitamin D preparations • Antibiotics • Bone health medications Outcome Measures Primary outcomes: • Changes in oxidative stress biomarkers. • Radiological evidence of fracture union. Secondary outcomes: • Drug utilization pattern. • Time to fracture healing. • Adverse drug reactions. Statistical Analysis Data were analyzed using SPSS software. Continuous variables were expressed as mean ± standard deviation. Comparisons were performed using paired t-tests and ANOVA. A p-value <0.05 was considered statistically significant.

RESULTS

Demographic Characteristics

Among 120 patients:

  • Males: 72 (60%)
  • Females: 48 (40%)

Mean age: 42.8 ± 13.4 years.

 

Fracture Distribution

Fracture Type

Number (%)

Tibia

38 (31.7)

Femur

29 (24.2)

Radius/Ulna

26 (21.7)

Humerus

17 (14.2)

Others

10 (8.3)

 

Oxidative Stress Biomarkers

MDA levels were significantly elevated at baseline and gradually decreased during follow-up.

Antioxidant markers including SOD, catalase, and GSH showed progressive improvement with fracture healing.

 

Drug Utilization Pattern

Drug Category

Frequency (%)

NSAIDs

92

Calcium Supplements

88

Vitamin D

84

Antibiotics

65

Opioid Analgesics

32

 

Association with Fracture Healing

Patients demonstrating lower MDA levels and higher antioxidant enzyme activity experienced faster radiological union and reduced recovery time.

DISCUSSION

The present study demonstrates a significant relationship between oxidative stress and fracture healing. Elevated MDA levels observed immediately after injury indicate increased lipid peroxidation secondary to tissue damage. Progressive reductions in oxidative stress markers during follow-up suggest restoration of redox balance as healing progresses. Similar findings have been reported in previous experimental and clinical studies evaluating oxidative stress in skeletal injury. Calcium and vitamin D supplementation were frequently prescribed owing to their established roles in bone mineralization and remodeling. Appropriate analgesic therapy contributed to improved patient comfort and rehabilitation. Monitoring oxidative stress biomarkers may serve as a useful adjunct in predicting fracture healing outcomes and identifying patients at risk for delayed union.

 

Limitations

  • Single-center study.
  • Moderate sample size.
  • Limited duration of follow-up.
  • Lack of advanced molecular biomarker analysis.
CONCLUSION

Oxidative stress significantly influences fracture healing in orthopedic patients. Elevated MDA and reduced antioxidant enzyme activities are associated with delayed recovery. Pharmacological interventions including calcium, vitamin D, and appropriate analgesic therapy contribute positively to fracture healing. Routine monitoring of oxidative stress biomarkers may enhance clinical decision-making and improve patient outcomes.

REFERENCES
  1. Claes L, Recknagel S, Ignatius A. Fracture healing under healthy and inflammatory conditions. Nat Rev Rheumatol. 2012;8(3):133-143.
  2. Einhorn TA, Gerstenfeld LC. Fracture healing: mechanisms and interventions. Nat Rev Rheumatol. 2015;11(1):45-54.
  3. Giannoudis PV, Einhorn TA, Marsh D. Fracture healing: the diamond concept. Injury. 2007;38(Suppl 4):S3-S6.
  4. Almeida M, Han L, Martin-Millan M, O'Brien CA, Manolagas SC. Oxidative stress antagonizes Wnt signaling in osteoblast precursors. J Biol Chem. 2007;282(37):27298-27305.
  5. Manolagas SC. From estrogen-centric to aging and oxidative stress perspectives. Bone. 2010;47(4):727-737.
  6. Lean JM, Davies JT, Fuller K, et al. A crucial role for ROS in osteoclast differentiation. J Clin Invest. 2003;112(3):369-378.
  7. Sendur OF, Turan Y, Tastaban E, Serter M. Antioxidant status in patients with osteoporosis. Clin Rheumatol. 2009;28(7):797-802.
  8. Basu S, Michaelsson K, Olofsson H, Johansson S, Melhus H. Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun. 2001;288(1):275-279.
  9. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions. Int J Biochem Cell Biol. 2007;39(1):44-84.
  10. Domazetovic V, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT. Oxidative stress in bone remodeling. Clin Cases Miner Bone Metab. 2017;14(2):209-216.
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