How does smoking tobacco affect bone repair

The effect of vitamin C on wound healing in mandibular fracture patients

detailed description

In a prospective, randomized clinical trial of de novo patients with mandibular fractures undergoing intraoral surgical repair with coating, the researchers will:

1. Compare the effects of adding vitamin C to placebo on soft tissue wound healing. measured by a) soft tissue repair biomarkers (procollagen I and III, matrix metallo-proteinases 1,2,3 & 9, C-reactive protein, neutrophil count, interleukins 6 & 8, TBARS and TEAC) and b) clinical results (wound dehiscence and wound score).

Hypothesis 1: Additional vitamin C improves soft tissue healing after mandibular fracture, as measured by improved procollagen I, other biomarker values, and clinical results compared to placebo.

Reason. The clinical literature describes impaired soft tissue wound healing in patients with mandibular fractures, including wound infection, wound dehiscence, and plate exposure. Vitamin C is a necessary cofactor for the production of type I and III collagen as well as procollagen, the precursor to collagen, via hydroxylation of proline and lysine. In the case of vitamin C deficiency, the collagen production is abnormal, leading to defective vascular and connective tissue formation with the breakdown of unstable collagen molecules 90-91,34, 63, 108,109

Investigators will collect a number of solid clinical results, including the clinician's rating and wound healing score to measure soft tissue healing. Biomarkers for soft tissue Wound healing in tissue is also used to measure biochemical healing pathways. Precursors of collagen, procollagen I and III are widely used biomarkers for collagen production in wound healing research. The researchers will evaluate these levels at baseline and 3 to 5 weeks postoperatively to evaluate the effect of vitamin C on collagen production. In addition, the antioxidant effects of vitamin C are critical during the ordered phases of wound healing from the inflammatory phase (including the initial hemostatic cascade) to the proliferative phase. Antioxidant deficiency during these phases leads to unbalanced proteolytic enzyme cascades (including matrix, metalloproteinases or MMPs) with resulting tissue destruction and an excessively abundant inflammatory environment. Furthermore, the antioxidant deficit results from vitamin C deficiency leading to reduced chemotaxis of monocytes and neutrophils and reduced bactericidal oxidative burst abilities. Therefore, the researchers will additionally measure the effects of vitamin C supplementation on proteolytic enzyme signaling pathways (MMPs) and systemic markers for infection and inflammation (neutrophil counts, c-reactive protein levels, interleukins (IL) 1 and 6). Finally, the researchers will use indicators of oxidative stress at baseline and after 6 weeks to measure the effects of vitamin C supplementation on antioxidant capacity (TBARS and TEAC).

2. Compare the effects of adding vitamin C to placebo on bone repair as measured by a) bone repair biomarkers (alkaline phosphatase, TRACP 5b, osteocalcin, RANKL, osteoprotegerin, and carboxy-terminal collagen crosslinks) and b) clinical results (radiographic imaging and Pain).

Hypothesis 2: Additional vitamin C improves bone healing after a lower jaw fracture. measured by improved bone healing biomarkers and more robust radiological bone imaging compared to placebo.

Rationale. Literature, from animal studies to randomized clinical trials, supports the idea that vitamin C is necessary for bone health and healing. Animal studies show that vitamin C promotes bone formation / mineralization, strengthens corneal development, and supports bone maintenance Studies show that supplemental vitamin C prevents fractures in menopausal women and may be protection against arthritis.10,11,12,69 Several well done randomized controlled clinical studies have shown that supplemental vitamin C reduces regional pain syndrome after distal radius fractures and less robust data suggests this to foot and ankle fractures. Well-conducted randomized controlled clinical trials are required to conduct vitamin C-guidelines for traumatic facial fractures.

Researchers will use a comprehensive set of biochemical, clinical, and radiological outcome measures to evaluate bone healing after mandibular fracture. The assessment of the biomarker includes the assessment of the number of osteoblasts and osteoclasts (alkaline phosphatase or TRACP 5b), osteoblast activity (osteocalcin), osteoclast differentiation (receptor activator for core factor, B-ligand or RANKL and osteoprotegerin or deception receptor for RANKL) and osteoclast activity () Collagen cross-links). Researchers measure clinical outcomes approximately 1 and 3 to 5 weeks postoperatively. Finally, each subject undergoes a high contrast CT mandible 3 to 5 weeks postoperatively for radiographic assessment of bone healing CT scan may or may not be standard of care.30,36,135

3. Determine the effects of supplemental vitamin C on soft tissue and bone healing from smoking status in patients with traumatic mandibular fracture.

Hypothesis 3: Current smokers have a higher prevalence of vitamin C deficiency than baseline non-smokers, and vitamin C supplementation improves soft tissue and bone healing more in smokers than in nonsmokers.

Reason. Despite clinical evidence of smoke-related impairment of wound healing, much is unknown about the pathophysiological mechanisms underlying this effect. 21. It is postulated that after injury, smoking impedes the inflammatory phase of wound healing by decreasing cellular chemotactic responsiveness, migratory function and oxidative killing of bacteria and by creating an imbalance in protease-protease-inhibitor relationships. The proliferative The wound healing phase may also be impaired by smoking with decreased fibroblasts. Proliferation and migration lead to decreased collagen production.124-30 Increases in oxidative stress and hypoxia further decrease healing in smokers.62,74,76,102 Vitamin C is postulated to make an important contribution to reduced wound healing smokers. Both population and experimental studies have shown that smokers are more likely to be deficient in vitamin C, with 25% of female smokers and 30% of male smokers being severely deficient. This deficiency is likely secondary to systemic exhaustion from the many reactive oxygen species in tobacco smoke and a diet devoid of antioxidants. The researchers will evaluate the effects of vitamin C on wound healing in current versus nonsmokers using a detailed assessment of tobacco use.

This project brings together a multidisciplinary team with expertise in wound healing. Maxillofacial surgery, medical effects of tobacco use, fracture repair, bone biomechanics, and conducting clinical studies. The proposed work will define specific effects of additional vitamin C for soft tissue and bone healing, with additional attention to smoking status in patients with mandibular fractures. For the many patients at high risk of vitamin C deficiency and poor wound healing, this investigation will critically provide an understanding of the role of oxidative stress and antioxidants in the mechanisms of impaired healing. These data provide pilot data to support randomized controlled trials of interventions to improve postoperative wound healing in patients with mandibular and other traumatic fractures. Establishing the safety and effectiveness of supplemental vitamin C. in the perioperative setting will improve wound healing results for thousands of patients undergoing traumatic fracture surgery and could be a transformative step in treatment guidelines for any smoker undergoing surgery. .