Published September 26, 2022 | Version v1

Does Local Delivery of Simvastatin-Loaded Gelatin Sponge Accelerate Mandibular Fracture Healing?

  • 1. Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Damascus University, Damascus, Syria
  • 2. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Syrian Private University, Damascus, Syria

Description

Objective: The aim of this study was to assess the effect of local application of 10mg simvastatin on bone healing in mandibular fractures. Methodology: Participants with anterior mandibular fractures were randomly assigned into the two groups of this partially-blinded randomized clinical study. The mandibular fractures were managed via standard technique. Simvastatin-loaded gelatin sponge was locally applied along the fracture line after open reduction and internal fixation and before suturing in the study group. Only saline with gelatin sponge was used as a placebo in the control group. Participants were radiographically followed up after 1 week, 2 months, and 4 months. CBCT images were used to measure grey-scale values, and to indicate fracture union at the 2-month and 4-month follow-ups. Results: 24 anterior mandibular fractures (n=24) were included in all stages of this study. Mean participants age was 30.8 (± 11.7) years. Comparisons showed significant differences in mean grey-scale values at 2-month (P=0.022) and 4-month (P=0.009) follow-ups between the simvastatin and control groups. Differences regarding fracture union between the simvastatin and control groups were insignificant after 2 months (P=0.273), but significant after 4 months (P=0.003). Conclusion: It can be concluded that local application of 10mg simvastatin with gelatin sponge carrier along the fracture lines may hasten the bone healing in mandibular fractures.

Files

JRMDS-22-52818.pdf

Files (594.2 kB)

Name Size
md5:cdf13856495c5da99baa960efcaa7d3f
594.2 kB Preview Download

Additional details

References

  • Rashid S, Kundi JA, Sarfaraz A, et al. Patterns of mandibular fractures and associated comorbidities in Peshawar, Khyber Pakhtunkhwa. Cureus 2019; 11.
  • Barde D, Mudhol A, Madan R. Prevalence and pattern of mandibular fracture in Central India. Natl J Maxillofac Surg 2014; 5:153-156.
  • Dell' Aversana Orabona G, Iaconetta G, Abbate V, et al. Bifocal mandibular fractures: Which should be treated first? J Craniofac Surg 2012; 23:1723-1727.
  • Jha SG, Sinha V, Samanth TU, et al. Management of mandible fracture by plating and wiring: An otolaryngologist perspective at teritiary care center. Indian J Otolaryngol Head Neck Surg 2019; 71:417-424
  • Hong H, Song T, Liu Y, et al. The effectiveness and safety of parathyroid hormone in fracture healing: A meta-analysis. Clinics 2019; 74:e800.
  • Heyer FL, de Jong JJ, Willems PC, et al. The effect of bolus Vitamin D3 supplementation on distal radius fracture healing: A randomized controlled trial using HR-pQCT. J Bone Miner Res 2021; 36:1492-1501.
  • Einhorn TA, Gerstenfeld LC. Fracture healing: Mechanisms and interventions. Nat Rev Rheumatol 2015; 11:45-54.
  • Buettner MF, Wolkenhauer D. Hyperbaric oxygen therapy in the treatment of open fractures and crush injuries. Emerg Med Clin North Am 2007; 25:177-188.
  • Faßbender M, Minkwitz S, Strobel C, et al. Stimulation of bone healing by sustained bone morphogenetic protein 2 (BMP-2) delivery. Int J Mol Sci 2014; 15:8539.
  • Rosselli JE, Martins DM, Martins JL, et al. The effect of simvastatin on the regeneration of surgical cavities in the femurs of rabbits. Acta Cir Bras 2014; 29:87-92.
  • Maeda T, Matsunuma A, Kurahashi I, et al. Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells. J Cell Biochem 2004; 92:458-471.
  • Halloran D, Durbano HW, Nohe A. Bone morphogenetic protein-2 in development and bone homeostasis. J Dev Biol 2020; 8:19.
  • Degala S, Bathija NA. Evaluation of the efficacy of simvastatin in bone regeneration after surgical removal of bilaterally impacted third molars-A split-mouth randomized clinical trial. J Oral Maxillofac Surg 2018; 76:1847-1858.
  • Kawai T, Murakami S, Hiranuma H, et al. Radiographic changes during bone healing after mandibular fractures. Br J Oral Maxillofac Surg 1997; 35:312-318.
  • Street J, Bao M, deGuzman L, et al. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci 2002; 99:9656-9661.
  • Young S, Patel ZS, Kretlow JD, et al. Dose effect of dual delivery of vascular endothelial growth factor and bone morphogenetic protein-2 on bone regeneration in a rat critical-size defect model. Tissue Eng 2009; 15:2347-2362.
  • Patel ZS, Young S, Tabata Y, et al. Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. Bone 2008; 43:931-40.
  • Shah SR, Werlang CA, Kasper FK, et al. Novel applications of statins for bone regeneration. Natl Sci Rev 2015; 2:85-99.
  • Moshiri A, Sharifi AM, Oryan A. Role of simvastatin on fracture healing and osteoporosis: A systematic review on in vivo investigations. Clin Exp Pharmacol Physiol 2016; 43:659-684.
  • Jadhav SB, Jain GK. Statins and osteoporosis: new role for old drugs. J Pharm Pharmacol. 2006; 58(1):3-18.
  • Zhang J, Wang H, Shi J, et al. Combination of simvastatin, calcium silicate/gypsum, and gelatin and bone regeneration in rabbit calvarial defects. Sci Rep 2016; 6:23422.
  • Gutierrez GE, Lalka D, Garrett IR, et al. Transdermal application of lovastatin to rats causes profound increases in bone formation and plasma concentrations. Osteoporos Int 2006; 17:1033-1042.
  • Fuster-Torres MÁ, Peñarrocha-Diago M, PeñarrochaOltra D, et al. Relationships between bone density values from cone beam computed tomography, maximum insertion torque, and resonance frequency analysis at implant placement: A pilot study. Int J Oral Maxillofac Implants 2011; 26:1051-1056.
  • Albassal A, Al-Khanati NM, Harfouch M. Could a digital panoramic X-ray not detect a displaced fracture of the mandible?. Quant Imaging Med Surg 2021; 11:3890-3892.
  • Albassal A, Al-Khanati NM, Harfouch M. Traumatic genial tubercle fracture: A case description with 9-month radiographic follow-up and a literature analysis. Quant Imaging Med Surg 2021; 12:2579.
  • Al-Zahrani MS, Elfirt EY, Al-Ahmari MM, et al. Comparison of cone beam computed tomographyderived alveolar bone density between subjects with and without aggressive periodontitis. J Clin Diagn Res 2017; 11:ZC118-ZC121.
  • Bastami F, Shahab S, Parsa A, et al. Can gray values derived from CT and cone beam CT estimate new bone formation? An in vivo study. Oral Maxillofac Surg 2018; 22:13-20.
  • Al-Khanati NM, Al-Moudallal Y. Effect of intrasocket application of manuka honey on postsurgical pain of impacted mandibular third molars surgery: Split-mouth randomized controlled trial. J Maxillofac Oral Surg 2019; 18:147-152.
  • Hassan B, Al-Khanati NM, Bahhah H. Effect of lingualbased flap design on postoperative pain of impacted mandibular third molar surgery: Split-mouth randomized clinical trial. Med Oral Patol Oral Cir Bucal 2020; 25:e660-e667.
  • Hamzeh A, Ayoub R, Issa S, et al. War-related ocular injuries in Damascus during the Syrian crisis. Injury 2021; 52:299-304.
  • Wu J, Min A, Wang W, et al. Trends in the incidence, prevalence and years lived with disability of facial fracture at global, regional and national levels from 1990 to 2017. Peer J 2021; 9:e10693.
  • Gupta S, Verma P, Tikku AP, et al. Effect of local application of simvastatin in bone regeneration of periapical defects-a clinico-radiographic study. J Oral Biol Craniofac Res 2020; 10:583-591.