Zachary NaPier1, Linda E A Kanim2, Trevor J Nelson3, Khosrowdad Salehi4, Yasaman Arabi4, Juliane D Glaeser4, Dmitriy Sheyn5, Melodie F Metzger6. 1. Department of Orthopedics, Cedars-Sinai, Los Angeles, CA, USA. 2. Department of Orthopedics, Cedars-Sinai, Los Angeles, CA, USA; Orthopedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Davis Building 6006, Los Angeles, CA 90048, USA. 3. Department of Orthopedics, Cedars-Sinai, Los Angeles, CA, USA; Cedars-Sinai Orthopedic Biomechanics Laboratory, Los Angeles, CA, USA. 4. Department of Orthopedics, Cedars-Sinai, Los Angeles, CA, USA; Orthopedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Davis Building 6006, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 5. Department of Orthopedics, Cedars-Sinai, Los Angeles, CA, USA; Orthopedic Stem Cell Research Laboratory, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Davis Building 6006, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Department of Surgery, Cedars-Sinai, Los Angeles, CA, USA; Department of Biomedical Sciences, Cedars-Sinai, Los Angeles, CA, USA. 6. Department of Orthopedics, Cedars-Sinai, Los Angeles, CA, USA; Cedars-Sinai Orthopedic Biomechanics Laboratory, Los Angeles, CA, USA. Electronic address: Melodie.Metzger@cshs.org.
Abstract
STUDY DESIGN: Experimental animal model. OBJECTIVE: The purpose of this study was to evaluate the hypothesis that insulin dependent diabetes mellitus (IDDM) will inhibit the formation of a solid bony union after spinal fusion surgery via an alteration of the microenvironment at the fusion site in a rat model. SUMMARY OF BACKGROUND DATA: Previous studies report diabetes mellitus (DM) and specifically IDDM as a risk factor for complications and poor surgical outcomes following spinal fusion. METHODS: Twenty control and 22 diabetic rats were obtained at 5 weeks of age. At 20 weeks of age, all animals underwent posterolateral lumbar fusion surgery using a tailbone autograft with diabetic rats receiving an implantable time release insulin pellet. A subset of rats was sacrificed 1-week postsurgery for growth factor (PDGF, IGF-I, TGF-β, and VEGF) and proinflammatory cytokine ELISA analysis. All other rats were sacrificed 3-months postsurgery for fusion evaluation via manual palpation and micro CT. Glycated hemoglobin (HbA1c) was measured at surgery and sacrifice on all animals. RESULTS: Compared with healthy rats undergoing spinal fusion, rats with IDDM demonstrated a significant reduction in manual palpation fusion rates (16.7% vs. 43%, p<.05). Average bone mineral density, bone volume, and bone volume fraction were also significantly reduced and negatively correlated to blood glucose levels. IL-1B, IL-5, IL-10, TNF-α, and KC/GRO were significantly elevated in fusion beds of IDDM rats. CONCLUSIONS: This study demonstrates that rats with IDDM demonstrate a reduced rate and quality of spinal fusion with increased local levels of inflammatory cytokines. Targeted modalities are required to improve bone healing in this growing, high-risk population. CLINICAL SIGNIFICANCE: This is the first translational animal model of IDDM to evaluate the rate and quality of spinal fusion while controlling for other surgical and patient-related risk factors. Our findings demonstrate the complex nature by which IDDM impairs bone healing and highlight the need for additional basic science research to further elucidate this mechanism in order to develop more effective therapeutic interventions.
STUDY DESIGN: Experimental animal model. OBJECTIVE: The purpose of this study was to evaluate the hypothesis that insulin dependent diabetes mellitus (IDDM) will inhibit the formation of a solid bony union after spinal fusion surgery via an alteration of the microenvironment at the fusion site in a rat model. SUMMARY OF BACKGROUND DATA: Previous studies report diabetes mellitus (DM) and specifically IDDM as a risk factor for complications and poor surgical outcomes following spinal fusion. METHODS: Twenty control and 22 diabeticrats were obtained at 5 weeks of age. At 20 weeks of age, all animals underwent posterolateral lumbar fusion surgery using a tailbone autograft with diabeticrats receiving an implantable time release insulin pellet. A subset of rats was sacrificed 1-week postsurgery for growth factor (PDGF, IGF-I, TGF-β, and VEGF) and proinflammatory cytokine ELISA analysis. All other rats were sacrificed 3-months postsurgery for fusion evaluation via manual palpation and micro CT. Glycated hemoglobin (HbA1c) was measured at surgery and sacrifice on all animals. RESULTS: Compared with healthy rats undergoing spinal fusion, rats with IDDM demonstrated a significant reduction in manual palpation fusion rates (16.7% vs. 43%, p<.05). Average bone mineral density, bone volume, and bone volume fraction were also significantly reduced and negatively correlated to blood glucose levels. IL-1B, IL-5, IL-10, TNF-α, and KC/GRO were significantly elevated in fusion beds of IDDMrats. CONCLUSIONS: This study demonstrates that rats with IDDM demonstrate a reduced rate and quality of spinal fusion with increased local levels of inflammatory cytokines. Targeted modalities are required to improve bone healing in this growing, high-risk population. CLINICAL SIGNIFICANCE: This is the first translational animal model of IDDM to evaluate the rate and quality of spinal fusion while controlling for other surgical and patient-related risk factors. Our findings demonstrate the complex nature by which IDDM impairs bone healing and highlight the need for additional basic science research to further elucidate this mechanism in order to develop more effective therapeutic interventions.
Authors: Melodie F Metzger; Linda E A Kanim; Li Zhao; Samuel T Robinson; Rick B Delamarter Journal: Spine (Phila Pa 1976) Date: 2015-04-15 Impact factor: 3.468
Authors: Ashish B Shah; William Davis; Zachary L Littlefield; Sean Young; Bradley Alexander; Nicholas A Andrews; Ankit Khurana; Benjamin Cage; Tanvee Sinha; Gerald McGwin; Ashish Shah Journal: Indian J Orthop Date: 2022-04-25 Impact factor: 1.033