{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:15:02Z","timestamp":1790712902692,"version":"4.1.0"},"reference-count":42,"publisher":"ASME International","issue":"1","license":[{"start":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T00:00:00Z","timestamp":1731024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.asme.org\/publications-submissions\/publishing-information\/legal-policies"}],"content-domain":{"domain":["asmedigitalcollection.asme.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Cigarette smoking adversely affects fracture repair, causing delayed healing or nonunion rates twice those seen in nonsmokers. Purpose: We sought to investigate if cigarette smoke differentially affects intramembranous and endochondral healing of fractures. We hypothesize that healing via endochondral ossification will be preferentially impaired compared to intramembranous ossification. Methods: We utilized a bilateral femur fracture model in Sprague Dawley rats to examine effects of cigarette smoke exposure on healing of femur fractures, treated with either locked intramedullary nail or compression plating to induce endochondral and membranous ossification, respectively. Animals were exposed to tobacco smoke 30\u2009days before and after surgery; evaluations included radiographs, histomorphometry, and micro-CT at 10\u2009days, 1, 3, and 6\u2009months postoperation, and biomechanical testing at 3 and 6\u2009months. Results: Sixty-eight animals were randomized to control or exposure (two died perioperatively); 89% of femora achieved union when harvested at 3 or 6\u2009months. Smoke exposure delayed cartilaginous callus formation and bone maturation in nailed fractures compared to plated fractures and controls in the same animals. Plated fractures in exposed animals exhibited little cartilage callus and healed like control animals. At 3\u2009months, plated fractures were stiffer and stronger than nailed fractures in both groups. These differences vanished by 6\u2009months. Conclusions: Plated fractures healed more rapidly and completely than nailed fractures under both control and smoke-exposed conditions. Clinical Relevance: Using compression plating instead of IM nailing for closed long bone fractures may lead to better outcomes in patients who smoke compared to current results with nailing.<\/jats:p>","DOI":"10.1115\/1.4066796","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T09:58:33Z","timestamp":1728467913000},"update-policy":"https:\/\/doi.org\/10.1115\/crossmarkpolicy-asme","source":"Crossref","is-referenced-by-count":4,"title":["Cigarette Smoke Exposure Impairs Fracture Healing in a Rat Model: Preferential Impairment of Endochondral Over Membranous Healing"],"prefix":"10.1115","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2376-5471","authenticated-orcid":false,"given":"Russell A.","family":"Reeves","sequence":"first","affiliation":[{"name":"David Geffen School of Medicine, Department of Radiology, University of California Los Angeles , 855 Tiverton Dr., Los Angeles, CA 90024"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongren","family":"Wu","sequence":"additional","affiliation":[{"name":"Clemson-MUSC Bioengineering Program, Department of Bioengineering, Clemson University , 212 Bioengineering Building, 68 President Street, Charleston, SC 29425 ; , Bioengineering Building 227, 68 President Street, Charleston, SC 29425 ; , Chattanooga, TN 37403"},{"name":"Department of Orthopaedics and Physical Medicine, Medical University of South Carolina , 212 Bioengineering Building, 68 President Street, Charleston, SC 29425 ; , Bioengineering Building 227, 68 President Street, Charleston, SC 29425 ; , Chattanooga, TN 37403"},{"name":"Department of Orthopaedics, University of Tennessee College of Medicine , 212 Bioengineering Building, 68 President Street, Charleston, SC 29425 ; , Bioengineering Building 227, 68 President Street, Charleston, SC 29425 ; , Chattanooga, TN 37403"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Lex","family":"Hanna","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, University of Tennessee College of Medicine , Chattanooga, TN 37403"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Franciscan Orthopaedic Associates , Gig Harbor, WA 98332"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander M.","family":"Chiaramonti","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Physical Medicine, Medical University of South Carolina , Bioengineering Building 227, 68 President Street, Charleston, SC 29425"},{"id":[{"id":"https:\/\/ror.org\/012jban78","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical University of South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth K.","family":"Nadeau","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Physical Medicine, Medical University of South Carolina , Bioengineering Building 227, 68 President Street, Charleston, SC 29425"},{"id":[{"id":"https:\/\/ror.org\/012jban78","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical University of South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Westchester Medical Center , Valhalla, NY 10595"},{"id":[{"id":"https:\/\/ror.org\/03fcgva33","id-type":"ROR","asserted-by":"publisher"}],"name":"Westchester Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip A.","family":"Westbrook","sequence":"additional","affiliation":[{"name":"Department of Urology, NYU Langone , Long Island, NY 11530"},{"id":[{"id":"https:\/\/ror.org\/005dvqh91","id-type":"ROR","asserted-by":"publisher"}],"name":"NYU Langone Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn D.","family":"Hefter","sequence":"additional","affiliation":[{"name":"Zimmer Biomet , Warsaw, IN 46580"},{"id":[{"id":"https:\/\/ror.org\/02bn55144","id-type":"ROR","asserted-by":"publisher"}],"name":"Zimmer Biomet (United States)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan C.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mount Auburn Hospital , Boston, MA 02138"},{"id":[{"id":"https:\/\/ror.org\/00nhpk003","id-type":"ROR","asserted-by":"publisher"}],"name":"Mount Auburn Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Barfield","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Physical Medicine, Medical University of South Carolina , Bioengineering Building 227, 68 President Street, Charleston, SC 29425"},{"id":[{"id":"https:\/\/ror.org\/012jban78","id-type":"ROR","asserted-by":"publisher"}],"name":"Medical University of South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Vincent D.","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics and Physical Medicine, Medical University of South Carolina , Bioengineering Building 227, 68 President Street, Charleston, SC 29425 ; , 1 Medical Center Drive, Lebanon, NH 03756"},{"name":"Department of Orthopaedics, Dartmouth-Hitchcock Medical Center and Geisel School of Medicine at Dartmouth , Bioengineering Building 227, 68 President Street, Charleston, SC 29425 ; , 1 Medical Center Drive, Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"33","published-online":{"date-parts":[[2024,11,8]]},"reference":[{"issue":"3","key":"2024112615581889200_bib1","first-page":"285","article-title":"The Effect of Smoking on Fracture Healing and on Various Orthopaedic Procedures","volume":"78","year":"2012","journal-title":"Acta Orthop. Belg."},{"issue":"6","key":"2024112615581889200_bib2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1302\/2046-3758.26.2000142","article-title":"The Effect of Smoking on Bone Healing: A Systematic Review","volume":"2","year":"2013","journal-title":"Bone Jt. Res."},{"issue":"4","key":"2024112615581889200_bib3","first-page":"268","article-title":"Adverse Effects of Smoking on Musculoskeletal Health","volume":"114","year":"2017","journal-title":"Mo Med."},{"issue":"1","key":"2024112615581889200_bib4","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1186\/s13018-020-01904-2","article-title":"Prevalence and Influencing Factors of Nonunion in Patients With Tibial Fracture: Systematic Review and Meta-Analysis","volume":"15","year":"2020","journal-title":"J. Orthop. Surg."},{"issue":"46","key":"2024112615581889200_bib5","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.15585\/mmwr.mm6946a4","article-title":"Tobacco Product Use Among Adults - United States, 2019","volume":"69","year":"2020","journal-title":"MMWR Morb. Mortal Wkly. Rep."},{"issue":"3","key":"2024112615581889200_bib6","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.amepre.2014.10.012","article-title":"Annual Healthcare Spending Attributable to Cigarette Smoking: An Update","volume":"48","year":"2015","journal-title":"Am. J. Prev. Med."},{"issue":"4","key":"2024112615581889200_bib7","doi-asserted-by":"crossref","first-page":"28","DOI":"10.7748\/en.22.4.28.e1219","article-title":"How Smoking Can Hinder Fracture Healing","volume":"22","year":"2014","journal-title":"Emerg. Nurse"},{"issue":"8","key":"2024112615581889200_bib8","doi-asserted-by":"crossref","first-page":"674","DOI":"10.2106\/JBJS.M.00081","article-title":"Cigarette Smoking Increases Complications Following Fracture: A Systematic Review","volume":"96","year":"2014","journal-title":"J. Bone Jt. Surg. Am."},{"issue":"3","key":"2024112615581889200_bib9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/BOT.0000000000000488","article-title":"Factors Associated With Development of Nonunion or Delayed Healing After an Open Long Bone Fracture: A Prospective Cohort Study of 736 Subjects","volume":"30","year":"2016","journal-title":"J. Orthop. Trauma"},{"issue":"355 Suppl","key":"2024112615581889200_bib10","first-page":"S7","article-title":"The Cell and Molecular Biology of Fracture Healing","volume":"355S","year":"1998","journal-title":"Clin. Orthop. Relat. Res."},{"issue":"6","key":"2024112615581889200_bib11","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S0748-7983(96)92450-6","article-title":"Treatment of Pathological Fractures of the Humeral Shaft Due to Bone Metastases: A Comparison of Intramedullary Locking Nail and Plate Osteosynthesis With Adjunctive Bone Cement","volume":"22","year":"1996","journal-title":"Eur. J. Surg. Oncol."},{"issue":"11","key":"2024112615581889200_bib12","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.injury.2010.09.018","article-title":"Protocol of Surgical Treatment of Long Bone Pathological Fractures","volume":"41","year":"2010","journal-title":"Injury"},{"issue":"5","key":"2024112615581889200_bib13","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s00590-013-1242-x","article-title":"Plate Osteosynthesis Versus Intramedullary Nailing for Both Forearm Bones Fractures","volume":"24","year":"2014","journal-title":"Eur. J. Orthop. Surg. Traumatol."},{"issue":"1","key":"2024112615581889200_bib14","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s00590-013-1362-3","article-title":"Plate Fixation Versus Intramedullary Nailing for Displaced Extra-Articular Distal Tibia Fractures: A System Review","volume":"25","year":"2015","journal-title":"Eur. J. Orthop. Surg. Traumatol."},{"issue":"5","key":"2024112615581889200_bib15","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/S0736-0266(02)00017-7","article-title":"A Model for Intramembranous Ossification During Fracture Healing","volume":"20","year":"2002","journal-title":"J. Orthop. Res."},{"issue":"10","key":"2024112615581889200_bib16","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1097\/CORR.0000000000000395","article-title":"External Beam Irradiation Preferentially Inhibits the Endochondral Pathway of Fracture Healing: A Rat Model","volume":"476","year":"2018","journal-title":"Clin. Orthop. Relat. Res."},{"issue":"3","key":"2024112615581889200_bib17","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1302\/2046-3758.93.BJR-2019-0089.R1","article-title":"Cigarette Smoke Inhalation Impairs Angiogenesis in Early Bone Healing Processes and Delays Fracture Union","volume":"9","year":"2020","journal-title":"Bone Jt. Res."},{"issue":"12","key":"2024112615581889200_bib18","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1002\/jor.20263","article-title":"Smoking Delays Chondrogenesis in a Mouse Model of Closed Tibial Fracture Healing","volume":"24","year":"2006","journal-title":"J. Orthop. Res."},{"issue":"1","key":"2024112615581889200_bib19","first-page":"186","article-title":"Smoking Alters Inflammation and Skeletal Stem and Progenitor Cell Activity During Fracture Healing in Different Murine Strains","volume":"36","year":"2021","journal-title":"J. Bone Min. Res."},{"issue":"3","key":"2024112615581889200_bib20","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1007\/s11999-016-5184-6","article-title":"Exposure to Secondhand Smoke Impairs Fracture Healing in Rats","volume":"475","year":"2017","journal-title":"Clin. Orthop. Relat. Res."},{"issue":"3","key":"2024112615581889200_bib21","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1002\/jcp.22819","article-title":"Aryl Hydrocarbon Receptor-Mediated Impairment of Chondrogenesis and Fracture Healing by Cigarette Smoke and Benzo(a)Pyrene","volume":"227","year":"2012","journal-title":"J. Cell. Physiol."},{"issue":"1","key":"2024112615581889200_bib22","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1097\/00005373-199901000-00018","article-title":"Bone Healing of Tibial Lengthening Is Delayed by Cigarette Smoking: Study of Bone Mineral Density and Torsional Strength on Rabbits","volume":"46","year":"1999","journal-title":"J. Trauma"},{"issue":"1","key":"2024112615581889200_bib23","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3109\/08958379409029697","article-title":"Sidestream Cigarette Smoke and Exposure System for Environmental Tobacco Smoke Studies","volume":"6","year":"1994","journal-title":"Inhalation Toxicol."},{"issue":"3","key":"2024112615581889200_bib24","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1177\/0192623310364028","article-title":"Effects of Short-Term Cigarette Smoke Exposure on Fischer 344 Rats and on Selected Lung Proteins","volume":"38","year":"2010","journal-title":"Toxicol. Pathol."},{"issue":"5","key":"2024112615581889200_bib25","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/clpt.1994.169","article-title":"Metabolism of Nicotine to Cotinine Studied by a Dual Stable Isotope Method","volume":"56","year":"1994","journal-title":"Clin. Pharmacol. Ther."},{"issue":"7","key":"2024112615581889200_bib26","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1080\/08958370801935174","article-title":"Toxicological Comparisons of Three Styles of a Commercial U.S. Cigarette (Marlboro\u00ae) With the 1R4F Reference Cigarette","volume":"20","year":"2008","journal-title":"Inhal. Toxicol."},{"issue":"12","key":"2024112615581889200_bib27","first-page":"1448","article-title":"Residence Times and Half-Lives of Nicotine Metabolites in Rat Brain After Acute Peripheral Administration of [2\u2032-(14)C]Nicotine","volume":"27","year":"1999","journal-title":"Drug Metab. Dispos. Biol. Fate Chem."},{"issue":"7","key":"2024112615581889200_bib28","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An Open-Source Platform for Biological-Image Analysis","volume":"9","year":"2012","journal-title":"Nat. Methods"},{"issue":"2","key":"2024112615581889200_bib29","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: A Flexible Statistical Power Analysis Program for the Social, Behavioral, and Biomedical Sciences","volume":"39","year":"2007","journal-title":"Behav. Res. Methods"},{"issue":"353","key":"2024112615581889200_bib30","first-page":"231","article-title":"Effect of Nicotine on the Rate and Strength of Long Bone Fracture Healing","volume":"353","year":"1998","journal-title":"Clin. Orthop. Relat. Res."},{"issue":"3","key":"2024112615581889200_bib31","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1002\/jor.21008","article-title":"An Internal Locking Plate to Study Intramembranous Bone Healing in a Mouse Femur Fracture Model","volume":"28","year":"2010","journal-title":"J. Orthop. Res."},{"issue":"4","key":"2024112615581889200_bib32","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1007\/s10856-008-3372-y","article-title":"Experiment Study on Fracture Fixation With Low Rigidity Titanium Alloy: Plate Fixation of Tibia Fracture Model in Rabbit","volume":"19","year":"2008","journal-title":"J. Mater. Sci. Mater. Med."},{"issue":"2","key":"2024112615581889200_bib33","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/jor.1100060218","article-title":"The Influence of Different Degrees of Stiffness of Fixation Plates on Experimental Bone Healing","volume":"6","year":"1988","journal-title":"J. Orthop. Res."},{"key":"2024112615581889200_bib34","first-page":"1","article-title":"Concept of the Law of Bone Remodeling","volume-title":"The Law of Bone Remodeling","year":"1986"},{"issue":"5","key":"2024112615581889200_bib35","first-page":"186","article-title":"Smoking Impairs Hematoma Formation and Dysregulates Angiogenesis as the First Steps of Fracture Healing","volume":"9","year":"2022","journal-title":"Bioeng. Basel Switz."},{"issue":"1","key":"2024112615581889200_bib36","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/jor.1100020115","article-title":"Production of a Standard Closed Fracture in Laboratory Animal Bone","volume":"2","year":"1984","journal-title":"J. Orthop. Res."},{"issue":"3","key":"2024112615581889200_bib37","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/S0736-0266(02)00209-7","article-title":"Development of an Atrophic Nonunion Model and Comparison to a Closed Healing Fracture in Rat Femur","volume":"21","year":"2003","journal-title":"J. Orthop. Res."},{"issue":"2","key":"2024112615581889200_bib38","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1002\/jor.1100070204","article-title":"The Effect of Radiation on the Fracture Repair Process. A Biomechanical Evaluation of a Closed Fracture in a Rat Model","volume":"7","year":"1989","journal-title":"J. Orthop. Res."},{"issue":"8","key":"2024112615581889200_bib39","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1002\/jor.22351","article-title":"Effects of Radiation and Surgery on Healing of Femoral Fractures in a Rat Model","volume":"31","year":"2013","journal-title":"J. Orthop. Res."},{"issue":"9","key":"2024112615581889200_bib40","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1002\/jor.21106","article-title":"Effect of Nicotine and Tobacco Administration Method on the Mechanical Properties of Healing Bone Following Closed Fracture","volume":"28","year":"2010","journal-title":"J Orthop. Res."},{"issue":"4","key":"2024112615581889200_bib41","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.injury.2015.01.033","article-title":"Novel Rat Model of Nonunion Fracture With Vascular Deficit","volume":"46","year":"2015","journal-title":"Injury"},{"issue":"1","key":"2024112615581889200_bib42","doi-asserted-by":"crossref","first-page":"L1","DOI":"10.1152\/ajplung.90200.2008","article-title":"Animal Models of Chronic Obstructive Pulmonary Disease","volume":"295","year":"2008","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."}],"container-title":["Journal of Biomechanical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/asmedigitalcollection.asme.org\/biomechanical\/article-pdf\/147\/1\/011005\/7411230\/bio_147_01_011005.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/asmedigitalcollection.asme.org\/biomechanical\/article-pdf\/147\/1\/011005\/7411230\/bio_147_01_011005.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T11:04:04Z","timestamp":1732619044000},"score":1,"resource":{"primary":{"URL":"https:\/\/asmedigitalcollection.asme.org\/biomechanical\/article\/147\/1\/011005\/1207122\/Cigarette-Smoke-Exposure-Impairs-Fracture-Healing"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,8]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,1]]}},"URL":"https:\/\/doi.org\/10.1115\/1.4066796","relation":{},"ISSN":["0148-0731","1528-8951"],"issn-type":[{"value":"0148-0731","type":"print"},{"value":"1528-8951","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,8]]},"article-number":"011005"}}