{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T01:31:50Z","timestamp":1793323910526,"version":"4.5.0"},"reference-count":16,"publisher":"Open Medical Publishing","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"\n Background<\/jats:title>\n Impaired bone regeneration remains a major challenge in orthopedic reconstruction, particularly in distraction osteogenesis, limb reconstruction, and delayed union, where prolonged healing increases treatment burden and complication risk. Adjunctive biophysical stimulation, including low-intensity pulsed ultrasound and pulsed electromagnetic field stimulation, has been investigated as a noninvasive strategy to improve bone-healing outcomes, but evidence in reconstructive orthopedic settings remains limited and heterogeneous.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA 2020. PubMed\/MEDLINE, Scopus, and Web of Science were searched from database inception to March 21, 2026. Eligible studies evaluated adjunctive low-intensity pulsed ultrasound or pulsed electromagnetic field stimulation in distraction osteogenesis, limb reconstruction, or delayed union using comparative control groups. Random-effects meta-analysis was performed for clinically comparable outcomes. Fixation-normalized healing outcomes were pooled as mean differences, radiographic healing outcomes as standardized mean differences, and methodological quality was assessed using RoB 2.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Seven randomized controlled trials met eligibility criteria for qualitative synthesis. Two studies contributed to quantitative pooling of fixation-normalized healing efficiency, demonstrating significantly shorter healing duration with adjunctive intervention compared with control (mean difference, \u221216.78 days\/cm; 95% CI, \u221222.72 to \u221210.83; P < 0.001; I\u00b2 = 0%). Three studies contributed to radiographic meta-analysis, showing a significant benefit favoring adjunctive biophysical stimulation (SMD, 0.40; 95% CI, 0.07\u20130.74; P = 0.02; I\u00b2 = 42.1%). Secondary clinical burden and safety outcomes were not suitable for quantitative pooling because of heterogeneous reporting. Six studies were judged as having some concerns and one as high risk of bias.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Adjunctive biophysical stimulation was associated with favorable healing-related outcomes in selected distraction osteogenesis, limb reconstruction, and delayed-union settings. However, the evidence base remains limited by small study numbers, methodological heterogeneity, and inconsistent outcome reporting, supporting the need for larger contemporary randomized trials.<\/jats:p>\n <\/jats:sec>","DOI":"10.52965\/001c.165096","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:51:12Z","timestamp":1786369872000},"source":"Crossref","is-referenced-by-count":0,"title":["A Meta-analysis of Randomized Controlled Trials of Adjunctive Biophysical Stimulation for Bone Regeneration Across Distraction Osteogenesis, Limb Reconstruction, and Delayed Union"],"prefix":"10.52965","volume":"18","author":[{"given":"Mohammed M.","family":"Tarabishi","sequence":"first","affiliation":[{"name":"King Fahad Medical City, Riyadh, Saudi Arabia","department":["Reconstructive Orthopaedic Department"]},{"name":"King Fahad Medical City (KFMC), Riyadh, Saudi Arabia","department":["Consultant Orthopaedic Surgeon, Foot & Ankle Reconstruction, Adult and Pediatric Limb Lengthening, Deformity Correction, and Limb Reconstruction"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"30777","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"issue":"3","key":"ref1","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1002\/jum.15738","article-title":"Low-intensity pulsed ultrasound stimulation for bone fractures healing: a review","volume":"41","author":"P. Palanisamy","year":"2022","journal-title":"J Ultrasound Med"},{"issue":"14","key":"ref2","doi-asserted-by":"publisher","first-page":"7403","DOI":"10.3390\/ijms22147403","article-title":"Pulsed electromagnetic fields in bone healing: molecular pathways and clinical applications","volume":"22","author":"L. Caliogna","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"5","key":"ref3","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1002\/bem.22271","article-title":"Effectiveness of pulsed electromagnetic fields on bone healing: a systematic review and meta-analysis of randomized controlled trials","volume":"41","author":"L. Peng","year":"2020","journal-title":"Bioelectromagnetics"},{"issue":"6","key":"ref4","doi-asserted-by":"publisher","first-page":"989","DOI":"10.23736\/S1973-9087.24.08226-1","article-title":"Effects of pulsed electromagnetic fields on bone fractures: a systematic review update","volume":"60","author":"A. Picelli","year":"2024","journal-title":"Eur J Phys Rehabil Med"},{"issue":"4","key":"ref5","doi-asserted-by":"publisher","first-page":"e37704","DOI":"10.7759\/cureus.37704","article-title":"Biophysical enhancement in fracture healing: a review of the literature","volume":"15","author":"I. D. Aifantis","year":"2023","journal-title":"Cureus"},{"issue":"1","key":"ref6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1515\/mr-2024-0023","article-title":"Biophysical stimuli for promoting bone repair and regeneration","volume":"5","author":"Y. Bai","year":"2024","journal-title":"Med Rev (Berl)"},{"issue":"4","key":"ref7","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1136\/bjsports-2021-103987","article-title":"Implementing the 27 PRISMA 2020 statement items for systematic reviews in the sport and exercise medicine, musculoskeletal rehabilitation and sports science fields: the PERSiST guidance","volume":"56","author":"C. L. Ardern","year":"2022","journal-title":"Br J Sports Med"},{"issue":"4","key":"ref8","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1080\/17453674.2017.1321351","article-title":"The risk of non-union per fracture: current myths and revised figures from a population of over 4 million adults","volume":"88","author":"L. A. Mills","year":"2017","journal-title":"Acta Orthop"},{"issue":"6","key":"ref9","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.injury.2011.03.031","article-title":"The biology of fracture healing","volume":"42","author":"R. Marsell","year":"2011","journal-title":"Injury"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"101760","DOI":"10.1016\/j.bonr.2024.101760","article-title":"Orthobiologics in delayed union and non-union of adult long bones fractures: a systematic review","volume":"21","author":"L. Impieri","year":"2024","journal-title":"Bone Rep"},{"issue":"1","key":"ref11","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s10195-025-00843-0","article-title":"Risk factors associated with delayed union after open reduction and plate fixation for humeral diaphyseal fractures","volume":"26","author":"Y. R. Kuo","year":"2025","journal-title":"J Orthop Traumatol"},{"issue":"238","key":"ref12","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1097\/00003086-198901000-00038","article-title":"The tension-stress effect on the genesis and growth of tissues. Part I. The influence of stability of fixation and soft-tissue preservation","author":"G. A. Ilizarov","year":"1989","journal-title":"Clin Orthop Relat Res"},{"issue":"239","key":"ref13","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1097\/00003086-198902000-00029","article-title":"The tension-stress effect on the genesis and growth of tissues: Part II. The influence of the rate and frequency of distraction","author":"G. A. Ilizarov","year":"1989","journal-title":"Clin Orthop Relat Res"},{"issue":"6","key":"ref14","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/8756-3282(96)00070-1","article-title":"Effect of pulsed electromagnetic fields on bone formation and bone loss during limb lengthening","volume":"18","author":"K. S. Eyres","year":"1996","journal-title":"Bone"},{"issue":"8","key":"ref15","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1002\/jbmr.3475","article-title":"A randomized, double-blind, placebo-controlled, phase 3 trial evaluating the efficacy of burosumab, an anti-FGF23 antibody, in adults with X-linked hypophosphatemia: week 24 primary analysis","volume":"33","author":"K. L. Insogna","year":"2018","journal-title":"J Bone Miner Res"},{"issue":"4","key":"ref16","doi-asserted-by":"publisher","first-page":"e470","DOI":"10.5435\/JAAOS-D-21-00542","article-title":"Fifth metatarsal Jones fractures: diagnosis and treatment","volume":"30","author":"J. A. Metzl","year":"2022","journal-title":"J Am Acad Orthop Surg"}],"container-title":["Orthopedic Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/orthopedicreviews.openmedicalpublishing.org\/article\/165096-a-meta-analysis-of-randomized-controlled-trials-of-adjunctive-biophysical-stimulation-for-bone-regeneration-across-distraction-osteogenesis-limb-reco","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:46:09Z","timestamp":1793321169000},"score":1,"resource":{"primary":{"URL":"https:\/\/orthopedicreviews.openmedicalpublishing.org\/article\/165096-a-meta-analysis-of-randomized-controlled-trials-of-adjunctive-biophysical-stimulation-for-bone-regeneration-across-distraction-osteogenesis-limb-reco"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,10]]},"references-count":16,"URL":"https:\/\/doi.org\/10.52965\/001c.165096","relation":{},"ISSN":["2035-8164"],"issn-type":[{"value":"2035-8164","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,10]]}}}