{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:15:29Z","timestamp":1790252129825,"version":"4.1.0"},"reference-count":149,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,8,17]],"date-time":"2018-08-17T00:00:00Z","timestamp":1534464000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this era of aging societies, the number of elderly individuals who undergo spinal arthrodesis for various degenerative diseases is increasing. Poor bone quality and osteogenic ability in older patients, due to osteoporosis, often interfere with achieving bone fusion after spinal arthrodesis. Enhancement of bone fusion requires shifting bone homeostasis toward increased bone formation and reduced resorption. Several biological enhancement strategies of bone formation have been conducted in animal models of spinal arthrodesis and human clinical trials. Pharmacological agents for osteoporosis have also been shown to be effective in enhancing bone fusion. Cytokines, which activate bone formation, such as bone morphogenetic proteins, have already been clinically used to enhance bone fusion for spinal arthrodesis. Recently, stem cells have attracted considerable attention as a cell source of osteoblasts, promising effects in enhancing bone fusion. Drug delivery systems will also need to be further developed to assure the safe delivery of bone-enhancing agents to the site of spinal arthrodesis. Our aim in this review is to appraise the current state of knowledge and evidence regarding bone enhancement strategies for spinal fusion for degenerative spinal disorders, and to identify future directions for biological bone enhancement strategies, including pharmacological, cell and gene therapy approaches.<\/jats:p>","DOI":"10.3390\/ijms19082430","type":"journal-article","created":{"date-parts":[[2018,8,17]],"date-time":"2018-08-17T10:54:25Z","timestamp":1534503265000},"page":"2430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["The Biological Enhancement of Spinal Fusion for Spinal Degenerative Disease"],"prefix":"10.3390","volume":"19","author":[{"given":"Takahiro","family":"Makino","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Tsukazaki","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Ukon","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Tateiwa","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4882-2997","authenticated-orcid":false,"given":"Takashi","family":"Kaito","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1097\/BRS.0b013e31820cccfb","article-title":"Spinal fusion in the United States: Analysis of trends from 1998 to 2008","volume":"37","author":"Rajaee","year":"2012","journal-title":"Spine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1097\/00007632-200301010-00012","article-title":"Pseudoarthrosis of the cervical spine: A comparison of radiographic diagnostic measures","volume":"28","author":"Cannada","year":"2003","journal-title":"Spine"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kornblum, M.B., Fischgrund, J.S., Herkowitz, H.N., Abraham, D.A., Berkower, D.L., and Ditkoff, J.S. 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