{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T14:19:05Z","timestamp":1783693145041,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Titanium trabecular cages (TTCs) are emerging implants designed to achieve immediate and long-term spinal fixation with early osseointegration. However, a clear radiological and clinical demonstration of their efficacy has not yet been obtained. The purpose of this study was to evaluate the reactive bone activity of adjacent plates after insertion of custom-made titanium trabecular cages for the lumbar interbody with positron emission tomography (PET)\/computed tomography (CT) 18F sodium fluoride (18F-NaF). Methods: This was an observational clinical study that included patients who underwent surgery for degenerative disease with lumbar interbody fusion performed with custom-made TTCs. Data related to the metabolic-reparative reaction following the surgery and its relationship with clinical follow-up from PET\/CT performed at different weeks were evaluated. PET\/CTs provided reliable data, such as areas showing abnormally high increases in uptake using a volumetric region of interest (VOI) comprising the upper (UP) and lower (DOWN) limits of the cage. Results: A total of 15 patients was selected for PET examination. Timing of PET\/CTs ranged from one week to a maximum of 100 weeks after surgery. The analysis showed a negative correlation between the variables SUVmaxDOWN\/time (r = \u22120.48, p = 0.04), ratio-DOWN\/time (r = \u22120.53, p = 0.02), and ratio-MEAN\/time (r = \u22120.5, p = 0.03). Shapiro\u2212Wilk normality tests showed significant results for the variables ratio-DOWN (p = 0.002), ratio-UP (0.013), and ratio-MEAN (0.002). Conclusions: 18F-NaF PET\/CT has proven to be a reliable tool for investigating the metabolic-reparative reaction following implantation of TTCs, demonstrating radiologically how this type of cage can induce reparative osteoblastic activity at the level of the vertebral endplate surface. This study further confirms how electron-beam melting (EBM)-molded titanium trabecular cages represent a promising material for reducing hardware complication rates and promoting fusion.<\/jats:p>","DOI":"10.3390\/diagnostics12102296","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T21:14:28Z","timestamp":1664140468000},"page":"2296","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Efficacy of Trabecular Titanium Cages to Induce  Reparative Bone Activity after Lumbar Arthrodesis Studied through the 18f-Naf PET\/CT Scan: Observational Clinical In-Vivo Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Fabio","family":"Cofano","sequence":"first","affiliation":[{"name":"Neurosurgery Unit, Department of Neuroscience, University of Turin, 10124 Turin, Italy"},{"name":"Spine Surgery Unit, Humanitas Gradenigo, 10153 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6550-5534","authenticated-orcid":false,"given":"Daniele","family":"Armocida","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Department of Human Neuroscience, Sapienza Universit\u00e0 of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4398-8368","authenticated-orcid":false,"given":"Livia","family":"Ruffini","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, University Hospital of Parma, 43100 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Scarlattei","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, University Hospital of Parma, 43100 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Baldari","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, University Hospital of Parma, 43100 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Di Perna","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Department of Neuroscience, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Pilloni","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit ASST Fatebenefratelli Sacco, 20121 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Zenga","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Department of Neuroscience, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Ballante","sequence":"additional","affiliation":[{"name":"BioData Science Center, IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Department of Mathematics, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2692-7133","authenticated-orcid":false,"given":"Diego","family":"Garbossa","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Department of Neuroscience, University of Turin, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6131-9547","authenticated-orcid":false,"given":"Fulvio","family":"Tartara","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, ICCS Citt\u00e0 Studi, 20131 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S0140-6736(99)01312-4","article-title":"Epidemiological features of chronic low-back pain","volume":"354","author":"Andersson","year":"1999","journal-title":"Lancet"},{"key":"ref_2","first-page":"2","article-title":"Lumbar interbody fusion: Techniques, indications and comparison of interbody fusion options including PLIF, TLIF, MI-TLIF, OLIF\/ATP, LLIF and ALIF","volume":"1","author":"Mobbs","year":"2015","journal-title":"J. Spine Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00064-010-8054-5","article-title":"The minimally invasive anterolateral approach to L2-5","volume":"22","author":"Mehren","year":"2010","journal-title":"Oper. Orthop. Traumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"E10","DOI":"10.3171\/2015.7.FOCUS15292","article-title":"Lumbar pseudarthrosis: A review of current diagnosis and treatment","volume":"39","author":"Chun","year":"2015","journal-title":"Neurosurg. Focus"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1007\/s00586-014-3454-0","article-title":"Pelvic incidencelumbar lordosis mismatch predisposes to adjacent segment disease after lumbar spinal fusion","volume":"24","author":"Rothenfluh","year":"2015","journal-title":"Eur. Spine J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3171\/2016.9.SPINE16232","article-title":"Spinopelvic sagittal imbalance as a risk factor for adjacent-segment disease after single-segment posterior lumbar interbody fusion","volume":"26","author":"Matsumoto","year":"2017","journal-title":"J. Neurosurg. Spine"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1097\/BRS.0000000000002137","article-title":"Risk factors for poor patientreported quality of life outcomes after posterior lumbar interbody fusion: An analysis of two-year follow-up","volume":"42","author":"Makino","year":"2017","journal-title":"Spine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"476","DOI":"10.3171\/2012.8.SPINE111121","article-title":"Lordosis restoration after anterior longitudinal ligament release and placement of lateral hyperlordotic interbody cages during the minimally invasive lateral transpsoas approach: A radiographic study in cadavers","volume":"17","author":"Uribe","year":"2012","journal-title":"J. Neurosurg. Spine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S1529-9430(03)00061-5","article-title":"Anterior lumbar fusion with paired BAK standard and paired BAK Proximity cages: Subsidence incidence, subsidence factors, and clinical outcome","volume":"3","author":"Beutler","year":"2003","journal-title":"Spine J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s00586-004-0817-y","article-title":"Subsidence after anterior lumbar interbody fusion using paired stand-alone rectangular cages","volume":"15","author":"Choi","year":"2006","journal-title":"Eur. Spine J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1097\/BRS.0b013e3182458b2f","article-title":"Subsidence of polyetheretherketone intervertebral cages in minimally invasive lateral retroperitoneal transpsoas lumbar interbody fusion","volume":"37","author":"Le","year":"2012","journal-title":"Spine (Phila Pa 1976)"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3171\/2013.4.SPINE12319","article-title":"Radiographic and clinical evaluation of cage subsidence after stand-alone lateral interbody fusion","volume":"19","author":"Marchi","year":"2013","journal-title":"J. Neurosurg. Spine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1016\/j.wneu.2021.08.127","article-title":"Minimally invasive transforaminal lumbar interbody fusion using expandable cages: Increased risk of late postoperative subsidence without a real improvement of perioperative outcomes: A clinical monocentric study","volume":"156","author":"Armocida","year":"2021","journal-title":"World Neurosurg."},{"key":"ref_14","first-page":"101","article-title":"Biomaterials in Spinal Implants: A Review","volume":"4","author":"Warburton","year":"2019","journal-title":"Neurospine"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bari, E., Tartara, F., Cofano, F., Di Perna, G., Garbossa, D., Perteghella, S., Sorlini, M., Mandracchia, D., Giovannelli, L., and Gaetani, P. (2021). Freeze-dried secretome (lyosecretome) from mesenchymal stem\/stromal cells promotes the osteoinductive and osteoconductive properties of titanium cages. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168445"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ragni, E., Orfei, C.P., Bidossi, A., De Vecchi, E., Francaviglia, N., Romano, A., Maestretti, G., Tartara, F., and de Girolamo, L. (2021). Superior osteo-inductive and osteo-conductive properties of trabecular titanium vs. PEEK scaffolds on human mesenchymal stem cells: A proof of concept for the use of fusion cages. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052379"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18284","DOI":"10.1038\/s41598-020-75385-y","article-title":"Osteogenic potential of human adipose derived stem cells (hASCs) seeded on titanium trabecular spinal cages","volume":"10","author":"Caliogna","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1016\/j.spinee.2018.02.018","article-title":"Bony ingrowth potential of 3D-printed porous titanium alloy: A direct comparison of interbody cage materials in an in vivo ovine lumbar fusion model","volume":"18","author":"McGilvray","year":"2018","journal-title":"Spine J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.spinee.2012.02.002","article-title":"Osteoblasts exhibit a more differentiated phenotype and increased bone morphogenetic protein production on titanium alloy substrates than on poly-ether-ether-ketone","volume":"12","author":"Gittens","year":"2012","journal-title":"Spine J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s00223-021-00874-9","article-title":"Bone histomorphometry and 18F-sodium fluoride positron emission tomography imaging: Comparison between only bone turnover-based and unified TMV-based classification of renal osteodystrophy","volume":"109","author":"Aaltonen","year":"2021","journal-title":"Calcif. Tissue Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1097\/MNM.0000000000000720","article-title":"Normal bone and soft tissue distribution of fluorine-18-sodium fluoride and artifacts on 18F-NaF PET\/CT bone scan: A pictorial review","volume":"38","author":"Sarikaya","year":"2017","journal-title":"Nucl. Med. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1007\/s00586-014-3227-9","article-title":"Classification of sagittal imbalance based on spinal alignment and compensatory mechanisms","volume":"23","author":"Lamartina","year":"2014","journal-title":"Eur. Spine J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1016\/j.spinee.2014.08.189","article-title":"Fine-tuned surgical planning in adult spinal deformity: Determining the lumbar lordosis necessary by accounting for both thoracic kyphosis and pelvic incidence","volume":"14","author":"Schwab","year":"2014","journal-title":"Spine J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s10143-017-0939-4","article-title":"Intraoperative neurophysiological monitoring during spinal surgery: Technical review in open and minimally invasive approaches","volume":"42","author":"Cofano","year":"2019","journal-title":"Neurosurg. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1007\/s00259-015-3138-y","article-title":"(18)F-NaF PET\/CT: EANM procedure guidelines for bone imaging","volume":"42","author":"Beheshti","year":"2015","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.2967\/jnumed.110.082263","article-title":"SNM practice guideline for sodium 18F-fluoride PET\/CT bone scans 1.0","volume":"51","author":"Segall","year":"2010","journal-title":"J. Nucl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1053\/j.sult.2010.10.001","article-title":"Positron emission tomography-computed tomography standardized uptake values in clinical practice and assessing response to therapy","volume":"31","author":"Kinahan","year":"2010","journal-title":"Semin. Ultrasound CT MR"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11S","DOI":"10.2967\/jnumed.108.057182","article-title":"Standards for PET image acquisition and quantitative data analysis","volume":"50","author":"Boellaard","year":"2009","journal-title":"J. Nucl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/os.12098","article-title":"Spine interbody implants: Material selection and modification, functionalization and bioactivation of surfaces to improve osseointegration","volume":"6","author":"Rao","year":"2014","journal-title":"Orthop. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1016\/S0266-3538(00)00241-4","article-title":"Biomedical applications of polymer-composite materials: A review","volume":"61","author":"Ramakrishna","year":"2001","journal-title":"Compos. Sci. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.bone.2007.09.055","article-title":"Microstimulation at the bone-implant interface upregulates osteoclast activation pathways","volume":"42","author":"Stadelmann","year":"2008","journal-title":"Bone"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E591","DOI":"10.1097\/BRS.0b013e3181ab8b9a","article-title":"The efficacy of the synthetic interbody cage and Grafton for anterior cervical fusion","volume":"34","author":"Park","year":"2009","journal-title":"Spine (Phila Pa 1976)"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4845","DOI":"10.1016\/j.biomaterials.2007.07.013","article-title":"PEEK biomaterials in trauma, orthopedic, and spinal implants","volume":"28","author":"Kurtz","year":"2007","journal-title":"Biomaterials"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1007\/s00586-011-1728-3","article-title":"A novel synthetic material for spinal fusion: A prospective clinical trial of porous bioactive titanium metal for lumbar interbody fusion","volume":"20","author":"Fujibayashi","year":"2011","journal-title":"Eur. Spine J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3171\/SPI-07\/10\/435","article-title":"A porous bioactive titanium implant for spinal interbody fusion: An experimental study using a canine model","volume":"7","author":"Takemoto","year":"2007","journal-title":"J. Neurosurg. Spine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e581","DOI":"10.1016\/j.wneu.2017.12.127","article-title":"Biomechanical analysis of porous additive manufactured cages for lateral lumbar interbody fusion: A finite element analysis","volume":"111","author":"Zhang","year":"2018","journal-title":"World Neurosurg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1007\/s00586-019-06191-y","article-title":"Custom-made trabecular titanium implants for the treatment of lumbar degenerative discopathy via ALIF\/XLIF techniques: Rationale for use and preliminary results","volume":"29","author":"Tartara","year":"2020","journal-title":"Eur. Spine J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1007\/s00586-010-1643-z","article-title":"Assessment of successful incorporation of cages after cervical or lumbar intercorporal fusion with [(18)F]fluoride positron-emission tomography\/computed tomography","volume":"20","author":"Fischer","year":"2011","journal-title":"Eur. Spine J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1097\/MNM.0000000000000891","article-title":"Quantitative evaluation of normal spinal osseous metabolism with 18F-NaF PET\/CT","volume":"39","author":"Ayubcha","year":"2018","journal-title":"Nucl. Med. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/2191-219X-2-42","article-title":"Assessment of bone graft incorporation by 18F-fluoride positron-emission tomography\/computed tomography in patients with persisting symptoms after posterior lumbar interbody fusion","volume":"2","author":"Brans","year":"2012","journal-title":"EJNMMI Res."},{"key":"ref_41","first-page":"272","article-title":"The value of (18)F-fluoride PET\/CT in the assessment of screw loosening in patients after intervertebral fusion stabilization","volume":"42","author":"Seifen","year":"2015","journal-title":"EJNMMI"},{"key":"ref_42","first-page":"1891","article-title":"Pseudarthrosis after lumbar spinal fusion: The role of 18F-fluoride PET\/CT","volume":"42","author":"Peters","year":"2015","journal-title":"EJNMMI"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s12306-017-0465-0","article-title":"Utility of 18F sodium fluoride PET\/CT imaging in the evaluation of postoperative pain following surgical spine fusion","volume":"101","author":"Pouldar","year":"2017","journal-title":"Muscoloskelet Surg."},{"key":"ref_44","first-page":"1737","article-title":"Initial investigation of 18F-NaF PET\/CT for identification of vertebral sites amenable to surgical revision after spinal fusion surgery","volume":"39","author":"Quon","year":"2012","journal-title":"EJNMMI"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/10\/2296\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:38:13Z","timestamp":1760143093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/10\/2296"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,23]]},"references-count":44,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["diagnostics12102296"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12102296","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,23]]}}}