{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:24:55Z","timestamp":1784823895339,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Catholic University of Korea Daejeon St. Mary\u2019s Hospital","award":["CMCDJ-P-2025-017"],"award-info":[{"award-number":["CMCDJ-P-2025-017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Poly (methyl methacrylate) (PMMA) bone cement is widely used in percutaneous vertebroplasty to stabilize osteoporotic vertebral compression fractures. However, its clinical application is limited by its high compressive modulus, risk of thermal necrosis, and poor bone integration, unlike conventional PMMA formulations used in vertebrae or joint arthroplasty, which can reach polymerization temperatures exceeding 100 \u00b0C. Spine-specific PMMA is formulated to cure at a reduced polymerization temperature, thereby minimizing the rise in core temperature during the setting process. Consistent with our hypothesis, this moderate thermal output induces localized thermal injury that triggers osteogenic responses and extracellular matrix production, thereby enhancing osteoblast activity in the surrounding bone. This study aimed to evaluate bone remodeling following spine-specific PMMA injection in an osteoporotic Sprague-Dawley (SD) rat model. Twenty-four osteoporotic female SD rats were randomly assigned to three groups: Control (untreated), OVX + spine-specific PMMA (OVX + PMMA), and OVX (OVX + Defect). Bone regeneration was assessed using dual-energy X-ray absorptiometry (DXA), micro-computed tomography (Micro-CT), quantitative PCR (qPCR), immunohistochemistry (IHC), and Western blotting. At 12 weeks post-injection, the OVX + PMMA group exhibited significantly greater bone regeneration than the OVX group. Micro-CT analysis demonstrated a marked increase in trabecular thickness in the PMMA-treated group. Notably, bone formation was more pronounced in regions surrounding the cement compared to adjacent untreated areas. This suggests that spine-specific PMMA promotes osteogenesis via localized thermal necrosis and subsequent osteoblast recruitment. These findings highlight the dual role of spine-specific PMMA in both structural stabilization and biologically driven bone regeneration. Further research is warranted to optimize its clinical applications while minimizing potential adverse effects.<\/jats:p>","DOI":"10.3390\/ijms26104786","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T09:30:38Z","timestamp":1747387838000},"page":"4786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Low-Temperature Spine-Specific PMMA Enhances Bone Regeneration via Localized Thermal Necrosis in an Osteoporotic Rat Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7146-8553","authenticated-orcid":false,"given":"Md Amit Hasan","family":"Tanvir","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Daejeon St. Mary\u2019s Hospital, The Catholic University of Korea, Seoul 34943, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9750-7501","authenticated-orcid":false,"given":"Md Abdul","family":"Khaleque","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Daejeon St. Mary\u2019s Hospital, The Catholic University of Korea, Seoul 34943, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Daejeon St. Mary\u2019s Hospital, The Catholic University of Korea, Seoul 34943, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Eun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Daejeon St. Mary\u2019s Hospital, The Catholic University of Korea, Seoul 34943, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6779-8075","authenticated-orcid":false,"given":"Hwan-Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Daejeon St. Mary\u2019s Hospital, The Catholic University of Korea, Seoul 34943, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2383-6444","authenticated-orcid":false,"given":"Young-Yul","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Daejeon St. Mary\u2019s Hospital, The Catholic University of Korea, Seoul 34943, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s40266-017-0492-4","article-title":"Pain in Osteoporosis: From Pathophysiology to Therapeutic Approach","volume":"34","author":"Catalano","year":"2017","journal-title":"Drugs Aging"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1186\/s13018-021-02772-0","article-title":"The global prevalence of osteoporosis in the world: A comprehensive systematic review and meta-analysis","volume":"16","author":"Salari","year":"2021","journal-title":"J. Orthop. Surg. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.biopha.2016.09.045","article-title":"Animal models for glucocorticoid-induced postmenopausal osteoporosis: An updated review","volume":"84","author":"Zhang","year":"2016","journal-title":"Biomed Pharmacother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.berh.2014.01.002","article-title":"Osteoporosis and fragility fractures: Vertebral fractures","volume":"27","author":"Gerdhem","year":"2013","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"k1551","DOI":"10.1136\/bmj.k1551","article-title":"Vertebroplasty versus sham procedure for painful acute osteoporotic vertebral compression fractures (VERTOS IV): Randomised sham controlled clinical trial","volume":"361","author":"Firanescu","year":"2018","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6544","DOI":"10.7150\/thno.44428","article-title":"Bioactive poly (methyl methacrylate) bone cement for the treatment of osteoporotic vertebral compression fractures","volume":"10","author":"Zhu","year":"2020","journal-title":"Theranostics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3897","DOI":"10.1016\/j.biomaterials.2006.03.002","article-title":"Mechanical and histological evaluation of a PMMA-based bone cement modified with gamma-methacryloxypropyltrimethoxysilane and calcium acetate","volume":"27","author":"Tsukeoka","year":"2006","journal-title":"Biomaterials"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Tanvir, M.A.H., Khaleque, M.A., Kim, G.H., Yoo, W.Y., and Kim, Y.Y. (2024). The role of bioceramics for bone regeneration: History, mechanisms, and future perspectives. Biomimetics, 9.","DOI":"10.20944\/preprints202404.0387.v1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1111\/os.13822","article-title":"Open surgical treatments of osteoporotic vertebral compression fractures","volume":"15","author":"Li","year":"2023","journal-title":"Orthop. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Gong, Y., Zhang, B., and Yan, L. (2022). A preliminary review of modified polymethyl methacrylate and calcium-based bone cement for improving properties in osteoporotic vertebral compression fractures. Front. Mater., 9.","DOI":"10.3389\/fmats.2022.912713"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.actbio.2018.03.014","article-title":"In vivo response to a low-modulus PMMA bone cement in an ovine model","volume":"72","author":"Robo","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Walczak, K., Thiele, J., Geisler, D., Boening, K., and Wieckiewicz, M. (2018). Effect of Chemical Disinfection on Chitosan Coated PMMA and PETG Surfaces-An In Vitro Study. Polymers, 10.","DOI":"10.3390\/polym10050536"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.matdes.2018.05.045","article-title":"Small intestinal submucosa\/polymethyl methacrylate composite bone cement for vertebral repair","volume":"154","author":"Zhang","year":"2018","journal-title":"Mater. Des."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"118306","DOI":"10.1016\/j.compstruct.2024.118306","article-title":"Effect of various admixtures on selected mechanical properties of medium viscosity bone cements: Part 1\u2014\u03b1\/\u03b2 tricalcium phosphate (TCP)","volume":"343","author":"Szabelski","year":"2024","journal-title":"Compos. Struct."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"118308","DOI":"10.1016\/j.compstruct.2024.118308","article-title":"Effect of various admixtures on selected mechanical properties of medium viscosity bone cements: Part 2\u2014Hydroxyapatite","volume":"343","author":"Szabelski","year":"2024","journal-title":"Compos. Struct."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"118307","DOI":"10.1016\/j.compstruct.2024.118307","article-title":"Effect of various admixtures on selected mechanical properties of medium viscosity bone cements: Part 3\u2014Glassy carbon","volume":"343","author":"Szabelski","year":"2024","journal-title":"Compos. Struct."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.msec.2016.11.113","article-title":"Development and characterization of a novel porous small intestine submucosa-hydroxyapatite scaffold for bone regeneration","volume":"72","author":"Buttigieg","year":"2017","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1177\/1602400223","article-title":"Compression and Flexural Strength of Bone Cement Mixed with Blood","volume":"24","author":"Tan","year":"2016","journal-title":"J. Orthop. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Szoradi, G.T., Feier, A.M., Zuh, S.G., Russu, O.M., and Pop, T.S. (2024). Polymethyl Methacrylate Bone Cement Polymerization Induced Thermal Necrosis at the Cement\u2013Bone Interface: A Narrative Review. Appl. Sci., 14.","DOI":"10.3390\/app142411651"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Khaleque, M.A., Kim, J.H., Hwang, B.J., Kang, J.K., Quan, M., and Kim, Y.Y. (2023). Role of necroptosis in intervertebral disc degeneration. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015292"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"76","DOI":"10.13004\/jknts.2006.2.1.76","article-title":"Spontaneous Bursting Collapse of a PMMA Augmented Vertebra: A Rare Complication of Vertebroplasty: A Case Report","volume":"2","author":"Shin","year":"2006","journal-title":"J. Korean Neurotraumatol. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yin, J., Guan, Q., Chen, M., Cao, Y., Zou, J., and Zhang, L. (2025). Effects of Thermal Environment on Bone Microenvironment: A Narrative Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083501"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4088","DOI":"10.1016\/j.febslet.2015.11.021","article-title":"Extracellular heat shock protein 70 promotes osteogenesis of human mesenchymal stem cells through activation of the ERK signaling pathway","volume":"589","author":"Chen","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3109\/02656736.2014.988662","article-title":"In vivo heat-stimulus-triggered osteogenesis","volume":"31","author":"Ikuta","year":"2015","journal-title":"Int. J. Hyperth."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1089\/ten.tec.2013.0087","article-title":"Mild heat stress enhances angiogenesis in a co-culture system consisting of primary human osteoblasts and outgrowth endothelial cells","volume":"20","author":"Li","year":"2014","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Cheng, J., Ju, S., and Zhang, Z. (2023). Osteoporotic vertebral compression fractures caused by Cushing\u2019s syndrome in young women: Case report and literature review. BMC Musculoskelet. Disord., 24.","DOI":"10.1186\/s12891-023-06253-9"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.spinee.2017.11.001","article-title":"Kyphoplasty for osteoporotic vertebral fractures with posterior wall injury","volume":"18","author":"Abdelgawaad","year":"2018","journal-title":"Spine J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1002\/jor.20575","article-title":"Experimental micromechanics of the cement-bone interface","volume":"26","author":"Mann","year":"2008","journal-title":"J. Orthop. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"DiPisa, J.A., Sih, G.S., and Berman, A.T. (1976). The temperature problem at the bone-acrylic cement interface of the total hip replacement. Clin. Orthop. Relat. Res., 95\u201398.","DOI":"10.1097\/00003086-197611000-00013"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1177\/147323000203000307","article-title":"Effects of stem design and pre-cooling prostheses on the heat generated by bone cement in an in vitro model","volume":"30","author":"Rodop","year":"2002","journal-title":"J. Int. Med. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/jor.22812","article-title":"Unilateral heat accelerates bone elongation and lengthens extremities of growing mice","volume":"33","author":"Serrat","year":"2015","journal-title":"J. Orthop. Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ota, T., Nishida, Y., Ikuta, K., Kato, R., Kozawa, E., Hamada, S., Sakai, T., and Ishiguro, N. (2017). Heat-stimuli-enhanced osteogenesis using clinically available biomaterials. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181404"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1089\/ten.tea.2012.0070","article-title":"Enhanced osteogenesis of human mesenchymal stem cells by periodic heat shock in self-assembling peptide hydrogel","volume":"19","author":"Chen","year":"2013","journal-title":"Tissue Eng. Part A"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.bone.2010.04.604","article-title":"Ultrasound-induced activation of Wnt signaling in human MG-63 osteoblastic cells","volume":"47","author":"Olkku","year":"2010","journal-title":"Bone"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"259","DOI":"10.4184\/jkss.2009.16.4.259","article-title":"Mechanical properties of blood-mixed PMMA in percutaneous vertebroplasty","volume":"16","author":"Ahn","year":"2009","journal-title":"J. Korean Soc. Spine Surg."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4786\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:34:04Z","timestamp":1760031244000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/10\/4786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,16]]},"references-count":35,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26104786"],"URL":"https:\/\/doi.org\/10.3390\/ijms26104786","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,16]]}}}