{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:58:32Z","timestamp":1793059112680,"version":"4.5.0"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2018,9,15]],"date-time":"2018-09-15T00:00:00Z","timestamp":1536969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["International Orthopaedics (SICOT)"],"published-print":{"date-parts":[[2018,11]]},"DOI":"10.1007\/s00264-018-4153-y","type":"journal-article","created":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T03:39:41Z","timestamp":1537069181000},"page":"2619-2626","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Bone morphogenetic proteins in fracture repair"],"prefix":"10.1007","volume":"42","author":[{"given":"Ivo","family":"Dumic-Cule","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Peric","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucija","family":"Kucko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovorka","family":"Grgurevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Pecina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slobodan","family":"Vukicevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,9,15]]},"reference":[{"key":"4153_CR1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s11657-013-0137-0","volume":"8","author":"A Svedbom","year":"2013","unstructured":"Svedbom A, Hernlund E, Ivergard M, Compston J, Cooper C, Stenmark J et al (2013) Osteoporosis in the European Union: a compendium of country-specific reports. Arc Osteoporos 8:137. \n                    https:\/\/doi.org\/10.1007\/s11657-013-0137-0","journal-title":"Arc Osteoporos"},{"key":"4153_CR2","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1097\/BOR.0000000000000365","volume":"29","author":"JA Cauley","year":"2017","unstructured":"Cauley JA (2017) Osteoporosis: fracture epidemiology update 2016. Curr Opin Rheumatol 29:150\u20131562. \n                    https:\/\/doi.org\/10.1097\/BOR.0000000000000365","journal-title":"Curr Opin Rheumatol"},{"key":"4153_CR3","doi-asserted-by":"publisher","first-page":"005","DOI":"10.1007\/s00264-015-2728-4","volume":"39","author":"I Dumic-Cule","year":"2015","unstructured":"Dumic-Cule I, Pecina M, Jelic M, Jankolija M, Popek I, Grgurevic L et al (2015) Biological aspects of segmental bone defects management. Int Orthop 39:005\u20131011. \n                    https:\/\/doi.org\/10.1007\/s00264-015-2728-4","journal-title":"Int Orthop"},{"key":"4153_CR4","doi-asserted-by":"publisher","unstructured":"Dimitriou R, Carr IM, West RM, Markham AF, Giannoudis PV (2011) Genetic predisposition to fracture non-union: a case control study of a preliminary single nucleotide polymorphisms analysis of the BMP pathway. BMC Musculoskelet Disord 12(44). \n                    https:\/\/doi.org\/10.1186\/1471-2474-12-44","DOI":"10.1186\/1471-2474-12-44"},{"key":"4153_CR5","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1302\/0301-620X.95B11.32896","volume":"95-B","author":"J Petrie","year":"2013","unstructured":"Petrie J, Sassoon A, Haidukewych GJ (2013) When femoral fracture fixation fails: salvage options. Bone Joint J 95-B:7\u201310. \n                    https:\/\/doi.org\/10.1302\/0301-620X.95B11.32896","journal-title":"Bone Joint J"},{"key":"4153_CR6","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1007\/s00264-011-1243-5","volume":"35","author":"Y Chen","year":"2011","unstructured":"Chen Y, Guo Q, Pan X, Qin L, Zhang P (2011) Smoking and impaired bone healing: will activation of cholinergic anti-inflammatory pathway be the bridge? Int Orthop 35:1267\u20131270. \n                    https:\/\/doi.org\/10.1007\/s00264-011-1243-5","journal-title":"Int Orthop"},{"key":"4153_CR7","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1007\/s00264-015-3046-6","volume":"40","author":"CH Flouzat-Lachaniette","year":"2016","unstructured":"Flouzat-Lachaniette CH, Heyberger C, Bouthors C, Roubineau F, Chevallier N, Rouard H, Hernigou P (2016) Osteogenic progenitors in bone marrow aspirates have clinical potential for tibial non-unions healing in diabetic patients. Int Orthop 40:1375\u20131379. \n                    https:\/\/doi.org\/10.1007\/s00264-015-3046-6","journal-title":"Int Orthop"},{"key":"4153_CR8","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.1007\/s00264-015-2738-2","volume":"39","author":"P Hernigou","year":"2015","unstructured":"Hernigou P, Guissou I, Homma Y, Poignard A, Chevallier N, Rouard H, Flouzat Lachaniette CH (2015) Percutaneous injection of bone marrow mesenchymal stem cells for ankle non-unions decreases complications in patients with diabetes. Int Orthop 39:1639\u20131643. \n                    https:\/\/doi.org\/10.1007\/s00264-015-2738-2","journal-title":"Int Orthop"},{"key":"4153_CR9","first-page":"661","volume":"33","author":"S Vukicevic","year":"1995","unstructured":"Vukicevic S, Stavljenic A, Pecina M (1995) Discovery and clinical applications of bone morphogenetic proteins. Eur J Clin Chem Clin Biochem 33:661\u2013671","journal-title":"Eur J Clin Chem Clin Biochem"},{"key":"4153_CR10","doi-asserted-by":"crossref","unstructured":"Vukicevic S, Sampath TK (2008) Bone morphogenetic proteins: from local to systemic therapeutics. Basel-Boston-Berlin: Birkauser Verlag AG","DOI":"10.1007\/978-3-7643-8552-1"},{"key":"4153_CR11","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.cytogfr.2015.12.009","volume":"27","author":"L Grgurevic","year":"2016","unstructured":"Grgurevic L, Christensen GL, Schulz TJ, Vukicevic S (2016) Bone morphogenetic proteins in inflammation, glucose homeostasis and adipose tissue energy metabolism. Cytokine Growth Factor Rev 27:105\u2013118. \n                    https:\/\/doi.org\/10.1016\/j.cytogfr.2015.12.009","journal-title":"Cytokine Growth Factor Rev"},{"key":"4153_CR12","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1126\/science.150.3698.893","volume":"150","author":"MR Urist","year":"1965","unstructured":"Urist MR (1965) Bone: formation by autoinduction. Science 150:893\u2013899","journal-title":"Science"},{"key":"4153_CR13","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1007\/s00264-017-3402-9","volume":"41","author":"L Grgurevic","year":"2017","unstructured":"Grgurevic L, Pecina M, Vukicevic S (2017) Marshall R. Urist and the discovery of bone morphogenetic proteins. Int Orthop 41:1065\u20131069. \n                    https:\/\/doi.org\/10.1007\/s00264-017-3402-9","journal-title":"Int Orthop"},{"key":"4153_CR14","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1073\/pnas.69.6.1601","volume":"69","author":"AH Reddi","year":"1972","unstructured":"Reddi AH, Huggins C (1972) Biochemical sequences in the transformation of normal fibroblasts in adolescent rats. Proc Natl Acta Sci USA 69:1601\u20131605","journal-title":"Proc Natl Acta Sci USA"},{"key":"4153_CR15","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1007\/s00264-013-2201-1","volume":"38","author":"S Vukicevic","year":"2014","unstructured":"Vukicevic S, Oppermann H, Verbanac D, Jankolija M, Popek I, Curak J et al (2014) The clinical use of bone morphogenetic proteins (BMPs) revisited: a novel BMP6 biocompatible carrier device OSTEOGROW for bone healing. Int Orthop 38:635\u2013647. \n                    https:\/\/doi.org\/10.1007\/s00264-013-2201-1","journal-title":"Int Orthop"},{"key":"4153_CR16","volume-title":"Bone Morphogenetic Proteins: Systems Biology Regulators","year":"2017","unstructured":"Vukicevic S, Sampath TK (ed) (2017) Bone morphogenetic proteins: systems biology regulators, 1st edn Springer International Publishing AG, Switzerland"},{"key":"4153_CR17","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1007\/s00264-012-1750-z","volume":"37","author":"LJ Baardewijk van","year":"2013","unstructured":"van Baardewijk LJ, van der Ende J, Lissenberg-Thunnissen S, Romijn LM, Hawinkels LJ, Sier CF, Schipper IB (2013) Circulating bone morphogenetic protein levels and delayed fracture healing. Int Orthop 37:523\u2013527. \n                    https:\/\/doi.org\/10.1007\/s00264-012-1750-z","journal-title":"Int Orthop"},{"key":"4153_CR18","doi-asserted-by":"publisher","first-page":"2007","DOI":"10.1359\/jbmr.080809","volume":"23","author":"N Kamiya","year":"2008","unstructured":"Kamiya N, Ye L, Kobayashi T, Lucas DJ, Mochida Y, Yamauchi M et al (2008) Disruption of BMP signaling in osteoblasts through type IA receptor (BMPRIA) increases bone mass. J Bone Miner Res 23:2007\u20132017. \n                    https:\/\/doi.org\/10.1359\/jbmr.080809","journal-title":"J Bone Miner Res"},{"key":"4153_CR19","doi-asserted-by":"publisher","first-page":"2511","DOI":"10.1002\/jbmr.477","volume":"26","author":"M Okamoto","year":"2011","unstructured":"Okamoto M, Murai J, Imai Y, Ikegami D, Kamiya N, Kato S et al (2011) Conditional deletion of Bmpr1a in differentiated osteoclasts increases osteoblastic bone formation, increasing volume of remodeling bone in mice. J Bone Miner Res 26:2511\u20132522. \n                    https:\/\/doi.org\/10.1002\/jbmr.477","journal-title":"J Bone Miner Res"},{"key":"4153_CR20","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1359\/jbmr.060411","volume":"21","author":"M Okamoto","year":"2006","unstructured":"Okamoto M, Murai J, Yoshikawa H, Tsumaki N (2006) Bone morphogenetic proteins in bone stimulate osteoclasts and osteoblasts during bone development. J Bone Miner Res 21:1022\u20131033. \n                    https:\/\/doi.org\/10.1359\/jbmr.060411","journal-title":"J Bone Miner Res"},{"key":"4153_CR21","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1002\/jbmr.29","volume":"25","author":"S Minear","year":"2010","unstructured":"Minear S, Leucht P, Miller S, Helms JA (2010) rBMP represses Wnt signaling and influences skeletal progenitor cell fate specification during bone repair. J Bone Miner Res 25:1196\u20131207. \n                    https:\/\/doi.org\/10.1002\/jbmr.29","journal-title":"J Bone Miner Res"},{"key":"4153_CR22","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1359\/jbmr.090806","volume":"25","author":"N Kamiya","year":"2010","unstructured":"Kamiya N, Kobayashi T, Mochida Y, Yu PB, Yamauchi M, Kronenberg HM et al (2010) Wnt inhibitors Dkk1 and Sost are downstream targets of BMP signaling through the type IA receptor (BMPRIA) in osteoblasts. J Bone Miner Res 25:200\u2013210. \n                    https:\/\/doi.org\/10.1359\/jbmr.090806","journal-title":"J Bone Miner Res"},{"key":"4153_CR23","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1007\/s00264-017-3613-0","volume":"41","author":"EM Giles","year":"2017","unstructured":"Giles EM, Godbout C, Chi W, Glick MA, Lin T, Li R, Schemitsch EH, Nauth A (2017) Subtypes of endothelial progenitor cells affect healing of segmental bone defects differently. Int Orthop 41:2337\u20132343. \n                    https:\/\/doi.org\/10.1007\/s00264-017-3613-0","journal-title":"Int Orthop"},{"key":"4153_CR24","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.biomaterials.2016.01.059","volume":"86","author":"J Bolander","year":"2016","unstructured":"Bolander J, Chai YC, Geris L, Schrooten J, Lambrechts D, Roberts SJ, Luyten FP (2016) Early BMP, Wnt and Ca(2+)\/PKC pathway activation predicts the bone forming capacity of periosteal cells in combination with calcium phosphates. Biomaterials 86:106\u2013118. \n                    https:\/\/doi.org\/10.1016\/j.biomaterials.2016.01.059","journal-title":"Biomaterials"},{"issue":"4","key":"4153_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3171\/foc.2001.10.4.2","volume":"10","author":"Iain H. Kalfas","year":"2001","unstructured":"Kalfas IH (2001) Principles of bone healing. Neurosurg Focus 10:E1-. \n                    https:\/\/doi.org\/10.3171\/foc.2001.10.4.2","journal-title":"Neurosurgical Focus"},{"issue":"Suppl 2","key":"4153_CR26","doi-asserted-by":"publisher","first-page":"S499","DOI":"10.1002\/jbmr.5650081313","volume":"8","author":"AH Reddi","year":"1993","unstructured":"Reddi AH, Cunningham NS (1993) Initiation and promotion of bone differentiation by bone morphogenetic proteins. J Bone Miner Res 8(Suppl 2):S499\u2013S502. \n                    https:\/\/doi.org\/10.1002\/jbmr.5650081313","journal-title":"J Bone Miner Res"},{"key":"4153_CR27","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1016\/j.injury.2005.07.019","volume":"36","author":"R Dimitriou","year":"2005","unstructured":"Dimitriou R, Tsiridis E, Giannoudis PV (2005) Current concepts of molecular aspects of bone healing. Injury 36:1392\u20131404. \n                    https:\/\/doi.org\/10.1016\/j.injury.2005.07.019","journal-title":"Injury"},{"key":"4153_CR28","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1359\/jbmr.2002.17.3.513","volume":"17","author":"TJ Cho","year":"2002","unstructured":"Cho TJ, Gerstenfeld LC, Einhorn TA (2002) Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing. J Bone Miner Res 17:513\u2013520. \n                    https:\/\/doi.org\/10.1359\/jbmr.2002.17.3.513","journal-title":"J Bone Miner Res"},{"key":"4153_CR29","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1016\/j.bone.2007.01.001","volume":"40","author":"CM Edgar","year":"2007","unstructured":"Edgar CM, Chakravarthy V, Barnes G, Kakar S, Gerstenfeld LC, Einhorn TA (2007) Autogenous regulation of a network of bone morphogenetic proteins (BMPs) mediates the osteogenic differentiation in murine marrow stromal cells. Bone 40:1389\u20131398. \n                    https:\/\/doi.org\/10.1016\/j.bone.2007.01.001","journal-title":"Bone"},{"key":"4153_CR30","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.1016\/j.urolonc.2003.12.008","volume":"85-A","author":"H Cheng","year":"2003","unstructured":"Cheng H, Jiang W, Phillips FM, Haydon RC, Peng Y, Zhou L et al (2003) Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am 85-A:1544\u20131552. \n                    https:\/\/doi.org\/10.1016\/j.urolonc.2003.12.008","journal-title":"J Bone Joint Surg Am"},{"key":"4153_CR31","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1083\/jcb.123.4.921","volume":"123","author":"I Asahina","year":"1993","unstructured":"Asahina I, Sampath TK, Nishimura I, Hauschka PV (1993) Human osteogenic protein-1 induces both chondroblastic and osteoblastic differentiation of osteoprogenitor cells derived from newborn rat calvaria. J Cell Biol 123:921\u2013933. \n                    https:\/\/doi.org\/10.1083\/jcb.123.4.921","journal-title":"J Cell Biol"},{"key":"4153_CR32","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/S8756-3282(98)00056-8","volume":"22","author":"T Onishi","year":"1998","unstructured":"Onishi T, Ishidou Y, Nagamine T, Yone K, Imamura T, Kato M et al (1998) Distinct and overlapping patterns of localization of bone morphogenetic protein (BMP) family members and a BMP type II receptor during fracture healing in rats. Bone 22:605\u2013612. \n                    https:\/\/doi.org\/10.1016\/S8756-3282(98)00056-8","journal-title":"Bone"},{"key":"4153_CR33","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1002\/jbmr.3190","volume":"32","author":"M Dejaeger","year":"2017","unstructured":"Dejaeger M, B\u00f6hm AM, Dirckx N, Devriese J, Nefyodova E, Cardoen R, St-Arnaud R, Tournoy J, Luyten FP, Maes C (2017) Integrin-linked kinase regulates bone formation by controlling cytoskeletal organization and modulating BMP and Wnt signaling in Osteoprogenitors. J Bone Miner Res 32:2087\u20132102. \n                    https:\/\/doi.org\/10.1002\/jbmr.3190","journal-title":"J Bone Miner Res"},{"key":"4153_CR34","doi-asserted-by":"publisher","first-page":"3620","DOI":"10.1111\/bph.12724","volume":"171","author":"IH Ali","year":"2014","unstructured":"Ali IH, Brazil DP (2014) Bone morphogenetic proteins and their antagonists: current and emerging clinical uses. Br J Pharmacol 171:3620\u20133632. \n                    https:\/\/doi.org\/10.1111\/bph.12724","journal-title":"Br J Pharmacol"},{"key":"4153_CR35","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/S8756-3282(03)00191-1","volume":"33","author":"P Kloen","year":"2003","unstructured":"Kloen P, Di PM, Borens O, Richmond J, Perino G, Helfet DL, Goumans MJ (2003) BMP signaling components are expressed in human fracture callus. Bone 33:362\u2013371. \n                    https:\/\/doi.org\/10.1016\/S8756-3282(03)00191-1","journal-title":"Bone"},{"key":"4153_CR36","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s00264-008-0691-z","volume":"33","author":"FN Kwong","year":"2009","unstructured":"Kwong FN, Hoyland JA, Evans CH, Freemont AJ (2009) Regional and cellular localisation of BMPs and their inhibitors\u2019 expression in human fractures. Int Orthop 33:281\u2013288. \n                    https:\/\/doi.org\/10.1007\/s00264-008-0691-z","journal-title":"Int Orthop"},{"key":"4153_CR37","doi-asserted-by":"publisher","first-page":"26450","DOI":"10.1074\/jbc.M703282200","volume":"282","author":"DC Wan","year":"2007","unstructured":"Wan DC, Pomerantz JH, Brunet LJ, Kim JB, Chou YF, Wu BM et al (2007) Noggin suppression enhances in vitro osteogenesis and accelerates in vivo bone formation. J Biol Chem 282:26450\u201326459. \n                    https:\/\/doi.org\/10.1074\/jbc.M703282200","journal-title":"J Biol Chem"},{"key":"4153_CR38","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1097\/01.bot.0000177108.38461.9c","volume":"19","author":"A Chhabra","year":"2005","unstructured":"Chhabra A, Zijerdi D, Zhang J, Kline A, Balian G, Hurwitz S (2005) BMP-14 deficiency inhibits long bone fracture healing: a biochemical, histologic, and radiographic assessment. J Orthop Trauma 19:629\u2013634. \n                    https:\/\/doi.org\/10.1097\/01.bot.0000177108.38461.9c","journal-title":"J Orthop Trauma"},{"key":"4153_CR39","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1002\/jor.20182","volume":"24","author":"T Niikura","year":"2006","unstructured":"Niikura T, Hak DJ, Reddi AH (2006) Global gene profiling reveals a downregulation of BMP gene expression in experimental atrophic nonunions compared to standard healing fractures. J Orthop Res 24:1463\u20131471. \n                    https:\/\/doi.org\/10.1002\/jor.20182","journal-title":"J Orthop Res"},{"key":"4153_CR40","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1002\/jor.20794","volume":"27","author":"FN Kwong","year":"2009","unstructured":"Kwong FN, Hoyland JA, Freemont AJ, Evans CH (2009) Altered relative expression of BMPs and BMP inhibitors in cartilaginous areas of human fractures progressing towards nonunion. J Orthop Res 27:752\u2013757. \n                    https:\/\/doi.org\/10.1002\/jor.20794","journal-title":"J Orthop Res"},{"key":"4153_CR41","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.bone.2012.03.032","volume":"51","author":"P Kloen","year":"2012","unstructured":"Kloen P, Lauzier D, Hamdy RC (2012) Co-expression of BMPs and BMP-inhibitors in human fractures and non-unions. Bone 51:59\u201368. \n                    https:\/\/doi.org\/10.1016\/j.bone.2012.03.032","journal-title":"Bone"},{"key":"4153_CR42","doi-asserted-by":"publisher","first-page":"890","DOI":"10.7326\/0003-4819-158-12-201306180-00006","volume":"158","author":"R Fu","year":"2013","unstructured":"Fu R, Selph S, McDonagh M, Peterson K, Tiwari A, Chou R et al (2013) Effectiveness and harms of recombinant human bone morphogenetic protein-2 in spine fusion: a systematic review and meta-analysis. Ann Intern Med 158:890\u2013902. \n                    https:\/\/doi.org\/10.7326\/0003-4819-158-12-201306180-00006","journal-title":"Ann Intern Med"},{"key":"4153_CR43","doi-asserted-by":"publisher","first-page":"877","DOI":"10.7326\/0003-4819-158-12-201306180-00005","volume":"158","author":"MC Simmonds","year":"2013","unstructured":"Simmonds MC, Brown JV, Heirs MK, Higgins JP, Mannion RJ, Rodgers MA et al (2013) Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data. Ann Intern Med 158:877\u2013889. \n                    https:\/\/doi.org\/10.7326\/0003-4819-158-12-201306180-00005","journal-title":"Ann Intern Med"},{"key":"4153_CR44","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.2106\/00004623-200212000-00001","volume":"84-A","author":"S Govender","year":"2002","unstructured":"Govender S, Csimma C, Genant HK, Valentin-Opran A, Amit Y, Arbel R et al (2002) Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am 84-A:2123\u20132134. \n                    https:\/\/doi.org\/10.2106\/00004623-200212000-00001","journal-title":"J Bone Joint Surg Am"},{"issue":"Suppl 1","key":"4153_CR45","doi-asserted-by":"publisher","first-page":"S151","DOI":"10.2106\/00004623-200100002-00010","volume":"83-A","author":"GE Friedlaender","year":"2001","unstructured":"Friedlaender GE, Perry CR, Cole JD, Cook SD, Cierny G, Muschler GF et al (2001) Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am 83-A(Suppl 1):S151\u2013S158. \n                    https:\/\/doi.org\/10.2106\/00004623-200100002-00010","journal-title":"J Bone Joint Surg Am"},{"key":"4153_CR46","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/978-3-319-47507-3_8","volume-title":"Bone morphogenetic proteins: systems biology regulators","author":"PV Giannoudis","year":"2017","unstructured":"Giannoudis PV, Kanakaris NK (2017) BMPs in orthopaedic medicine: promises and challenges. In: Vukicevic S, Sampath TK (eds) Bone morphogenetic proteins: systems biology regulators, 1st edn. Springer International Publishing AG, Switzerland, pp 187\u2013214","edition":"1"},{"key":"4153_CR47","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/s002640100262","volume":"25","author":"M Pecina","year":"2001","unstructured":"Pecina M, Giltaij LR, Vukicevic S (2001) Orthopaedic applications of osteogenic protein-1 (BMP-7). Int Orthop 25:203\u2013208. \n                    https:\/\/doi.org\/10.1007\/s002640100262","journal-title":"Int Orthop"},{"key":"4153_CR48","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1007\/s00264-003-0475-4","volume":"27","author":"M Pecina","year":"2003","unstructured":"Pecina M, Haspl M, Jelic M, Vukicevic S (2003) Repair of a resistant tibial non-union with a recombinant bone morphogenetic protein-7 (rhBMP-7). Int Orthop 27:320\u2013321. \n                    https:\/\/doi.org\/10.1007\/s00264-003-0475-4","journal-title":"Int Orthop"},{"key":"4153_CR49","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1007\/s00264-005-0045-z","volume":"30","author":"R Bilic","year":"2006","unstructured":"Bilic R, Simic P, Jelic M, Stern-Padovan R, Dodig D, van Meerdervoort HP et al (2006) Osteogenic protein-1 (BMP-7) accelerates healing of scaphoid non-union with proximal pole sclerosis. Int Orthop 30:128\u2013134. \n                    https:\/\/doi.org\/10.1007\/s00264-005-0045-z","journal-title":"Int Orthop"},{"key":"4153_CR50","doi-asserted-by":"publisher","first-page":"3239","DOI":"10.1007\/s11999-009-0846-2","volume":"467","author":"PV Giannoudis","year":"2009","unstructured":"Giannoudis PV, Kanakaris NK, Dimitriou R, Gill I, Kolimarala V, Montgomery RJ (2009) The synergistic effect of autograft and BMP-7 in the treatment of atrophic nonunions. Clin Orthop Relat Res 467:3239\u20133248. \n                    https:\/\/doi.org\/10.1007\/s11999-009-0846-2","journal-title":"Clin Orthop Relat Res"},{"key":"4153_CR51","first-page":"567","volume":"38","author":"CH Crawford III","year":"2009","unstructured":"Crawford CH III, Seligson D (2009) Atrophic nonunion of humeral diaphysis treated with locking plate and recombinant bone morphogenetic protein: nine cases. Am J Orthop (Belle Mead NJ) 38:567\u2013570","journal-title":"Am J Orthop (Belle Mead NJ)"},{"key":"4153_CR52","doi-asserted-by":"publisher","first-page":"2339","DOI":"10.1007\/s00264-016-3262-8","volume":"40","author":"C R\u00fcden von","year":"2016","unstructured":"von R\u00fcden C, Morgenstern M, Friederichs J, Augat P, Hackl S, Woltmann A, B\u00fchren V, Hierholzer C (2016) Comparative study suggests that human bone morphogenetic proteins have no influence on the outcome of operative treatment of aseptic clavicle non-unions. Int Orthop 40:2339\u20132345. \n                    https:\/\/doi.org\/10.1007\/s00264-016-3262-8","journal-title":"Int Orthop"},{"key":"4153_CR53","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1007\/s00264-014-2534-4","volume":"38","author":"A Courvoisier","year":"2014","unstructured":"Courvoisier A, Sailhan F, Laffen\u00eatre O, Obert L, French Study Group of BMP in Orthopedic Surgery (2014) Bone morphogenetic protein and orthopaedic surgery: can we legitimate its off-label use? Int Orthop 38:2601\u20132605. \n                    https:\/\/doi.org\/10.1007\/s00264-014-2534-4","journal-title":"Int Orthop"},{"key":"4153_CR54","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.1007\/s00264-016-3149-8","volume":"40","author":"A Faundez","year":"2016","unstructured":"Faundez A, Tournier C, Garcia M, Aunoble S, Le Huec JC (2016) Bone morphogenetic protein use in spine surgery-complications and outcomes: a systematic review. Int Orthop 40:1309\u20131319. \n                    https:\/\/doi.org\/10.1007\/s00264-016-3149-8","journal-title":"Int Orthop"},{"key":"4153_CR55","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1001\/jama.2009.956","volume":"302","author":"KS Cahill","year":"2009","unstructured":"Cahill KS, Chi JH, Day A, Claus EB (2009) Prevalence, complications, and hospital charges associated with use of bone-morphogenetic proteins in spinal fusion procedures. JAMA 302:58\u201366. \n                    https:\/\/doi.org\/10.1001\/jama.2009.956","journal-title":"JAMA"},{"key":"4153_CR56","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1007\/s005860050210","volume":"8","author":"M Laursen","year":"1999","unstructured":"Laursen M, H\u00f8y K, Hansen ES, Gelineck J, Christensen FB, B\u00fcnger CE (1999) Recombinant bone morphogenetic protein-7 as an intracorporal bone growth stimulator in unstable thoracolumbar burst fractures in humans: preliminary results. Eur Spine J 8:485\u2013490","journal-title":"Eur Spine J"},{"key":"4153_CR57","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/978-3-319-47507-3_11","volume-title":"Bone morphogenetic proteins: systems biology regulators","author":"UME Wikesj\u00f6","year":"2017","unstructured":"Wikesj\u00f6 UME, Susin C (2017) BMPs in dental medicine: promises and challenges. In: Vukicevic S, Sampath TK (eds) Bone morphogenetic proteins: systems biology regulators, 1st edn. Springer International Publishing AG, Switzerland, pp 249\u2013270","edition":"1"},{"key":"4153_CR58","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1902\/jop.2005.76.4.605","volume":"76","author":"JP Fiorellini","year":"2005","unstructured":"Fiorellini JP, Howell TH, Cochran D, Malmquist J, Lilly LC, Spagnoli D et al (2005) Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation. J Periodontol 76:605\u2013613. \n                    https:\/\/doi.org\/10.1902\/jop.2005.76.4.605","journal-title":"J Periodontol"},{"key":"4153_CR59","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1016\/j.joms.2009.04.085","volume":"67","author":"RG Triplett","year":"2009","unstructured":"Triplett RG, Nevins M, Marx RE, Spagnoli DB, Oates TW, Moy PK et al (2009) Pivotal, randomized, parallel evaluation of recombinant human bone morphogenetic protein-2\/absorbable collagen sponge and autogenous bone graft for maxillary sinus floor augmentation. J Oral Maxillofac Surg 67:1947\u20131960. \n                    https:\/\/doi.org\/10.1016\/j.joms.2009.04.085","journal-title":"J Oral Maxillofac Surg"},{"key":"4153_CR60","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1001\/jamafacial.2013.650","volume":"15","author":"SC Desai","year":"2013","unstructured":"Desai SC, Sclaroff A, Nussenbaum B (2013) Use of recombinant human bone morphogenetic protein 2 for mandible reconstruction. JAMA Facial Plast Surg 15:204\u2013209. \n                    https:\/\/doi.org\/10.1001\/jamafacial.2013.650","journal-title":"JAMA Facial Plast Surg"},{"key":"4153_CR61","first-page":"67","volume":"74","author":"CM Clokie","year":"2008","unstructured":"Clokie CM, Sandor GK (2008) Reconstruction of 10 major mandibular defects using bioimplants containing BMP-7. J Can Dent Assoc 74:67\u201372","journal-title":"J Can Dent Assoc"},{"issue":"Suppl 2","key":"4153_CR62","doi-asserted-by":"publisher","first-page":"S73","DOI":"10.1016\/S0020-1383(08)70018-4","volume":"39","author":"I Ekrol","year":"2008","unstructured":"Ekrol I, Hajducka C, Court-Brown C, McQueen MM (2008) A comparison of rhBMP-7 (OP-1) and autogenous graft for metaphyseal defects after osteotomy of the distal radius. Injury 39(Suppl 2):S73\u2013S82. \n                    https:\/\/doi.org\/10.1016\/S0020-1383(08)70018-4","journal-title":"Injury"},{"key":"4153_CR63","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1007\/s00264-014-2425-8","volume":"38","author":"I Dumic-Cule","year":"2014","unstructured":"Dumic-Cule I, Brkljacic J, Rogic D, Bordukalo-Niksic T, Tikvica Luetic A, Draca N et al (2014) Systemically available bone morphogenetic protein two and seven affect bone metabolism. Int Orthop 38:1979\u20131985. \n                    https:\/\/doi.org\/10.1007\/s00264-014-2425-8","journal-title":"Int Orthop"},{"key":"4153_CR64","doi-asserted-by":"publisher","first-page":"E277","DOI":"10.1097\/01.brs.0000216442.12092.01","volume":"31","author":"BB Pradhan","year":"2006","unstructured":"Pradhan BB, Bae HW, Dawson EG, Patel VV, Delamarter RB (2006) Graft resorption with the use of bone morphogenetic protein: lessons from anterior lumbar interbody fusion using femoral ring allografts and recombinant human bone morphogenetic protein-2. Spine (Phila Pa 1976) 31:E277\u2013E284. \n                    https:\/\/doi.org\/10.1097\/01.brs.0000216442.12092.01","journal-title":"Spine (Phila Pa 1976)"},{"key":"4153_CR65","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1007\/s00264-017-3471-9","volume":"41","author":"GS Krishnakumar","year":"2017","unstructured":"Krishnakumar GS, Roffi A, Reale D, Kon E, Filardo G (2017) Clinical application of bone morphogenetic proteins for bone healing: a systematic review. Int Orthop 41:1073\u20131083. \n                    https:\/\/doi.org\/10.1007\/s00264-017-3471-9","journal-title":"Int Orthop"},{"key":"4153_CR66","doi-asserted-by":"publisher","first-page":"2415","DOI":"10.1007\/s00264-017-3550-y","volume":"41","author":"S Vukicevic","year":"2017","unstructured":"Vukicevic S, Grgurevic L, Pecina M (2017) Clinical need for bone morphogenetic proteins. Int Orthop 41:2415\u20132416. \n                    https:\/\/doi.org\/10.1007\/s00264-017-3550-y","journal-title":"Int Orthop"},{"key":"4153_CR67","doi-asserted-by":"publisher","first-page":"12169","DOI":"10.1074\/jbc.M109.087197","volume":"285","author":"K Song","year":"2010","unstructured":"Song K, Krause C, Shi S, Patterson M, Suto R, Grgurevic L et al (2010) Identification of a key residue mediating bone morphogenetic protein (BMP)-6 resistance to noggin inhibition allows for engineered BMPs with superior agonist activity. J Biol Chem 285:12169\u201312180. \n                    https:\/\/doi.org\/10.1074\/jbc.M109.087197","journal-title":"J Biol Chem"}],"container-title":["International Orthopaedics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00264-018-4153-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00264-018-4153-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00264-018-4153-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,14]],"date-time":"2019-09-14T19:07:18Z","timestamp":1568488038000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00264-018-4153-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,15]]},"references-count":67,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["4153"],"URL":"https:\/\/doi.org\/10.1007\/s00264-018-4153-y","relation":{},"ISSN":["0341-2695","1432-5195"],"issn-type":[{"value":"0341-2695","type":"print"},{"value":"1432-5195","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,15]]},"assertion":[{"value":"5 September 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 September 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"IDC, LK, and Marko Pecina declare no conflict of interest. Mihaela Peric is employed by School of Medicine, University of Zagreb and is actively involved in OSTEOproSPINE program and clinical testing in patients with posterolateral spinal fusion. LG is employed by School of Medicine, University of Zagreb and actively leads the development of the final Osteogrow drug product in patients with distal radius fracture, high tibial osteotomy, and lumbar back pain. SV is employed by School of Medicine, University of Zagreb and is founder of Genera Research, a Croatian biotechnology company conducting clinical trials with Osteogrow.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}