Bone substitutes in the Netherlands - a systematic literature review.

Autologous bone grafting is currently considered as the gold standard to restore bone defects. However, clinical benefit is not guaranteed and there is an associated 8-39% complication rate. This has resulted in the development of alternative (synthetic) bone substitutes. The aim of this systematic literature review was to provide a comprehensive overview of literature data of bone substitutes registered in the Netherlands for use in trauma and orthopedic surgery. Brand names of selected products were used as search terms in three available databases: Embase, PubMed and Cochrane. Manuscripts written in English, German or Dutch that reported on structural, biological or biomechanical properties of the pure product or on its use in trauma and orthopedic surgery were included. The primary search resulted in 475 manuscripts from PubMed, 653 from Embase and 10 from Cochrane. Of these, 218 met the final inclusion criteria. Of each product, structural, biological and biomechanical characteristics as well as their clinical indications in trauma and orthopedic surgery are provided. All included products possess osteoconductive properties but differ in resorption time and biomechanical properties. They have been used for a wide range of clinical applications; however, the overall level of clinical evidence is low. The requirements of an optimal bone substitute are related to the size and location of the defect. Calcium phosphate grafts have been used for most trauma and orthopedic surgery procedures. Calcium sulphates were mainly used to restore bone defects after tumour resection surgery but offer minimal structural support. Bioactive glass remains a potential alternative; however, its use has only been studied to a limited extent.

[1]  S. Galandiuk,et al.  Systematic reviews and meta‐analysis for the surgeon scientist , 2006, The British journal of surgery.

[2]  K. Adalberth,et al.  Norian SRS Versus Functional Treatment in Redisplaced Distal Radial Fractures: A Randomized Study in 20 Patients , 2002, Journal of hand surgery.

[3]  T A Einhorn,et al.  Enhancement of fracture-healing. , 1995, The Journal of bone and joint surgery. American volume.

[4]  S. Tröster,et al.  [Hydroxyapatite ceramics in clinical application. Histological findings in 23 patients]. , 1997, European Journal of Trauma.

[5]  S. Jansen-Varnum,et al.  In vitro evaluation of orthopedic composite cytotoxicity: assessing the potential for postsurgical production of hydroxyl radicals. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[6]  J. Andrew,et al.  Controlled Trial of Distal Radial Fractures Treated with a Resorbable Bone Mineral Substitute , 2002, Journal of hand surgery.

[7]  T. Steffen,et al.  Porous tricalcium phosphate and transforming growth factor used for anterior spine surgery , 2001, European Spine Journal.

[8]  H. Kock,et al.  Augmentation von Wirbelkörperfrakturen mit einem neuen Calciumphosphat-Zement nach Ballon-Kyphoplastie , 2004, Der Orthopäde.

[9]  J. Wiltfang,et al.  Ectopic bone formation with the help of growth factor bFGF. , 1996, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[10]  Arun K Gosain,et al.  A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: part I. , 2002, Plastic and reconstructive surgery.

[11]  J. Jansen,et al.  Biocompatibility and degradation of poly(DL-lactic-co-glycolic acid)/calcium phosphate cement composites. , 2005, Journal of biomedical materials research. Part A.

[12]  N. Wachter,et al.  First histological observations on the incorporation of a novel calcium phosphate bone substitute material in human cancellous bone. , 2001, Journal of biomedical materials research.

[13]  R. Schnettler,et al.  Defect filling with demineralized bone matrix. , 1998, Der Orthopäde.

[14]  L. Ryd,et al.  Radiostereometric analysis of distal radial fracture displacement during treatment: A randomized study comparing Norian SRS and external fixation in 23 patients , 2001, Acta orthopaedica Scandinavica.

[15]  K. Bachus,et al.  Biological effects of calcium sulfate as a bone graft substitute in ovine metaphyseal defects. , 2006, Journal of biomedical materials research. Part A.

[16]  G. Gualtieri,et al.  Comparison of a new bisphenol-a-glycidyl dimethacrylate-based cortical bone void filler with polymethyl methacrylate , 2001, European Spine Journal.

[17]  M. Reinhold,et al.  Successful posterior interlaminar fusion at the thoracic spine by sole use of β-tricalcium phosphate , 2006, Archives of Orthopaedic and Trauma Surgery.

[18]  X. Zhang,et al.  Osseous substance formation induced in porous calcium phosphate ceramics in soft tissues. , 1994, Biomaterials.

[19]  W. Bonfield,et al.  Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes. , 2004, Journal of biomedical materials research. Part A.

[20]  P. Mattsson,et al.  The Effect of Augmentation With Resorbable or Conventional Bone Cement on the Holding Strength for Femoral Neck Fracture Devices , 2002, Journal of orthopaedic trauma.

[21]  Arun K Gosain,et al.  A 1-year study of osteoinduction in hydroxyapatite-derived biomaterials in an adult sheep model: part II. Bioengineering implants to optimize bone replacement in reconstruction of cranial defects. , 2004, Plastic and reconstructive surgery.

[22]  M. Gschwentner,et al.  Injectable calcium phosphate bone cement Norian SRS for the treatment of intra-articular compression fractures of the distal radius in osteoporotic women , 2003, Archives of Orthopaedic and Trauma Surgery.

[23]  J. Hegeman,et al.  Augmented pin fixation with Cortoss® for an unstable AO-A3 type distal radius fracture in a patient with a manifest osteoporosis , 2008, Archives of Orthopaedic and Trauma Surgery.

[24]  A G Mikos,et al.  Injectable PLGA microsphere/calcium phosphate cements: physical properties and degradation characteristics , 2006, Journal of biomaterials science. Polymer edition.

[25]  S. Wolfe,et al.  Augmentation of distal radius fracture fixation with coralline hydroxyapatite bone graft substitute. , 1999, The Journal of hand surgery.

[26]  Arun K Gosain,et al.  A 1-Year Study of Hydroxyapatite-Derived Biomaterials in an Adult Sheep Model: III. Comparison with Autogenous Bone Graft for Facial Augmentation , 2005, Plastic and reconstructive surgery.

[27]  D. Forrester,et al.  The Use of Calcium Sulfate in the Treatment of Benign Bone Lesions: A Preliminary Report , 2001, The Journal of bone and joint surgery. American volume.

[28]  Leung Kwok-Sui,et al.  Novel approach for quantification of porosity for biomaterial implants using microcomputed tomography (microCT). , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

[29]  O. Clarkin,et al.  Comparison of failure mechanisms for cements used in skeletal luting applications , 2009, Journal of materials science. Materials in medicine.

[30]  J. Sandbank,et al.  Inflammatory reactions associated with a calcium sulfate bone substitute. , 1999, Annals of transplantation.

[31]  L L Hench,et al.  Direct chemical bond of bioactive glass-ceramic materials to bone and muscle. , 1973, Journal of biomedical materials research.

[32]  D. Thordarson,et al.  Ingrowth of bone into absorbable bone cement: an in vivo microscopic evaluation. , 2003, American journal of orthopedics.

[33]  E. Panagiotopoulos,et al.  Use of injectable calcium phosphate in the treatment of intra-articular distal radius fractures. , 2002, Orthopedics.

[34]  H. Kock,et al.  [Balloon kyphoplasty of vertebral compression fractures with a new calcium phosphate cement]. , 2004, Der Orthopade.

[35]  A. Reisner,et al.  Hydroxyapatite Cement in Craniofacial Reconstruction: Experience in 150 Patients , 2006, Plastic and reconstructive surgery.

[36]  K. Hing Bone repair in the twenty–first century: biology, chemistry or engineering? , 2004, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[37]  S F Hulbert,et al.  Potential of ceramic materials as permanently implantable skeletal prostheses. , 1970, Journal of biomedical materials research.

[38]  W. Bonfield,et al.  Biomechanical assessment of bone ingrowth in porous hydroxyapatite , 1997, Journal of materials science. Materials in medicine.

[39]  P. Aspenberg,et al.  Injectable Calcium Phosphate in the Treatment of Distal Radial Fractures , 1996, Journal of hand surgery.

[40]  M. U. Helber,et al.  [Metaphyseal defect substitute: hydroxylapatite ceramic. Results of a 3 to 4 year follow up]. , 2000, Der Unfallchirurg.

[41]  U. Ripamonti,et al.  Bone Differentiation in Porous Hydroxyapatite in Baboons Is Regulated by the Geometry of the Substratum: Implications for Reconstructive Craniofacial Surgery , 1994, Plastic and reconstructive surgery.

[42]  Richard E. Buckley,et al.  Benign Calcaneal Bone Cyst and Pathologic Fracture—Surgical Treatment with Injectable Calcium-Phosphate Bone Cement (Norian®): A Case Report , 2001, Foot & ankle international.

[43]  A. Wymenga,et al.  Tricalcium phosphate granules or rigid wedge preforms in open wedge high tibial osteotomy: a radiological study with a new evaluation system. , 2004, The Knee.

[44]  J. Hollinger,et al.  Bone healing response to an injectable calcium phosphate cement with enhanced radiopacity. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[45]  Eleftherios Tsiridis,et al.  Bone substitutes: an update. , 2005, Injury.

[46]  E. Scarano,et al.  Balloon kyphoplasty in traumatic fractures of the thoracolumbar junction. Preliminary experience in 12 cases. , 2005, Journal of neurosurgical sciences.

[47]  N. Sharkey,et al.  Bone ingrowth and mechanical properties of coralline hydroxyapatite 1 yr after implantation. , 1993, Biomaterials.

[48]  Banwart Jc,et al.  Iliac crest bone graft harvest donor site morbidity. A statistical evaluation. , 1995 .

[49]  Li-Chun Lin,et al.  Evaluation of Bone Growth Using Artificial Bone Substitute (Osteoset®) and Platelet Gel Mixtures: A Preliminarily Study in Dogs , 2009, Artificial cells, blood substitutes, and immobilization biotechnology.

[50]  M. Amling,et al.  [Mechanical failure of porous hydroxyapatite ceramics 7.5 years after implantation in the proximal tibial]. , 2004, Der Unfallchirurg.

[51]  F. Bakker,et al.  Properties of calcium phosphate ceramics in relation to their in vivo behavior. , 2000, The Journal of trauma.

[52]  C. Kelly,et al.  Treatment of benign bone lesions with an injectable calcium sulfate-based bone graft substitute. , 2004, Orthopedics.

[53]  K. Donath,et al.  Reactions and complications after the implantation of Endobon including morphological examination of explants , 1999, Archives of Orthopaedic and Trauma Surgery.

[54]  S. Goldstein,et al.  Hip screw augmentation with an in situ-setting calcium phosphate cement: an in vitro biomechanical analysis. , 1997, Journal of orthopaedic trauma.

[55]  J. van den Dolder,et al.  The cytocompatibility and early osteogenic characteristics of an injectable calcium phosphate cement. , 2006, Tissue engineering.

[56]  M. Bohner,et al.  Assessment of the suitability of a new brushite calcium phosphate cement for cranioplasty - an experimental study in sheep. , 2005, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[57]  Harner Cf,et al.  Evaluation of collagen ceramic composite graft materials in a spinal fusion model. , 1997 .

[58]  A. Patyk,et al.  Einfluss unterschiedlicher Anrührflüssigkeiten auf die mechanischen und mikromorphologischen In-vitro-Eigenschaften von Hydroxylapatitzement , 2005, Mund-, Kiefer- und Gesichtschirurgie.

[59]  E. Schneider,et al.  Resorption patterns of calcium-phosphate cements in bone. , 2003, Journal of biomedical materials research. Part A.

[60]  Chikara Ohtsuki,et al.  Bioactive ceramic-based materials with designed reactivity for bone tissue regeneration , 2009, Journal of The Royal Society Interface.

[61]  Marc A. Asher,et al.  Iliac Crest Bone Graft Harvest Donor Site Morbidity: A Statistical Evaluation , 1995, Spine.

[62]  O. Clarkin,et al.  Comparison of an experimental bone cement with surgical Simplex® P, Spineplex® and Cortoss® , 2008, Journal of materials science. Materials in medicine.

[63]  K. Dickson,et al.  The use of BoneSource hydroxyapatite cement for traumatic metaphyseal bone void filling. , 2002, The Journal of trauma.

[64]  F. Bakker,et al.  Bone morphogenetic proteins. Development and clinical efficacy in the treatment of fractures and bone defects. , 2005, The Journal of bone and joint surgery. American volume.

[65]  I. Berger,et al.  Evaluation of a novel nanocrystalline hydroxyapatite paste and a solid hydroxyapatite ceramic for the treatment of critical size bone defects (CSD) in rabbits , 2008, Journal of materials science. Materials in medicine.

[66]  H. Parvataneni,et al.  Bone grafting for spinal fusion. , 1999, The Orthopedic clinics of North America.

[67]  H. Tscherne,et al.  Use of an Injectable Calcium Phosphate Bone Cement in the Treatment of Tibial Plateau Fractures: A Prospective Study of Twenty-Six Cases With Twenty-Month Mean Follow-Up , 2002, Journal of orthopaedic trauma.

[68]  R. Reck Tissue reactions to glass ceramics in the middle ear. , 1981, Clinical otolaryngology and allied sciences.

[69]  William A. Pierce,et al.  In vitro strength comparison of hydroxyapatite cement and polymethylmethacrylate in subchondral defects in caprine femora , 1998, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[70]  Wuisman Pi,et al.  Bone transplantation and bone replacement materials , 1998 .

[71]  L. Munuera,et al.  Treatment of fractures of the distal radius with a remodellable bone cement: a prospective, randomised study using Norian SRS. , 2000, The Journal of bone and joint surgery. British volume.

[72]  R. Moreira,et al.  Histological and histomorphometric analyses of calcium phosphate cement in rabbit calvaria. , 2008, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[73]  Sergey V. Dorozhkin,et al.  Bioceramics of calcium orthophosphates. , 2010, Biomaterials.

[74]  J. Jansen,et al.  Histological evaluation of the bone response to calcium phosphate cement implanted in cortical bone. , 2003, Biomaterials.

[75]  A. Gangi,et al.  Clinical results of an open prospective study of a bis-GMA composite in percutaneous vertebral augmentation , 2005, European Spine Journal.

[76]  M. Asselmeier,et al.  A review of allograft processing and sterilization techniques and their role in transmission of the human immunodeficiency virus , 1993, The American journal of sports medicine.

[77]  Y. An,et al.  A comparison of ProOsteon, DBX, and collagraft in a rabbit model. , 2006, Journal of biomedical materials research. Part B, Applied biomaterials.

[78]  H. Kock,et al.  Verwendung von nanokristallinem Hydroxyapatit (Ostim®) bei der Versorgung von Radiusfrakturen , 2008, Zentralblatt fur Chirurgie.

[79]  J. Planell,et al.  Effects of novel calcium phosphate cements on human bone marrow fibroblastic cells. , 1998, Tissue engineering.

[80]  L. Mathieu,et al.  Augmentation of bone defect healing using a new biocomposite scaffold: an in vivo study in sheep. , 2010, Acta biomaterialia.

[81]  A. Ladd,et al.  Repair of five distal radius fractures with an investigational cancellous bone cement: a preliminary report. , 1997, Journal of orthopaedic trauma.

[82]  R. Leemans,et al.  An injectable calcium phosphate cement as a bone-graft substitute in the treatment of displaced lateral tibial plateau fractures. , 2003, Injury.

[83]  H. Burchardt The biology of bone graft repair. , 1983, Clinical orthopaedics and related research.

[84]  H. Lill,et al.  Tibiakopfplateaufrakturen – Erste Erfahrungen mit einem resorbierbaren Knochenzement zur Augmentation , 2003, Der Unfallchirurg.

[85]  A. Ladd,et al.  Norian SRS cement compared with conventional fixation in distal radial fractures. A randomized study. , 2003, The Journal of bone and joint surgery. American volume.

[86]  R. Dauskardt,et al.  Mechanical properties of carbonated apatite bone mineral substitute: strength, fracture and fatigue behaviour , 1997, Journal of materials science. Materials in medicine.

[87]  C. Frei,et al.  Untersuchungen über den klinischen Einsatz von Brushite- und Hydroxylapatit-Zement beim Schaf , 2005 .

[88]  H. Feifel [Bone regeneration in Pro Osteon 500 alone and in combination with Colloss in the patellar gliding model of the rabbit]. , 2000, Mund-, Kiefer- und Gesichtschirurgie : MKG.

[89]  R. Page,et al.  Severely impacted valgus proximal humeral fractures. Results of operative treatment. , 2003, The Journal of bone and joint surgery. American volume.

[90]  N. Haas,et al.  Osseous integration of hydroxyapatite grafts in metaphyseal bone defects of the proximal tibia (CT-study). , 2002, Acta chirurgiae orthopaedicae et traumatologiae Cechoslovaca.

[91]  P. Giannoudis,et al.  BMPs: Options, Indications, and Effectiveness , 2010, Journal of orthopaedic trauma.

[92]  S. Stevenson,et al.  The response to bone allografts. , 1992, The Journal of bone and joint surgery. American volume.

[93]  M. Beuerlein,et al.  Calcium Sulfates: What Is the Evidence? , 2010, Journal of orthopaedic trauma.

[94]  D. Lew,et al.  Short-Term Bone Responses to Hydroxyapatite Cement , 2002, Implant dentistry.

[95]  G. Michler,et al.  Nanocrystalline hydroxyapatite for bone repair: an animal study , 2010, Journal of materials science. Materials in medicine.

[96]  C. Friedman,et al.  Synthetic bone graft substitutes. , 1994, Otolaryngologic clinics of North America.

[97]  I Smith,et al.  Convulsions and Coma Associated with Iatrogenically Elevated CSF Calcium Levels Post Spinal Surgery: A Case Report. , 2005, Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine.

[98]  J. Rueger,et al.  Langzeitergebnisse nach Anwendung einer porösen Hydroxylapatitkeramik (Endobon) zur operativen Versorgung von Tibiakopffrakturen , 2002, Der Unfallchirurg.

[99]  P. Mattsson,et al.  Stability of Internally Fixed Femoral Neck Fractures Augmented with Resorbable Cement , 2003, Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society.

[100]  P. Patka,et al.  BOTTRANSPLANTATEN EN BOTVERVANGENDE MATERIALEN , 1998 .

[101]  T. Turner,et al.  Effects of altered crystalline structure and increased initial compressive strength of calcium sulfate bone graft substitute pellets on new bone formation. , 2004, Orthopedics.

[102]  M. Gelinsky,et al.  Proliferation and differentiation of osteoblasts on Biocement D modified with collagen type I and citric acid. , 2004, Journal of biomedical materials research. Part B, Applied biomaterials.

[103]  W. Bonfield,et al.  Quantification of bone ingrowth within bone-derived porous hydroxyapatite implants of varying density , 1999, Journal of materials science. Materials in medicine.

[104]  K. Marra,et al.  Calcium Aluminate, RGD-Modified Calcium Aluminate, and &bgr;-Tricalcium Phosphate Implants in a Calvarial Defect , 2009, The Journal of craniofacial surgery.

[105]  F. Melsen,et al.  Tissue reaction and material characteristics of four bone substitutes. , 1996, The International journal of oral & maxillofacial implants.

[106]  H.-P. Meinzer,et al.  Osseous integration of calcium phosphate in osteoporotic vertebral fractures after kyphoplasty: initial results from a clinical and experimental pilot study , 2006, Osteoporosis International.

[107]  P. Aspenberg,et al.  Norian SRS versus external fixation in redisplaced distal radial fractures. A randomized study in 40 patients. , 1999, Acta orthopaedica Scandinavica.

[108]  R. Legeros,et al.  Properties of osteoconductive biomaterials: calcium phosphates. , 2002, Clinical orthopaedics and related research.

[109]  W. Virkus,et al.  Functional outcomes of bone graft substitutes for benign bone tumors. , 2004, Orthopedics.

[110]  M Bohner,et al.  In vivo behavior of three different injectable hydraulic calcium phosphate cements. , 2004, Biomaterials.

[111]  H. Aro,et al.  Molecular Basis for Action of Bioactive Glasses as Bone Graft Substitute , 2006, Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society.

[112]  Wen‐Cheng Chen,et al.  In vivo testing of nanoparticle-treated TTCP/DCPA-based ceramic surfaces. , 2009, Acta biomaterialia.

[113]  A. Joist,et al.  The Use of an in situ Curing Hydroxyapatite Cement as an Alternative to Bone Graft Following Removal of Enchondroma of the Hand , 2000, Journal of hand surgery.

[114]  S. Evans,et al.  Bone cement or bone substitute augmentation of pedicle screws improves pullout strength in posterior spinal fixation , 2002, Journal of materials science. Materials in medicine.

[115]  A. Reinstorf,et al.  Influence of osteocalcin and collagen I on the mechanical and biological properties of Biocement D. , 2002, Biomolecular engineering.

[116]  R. Leighton,et al.  A Multicenter , Prospective , Randomized Study Phosphate Cement for Defect Augmentation in Tibial Plateau Comparison of Autogenous Bone Graft and Endothermic Calcium , 2008 .

[117]  H. Redl,et al.  Simultaneous in vivo comparison of bone substitutes in a guided bone regeneration model. , 2008, Biomaterials.

[118]  O. Clarkin,et al.  Comparison of an experimental bone cement with a commercial control, Hydroset™ , 2009, Journal of materials science. Materials in medicine.

[119]  G. Sándor,et al.  Closure of Critical Sized Defects With Allogenic and Alloplastic Bone Substitutes , 2002, The Journal of craniofacial surgery.

[120]  P. Buma,et al.  Mechanism of bone incorporation of beta-TCP bone substitute in open wedge tibial osteotomy in patients. , 2005, Biomaterials.

[121]  T. J. Cypher,et al.  Biological principles of bone graft healing. , 1996, The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons.

[122]  P. Zeman,et al.  [Long-term results of calcaneal fracture treatment by open reduction and internal fixation using a calcaneal locking compression plate from an extended lateral approach]. , 2008, Acta chirurgiae orthopaedicae et traumatologiae Cechoslovaca.

[123]  J. Koebke,et al.  Augmentation of intraarticular calcaneal fractures with injectable calcium phosphate cement: densitometry, histology, and functional outcome of 18 patients. , 2005, The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons.

[124]  Sabina Gheduzzi,et al.  Mechanical characterisation of three percutaneous vertebroplasty biomaterials , 2006, Journal of materials science. Materials in medicine.

[125]  O. Kilian,et al.  Enhancement of bone formation in hydroxyapatite implants by rhBMP-2 coating. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[126]  M. Bohner Physical and chemical aspects of calcium phosphates used in spinal surgery , 2001, European Spine Journal.

[127]  M. Libicher,et al.  Calcium-Phosphate and Polymethylmethacrylate Cement in Long-term Outcome After Kyphoplasty of Painful Osteoporotic Vertebral Fractures , 2008, Spine.

[128]  T. Turner,et al.  Healing of large defects treated with calcium sulfate pellets containing demineralized bone matrix particles. , 2003, Orthopedics.

[129]  M. Salai,et al.  Subtrochanteric femoral fractures due to simple bone cysts in children , 2006, Journal of pediatric orthopedics. Part B.

[130]  J. Watson The use of an injectable bone graft substitute in tibial metaphyseal fractures. , 2004, Orthopedics.

[131]  U. Gross,et al.  Madreporische Hydroxylapatitgranulate zur Füllung ossärer Defekte , 2001, Der Unfallchirurg.

[132]  G. Daculsi,et al.  Effect of the macroporosity for osseous substitution of calcium phosphate ceramics. , 1990, Biomaterials.

[133]  M. Urist,et al.  Bone: Formation by Autoinduction , 1965, Science.

[134]  C. Ulrich,et al.  Metaphysärer Defektersatz mit Hydrosylapatitkeramik 3- bis 4-Jahresnachuntersuchungs-Ergebnisse , 2000, Der Unfallchirurg.

[135]  Joseph A Buckwalter,et al.  Adverse reactions to OsteoSet bone graft substitute, the incidence in a consecutive series. , 2002, The Iowa orthopaedic journal.

[136]  W. Bonfield,et al.  Characterization of porous hydroxyapatite , 1999, Journal of materials science. Materials in medicine.

[137]  M Epple,et al.  A thorough physicochemical characterisation of 14 calcium phosphate-based bone substitution materials in comparison to natural bone. , 2004, Biomaterials.

[138]  J. Wiltfang,et al.  Bone regeneration in osseous defects using a resorbable nanoparticular hydroxyapatite. , 2005, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[139]  P. Kessler,et al.  Hydroxyapatite cement (BoneSource) for repair of critical sized calvarian defects--an experimental study. , 2003, Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery.

[140]  W. Walsh,et al.  Beta-TCP bone graft substitutes in a bilateral rabbit tibial defect model. , 2008, Biomaterials.

[141]  V. Alt,et al.  Calcium Phosphate-Based Bone Substitutes , 2004, European Journal of Trauma.

[142]  A. Jubel,et al.  [Use of the injectable bone cement Norian SRS for tibial plateau fractures. Results of a prospective 30-month follow-up study]. , 2004, Der Orthopade.

[143]  P. Mattsson,et al.  Unstable Trochanteric Fractures Augmented with Calcium Phosphate Cement , 2004, Scandinavian journal of surgery : SJS : official organ for the Finnish Surgical Society and the Scandinavian Surgical Society.

[144]  N. Gellrich,et al.  Comparative in vitro study of the proliferation and growth of human osteoblast-like cells on various biomaterials. , 2007, Journal of biomedical materials research. Part A.

[145]  S. Gitelis,et al.  The Treatment of Chronic Osteomyelitis with a Biodegradable Antibiotic-Impregnated Implant , 2002, Journal of orthopaedic surgery.

[146]  H. Kock,et al.  Open Reduction and Palmar Plate-Osteosynthesis in Combination with a Nanocrystalline Hydroxyapatite Spacer in the Treatment of Comminuted Fractures of the Distal Radius , 2006, Journal of hand surgery.

[147]  P. Mattsson,et al.  Resorbable cement for the augmentation of internally-fixed unstable trochanteric fractures. A prospective, randomised multicentre study. , 2005, The Journal of bone and joint surgery. British volume.

[148]  J. E. Jennings Arthroscopic management of tibial plateau fractures. , 1985, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[149]  C. Rossa,et al.  Cytotoxicity of two novel formulations of calcium phosphate cements: a comparative in vitro study. , 2003, Artificial organs.

[150]  A. Ekkernkamp,et al.  A new resorbable bone void filler in trauma: early clinical experience and histologic evaluation. , 2002, Orthopedics.

[151]  D. Wise,et al.  Bioresorbable bone graft substitutes of different osteoconductivities: a histologic evaluation of osteointegration of poly(propylene glycol-co-fumaric acid)-based cement implants in rats. , 2000, Biomaterials.

[152]  C. Kelly,et al.  The Use of a Surgical Grade Calcium Sulfate as a Bone Graft Substitute: Results of a Multicenter Trial , 2001, Clinical orthopaedics and related research.

[153]  A. Wee,et al.  Percutaneous Reduction and Injection of Norian Bone Cement for the Treatment of Displaced Intra-articular Calcaneal Fractures , 2009, Foot & ankle specialist.

[154]  R. Verheggen,et al.  Correction of Skull Defects Using Hydroxyapatite Cement (HAC) – Evidence Derived from Animal Experiments and Clinical Experience , 2001, Acta Neurochirurgica.

[155]  M. Bohner,et al.  [Investigation about the clinical use of brushite- and hydroxylapatite-cement in sheep]. , 2005, Schweizer Archiv fur Tierheilkunde.

[156]  J. Keating,et al.  Minimal internal fixation and calcium-phosphate cement in the treatment of fractures of the tibial plateau. A pilot study. , 2003, The Journal of bone and joint surgery. British volume.

[157]  T. Bauer,et al.  Histological evaluation of an impacted bone graft substitute composed of a combination of mineralized and demineralized allograft in a sheep vertebral bone defect. , 2007, Journal of biomedical materials research. Part A.

[158]  I. Berger,et al.  Void filling of tibia compression fracture zones using a novel resorbable nanocrystalline hydroxyapatite paste in combination with a hydroxyapatite ceramic core: first clinical results , 2006, Archives of Orthopaedic and Trauma Surgery.

[159]  X. Palazzi,et al.  Evaluation of a novel nanocrystalline hydroxyapatite paste Ostim® in comparison to Alpha-BSM® - more bone ingrowth inside the implanted material with Ostim® compared to Alpha BSM® , 2009, BMC musculoskeletal disorders.

[160]  Tae-Hong Lim,et al.  Vertebroplasty comparing injectable calcium phosphate cement compared with polymethylmethacrylate in a unique canine vertebral body large defect model. , 2008, The spine journal : official journal of the North American Spine Society.

[161]  Yuehuei H. An,et al.  Mechanical testing of bone and the bone-implant interface , 1999 .

[162]  Yu Bai,et al.  Treatment of tibial plateau fractures with high strength injectable calcium sulphate , 2009, International Orthopaedics.

[163]  D. P. O'brien,et al.  The safety and efficacy of vertebroplasty using Cortoss cement in a newly established vertebroplasty service , 2008, British journal of neurosurgery.

[164]  P. Aspenberg,et al.  Delayed surgery does not reduce the interface strength between the surface of a bone fracture and a self-curing injectable hydroxyapatite (Norian SRS). , 2001, Scandinavian journal of plastic and reconstructive surgery and hand surgery.

[165]  K. Becker,et al.  Osseous integration of bovine hydroxyapatite ceramic in metaphyseal bone defects of the distal radius. , 2000, The Journal of hand surgery.

[166]  S A Goldstein,et al.  Skeletal repair by in situ formation of the mineral phase of bone. , 1995, Science.

[167]  D. Thordarson,et al.  SRS Cancellous Bone Cement Augmentation of Calcaneal Fracture Fixation , 2005, Foot & ankle international.

[168]  J. Jansen,et al.  Trabecular bone response to injectable calcium phosphate (Ca-P) cement. , 2002, Journal of biomedical materials research.

[169]  R. Irwin,et al.  Coralline hydroxyapatite as bone substitute in orthopedic oncology. , 2001, American journal of orthopedics.

[170]  M. Zobitz,et al.  Subchondral defects in caprine femora augmented with in situ setting hydroxyapatite cement, polymethylmethacrylate, or autogenous bone graft: biomechanical and histomorphological analysis after two‐years , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[171]  Ivan Martin,et al.  Three-dimensional cell culture and tissue engineering in a T-CUP (tissue culture under perfusion). , 2007, Tissue engineering.

[172]  H. D. Sheets,et al.  Development of ceramic and ceramic composite devices for maxillofacial applications. , 1972, Journal of Biomedical Materials Research.

[173]  L. Plánka,et al.  ChronOS inject in children with benign bone lesions--does it increase the healing rate? , 2010, European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift fur Kinderchirurgie.

[174]  J. Planell,et al.  Effect of calcium carbonate on clinical compliance of apatitic calcium phosphate bone cement. , 1997, Journal of biomedical materials research.

[175]  H. Garg,et al.  The haemophilic pseudotumour – surgical treatment by excision and filling the defect with calcium‐phosphate cement granules , 2007, Haemophilia : the official journal of the World Federation of Hemophilia.

[176]  M. Clayer INJECTABLE FORM OF CALCIUM SULPHATE AS TREATMENT OF ANEURYSMAL BONE CYSTS , 2008, ANZ journal of surgery.

[177]  M. Jäger,et al.  Extensive H(+) release by bone substitutes affects biocompatibility in vitro testing. , 2006, Journal of biomedical materials research. Part A.

[178]  J. Thalgott,et al.  Anterior interbody fusion of the cervical spine with coralline hydroxyapatite. , 1999, Spine.

[179]  Yan Wang,et al.  Investigation of the histology and interfacial bonding between carbonated hydroxyapatite cement and bone , 2009, Biomedical materials.

[180]  T. Gotterbarm,et al.  The efficacy of Biobon™ and Ostim™ within metaphyseal defects using the Göttinger Minipig , 2009, Archives of Orthopaedic and Trauma Surgery.

[181]  J. Keating,et al.  Outcome of tibial plateau fractures managed with calcium phosphate cement. , 2004, Injury.

[182]  R. Jakob,et al.  Prospective study of standalone balloon kyphoplasty with calcium phosphate cement augmentation in traumatic fractures , 2007, European Spine Journal.

[183]  W. Baer,et al.  Spongy Hydroxyapatite in Hand Surgery – A Five Year Follow-Up , 2002, Journal of hand surgery.

[184]  M. Chapman,et al.  Morbidity at bone graft donor sites. , 1989, Journal of orthopaedic trauma.