title: Decreased extrusion of calcium phosphate cement versus high viscosity PMMA cement into spongious bone marrow-an ex vivo and in vivo study in sheep vertebrae.
abstract: Vertebroplasty or kyphoplasty of osteoporotic vertebral fractures bears the risk of pulmonary cement embolism (3.5%-23%) caused by leakage of commonly applied acrylic polymethylmethacrylate (PMMA) cement to spongious bone marrow or outside of the vertebrae. Ultraviscous cement and specific augmentation systems have been developed to reduce such adverse effects. Rapidly setting, resorbable, physiological calcium phosphate cement (CPC) may also represent a suitable alternative.
  
  
  
  This study aimed to compare the intravertebral extrusion of CPC and PMMA cement in an ex vivo and in vivo study in sheep.
  
  
  
  A prospective experimental animal study was carried out.
  
  
  
  Defects (diameter 5 mm; 15 mm depth) were created by a ventrolateral percutaneous approach in lumbar vertebrae of female Merino sheep (2-4 years) either ex vivo (n=17) or in vivo (n=6), and injected with: (1) CPC (L3); (2) CPC reinforced with 10% poly(l-lactide-co-glycolide) (PLGA) fibers (L4); or (3) PMMA cement (L5; Kyphon HV-R). Controls were untouched (L1) or empty defects (L2). The effects of the cement injections were assessed in vivo by blood gas analysis and ex vivo by computed tomography (CT), micro-CT (voxel size: 67 µm), histology, and biomechanical testing.
  
  
  
  Following ex vivo injection, micro-CT documented significantly increased extrusion of PMMA cement in comparison to CPC (+/- fibers) starting at a distance of 1 mm from the edge of the defect (confirmed by histology); this was also demonstrated by micro-CT following in vivo cement injection. In addition, blood gas analysis showed consistently significantly lower values for the fraction of oxygenized hemoglobin/total hemoglobin (FO2Hb) in the arterial blood until 25 minutes following injection of the PMMA cement (p ≤ .05 vs. CPC; 7, 15 minutes). Biomechanical testing following ex vivo injection showed significantly lower compressive strength and Young modulus than untouched controls for the empty defect (40% and 34% reduction, respectively) and all three cement-injected defects (21%-27% and 29%-32% reduction, respectively), without significant differences among the cements.
  
  
  
  Because of comparable compressive strength, but significantly lower cement extrusion into spongious bone marrow than PMMA cement, physiological CPC (+/- PLGA fibers) may represent an attractive alternative to PMMA for vertebroplasty or kyphoplasty of osteoporotic vertebral fractures to reduce the frequency or severity of adverse effects.
authors: Experimental Rheumatology Unit, Department of Orthopedics, Waldkrankenhaus "Rudolf Elle", Klosterlausnitzer Str. 81, Jena University Hospital, 07607, Eisenberg, Germany; Department of Orthopedics, Tongde Hospital of Zhejiang Province, No. 234 Gucui Road, 310012 Hangzhou, Zhejiang, China.
authors: Long
authors: L
authors: Xin
authors: Experimental Rheumatology Unit, Department of Orthopedics, Waldkrankenhaus "Rudolf Elle", Klosterlausnitzer Str. 81, Jena University Hospital, 07607, Eisenberg, Germany; Chair of Orthopedics, Department of Orthopedics, Waldkrankenhaus "Rudolf Elle", Jena University Hospital, Klosterlausnitzer Str. 81, 07607 Eisenberg, Germany.
authors: Matthias
authors: M
authors: Bungartz
authors: Chair of Materials Science, Otto Schott Institute of Materials Research, Friedrich Schiller, University Jena, Löbdergraben 32, 07743 Jena, Germany.
authors: Stefan
authors: S
authors: Maenz
authors: Experimental Rheumatology Unit, Department of Orthopedics, Waldkrankenhaus "Rudolf Elle", Klosterlausnitzer Str. 81, Jena University Hospital, 07607, Eisenberg, Germany.
authors: Victoria
authors: V
authors: Horbert
authors: Chair of Materials Science, Otto Schott Institute of Materials Research, Friedrich Schiller, University Jena, Löbdergraben 32, 07743 Jena, Germany.
authors: Max
authors: M
authors: Hennig
authors: BAM, Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205 Berlin, Germany.
authors: Bernhard
authors: B
authors: Illerhaus
authors: BAM, Federal Institute for Materials Research and Testing, Unter den Eichen 87, 12205 Berlin, Germany.
authors: Jens
authors: J
authors: Günster
authors: Chair of Materials Science, Otto Schott Institute of Materials Research, Friedrich Schiller, University Jena, Löbdergraben 32, 07743 Jena, Germany.
authors: Jörg
authors: J
authors: Bossert
authors: Institute of Laboratory Animal Sciences and Welfare, Jena University Hospital, Dornburger Str. 23, 07743 Jena, Germany.
authors: Sabine
authors: S
authors: Bischoff
authors: Experimental Rheumatology Unit, Department of Orthopedics, Waldkrankenhaus "Rudolf Elle", Klosterlausnitzer Str. 81, Jena University Hospital, 07607, Eisenberg, Germany.
authors: Juliane
authors: J
authors: Borowski
authors: Institute of Laboratory Animal Sciences and Welfare, Jena University Hospital, Dornburger Str. 23, 07743 Jena, Germany.
authors: Harald
authors: H
authors: Schubert
authors: Chair of Materials Science, Otto Schott Institute of Materials Research, Friedrich Schiller, University Jena, Löbdergraben 32, 07743 Jena, Germany.
authors: Klaus D
authors: KD
authors: Jandt
authors: Experimental Rheumatology Unit, Department of Orthopedics, Waldkrankenhaus "Rudolf Elle", Klosterlausnitzer Str. 81, Jena University Hospital, 07607, Eisenberg, Germany.
authors: Elke
authors: E
authors: Kunisch
authors: Experimental Rheumatology Unit, Department of Orthopedics, Waldkrankenhaus "Rudolf Elle", Klosterlausnitzer Str. 81, Jena University Hospital, 07607, Eisenberg, Germany. Electronic address: raimund.w.kinne@med.uni-jena.de.
authors: Raimund W
authors: RW
authors: Kinne
authors: Experimental Rheumatology Unit, Department of Orthopedics, Waldkrankenhaus "Rudolf Elle", Klosterlausnitzer Str. 81, Jena University Hospital, 07607, Eisenberg, Germany; Chair of Orthopedics, Department of Orthopedics, Waldkrankenhaus "Rudolf Elle", Jena University Hospital, Klosterlausnitzer Str. 81, 07607 Eisenberg, Germany.
authors: Olaf
authors: O
authors: Brinkmann
mesh_terms: D000818:Animals; D001843:Bone Cements / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D001853:Bone Marrow / Q000187:drug effects*; D002130:Calcium Phosphates / Q000009:adverse effects / Q000493:pharmacokinetics*; D019245:Compressive Strength; D005260:Female; D006801:Humans; D008159:Lumbar Vertebrae / Q000187:drug effects; D019904:Polymethyl Methacrylate / Q000009:adverse effects / Q000493:pharmacokinetics*; D011655:Pulmonary Embolism / Q000209:etiology*; D012756:Sheep; D054854:Vertebroplasty / Q000379:methods; D014783:Viscosity
chemical_list: D001843:Bone Cements; D002130:Calcium Phosphates; D019904:Polymethyl Methacrylate
keywords: Bone marrow extrusion; Brushite-forming calcium phosphate cement; Cement injection; Ex vivo; High-viscosity PMMA cement; In vivo; Large animal model; Sheep; Vertebroplasty