title: Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats.
abstract: The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden ; Department of Oral and Maxillofacial Surgery, Örebro University Hospital, Örebro, Sweden ; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Carina
authors.initials: C
authors.lastname: Cardemil
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden ; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Elgali
authors.affiliation: Applied Materials Science, Department of Engineering Sciences, Uppsala University, Uppsala, Sweden ; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden ; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Emanuelsson
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden ; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Norlindh
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden ; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Omar
authors.initials: O
authors.lastname: Omar
authors.affiliation: Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden ; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Thomsen
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology*; D002146:Bony Callus / Q000502:physiology*; D002130:Calcium Phosphates / Q000378:metabolism*; D017886:Durapatite / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017102:Fracture Healing / Q000502:physiology*; D020869:Gene Expression Profiling; D006652:Histological Techniques; D010052:Ovariectomy; D053245:RANK Ligand / Q000378:metabolism; D051381:Rats; D018003:Receptors, Calcitonin / Q000378:metabolism; D018709:Statistics, Nonparametric; D013324:Strontium / Q000378:metabolism*; D014961:X-Ray Diffraction
chemical_list: D002130:Calcium Phosphates; D053245:RANK Ligand; D018003:Receptors, Calcitonin; D017886:Durapatite; C020243:calcium phosphate; D013324:Strontium