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.

Loading deproteinized bovine bone with strontium enhances bone regeneration in rat calvarial critical size defects

“…Systemic administration of Sr (in the form of Sr ranelate-SrR) has been shown to improve bone quality and reduces the risk of fractures both in females with postmenopausal osteoporosis and osteoporotic men [17,18]. More recently, several experimental studies have shown promising results in terms of increased bone formation after Sr enrichment of various bone substitute materials, such as allogeneic bone [19], bioactive bioglass [20,21], calciumsilicon ceramic [22], calcium phosphate [23,24], and hydroxyapatite [25,26]. Furthermore, it was observed in recent experiments that Sr-loaded titanium implants presented significantly increased bone-to-implant contact, comparing to control implants [27][28][29].…”

The role of well-defined nanotopography of titanium implants on osseointegration: cellular and molecular events in vivo

“…This assumption is supported by recent results showing that CaP materials doped with strontium, an osteoclastic inhibitor, induced a higher amount of bone formation than CaP materials. 41,42 This was associated with a significant reduction of the osteoclastic gene expression of CatK and CTR, whereas the osteogenic gene expression of ALP and OC was not affected. 41,42 Nevertheless, further evidence is required on the role of controlled nanotopography on the osteoclastic resorption, for instance by exploring the effect on the RANKL/RANK/OPG triad.…”

“…41,42 This was associated with a significant reduction of the osteoclastic gene expression of CatK and CTR, whereas the osteogenic gene expression of ALP and OC was not affected. 41,42 Nevertheless, further evidence is required on the role of controlled nanotopography on the osteoclastic resorption, for instance by exploring the effect on the RANKL/RANK/OPG triad. Generally, few studies are available on the effect of nanotopography on osteoclasts, and contradictory findings to present observations have been reported showing that ceramics with less than 100 nm nanoscale grains and titanium implants with 70 nm TiO 2 nanotubes enhance the osteoclastic tartrateresistant acid phosphatase activity in vitro 43 and in vivo, 40 respectively.…”

Improving the bone forming ability of synthetic bone substitutes using trace element additions

“…silicon [121,122], zinc [123][124][125][126], strontium [122,127,128]) into synthetic bioceramics and improved biological performance was observed both in vitro and in vivo (e.g. silicon [49,121,129], zinc [39,[123][124][125][130][131][132][133][134][135][136][137][138][139][140], strontium [141,122,127,128,131,140,[142][143][144][145][146][147][148][149][150][151][152][153] and fluoride [64,65,67,69,<...>…”

“…tricalcium phosphate (TCP) [131,147], biphasic calcium phosphate (BCP) [283] and hydroxyapatite (HA) [153]) and subsequently be released when these materials dissolve in aqueous solutions [131,153]. As the Sr substitution of Ca can be obtained in a range varying from 0 to 100 mol % [53], which increases the solubility of the doped apatite [43], a sustained Sr release could be feasible.…”