Bone formation induced by strontium modified calcium phosphate cement in critical-size metaphyseal fracture defects in ovariectomized rats

Abstract

The first objective was to investigate new bone formation in a critical-size metaphyseal defect in the femur of ovariectomized rats filled with a strontium modified calcium phosphate cement (SrCPC) compared to calcium phosphate cement (CPC) and empty defects. Second, detection of strontium release from the materials as well as calcium and collagen mass distribution in the fracture defect should be targeted by time of flight secondary ion mass spectrometry (TOF-SIMS). 45 female Sprague-Dawley rats were randomly assigned to three different treatment groups: (1) SrCPC (n = 15), (2) CPC (n = 15), and (3) empty defect (n = 15). Bilateral ovariectomy was performed and three months after multi-deficient diet, the left femur of all animals underwent a 4 mm wedge-shaped metaphyseal osteotomy that was internally fixed with a T-shaped plate. The defect was then either filled with SrCPC or CPC or was left empty. After 6 weeks, histomorphometric analysis showed a statistically significant increase in bone formation of SrCPC compared to CPC (p = 0.005) and the empty defect (p = 0.002) in the former fracture defect zone. Furthermore, there was a statistically significant higher bone formation at the tissue-implant interface in the SrCPC group compared to the CPC group (p < 0.0001). These data were confirmed by immunohistochemistry revealing an increase in bone-morphogenic protein 2, osteocalcin and osteoprotegerin expression and a statistically significant higher gene expression of alkaline phosphatase, collagen10a1 and osteocalcin in the SrCPC group compared to CPC. TOF-SIMS analysis showed a high release of Sr from the SrCPC into the interface region in this area compared to CPC suggesting that improved bone formation is attributable to the released Sr from the SrCPC.

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

“…Thus, this study supports previously published pre-clinical in vivo reports, where various Sr-loaded bone substitute materials were shown to enhance bone formation in a variety of models, including the calvarial CSD in rats as herein [19,21,24,26]. For instance, 5 mm of CSD grafted with Sr-loaded bioglass particles showed significantly larger amounts of new bone compared with defects grafted with non-loaded bioglass or with non-grafted controls, after 8 weeks of healing [21].…”

“…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].…”

An in vivo study on the metabolism and osteogenic activity of bioabsorbable Mg–1Sr alloy

“…Sr increases osteoblast replication, differentiation, and bone matrix mineralization relying on calcium sensing receptor dependent mechanism [3][4][5]. Previous studies incorporated Sr into calcium phosphate coatings or bioactive glasses to stimulate the bone formation [6][7][8][9]. Nonetheless, long-lasting Sr release at a reasonably constant rate is hardly achieved in these cases due to low and unstable solubility of Sr in calcium phosphates and glasses [10,11].…”

Biomaterials for enhancement of bone healing in osteoporotic fractures

“…In order to elucidate the local release of Sr from SrCPC, TOF-SIMS analysis was used which showed a high release of strontium up to a distance of 5 mm to the implant. Sr, Ca and the collagen signal were found in the same areas of the newly formed bone suggesting that the released Sr from SrCPC was incorporated into the new bone [72].…”

“…The intention of this recently developed composite material is to use the osteoconductive calcium phosphate cement as a drug carrier for the local release of strontium into bone defects in order to leverage the osteoanabolic and anti-osteoclastic activity not in a systemic but local environment to achieve high strontium concentrations with subsequent enhancement of new bone formation. We recently reported that this strontium-enhanced SrCPC revealed a statistically significantly increased new bone formation with accelerated expression of BMP-2, osteocalcin, and OPG compared to plain CPC [72]. A high CD-31 expression showed concomitant new blood vessel formation.…”