A review of the latest insights into the mechanism of action of strontium in bone

Towards 3D Multi-Layer Scaffolds for Periodontal Tissue Engineering Applications: Addressing Manufacturing and Architectural Challenges

“…Additionally, it has been reported that Sr can act via the calcium-sensing receptor and promote the transductions of the mitogen-activated protein kinase signaling. Thus, the substitution of calcium with strontium in the HA structure can lead to a ceramic material with improved bioactivity and osteogenic properties [ 32 , 54 ]. Furthermore, based on the promising findings of a recent study, according to which the use of Sr-nHA enhanced the osteogenic potential and mineralization of human mesenchymal stromal cells, in this work Sr-nHA (2.46 wt%) was selected as reinforcing phase for the PCL polymeric matrix [ 34 ].…”

Building Osteogenic Microenvironments With Strontium-Substituted Calcium Phosphate Ceramics

“…The exact mechanism of the role of Sr in bone remains unclear, but it has been proposed that Sr acts on similar cellular targets as Ca 2+ by activating the calcium sensing receptor (CaSR), thus interacting with Ca-driven signaling pathways related to bone metabolism regulation ( Saidak and Marie, 2012 ). Furthermore, small animal trials and clinical trials have produced overwhelming evidence that Sr benefits bone remodeling and increases bone-mineral density, especially in the treatment of osteoporosis ( Meunier et al, 2004 ; Reginster et al, 2012 ; Marx et al, 2020 ). Taking these beneficial effects into consideration, it is likely that local Sr ion delivery will enhance osteoinduction and osseointegration at the bone-implant interface, contributing to a faster healing microenvironment.…”

“…Mounting evidence shows that Sr replacement of Ca in CaPs leads to increased solubility due to the expansion of the crystal structure, and the high local Sr 2+ , Ca 2+ , and PO 4 3– ionic concentrations are believed to be of great importance for osteoinduction and osteoconduction ( Bose et al, 2013 ; Neves et al, 2017 ). Current research shows that both Sr and Ca mediate key cellular functions in osteogenesis-related cells via Ca-sensing receptor (CaSR)-dependent mechanisms ( Marx et al, 2020 ). In the extracellular microenvironment, a high Ca concentration is a potent chemical signal for bMSCs osteogenic differentiation ( Dvorak and Riccardi, 2004 ; Barradas et al, 2012 ).…”

“…Previous studies have confirmed that CaPs modified with these bivalent trace metallic ions can lead to controlled degradation, increase the mechanical strength of the materials, and enhance bioactive properties. But among these bioactive ions, strontium (Sr) has gained great attention since strontium ranelate (SrRan) has been approved as an anti-osteoporotic drug for post-menopausal osteoporosis since it increases bone strength ( Neves et al, 2017 ; Marx et al, 2020 ). Recent findings suggest that oral administration of SrRan may have no anabolic action on bone formation in humans, and even inhibits osteogenic differentiation under the in vitro experiment conditions ( Wornham et al, 2014 ; Marx et al, 2020 ).…”

“…But among these bioactive ions, strontium (Sr) has gained great attention since strontium ranelate (SrRan) has been approved as an anti-osteoporotic drug for post-menopausal osteoporosis since it increases bone strength ( Neves et al, 2017 ; Marx et al, 2020 ). Recent findings suggest that oral administration of SrRan may have no anabolic action on bone formation in humans, and even inhibits osteogenic differentiation under the in vitro experiment conditions ( Wornham et al, 2014 ; Marx et al, 2020 ). However, the comprehensively described SrCaPs do exert positively influence on new bone formation and accelerate the healing process ( Neves et al, 2017 ).…”