Sr is a metabolic trace element closely related to calcium. Sr²⁺ ions are incorporated into bone by two main mechanisms: (a) a rapid uptake mechanism, dependent on osteoblast activity, whereby Sr²⁺ becomes absorbed via ion exchange processes with Ca²⁺ or binding to osteoid proteins, and (b) Sr²⁺ ions incorporate into the crystal lattice of the bone mineral phase. [34] When Sr²⁺ is present in higher levels than those required for normal cell physiology, it induces pharmacological effects on bone, through the activation of diverse cellular pathways [34].

Systemic use of non-radioactive Sr has showed promising results regarding the treatment of bone pathologies, such as osteoporosis and osteoarthritis [35,36,37], as it directly and positively interferes with bone mass, quality, and strength [38]. Further, in vitro studies have shown that Sr has the ability to increase bone formation [39, 40] while inhibiting osteoclast differentiation [41]. This dual action on bone remodeling, distinguishes Sr from the other traditional anti-osteoporotic agents, which either increase bone formation (intermittent parathyroid hormones) or inhibit bone resorption (bisphosphonates) [42]. Several mechanisms have been discussed for how systemic Sr-based therapy enhances bone formation [43,44,45,46]. Sr might activate the calcium-sensing (or another functionally different cation-sensing) receptor on osteoblasts, thereby leading to enhanced bone matrix production [46]. Another plausible mechanism is that Sr induces prostaglandin production and cyclooxygenase expression, thereby increasing osteoblastic differentiation [44]. Further, Sr might interact with fibroblast growth factor receptors, thereby increasing osteoblast synthetic activity [43]. At last, Sr also interacts with the mitogen-activated protein kinase (MAPK) signaling pathway, enhancing the differentiation of mesenchymal stem cells in osteogenic cells [45]. In regard with interfering with bone resorption, Sr enhances osteoprotegerin (OPG) expression in osteoblasts [40, 47, 48] thereby reducing osteoclastogenesis [42].

Based on this dual effect, studies have suggested the use of Sr as an adjunct therapy in situations where enhanced bone tissue formation is needed [24, 46, 49]. One could hypothesize that any event dependent on bone formation, such as the osseointegration of implants, could benefit of strontium supplementation, i.e., osseointegration is enhanced due to improved bone formation rate and bone quality surrounding the implants [1, 2].