All studies included in this review tested the hypothesis that non-radioactive Sr supplementation would enhance implant osseointegration. Overall, the results of the included studies suggest that the systemic Sr administration enhances peri-implant bone quality and implant osseointegration, however to a moderate extent. Positive results regarding implant osseointegration and the quality of peri-implant bone tissue, as evaluated by various methods (microtomography, histomorphometry, biomechanical, nanoindentation, and serum analysis) were observed in studies with both osteoporotic and healthy animals [29, 30, 32, 33]. However, the effect of Sr was not as pronounced as that achieved with systemic administration of bisphosphonates [30, 31]. As mentioned, systemic administration of bisphosphonates is known to lead to denser peri-implant bone, larger amounts of bone-to-implant contact, and overall enhancement of osseointegration-related parameters [11, 12, 50]. However, the reports on bisphosphonate-related osteonecrosis affecting the jaws [13] have practically removed these drugs from the group of possible alternatives for enhancing osseointegration [51].

In the present review, Sr was always used in the form of SRAN. In contrast to what is reported for bisphosphonates, no reports of major side-effects due to the SRAN treatment were found in the literature. However, it is relevant to mention that the literature is limited regarding the risks and pitfalls associated to systemic SRAN therapy. In fact, one population study conducted in France showed that osteoporotic patients with a history of venous thromboembolism presented cardiovascular side effects related to SR (104 cases in 39 months) [52]. In the same study, another important side effect, cutaneous toxicity, was mentioned connected to the first few weeks of drug administration. In this context, Sr dosage may be an important issue. SRAN dose in the studies included in the present review varied immensely (from 500 to 1000 mg/kg/day). It is a known fact that the anabolic effects of SR on bone remodeling are dose-dependent [23, 24], and indeed the positive effects of SR herein were observed with the higher doses [32, 33]. Clinical studies show efficacy regarding reduction of fracture risk in postmenopausal women with osteoporosis with a SRAN dose of 2 g/day [53]. Thus, a corresponding effective dose in a human adult with 60 kg of body weight would be 30–60 g/day. Despite the fact that high serum levels of strontium are required in rats in order to generate significant anabolic bone response [54], one could consider that if a dose 15 and 30 times higher than the clinical dose would be needed to have an effect on osseointegration, this could lead to toxicity in humans [55,56,57]. Clearly, this issue deserves further investigation.