However, a synergistic effect with other factors is conceivable. Some authors stated that implant osseointegration is not simply a wound healing phenomenon but rather complex foreign body reaction with activation of the immune system. Titanium and metal particle release is discussed as cause for implant failure as well as implant dentistry. It is assumed that metal particles influence the macrophage or lymphocyte pathways and provoke a release of pro-inflammatory cytokines, leading to an increased osteoclastogenesis and decreased osteoblastogenesis and consequently to peri-implant bone loss. This osteolytic effect could be enhanced by vitamin D deficiency, since Maier et al. demonstrated in an epidemiological study that vitamin D deficiency is associated with a higher risk to develop aseptic loosening around joint replacements caused by wear particles. Vitamin D could also be essential for the antibacterial response, as monocyte-macrophage reaction is influenced by vitamin D. Xu et al. demonstrated that vitamin D can inhibit Porphyromonas gingivalis-induced proinflammatory cytokine expression and improve the expression of anti-inflammatory cytokines in macrophages.

Interestingly, in the present investigation, the osseointegration of dental implants seems to be more influenced by the vitamin D level than the autologous graft incorporation as the graft incorporation was not compromised. The eventually minor effect of vitamin D on the incorporation of bone grafts appears to be addressed by the results of a current randomized, double-blind, and placebo-controlled clinical investigation with a high-dose vitamin D3 supplementation combined with calcium. The results could not demonstrate a statistically significant difference in the amount of bone formation or graft resorption after maxillary sinus augmentation compared to a placebo medication.

To overcome the shortcomings of this case reports, prospective, multicenter, and controlled studies must follow to affirm a potential relationship between vitamin D deficiency, osteoimmunology, and the early failure of dental implants. Currently, a general recommendation for a standardized vitamin D screening in dental implantology cannot be stated due to lack of evidence.