The use of magnesium (Mg)-based implant material regain interest recently. It is also suspected and observed that Mg-based implants induce bone formation in musculoskeletal implantation sites. However, except the fact it is also known that Mg is increasing general cell metabolism (especially because of its interdependence with ATP), no broad but still comprehensive researches have been led to understand the mechanical mechanisms implied in this phenomenon. In an (in vitro) attempt to reveal the underlying mechanisms of the possible osteoinductivity of magnesium, peripheral blood mononuclear cells (PBMC) were cultured / differentiated with different concentrations and types of extracellular magnesium (MgCl2 or Mg-extract i.e., degradation product of bulk material in cell culture media according to EN ISO standards) either in mono or in coculture (together with an osteoblast model). These studies had the goals to reveal (I) the effect of the type of Mg employed, (II) the effect of the Mg on osteoclast differentiation, and (III) if similar effects could be observed in a mono and in a coculture. MgCl2 and a Mg-extract exhibited different effects on osteoclast proliferation and differentiation. MgCl2 was able to enhance proliferation and osteoclast function up to a concentration of approximately 15 mM. The magnesium extract appeared to reduce cell metabolism, while protein contents and cell differentiation were less affected. Both substances activated osteoclastic resorption activity, but the magnesium extract exerted its positive effect at lower magnesium content. Consistent with in vivo observations where enhancement in osteoblast activity and a decrease in osteoclast numbers contributed to enhanced bone, in vitro data showed that higher concentrated Mg extract could lead to a promotion in the formation of osteoblasts but an inhibitory effect on the differentiation of osteoclasts. The Mg extract dual mode of action on the bone cell levels could contribute to enhanced bone formation caused by implantation of Mg-based alloys. Compared to monoculture, PBMC in coculture with osteoblasts exhibited higher tolerance to high Mg extract. Therefore cocultures consisting of both bone cells are a useful model for in vitro cytocompatibility assessment of Mg-based implants.