Calcium phosphate bioceramics have been studied as bone filler materials for years and have become a component of many commercial products. It is widely known that surface-reactive biomaterials may cause changes in the concentration of crucial ions in the surrounding environment, thereby affecting cell metabolism and viability. The aim of this study was to produce five cement-type biomaterials and characterize their phase composition using X-ray diffraction method, and porosity and pore size distribution using mercury intrusion porosimeter. We then evaluated ion interactions of the novel biomaterials with the surrounding environment (culture medium). A commercially available bone substitute, HydroSet™ (Stryker®), was used as a reference. MTT and NRU cytotoxicity tests were performed to assess the effect of changes in the concentration of crucial ions (calcium, magnesium, phosphate) on osteoblast metabolism and viability in vitro. Our study clearly indicated that various biomaterials demonstrated different ion reactivity and consequently may cause changes in ion concentration in the local environment. Critically low or high values of calcium, magnesium, and phosphate concentrations in the medium exerted cytotoxic effects on the cultured cells. Moreover, we discovered that the chemical composition of the culture medium had a substantial influence on ion interactions with biomaterials.