Calcium phosphate materials share a compositional similarity to natural bone, which makes them excellent for use in orthopedic applications. Although these materials are osteoconductive, they lack strong osteoinductive capabilities and recent research has focused on the addition of biologics and pharmacologics with varying successes. In this study, trace elements that have been proven to play important roles in bone health and bone formation were incorporated into β-tricalcium phosphate compacts in their oxide forms (SiO2, ZnO, SrO, and MgO). Cell material interactions were characterized using human fetal preosteoblastic cells. An MTT (3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyl tetrazolium bromide) assay was used to evaluate cellular proliferation. Cellular differentiation was evaluated using an enzymatic colorimetric alkaline phosphatase assay as well as immunohistochemistry for Runt-related transcription factor 2 (Runx2) expression. Results prove ZnO and MgO to be effective mitogenic factors and SiO2, ZnO, and SrO to be capable of inducing rapid cellular differentiation. MgO was found to have little effect on the modulation of osteoblastic differentiation, likely due to more aggressive inherent cellular regulation of Mg2+. In addition to the results from the study, a signaling mechanism is proposed as to the action of the dopants for further consideration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2417–2426, 2014.