Approximately 200 million people worldwide, including 25 million in the United States, suffer from osteoporosis. The pathophysiology of osteoporosis suggests that prevention through dietary intervention can be one of the most important actions. Diet can also be a successful alternative for minimizing bone loss and the need for osteoporosis related drug therapy. Conjugated linoleic acid (CLA) is the collective term used to describe positional and geometric isomers of linoleic acid with two conjugated double bonds. CLA has been shown to be biologically active in many systems, yet CLA’s effect on bone mass is not clearly established. The purpose of this research is to investigate CLA’s isomeric effect and synergy with dietary calcium on bone mass. CLA was observed to increase the body ash, representative of bone mass, in male ICR mice after 4-weeks of supplementation. CLA was also administered to mouse bone marrow mesenchymal stem cells during osteoblastic differentiation. CLA increased protein expression related to osteogenesis as well as increasing the calcium concentration of the osteoblastic matrix. In summary, this research provides evidence for the ability of CLA to preserve bone mass.