Alpha-bsm® is a first generation self-setting, injectable and moldable apatitic calcium phosphate cement (CPC) based on amorphous calcium phosphate (ACP). ACP was prepared using low temperature double decomposition technique, from a calcium solution (0.16 M), and phosphate solution (0.26 M) in a basic (pH~13) media. ACP was than stabilized using three crystal growth inhibitors (CO32-, Mg2+, P2O74-), freeze-dried, and heated (450 °C, 1h) to remove additional moisture and some inhibitors. Dicalcium phosphate dehydrate (DCPD) was also prepared using wet chemistry at room temperature from calcium and phosphate solution, respectively, 0.3 M and 0.15 M. ACP and DCPD powder were combined at a 1:1 ratio and ground to produce Alpha-bsm® bone cement. The cement is supplied as a powder and when mixed with an appropriate amount (0.8 ml/g) of physiological saline at room temperature, forms an injectable putty-like paste. The paste has a working time of about 45 minutes at room temperature, when stored in a moist environment. The setting reaction proceeds isothermically at body temperature (37°C) in less than 20 minutes, forming a hardened, porous (total porosity 50 to 60%), low crystalline (40% comparing with HA), apatitic calcium phosphate cement with a compressive strength range of 10 to 12 MPa. Extensive pre-clinical studies (rabbit radius critical sized defect, canine tibia osteotomy, sheep tibia, primate fibula fracture healing, and primate fibula critical size defect) demonstrate that Alpha-bsm® undergoes remodeling in conjunction with new bone formation. The next generation of Bone Substitute Materials (Beta-bsmTM and Gamma-bsm TM) are formulated based on the Alpha-bsm® chemistry but differ in powder processing (e.g. milling) technique. These materials are also self-setting, injectable and/or moldable apatitic calcium phosphate cements with improved handling and mechanical properties. The setting & hardening reaction of these new CPCs proceeds isothermically in less than 5 minutes at 37°C and once hardened demonstrate a compressive strength of 30 to 50 MPa. The final product (after full conversion) is a low crystalline (40% compared with Hydroxyapatite), calcium deficient (Ca/P atomic ratio = 1.45) carbonated apatite similar to the composition and structure of natural bone mineral (crystal size: length = 26 nm, width thickness = 8 nm). A desirable feature of these cements is their high surface chemistry (with specific surface area of about 180-200 m2/g) which is ideal for remodeling and controlled release of growth factors. A pilot rabbit critically sized femoral defect study comparing the three synthetic family products demonstrate that they share similar remodeling and resorption characteristics up to 52 weeks. Physico-chemical and mechanical performance of these next generation CPCs are favorable when compared with existing CPCs in the market, specifically material working time (at room temperature), cohesivity in a wet environment and fast setting & hardening rate (at body temperature).