The ruffled border is the most specific marker of the active osteoclast (OC) as it forms only when the cell is resorbing bone. We provide evidence that this complex cytoskeletal structure reflects insertion of lysosomal vesicles into the bone-apposed plasma membrane under the aegis of the Ca-sensing, exocytic protein, synaptotagmin VII (SytVII). In the manner, SytVII permits transport of matrix-degrading molecules into the resorptive microenvironment. SytVII also regulates secretion of bone matrix molecules by osteoblasts. Thus, SytVII-deficient mice experience suppressed bone resorption and formation with the latter deficiency predominant thereby yielding osteoporosis characterized by attenuated remodeling.