The osteoclasts attach to the bone surface where the extracellular calcium concentration decreases.

Osteoclasts demineralize and resorb bone once they attach to its surface. However, it's still unclear how the osteoclasts choose the specific sites for their attachments. It is postulated in this article that the decreased extracellular free ionized calcium concentration (Ca) can provide a microenvironment for osteoclasts to recognize and then initiate the attachment process. The osteoclasts initially attach to the bone surface via integrating its integrin αβ and RGD containing ligands in bone matrix. Through the interaction with RGD-containing ligand, the integrin αβ forms carboxylate oxygen noncovalent, which is further stabilized by accompanied electrostatic interaction between the Ca and the β subunit. There are two types of cation-binding sites on the β subunit: the high affinity Ca binding site ("LC" site) that activates the osteoclasts by promoting the combination; the low affinity Ca binding site ("I" site, also named ADMIDAS) that deactivates the osteoclasts by dissociating the combination and it can override the "LC" site's positive effect on osteoclasts when necessary. Normally the Ca concentration of bone extracellular fluid is maintained within a normal range by osteocytes, keeping the "I" sites activated. When the osteocytes' function stalls and the ambient Ca concentration falls below the affinity discrimination threshold between the "I" site and the "LC" site, the "LC" site's promoting function starts to out compete the "I" site in its inhibitory effect, in which case the inactive integrin αβ turns into an extended active form and the osteoclasts start to attach, signifying the initiation of bone resorption.