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Ca²⁺ is a ubiquitous intracellular messenger responsible for controlling numerous cellular processes including fertilization, mitosis, neuronal transmission, contraction and relaxation of muscles, gene transcription, and cell death. At rest, the cytoplasmic Ca²⁺ concentration [Ca²⁺]_i is approximately 100 nM, but this level rises to 500–1,000 nM upon activation. In osteoblasts, the elevation of [Ca²⁺]_i is a result of an increase in the release of Ca²⁺ from endoplasmic reticulum and/or extracellular Ca²⁺ influx through voltage gated Ca²⁺ channels. Many of the cellular effects of Ca²⁺ are mediated by the Ca²⁺ binding protein, calmodulin (CaM). Upon binding up to four calcium ions, CaM undergoes a conformational change, which enables it to bind to specific proteins eliciting a specific response. Calmodulin kinase II (CaMKII) is a major target of the Ca²⁺/CaM second messenger system. Once bound to Ca²⁺/CaM, the …