Bone adapts to its mechanical environment so that its form follows function, a mechanism known as Wolff’s law, or bone adaptation. Although the basic concepts of Wolff’s law have been generally accepted, the regulatory signals and the underlying cellular and molecular pathways, which mediate this adaptive process, are unknown. Failure of normal bone adaptation plays a significant role in the etiology of metabolic bone diseases such as osteoporosis and osteopetrosis, bone loss in space flight and failure of total joint replacements. During the past three decades, there have been extensive in vitro studies addressing mechano-signal transduction mechanisms in bone cells including osteoblasts, osteocytes, and osteoclasts [1–8].

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