Bone Signaling Pathways and Treatment of Osteoporosis

Apostolos I Gogakos; Moira S Cheung; JH Duncan Bassett; Graham R Williams


Expert Rev Endocrinol Metab. 2009;4(6):639-650. 

In This Article

Bone Remodeling Cycle

The continual process of adult bone remodeling is essential for the maintenance of bone mass and skeletal micro-architecture.[4] The basic multicellular unit of bone remodeling comprises osteocytes, osteoclasts and osteoblasts.[12] Over 95% of the surface of the normal adult skeleton is quiescent because osteocytes exert a resting inhibition of both osteoclastic bone resorption and osteoblastic bone formation.[11] By contrast, when local skeletal microdamage occurs or when there is a reduction in mechanical loading, osteocytes respond either by releasing cytokines and chemoattractants or by undergoing apoptosis. These responses result in local recruitment of osteoclast precursor cells and mature osteoclasts to initiate bone resorption.[4] Osteoclasts excavate a resorption cavity over a period of 3–5 weeks until this process is terminated by apoptosis and followed by recruitment of osteoblast precursors. Subsequently, osteoblasts undergo a program of maturation, during which they secrete and mineralize osteoid to replace the resorbed bone over a period of approximately 3 months.[11] Coupling of osteoclast and osteoblast activities via signaling between the two cell lineages regulates the bone remodeling cycle and results in skeletal homeostasis with preservation of bone strength.[13] In summary, the bone remodeling cycle is initiated and orchestrated by osteocytes, and regulated by coupled crosstalk between osteoblasts and osteoclasts.


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