Cellular senescence: a mechanism in the development of osteoporosis?

Osteoporosis is one of the most common diseases of the elderly. This leads to the hypothesis that the ageing of the organism is reflected as a cytoger ontological effect in a specific loss of bone cell function. Three underlyi ng pathogenetic mechanisms need to be considered: (1) cellular aging in gen eral, (2) impairment of the systemic stimulation of bone formation by e.g. decreasing hormone levels, and (3) lower cellular effectiveness of cytokine s and growth factors. Cellular aging consists of replicative and postmitoti c senescence. While the replicative senescence limits only the number of ce ll cycles,the postmitotic aging is influenced by endo- and exogenous factor s. These lead to genetic alterations known as delayed persistent genomic in stability and to an increasing impairment of specific cellular functions. I n the postmitotic phase, osteopenia caused by the decrease of systemically available sexual hormones is a major field of research. Osteopenia caused b y a decreased activity of locally effective cytokines and growth factors is becoming increasingly understood. New therapeutic strategies, which modula te the local osteoblast activity, e.g. in bone defect healing, are underdev elopment. In conclusion, cellular senescence is considered to be one elemen t in the development of bone loss. Potential therapeutic targets may open u p an additional path in the treatment of local and systemic osteopenias.