Age-related chronic diseases are an enormous burden to modern societies worldwide. Among these, osteoporosis, a condition that predisposes individuals to an increased risk of fractures, substantially contributes to increased mortality and health-care costs in elderly. It is now well accepted that advanced chronical age is one of the main risk factors for chronical diseases. Hence, targeting fundamental aging mechanisms such as senescence has become a promising option in the treatment of these diseases. Moreover, for osteoporosis, the main pathophysiological concepts arise from menopause causing estrogen deficiency, and from aging. Here, we focus on recent advances in the understanding of senescence-related mechanisms contributing to age-related bone loss. Furthermore, treatment options for senile osteoporosis targeting senescent cells are reviewed.

By expressing different genes and proteins that regulate osteoclast as well as osteoblast formation, osteocytes orchestrate bone metabolism. The aim of this project was the evaluation of the differences in the osteocytes’ secretory activity in the low bone mass mouse strain C57BL/6J and the high bone mass strain C3H/J. The femura of eight- and sixteen-week-old male C57BL/6J and C3H/J mice—six animals per group—were analyzed. Using immunohistochemistry, osteocytes expressing dickkopf 1, sclerostin, periostin, fibroblast growth factor 23 (FGF23), and osteoprotegerin were detected. By means of the OsteoMeasure-System, 92.173 osteocytes were counted. At the age of eight weeks, approximately twice as many cortical and trabecular osteocytes from the C57BL/6J mice compared to the C3H/J mice expressed dickkopf 1 (p < 0.005). The number of cortical osteocytes expressing sclerostin was also higher in the C57BL/6J mice (p < 0.05). In contrast, the cortical and trabecular osteocytes expressing periostin were twice as high in the C3H/J mice (p < 0.005). The dickkopf 1 expressing osteocytes of the C57BL/6J mice decreased with age and showed a strain-specific difference only in cortical bone by 16 weeks of age (p < 0.05). In the C3H/J mice, the amount of osteocytes expressing periostin tended to increase with age. Thus, strain-related differences were maintained in 16-week-old rodents (p < 0.005). No strain-specific differences in the expression of FGF23 or osteoprotegerin in the cortical compartment could be detected. This experimental study showed that the osteocytes’ protein expression reflects differences in bone characteristics and strain-related differences during skeletal maturation. Besides the osteocytes’ expression of sclerostin, their expression of dickkopf 1 and periostin seems to be important for bone properties as well.