Osteoporosis: The Result of an 'Aged' Bone Microenvironment

Abstract

Osteoporosis is an age-related progressive bone disease. Recent advances in epigenetics, cell biology, osteoimmunology, and genetic epidemiology have unraveled new mechanisms and players underlying the pathology of osteoporosis, supporting a model of age-related dysregulation and crosstalk in the bone microenvironment.

Keywords: Wnt signaling; aging; epigenetics; osteoimmunology; osteoporosis.

Figure 1. Overview of Age-Related Changes in the Bone Marrow Microenvironment

In young/healthy marrow, osteoblasts and osteoclasts are balanced via coupling agents such as RANKL, IGF-1 and PDGF-BB. Immune T/B cells reciprocally regulate bone cells through osteoimmune interactions, and MSCs are more prone to differentiate towards an osteolineage rather than into adipocytes. In old/osteoporotic marrow, accumulating ROS and pro-inflammatory cytokines can create a chronic inflammatory state. NF-κB activation can leads to T/B cell expansion, enhanced numbers of osteoclasts and suppressed numbers of osteoblasts. Epigenetic dysregulation can also result in an MSC shift from osteolineage to adipocytes. Thus, those changes, among many, can lead to a bone matrix that becomes thin and porous (osteoporotic) and susceptible to fracture. Abbreviations: OB, osteoblast; OC, osteoclast; MSC, mesenchymal stem cell; ROS, reactive oxidative species.