The Pathophysiology of Inflammatory Bone Loss

Inflammatory bone loss is caused by a complex pathway that begins with inflammatory cell production of cytokines, progresses to abnormal bone absorption, and culminates in the destruction of joints, bone fractures, and patient debility.

George Schett, MD, professor of internal medicine and rheumatology from Universitatsklinikum Erlanger, discussed the pathophysiology of bone loss at the 2014 American Society of Bone and Mineral Research Conference in Houston, Texas.

He began by noting that inflammation plays a significant role in body and bone homeostasis. A slight elevation of C-reactive protein (CRP), suggesting a small amount of inflammation, can increase a patient’s fracture risk. Therefore, patients with diseases that result in continuous inflammation have a much higher risk of fractures and loss of bone mass. Examples of these vulnerable patients include not only those with rheumatoid arthritis, osteoarthritis, and juvenile arthritis, but also patients with localized inflammation in one organ system like Crohn’s disease (gut inflammation) and patients with psoriasis (skin inflammation).

Dr Schett described patients suffering from chronic inflammatory diseases as “swimming in a sea of cytokines.” The path of inflammation-induced bone loss in rheumatoid arthritis begins when inflammatory cells produce large amounts of cytokines. Among other functions, cytokines encourage the activity of osteoclasts, resulting in increased bone absorption. As the osteoclasts accumulate, they dig tunnels underneath the cartilage, destroy joint architecture and debilitate patients.

Systemic inflammation associated with rheumatoid arthritis destroys cortical and trabecular bone structure. In order to stop the decline in bone mass, patients must be treated with anti-inflammatory medications to decrease cytokine levels. Cytokines decrease bone mass in a number of ways. Some, like TNF-alpha and IL-6, inhibit bone formation and suppress intrinsic repair mechanisms. Others, like B cells, interfere with the function of other cells

Therefore, cytokine blockers (such as TNF or IL-6 blockers) can end bone loss and also induce the repair of previous bone damage. Dr Schett noted that the development of targeted cytokine antibodies may lead to new modalities for bone repair in the future.