Arthritis and bone loss: a hen and egg story

In this review, we will discuss the relation between bone loss and inflammation in rheumatoid arthritis.

We highlight recent discoveries on the pathomechanisms of bone loss in rheumatoid arthritis and challenge traditional concepts by suggesting that bone loss may precede inflammation.

During the clinical course of rheumatoid arthritis, inflammation is the key trigger for progressive local and systemic bone damage. Inflammatory cytokines induce the expression of molecules supporting the differentiation of osteoclasts, which are the primary bone-resorbing cells. However, bone loss can be observed in patients with recent-onset rheumatoid arthritis, suggesting that the start of the destructive phase of disease may be much earlier than previously expected. Recent data suggest that bone loss already starts during the autoimmune phase of the disease long before inflammation starts. Antibodies against citrullinated proteins thereby seem to be an important trigger for bone loss in the preclinical disease phase of rheumatoid arthritis. Although traditional concepts preferred a 'hen-egg' concept with inflammation coming first, later triggering bone loss, new data suggest an alternative 'egg-hen' concept, where bone loss arises before the clinical disease onset and may be important for priming of the joint for susceptibility to chronic inflammation.