Bone loss in osteoporosis and rheumatoid arthritis diseases: The effects of disease mechanisms, age, gender and ethnic origin on responsiveness to treatment.

Abstract

Bone makes up a framework that provides protection for internal body organs. The homeostasis of bone is maintained by a balanced process involving old bone degradation and new bone formation. However, this balance can be altered in pathophysiological conditions such as in postmenopausal osteoporosis and in patients with rheumatoid arthritis (RA). In recent years, new therapies have been developed to reduce bone resorption. However, there is disparity in patients’ response to these therapies. The reasons are unclear although age, gender, ethnic background and lifestyle have all been suggested to play a part. For patients with chronic inflammatory conditions, treatment was revolutionised by the discovery and application of biologic therapies that target pro-inflammatory proteins and/or pathways. However, whilst the anti-inflammatory effect of these biologic agents is well-established, their effect on bone loss is just emerging. In RA, it is not clear whether the beneficial anti-inflammatory effects of biologic anti-tumour necrosis factor alpha (TNFα) agents are accompanied by parallel improvements in bone erosion/density, whether there are differences between patient groups and what factors influence the response. In order to address these issues, a database on the factors that influence responsiveness of patients with osteoporosis to bisphosphonates, a treatment that suppresses bone resorption, was established. Based on the outcome of this study, the influence of the key factor(s) that affect bone response to treatment in combination with excess pro-inflammatory cytokine production on bone response in RA patients was determined. Significant improvement in bone mineral density (BMD) and plasma levels of bone biomarkers has been shown in this study with biologic anti-TNFα agents. The improvement in BMD was not always consistent with improvement the clinical response to treatment as assessed by changes in disease activity score 28(DAS28). The study also provides a mechanistic explanation for how blockade of TNFα in patients can reverse the balance of bone loss in patients with RA. Thus, the data show that treatment of patients with biologic anti-TNFα agents reduces the number of osteoclast precursors (OCs) in the blood.