In healthy joints bone homeostasis is maintained through a tight balance between the actions of osteoclasts (bone resorbing cells) and ostoblasts (bone forming cells). Inflammation and the actions of hormones and cytokines can, however, result in an imbalance between bone resorption and bone formation, which can lead to the joint degeneration seen in rheumatic diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA).
Research over the past decade has focused on how bone homeostasis becomes unbalanced in RA and OA, in the hope that novel targets for the prevention of abnormal bone remodelling in these and other rheumatic diseases will be identified. Major advances have been made in our understanding of the mechanisms of action of glucocorticoids in RA, and the interplay between the immune system and the musculoskeletal system, as well as insights into the endocrinology of bone. Together, these advances will lead to the development of new and improved therapeutic approaches for protecting and rebuilding bone.
This Focus issue includes four Reviews and one Perspectives article, written by leading experts, that focus on the latest developments in the field of bone research, as outlined above, and on how these findings will translate into clinical practice.
RESEARCH HIGHLIGHT
Bone research: Autophagy is central to joint destruction in arthritis
Sarah Onuora
doi:10.1038/nrrheum.2012.171
Nature Reviews Rheumatology 8, 633 (2012)
REVIEWS
The multiple facets of glucocorticoid action in rheumatoid arthritis
Ulrike Baschant, Nancy E. Lane & Jan Tuckermann
doi:10.1038/nrrheum.2012.166
Nature Reviews Rheumatology 8, 645-655 (2012)
Despite their association with loss of bone mass and increased fracture risk, glucocorticoids have been an important component of rheumatoid arthritis therapy for more than 60 years. In this article, Ulrike Baschant and colleagues describe the tissue-specific, molecular and cellular mechanisms of glucocorticoid action, and suggest new criteria for selective glucocorticoid receptor agonists, which could have similar anti-inflammatory efficacy to traditional glucocorticoids without the adverse effects.
Bone erosion in rheumatoid arthritis: mechanisms, diagnosis and treatment
Georg Schett & Ellen Gravallese
doi:10.1038/nrrheum.2012.153
Nature Reviews Rheumatology 8, 656-664 (2012)
In this Review, the authors summarize the substantial progress that has been made in understanding the pathophysiology of bone erosions and discuss the improvements in the diagnosis, monitoring and treatment of such lesions.
Bone remodelling in osteoarthritis
David B. Burr & Maxime A. Gallant
doi:10.1038/nrrheum.2012.130
Nature Reviews Rheumatology 8, 665-673 (2012)
Subchondral bone remodelling in osteoarthritis (OA) is biphasic and spatially variable. Early-stage disease is associated with bone loss owing to increased bone remodelling. As disease progresses, the remodelling rate slows down leading to densification of the subchondral plate and complete loss of cartilage. In this article, Burr and Gallant review the current knowledge on OA and discuss the role of subchondral bone in the initiation and progression of disease. They also present a hypothetical model of OA pathogenesis.
The skeleton as an endocrine organ
Douglas J. DiGirolamo, Thomas L. Clemens & Stavroula Kousteni
doi:10.1038/nrrheum.2012.157
Nature Reviews Rheumatology 8, 674-683 (2012)
Increasing evidence points towards the skeleton as having an endocrine role in humans. In this Review, DiGirolamo and colleagues introduce the concept of the skeleton as an endocrine organ, summarizing the evolution of skeletal endocrine networks and the role of the skeleton in phosphate and glucose homeostasis.
PERSPECTIVES
New developments in osteoimmunology
Hiroshi Takayanagi
doi:10.1038/nrrheum.2012.167
Nature Reviews Rheumatology 8, 684-689 (2012)
Crosstalk between the skeletal and immune systems—especially immunomodulation of bone turnover, but increasingly also regulation of immune functions by bone cells—was recognized during research into arthritis and has evolved into the discipline of osteoimmunology. Hiroshi Takayanagi presents an update of advances in this area, focusing on the influences of T cells on bone remodelling, and relationships between osteoblasts and haematopoiesis.
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