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Autoimmune Diseases Rheumatoid Arthritis
Low-dose Prednisolone and Bone in Early Rheumatoid Arthritis
Inga-Lill Engvall, Birgitta Tengstrand and Ingiäld Hafström
Department of Rheumatology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm
Abstract
Rheumatoid arthritis (RA) is an inflammatory disease with a high incidence of bone loss. Bone loss in early RA is associated with the
inflammatory process, and the best way to prevent bone loss is to control disease activity. Glucocorticoids (GCs) reduce inflammatory
activity but also inhibit bone formation. Adding low-dose prednisolone to conventional treatment of RA has been shown to reduce
radiological progression of local bone erosions as well as peri-articular osteopenia; therefore, it seems that the negative effect of GCs on
bone formation is balanced by the ability of GCs to hamper disease activity and, consequently, the inflammatory-mediated increase in bone
resorption. It is debatable whether this is also true for generalised osteopenia. Reduced bone mineral density as a consequence of GC
treatment can be effectively prevented and treated by calcium and vitamin D supplements and treatment with bisphosphonates.
Keywords
Rheumatoid arthritis, prednisolone, bone loss, bone erosions, osteoporosis, bone resorption, bone formation
Disclosure: The authors have no conflicts of interest to declare.
Received: 10 July 2009 Accepted: 21 July 2009
Correspondence: Inga-Lill Engvall, Department of Rheumatology, R92, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. E: inga-lill.engvall@karolinska.se
Rheumatoid arthritis (RA) is a chronic inflammatory disease with a process by which osteoclasts resorb bone tissue and osteoblasts
high incidence of bone loss. Local bone erosions contribute to the produce new bone matrix that is subsequently mineralised. Bone
joint damage with subsequent physical impairment; over time, loss occurs when the balance shifts towards excess resorption.
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peri-articular and generalised osteopenia may develop into Bone loss in RA is presented in three different forms: local bone
osteoporosis with increased risk of fractures.
1–4
These effects on erosions, peri-articular osteopenia and generalised osteoporosis. It is
bone have an impact on morbidity and also on socioeconomic costs. suggested that the pathogenesis of these different forms of bone
The dominant contributor to bone loss in RA is the inflammatory loss has common pathways. This hypothesis is supported by the
process itself, and the best way to inhibit bone loss seems to be to finding that osteoclasts play a central role in the three
reduce the disease activity.
5
pathophysiological conditions and that the osteoclasts are
stimulated by the cytokine receptor activator of nuclear factor kappa
Cortisone was first given to a young woman with severe RA. The B ligand (RANKL) pathway.
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effect in this patient and 15 other patients, reported by Hench in 1949,
was impressive.
6
Systemic corticosteroid treatment was rapidly In RA there is a marked expansion of the synovium with infiltration by
adopted and used for patients with different rheumatic diseases and inflammatory cells and local cellular proliferation leading to an
other disorders such as asthma, and with a similar positive effect. In inflamed tissue, known as pannus. Activated macrophages,
1950, the Nobel Prize was awarded for the discovery of the structure lymphocytes and fibroblasts within the pannus produce cytokines
and biological effects of the adrenal cortex hormones. However, it was such as tumour necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6
not until 1959 that prednisolone, a cortisone analogue, showed and RANKL, which stimulate osteoclast differentiation and function,
significant beneficial effects compared with aspirin. The outcome resulting in increased bone resorption.
13
measure with the most significant beneficial effect was not a clinical
variable but radiological progression of erosions.
7
At this time, high Local Bone Erosions
doses were given and it was soon discovered that treatment with Osteoclasts are the primary cell type mediating local bone erosion in
glucocorticoids (GCs) was associated with a significant risk of RA; this has been shown in experimental models of murine arthritis.
undesirable side effects, which restricted its clinical use. In recent Either a deletion of the osteoclasts or pharmacological blockade of
years, treatment with low-dose GC has been re-evaluated because of osteoclastic activity protects against bone erosions, even in the
its ability to reduce radiographic damage in early RA.
8–10
presence of inflammation and cartilage destruction.
14–16
Effects of Inflammation on Bone The effect of inflammation on bone formation has not been fully
Bone tissue is responsive to mechanical forces and metabolic investigated, but the lack of effective bone formation at erosive sites
regulatory signals and thus undergoes continuous remodelling, a suggests that the inflammatory process may have a negative impact
44 © TOUCH BRIEFINGS 2009
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