STOCKHOLM, Sweden – In addition to relieving the symptoms of inflammatory arthritis, intraarticular corticosteroids also down-modulate bone destruction markers, which might be a sign of bone protection, Swedish researchers report in the May issue of Arthritis & Rheumatism.1

"Local delivery of corticosteroids at the site of inflammation in acute, severe flares of arthritis is a valuable therapeutic choice to combat inflammation that might also have a bone-protective effect without the increased risk of osteoporosis seen with long-term systemic administration of high doses," lead study author Anca Irinel Catrina, MD, PhD, a rheumatologist at the Karolinska Hospital/Institutet in Stockholm, Sweden, told CIAOMed.

"Local delivery of corticosteroids at the site of inflammation in acute, severe flares of arthritis is a valuable therapeutic choice to combat inflammation that might also have a bone protective effect without the increased risk of osteoporosis seen with long-term systemic administration of high doses." —Anca Irinel Catrina, MD, PhD
The researchers hypothesized that corticosteroids might decrease bone destruction through modulation of synovial inflammation based on findings from previous clinical studies. They evaluated synovial expression of nuclear factor B ligand (RANKL) and osteoprotegerin (OPG) and surface marker expression by immunohistochemical methods in synovial knee biopsy samples from 13 patients with inflammatory arthritis before and 2 weeks after intraarticular injection of triamcinolone hexacetonide. They also studied the effect of dexamethasone (DEX) on RANKL expression by lymphocytes from rheumatoid arthritis synovial fluids (RA SF) using flow cytometric analysis, as well as the in vitro effect of DEX on RANKL and OPG expression in osteoblast-like cells via Western blotting.

RANKL changes may explain steroid slowing of joint erosion

Specifically, researchers found that the intraarticular corticosteroids induced a decrease in the number of synovial T cells without influencing the number of macrophages (which was evaluated as both CD68+ and CD163+ cells). This change was matched by a decrease of synovial RANKL expression with a concomitant reduction of the RANKL/OPG ratio. Moreover, DEX downregulated RANKL expression on lymphocytes derived from RA SF, the study showed.

The new findings suggest that intraarticular steroids affect joint destruction by modulating the synovial RANKL/OPG system, the researchers conclude. "The observation that corticosteroids have a direct effect on the RANKL expression was somewhat unexpected, suggesting that corticosteroids might have different effects depending on the clinical condition; ie, inflammatory versus noninflammatory conditions," Dr. Catrina said.

Rationale for TNF inhibitors plus steroids

The in vitro pretreatment of osteoblast-like cells with tumor necrosis factor (TNF) showed an antiresorptive effect of DEX treatment through a similar downregulation of RANKL expression, Dr. Catrina and colleagues report.

Previously, the researchers found that infliximab and etanercept can decrease the RANKL/OPG ratio by upregulating synovial OPG expression.2 In contrast, the new study shows that steroids modulate the synovial RANKL/OPG system by downregulation of RANKL.

"The mechanism of action of corticosteroids is distinct from the mechanism of action we reported previously for TNF blocking agents, offering a rationale for combining these two therapeutic strategies," Dr. Catrina said.

References

  1. Makrygiannakis D, af Klint E, Catrina SB, et al. Intraarticular corticosteroids decrease synovial RANKL expression in inflammatory arthritis. Arthritis Rheum. 2006;54;1463-1472.
  2. Catrina AI, af Klint E, Ernestram S, et al. Anti-tumor necrosis factor therapy increases synovial osteoprotegerin expression in rheumatoid arthritis. Arthritis Rheum. 2006;54:76-81.