Antiinflammatory Treatment With Bisphosphonates in Ankylosing Spondylitis

Abstract and Introduction

Abstract

Purpose of review: Bisphosphonates are antiosteoclastic agents widely used in the treatment of bone diseases. They also have antiinflammatory properties suggested by a clinical amelioration in animal models of arthritis. Bisphosphonates act on cells from the monocyte/macrophage lineage and may modulate the generation of proinflammatory cytokines. Ankylosing spondylitis is characterized by bone marrow subchondral inflammation with the presence of T cells and macrophages, and osteoporosis is a well known complication of the disease. Thus, bisphosphonates may be reasonably used as a therapeutic agent in ankylosing spondylitis.
Recent findings: Different open trials have shown that the amino bisphosphonate pamidronate ameliorated the clinical symptoms of ankylosing spondylitis, mainly axial disease, and in one study, peripheral arthritis. Laboratory parameters of inflammation were, in general, not influenced while biochemical markers of bone turnover fell significantly under pamidronate. Imaging modifications of the inflammatory lesions using MRI were also improved with pamidronate. A dose-controlled study demonstrated a higher efficacy for 60 mg pamidronate compared with a 10 mg dose.
Summary: The amino bisphosphonate pamidronate has shown clinical and radiological amelioration in ankylosing spondylitis patients, although this improvement is mild and transient. Additional studies are required to better define the real impact of pamidronate on ankylosing spondylitis and its place among the different treatment options for the disease.

Introduction

Ankylosing spondylitis is a systemic and inflammatory rheumatic disease of the axial skeleton. For several years, NSAIDs and physiotherapy have been the mainstay of therapy while second-line treatments such as sulfasalzine or methotrexate have not proved to be sufficiently effective, particularly in axial disease. Conversely, tumour necrosis factor α (TNFα) agents have been shown to result in dramatic improvement in ankylosing spondylitis, ameliorating the different symptoms of the disease, as well as quality of life.^[1,2] Laboratory parameters of inflammation and imaging modifications of the inflammatory lesions using MRI were also ameliorated under TNFα antagonists.

Anti-TNFα agents are very effective in ankylosing spondylitis but some difficulties have emerged with the use of these molecules in clinical practice: they are associated with an increased risk of infection,^[3] their long-term safety has not been adequately studied and they are very expensive. Thus, potential alternative therapies for ankylosing spondylitis are of interest.

Bisphosphonates are widely used for the treatment of bone diseases, including Paget's disease, osteoporosis, hypercalcaemia and malignant bone diseases. Bisphosphonates are active and strong inhibitors of osteoclast activity.^[4] Besides these effects on bone, bisphosphonates also possess antiinflammatory properties, explaining therapeutic trials in inflammatory rheumatic diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis.

We discuss the relevance of the use of bisphosphonates in ankylosing spondylitis based upon recently published clinical trials.