Lories RJ et al. (2008) Inhibition of osteoclasts does not prevent joint ankylosis in a mouse model of spondyloarthritis. Rheumatology (Oxford) 47: 605–608

A current hypothesis of the pathogenesis of spondyloarthritis—that inflammation and tissue damage triggers an exaggerated repair response—is being challenged. Findings from human and mice studies now suggest that inflammation and new tissue formation might be uncoupled events. Lories et al. tested this concept by examining whether inhibition of bone erosion by bisphosphonate treatment reduced ankylosis in the DBA/1 mouse model of spondyloarthritis.

Male DBA/1 mice (8 weeks old) from different litters were caged together. Every 2 weeks, from 10 weeks of age until 24 weeks of age, these mice received 100 ng/g zoledronic acid (n = 9) or phosphate buffered saline (n = 9) by intraperitoneal injection. Clinical signs of arthritis were scored biweekly until mice were 26 weeks old; bone mineral density and content were then measured, mice were sacrificed, and the severity of arthritis was histologically assessed.

Although zoledronic acid significantly increased both bone mineral density and content at 26 weeks, this treatment did not affect the clinical incidence (8/9 placebo vs 7/9 zoledronic acid) or severity of spontaneous arthritis; the pattern of joint involvement and the onset of arthritis were also similar in both groups. Furthermore, the histomorphological appearance of arthritis or ankylosis was not influenced by bisphosphonate treatment.

These findings support the concept that inflammation and new tissue formation are uncoupled events in spondyloarthritis. However, previous observations that pamidronate treatment reduces symptoms and bone edema in patients with spondyloarthritis suggest that different bisphosphonates could have different clinical effects.