Loss and gain of bone in spondyloarthritis: what drives these opposing clinical features?

Abstract

The breadth of bone lesion types seen in spondyloarthritis is unprecedented in medicine and includes increased bone turnover, bone loss and fragility, osteitis, osteolysis and erosion, osteosclerosis, osteoproliferation of soft tissues adjacent to bone and spinal skeletal structure weakness. Remarkably, these effects can be present simultaneously in the same patient. The search for a potential unifying cause of effects on the skeleton necessarily focuses on inflammation arising from the dysregulation of immune response to microorganisms, particularly dysregulation of T_H17 lymphocytes, and the dysbiosis of established gut and other microbiota. The compelling notion that a common antecedent pathological mechanism affects existing bone and tissues with bone-forming potential (entheses), simultaneously with variable effect in the former but bone-forming in the latter, drives basic research forward and focuses our awareness on the effects on these bone mechanisms of the increasing portfolio of targeted immunotherapies used in the clinic.

Keywords: ankylosing spondylitis (AS); axial spondyloarthritis (axSpA); bone pathophysiology; enthesophyte; osteoimmunology; osteomicrobiology; osteoporosis; osteoproliferation; spondyloarthritis (SpA); syndesmophyte.

Figure 1.

Osteoproliferative lesions in spondyloarthritis. a. Romanus lesions (long arrows): osteosclerosis at the vertebral enthesis attachment of both the anterior longitudinal ligament and anterior intervertebral disc annulus. There is a syndesmophyte (arrowhead) arising from a previously fractured vertebra (short arrow). b. Erosion and osteosclerosis at the Achilles’ tendon insertion (thin arrow), osteoproliferation (enthesophyte) at the plantar fascia origin (wide arrow) and osteoproliferation (periosteal irregularity) of the os peroneum (arrowhead), which is a sesamoid bone in the peroneus longus tendon attached to the tendon on all its sides by entheses. We gratefully acknowledge Professor Andrew Grainger for the images.

Figure 2.

Effects of inflammation and stress loading on bone and enthesis tissue in spondyloarthritis. Direct effects of inflammation lead to bone loss (osteopaenia/osteoporosis and bone erosion) due to increased osteoclast activity. Inflammation further influences bone sclerosis and osteoproliferation both directly and indirectly. The stress-loading component influences entheseal pathophysiology, which can amplify the effects of inflammation in enthesial and ligament tissue to cause osteoproliferation.