Mechanical/Enthesial Origin for Ankylosing Spondylitis Axial Involvement? Clues from a Therapeutic Viewpoint

The role of inflammation in vertebral manifestations of ankylosing spondylitis has been controversial [1-5]. Inflammation has been interpreted as the source of the edema recognized in the vertebral [611] centra of some individuals with ankylosing spondylitis [12,13]. However, most syndesmophytes appear at sites without apparent inflammation and not all inflammatory lesions lead to syndesmophytes [14]. While syndesmophytes are not the only motion-limiting vertebral column alterations in ankylosing spondylitis [15], the zygapophyseal joints have not been sufficient analyzed to address the question of inflammation (other than erosive disease) at that site. Nitrous oxide, increased by injury [16], activates inflammatory cytokines and repair at sites of tendon insertion [17,18] and likely has similar effects at sites of ligament insertion. Prostaglandins, bone morphogenic and Wnt proteins are essential in new bone formation, but not tumor necrosis factor [19]. Inhibiting the latter clearly has clinical benefit [20], but its inhibition is not essential to controlling the back pain of ankylosing spondylitis.