Aberrant axial mineralization precedes spinal ankylosis: a molecular imaging study in ank/ank mice

• Published in: Arthritis research & therapy 2011-01, Vol.13 (5), p.R163-R163
• Main Authors: Las Heras, Facundo, DaCosta, Ralph S, Pritzker, Kenneth P H, Haroon, Nigil, Netchev, George, Tsui, Hing Wo, Chiu, Basil, Erwin, W Mark, Tsui, Florence W L, Inman, Robert D
• Format: Article
• Language: English
• Subjects: Animals; Ankylosing spondylitis; Axis, Cervical Vertebra - chemistry; Axis, Cervical Vertebra - metabolism; Axis, Cervical Vertebra - pathology; Calcification, Physiologic - genetics; Care and treatment; Development and progression; Diagnosis; Diagnostic imaging; Inflammation - genetics; Inflammation - metabolism; Inflammation - prevention & control; Mice; Mice, Transgenic; Molecular Imaging - methods; Spondylitis, Ankylosing - diagnosis; Spondylitis, Ankylosing - genetics; Spondylitis, Ankylosing - metabolism; Time Factors
• ISSN: 1478-6354; 1478-6362
• DOI: 10.1186/ar3482

The diagnosis of ankylosing spondylitis is made from a combination of clinical features and the presence of radiographic evidence that may be detected only after many years of inflammatory back pain. It is not uncommon to have a diagnosis confirmed 5 to 10 years after the initial onset of symptoms. Development of a more-sensitive molecular imaging technology to detect structural changes in the joints would lead to earlier diagnosis and quantitative tracking of ankylosis progression. Progressive ankylosis (ank/ank) mice have a loss of function in the Ank gene, which codes for a regulator of PPi transport. In this study, we used these ank/ank mutant mice to assess a noninvasive, quantitative measure of joint ankylosis with near-infrared (NIR) molecular imaging in vivo. Three age groups (8, 12, and 18 weeks) of ank/ank (15 mice) and wild-type littermates (12 +/+ mice) were assessed histologically and radiographically. Before imaging, OsteoSense 750 (bisphosphonate pamidronate) was injected i.v. Whole-body images were analyzed by using the multispectral Maestro imaging system. OsteoSense 750 signals in the paw joints were higher in ank/ank mice in all three age groups compared with controls. In the spine, significantly higher OsteoSense 750 signals were detected early, in 8-week-old ank/ank mice compared with controls, although minimal radiographic differences were noted at this time point. The molecular imaging changes in the ank/ank spine (8 weeks) were supported by histologic changes, including calcium apatite crystals at the edge of the vertebral bodies and new syndesmophyte formation. Changes in joint pathology of ank/ank mice, as evaluated by histologic and radiographic means, are qualitative, but only semiquantitative. In contrast, molecular imaging provides a quantitative assessment. Ankylosis in ank/ank mice developed simultaneously in distal and axial joints, contrary to the previous notion that it is a centripetal process. NIR imaging might be feasible for early disease diagnosis and for monitoring disease progression in ankylosing spondylitis.