Aberrant axial mineralization precedes spinal ankylosis: a molecular imaging study in ank/ank mice
1 Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
2 Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada
3 Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
4 Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
5 Toronto Western Research Institute, University Health Network, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada
6 Division of Orthopaedic Surgery, University of Toronto, 100 College Street, Toronto, Ontario M5G 1L5, Canada
7 Department of Immunology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
8 Department of Medical Biophysics, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
9 Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada
Arthritis Research & Therapy 2011, 13:R163 doi:10.1186/ar3482Published: 12 October 2011
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.