Open Access Research article

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

Facundo Las Heras12, Ralph S DaCosta38, Kenneth PH Pritzker24, Nigil Haroon15, George Netchev38, Hing Wo Tsui5, Basil Chiu5, W Mark Erwin69, Florence WL Tsui57* and Robert D Inman57*

Author affiliations

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

For all author emails, please log on.

Citation and License

Arthritis Research & Therapy 2011, 13:R163  doi:10.1186/ar3482

Published: 12 October 2011

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusions

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.