3 years ago

Tracking the progression of osteolytic and osteosclerotic lesions in mice using serial in vivo micro-CT: Applications to the assessment of bisphosphonate treatment efficacy

P. Kneissl, T. Damm, R.J. Tower, C.C. Glüer, C. Schem, S. Tiwari, A. Rambow, G.M. Campbell
The metastasis of tumour cells to bone can lead to osteolytic and osteosclerotic lesions, which cause severe, highly-localized bone destruction and abnormal bone apposition, respectively. Accurate quantification of lesion progression is critical to understand underlying mechanisms and assess treatment efficacy; however, standard structural parameters may be insensitive to local changes. We developed methods to quantify osteolytic and osteosclerotic lesions using micro-computed tomography (micro-CT) within in vivo mouse datasets. Two Balb/c datasets were used: (1) bone-homing MDA-MB-231 (osteolytic) cells injected into the left ventricle, treatment with alendronate or vehicle and weekly micro-CT (proximal tibia) for 4 weeks, and (2) MCF7 (osteosclerotic) cells injected into the right tibia and weekly micro-CT over 12 weeks. After registering images to baseline, osteolytic lesion volume was determined by summing all baseline bone voxels at distances greater than a threshold (150µm) from the nearest follow-up. Osteosclerotic lesions were determined by measuring the distance from each follow-up surface voxel to the nearest baseline surface and calculating the standard deviation of distance values (SDDT) of the surrounding voxels. Bone mineral density (BMD), bone volume density (BV/TV), and separation (Sp) were determined for comparison. Osteolytic lesions were observed one week after tumour cell injection; however, no corresponding BV/TV losses or Sp increases were observed, indicating that standard parameters were unable to detect early metastatic changes.. Lesion volume was smaller in the alendronate vs. control group (15.0%, p = 0.004 and 18.6%, p = 0.002 of control lesion volume at week 3 and 4, respectively). In the osteosclerotic dataset, increased SDDT was observed following injection, providing a potential new measure of osteosclerotic bone apposition. These data demonstrate that quantification of local structural change with serial micro-CT may overcome the limitations of standard mineral and microstructural parameters, and successfully separates metastatic and normal bone turnover. This article is protected by copyright. All rights reserved

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jbmr.3317

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