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

Research paper by G M GM Campbell, R J RJ Tower, T T Damm, P P Kneissl, A A Rambow, C C Schem, S S Tiwari, C C CC Glüer

Indexed on: 19 Oct '17Published on: 19 Oct '17Published in: Journal of Bone and Mineral Research


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.