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A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients.

ABSTRACT: PURPOSE:Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD. METHODS:We validated DECT in pre-clinical and phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck. RESULTS:Measured precision (3mg/cm(3)) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r=0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r=0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment. CONCLUSION:Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy.

SUBMITTER: Hui SK

PROVIDER: S-EPMC4336831 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients.

Hui Susanta K SK Arentsen Luke L Sueblinvong Thanasak T Brown Keenan K Bolan Pat P Ghebre Rahel G RG Downs Levi L Shanley Ryan R Hansen Karen E KE Minenko Anne G AG Takhashi Yutaka Y Yagi Masashi M Zhang Yan Y Geller Melissa M Reynolds Margaret M Lee Chung K CK Blaes Anne H AH Allen Sharon S Zobel Bruno Beomonte BB Le Chap C Froelich Jerry J Rosen Clifford C Yee Douglas D

Bone 20141220

<h4>Purpose</h4>Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD.<h4>Methods</h4>We validated DECT in pre-clinical and phase I clinical trials and verified with wa ...[more]

PMID: 25536285

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Project description:Genetic risk of low bone mineral density in women remains unclear. This study found that a large percentage of Caucasian women have a high genetic risk of osteoporosis, and genetic risk scores are significantly associated with BMD variation in a bone healthy sample of Caucasian women. INTRODUCTION:We aimed to examine the distribution of risk alleles in an independent sample and to determine if such genetic components are associated with bone mineral density (BMD) variation in the sample. METHODS:Existing genotype data of 1205 women in the cross-sectional Genomic Wide Scans for Female Osteoporosis Gene Study (GWSFO) were analyzed. Multi-loci genetic risk scores (GRSs) based on 62 BMD-associated single nucleotide polymorphisms (SNPs) were calculated. Regression analysis was employed to assess the association between GRSs and BMD. To examine the effect of SNPs clustered within key pathways associated with the development of osteoporosis, subtype weighted GRS specific to WNT signaling (6 SNPs), RANK-RANKL-OPG (3 SNPs), and mesenchymal stem differentiation (3 SNPs) were generated for analysis. RESULTS:The unweighted GRS ranged from 48 to 80. One third of the women carried 66% risk alleles. After adjusting for age, height, and body weight, each unit increase of weighted GRS was associated with a decrease in BMD of 0.097 at femur (p?<?0.0001) and 0.110 (p?<?0.0001) at lumbar spine. The weighted GRS accounted for only 3.17-4.52% of BMD variance. The WNT signaling pathway GRS (6 SNPs) and the RANK-RANKL-OPG signaling pathway GRS (3 SNPs) both were significantly associated with decreased BMD at femur neck (p?=?0.0004 and p?=?0.0063, respectively) and lumbar spine (p?<?0.0001 and p?=?0.0001, respectively), while the mesenchymal stem cell differentiation pathway (3 SNPs) GRSs were associated only with the lumbar spine BMD (p?=?0.045). CONCLUSIONS:A substantially large percentage of healthy Caucasian women have a high genetic risk of osteoporosis. Weighted GRS was significantly associated with decreased BMD. The contribution of subtype GRS to the BMD variation differs by specific biological pathway and skeletal regions.

Dataset Information

A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients.

Publications

A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients.

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