Spatial and Temporal Fracture Pattern in Breast and Gynecologic Cancer Survivors

Song, Hui; Arentsen, Luke; Wilcox, Anjali; Shanley, Ryan; Yee, Douglas; Ghebre, Rahel

doi:10.7150/jca.10288

Cited by 12 publications

(9 citation statements)

References 12 publications

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“…Our results also have implications for understanding the etiology of the increased fracture risk associated with in vivo radiation therapy treatment for cancer [2,8,[60][61][62][63][64][65]. We did not observe any change in mechanical behavior for ex vivo dose levels relevant to radiation therapy (i.e.…”

Section: Discussionmentioning

confidence: 62%

Effects of ex vivo ionizing radiation on collagen structure and whole-bone mechanical properties of mouse vertebrae

Pendleton

Emerzian

Liu

et al. 2019

Bone

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Bone can become brittle when exposed to ionizing radiation across a wide range of clinically relevant doses that span from radiotherapy (accumulative 50 Gy) to sterilization (~35,000 Gy). While irradiation-induced embrittlement has been attributed to changes in the collagen molecular structure, the relative role of collagen fragmentation versus non-enzymatic collagen crosslinking remains unclear. To better understand the effects of radiation on the bone material without cellular activity, we conducted an ex vivo x-ray radiation experiment on excised mouse lumbar vertebrae. Spinal tissue from twenty-week old, female, C57BL/6J mice were randomly assigned to a single x-ray radiation dose of either 0 (control), 50, 1,000, 17,000, or 35,000 Gy. Measurements were made for collagen fragmentation, non-enzymatic collagen crosslinking, and both monotonic and cyclic-loading compressive mechanical properties. We found that the group differences for mechanical properties were more consistent with those for collagen fragmentation than for non-enzymatic collagen crosslinking. Monotonic strength at 17,000 and 35,000 Gy was lower than that of the control by 50% and 73% respectively, (p < 0.001) but at 50 and 1,000 Gy was not different than the control. Consistent with those trends, collagen fragmentation only occurred at 17,000 and 35,000 Gy. By contrast, non-enzymatic collagen crosslinking was greater than control for all radiation doses (p < 0.001). All results were consistent both for monotonic and cyclic loading conditions. We conclude that the reductions in bone compressive monotonic strength and fatigue life due to ex vivo ionizing radiation are more likely caused by fragmentation of the collagen backbone than any increases in non-enzymatic collagen crosslinks.

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Section: Discussionmentioning

confidence: 62%

Effects of ex vivo ionizing radiation on collagen structure and whole-bone mechanical properties of mouse vertebrae

Pendleton

Emerzian

Liu

et al. 2019

Bone

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“…DECT is feasible for clinical studies since, against conventional wisdom, doses from DECT have been shown to be similar to single energy CT [15, 16]. A quick, accurate, and efficient method to examine both MAT and marrow corrected vBMD would be beneficial to the cancer survivor [17]. The current study is the first to characterize both MAT and accurate vBMD of mineralized tissue throughout the whole body.…”

Section: Introductionmentioning

confidence: 99%

Use of dual-energy computed tomography to measure skeletal-wide marrow composition and cancellous bone mineral density

et al. 2016

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Temporal and spatial variations in bone marrow adipose tissue (MAT) can be indicative of several pathologies and confound current methods of assessing immediate changes in bone mineral remodeling. We present a novel dual energy computed tomography (DECT) method to monitor MAT and marrow corrected volumetric BMD (mcvBMD) throughout the body. Twenty-three cancellous skeletal sites in 20 adult female cadavers aged 40–80 years old were measured using DECT (80kVp and 140kVp). vBMD was simultaneous recorded using QCT. MAT was further sampled using MRI. Thirteen lumbar vertebrae were then excised from the MRI-imaged donors and examined by microCT. After MAT correction throughout the skeleton, significant differences (p < 0.05) were found between QCT-derived vBMD and DECT-derived mcvBMD results. McvBMD was highly heterogeneous with a maximum at the posterior skull and minimum in the proximal humerus (574 mg/cc and 0.7 mg/cc, respectively). BV/TV and BMC have a nearly significant correlation with mcvBMD (r = 0.545, p=0.057 and r = 0.539, p=0.061, respectively). MAT assessed by DECT showed a significant correlation with MRI MAT results (r = 0.881, p<0.0001). Both DECT- and MRI-derived MAT had a significant influence on uncorrected vBMD (r = −0.86 and r = −0.818, p≤0.0001, respectively). Conversely, mcvBMD had no correlation with DECT- or MRI- derived MAT (r = 0.261 and r = 0.067). DECT can be used to assess MAT while simultaneously collecting mcvBMD values at each skeletal site. MAT is heterogeneous throughout the skeleton, highly variable, and should be accounted for in longitudinal mcvBMD studies. McvBMD accurately reflects the calcified tissue in cancellous bone.

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“…Bone marrow fat was associated with vertebral fracture in older adults and postmenopausal women (13). The rapid increase in marrow fat after cytotoxic cancer therapy in pre-clinical studies (14,15) and a recent retrospective clinical study revealing post treatment early fracture events (16) emphasizes the need to assess MF along with bone in cancer patients. However, changes in MF are not readily detected by a traditional dual-energy X-ray absorptiometry (DXA) scan, since DXA only calculates average BMD by superimposing cortical and cancellous BMD.…”

Section: Introductionmentioning

confidence: 99%

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

Song

Arentsen

Sueblinvong

et al. 2015

Bone

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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 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 12 months after treatment. BMD and MF percent and distribution were quantified in lumbar vertebrae and the right femoral neck. Results Measured precision (3 mg/cm3) 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 by 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.

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Spatial and Temporal Fracture Pattern in Breast and Gynecologic Cancer Survivors

Cited by 12 publications

References 12 publications

Effects of ex vivo ionizing radiation on collagen structure and whole-bone mechanical properties of mouse vertebrae

Effects of ex vivo ionizing radiation on collagen structure and whole-bone mechanical properties of mouse vertebrae

Use of dual-energy computed tomography to measure skeletal-wide marrow composition and cancellous bone mineral density

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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