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      Radiation-induced changes to bone composition extend beyond periosteal bone

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          Abstract

          Background

          Cancer patients receiving radiotherapy for soft tissue sarcomas are often at risk of post-irradiation (post-RTx) bone fragility fractures, but our understanding of factors controlling radiation-induced bone injury is limited. Previous studies have evaluated post-RTx changes to cortical bone composition in the periosteum of irradiated tibiae, but have not evaluated effects of irradiation in deeper tissues, such as endosteal or mid-cortical bone, and whether there are differential spatial effects of irradiation. In this study, we hypothesize that post-RTx changes to cortical bone composition are greater in endosteal compared to mid-cortical or periosteal bone.

          Methods

          A pre-clinical mouse model of limited field hindlimb irradiation was used to evaluate spatial and temporal post-RTx changes to the metaphyseal cortex of irradiated tibiae. Irradiation was delivered unilaterally to the hindlimbs of 12-wk old female BALB/cJ mice as 4 consecutive daily doses of 5 Gy each. RTx and non-RTx tibiae were obtained at 0, 2, 4, 8, and 12 wks post-RTx ( n = 9 mice/group/time). Raman spectroscopy was used to evaluate spatial and temporal post-RTx changes to cortical bone composition in age-matched RTx and non-RTx groups.

          Results

          Significant early spatial differences in mineral/matrix and collagen crosslink ratios were found between endosteal and periosteal or mid-cortical bone at 2-wks post-RTx. Although spatial differences were transient, mineral/matrix ratios significantly decreased and collagen crosslink ratios significantly increased with post-RTx time throughout the entire tibial metaphyseal cortex.

          Conclusions

          Irradiation negatively impacts the composition of cortical bone in a spatially-dependent manner starting as early as 2-wks post-RTx. Long-term progressive post-RTx changes across all cortical bone sites may eventually contribute to the increased risk of post-RTx bone fragility fractures.

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          Spectroscopic characterization of collagen cross-links in bone.

          K Verdelis, Jennifer Doty, A Boskey … (2001)
          Collagen is the most abundant protein of the organic matrix in mineralizing tissues. One of its most critical properties is its cross-linking pattern. The intermolecular cross-linking provides the fibrillar matrices with mechanical properties such as tensile strength and viscoelasticity. In this study, Fourier transform infrared (FTIR) spectroscopy and FTIR imaging (FTIRI) analyses were performed in a series of biochemically characterized samples including purified collagen cross-linked peptides, demineralized bovine bone collagen from animals of different ages, collagen from vitamin B6-deficient chick homogenized bone and their age- and sex-matched controls, and histologically stained thin sections from normal human iliac crest biopsy specimens. One region of the FTIR spectrum of particular interest (the amide I spectral region) was resolved into its underlying components. Of these components, the relative percent area ratio of two subbands at approximately 1660 cm(-1) and approximately 1690 cm(-1) was related to collagen cross-links that are abundant in mineralized tissues (i.e., pyridinoline [Pyr] and dehydrodihydroxylysinonorleucine [deH-DHLNL]). This study shows that it is feasible to monitor Pyr and DHLNL collagen cross-links spatial distribution in mineralized tissues. The spectroscopic parameter established in this study may be used in FTIRI analyses, thus enabling the calculation of relative Pyr/DHLNL amounts in thin (approximately 5 microm) calcified tissue sections with a spatial resolution of approximately 7 microm.
          Article 0 comments Cited 98 times – based on 0 reviews     Review now
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            Carbonate assignment and calibration in the Raman spectrum of apatite.

            Daniel S. Morris, Mary M J Tecklenburg, Ayorinde Awonusi (2007)
            A series of apatites with varying carbonate levels was prepared in order to assign the carbonate bands and calibrate for Raman analysis of natural materials. Overlap of carbonate bands with phosphate peaks was resolved by curve fitting. A peak at 1,071 cm(-1) was assigned to a combination of the carbonate nu(1) mode at 1,070 cm(-1) with a phosphate nu(3) mode at 1,076 cm(-1). In addition, the carbonate nu(4) mode was identified in apatite samples with >4% carbonate. The carbonate nu(4) bands at 715 and 689 cm(-1) identify the samples as B-type carbonated apatite. The carbonate content of apatite was calibrated to a carbonate Raman band, and the method was used to determine the carbonate content of a sample of bovine cortical bone, 7.7 +/- 0.4%.
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              Risk of pelvic fractures in older women following pelvic irradiation.

              Nancy Baxter, Samuel E. Tepper, E Habermann … (2005)
              Pelvic fractures, including hip fractures, are a major source of morbidity and mortality in older women. Although therapeutic pelvic irradiation could increase the risk of such fractures, this effect has not been studied. To determine if women who undergo pelvic irradiation for pelvic malignancies (anal, cervical, or rectal cancers) have a higher rate of pelvic fracture than women with pelvic malignancies who do not undergo irradiation. We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked to Medicare claims data. A total of 6428 women aged 65 years and older diagnosed with pelvic malignancies from 1986 through 1999 were included. We compared results for women who did (n = 2855) vs did not (n = 3573) undergo radiation therapy. To assess the influence of selection bias, we also evaluated the effect of irradiation on osteoporotic fractures in nonirradiated sites (arm and spine). We evaluated the effect of irradiation on the incidence of pelvic fractures over time, and adjusted for potential confounders using a proportional hazards model. Women who underwent radiation therapy were more likely to have a pelvic fracture than women who did not undergo radiation therapy (cumulative 5-year fracture rate, 14.0% vs 7.5% in women with anal cancer, 8.2% vs 5.9% in women with cervical cancer, and 11.2% vs 8.7% in women with rectal cancer); the difference was statistically significant and most fractures (90%) were hip fractures. We controlled for potential confounders including age, race, cancer stage, and geographic location. The impact of irradiation varied by cancer site: treatment for anal cancer was associated with a higher risk of pelvic fractures (hazard ratio, 3.16; 95% confidence interval, 1.48-6.73); than for cervical cancer (hazard ratio, 1.66; 95% confidence interval, 1.06-2.59); or rectal cancer (hazard ratio, 1.65; 95% confidence interval, 1.33-2.05). No statistically significant difference was found in the rate of arm or spine fractures between the irradiated and nonirradiated groups (hazard ratio, 1.15; 95% confidence interval, 0.89-1.48). Pelvic irradiation substantially increases the risk of pelvic fractures in older women. Given the high baseline risk of pelvic fracture, this finding is of particular concern.
              Article 0 comments Cited 70 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                David H. Kohn
                Journal
                Journal ID (nlm-ta): Bone Rep
                Journal ID (iso-abbrev): Bone Rep
                Title: Bone Reports
                Publisher: Elsevier
                ISSN (Electronic): 2352-1872
                Publication date PMC-release: 28 March 2020
                Publication date Collection: June 2020
                Publication date (Electronic): 28 March 2020
                Volume: 12
                Electronic Location Identifier: 100262
                Affiliations
                [a ]School of Dentistry, University of Michigan, Ann Arbor, MI, USA
                [b ]Department of Orthopedic Surgery, Upstate Medical University, Syracuse, NY, USA
                [c ]Department of Chemistry, University of Michigan, Ann Arbor, USA
                [d ]Department of Biomedical Engineering, University of Michigan, Ann Arbor, USA
                Author notes
                [* ]Corresponding author at: Departments of Biologic and Materials Sciences and Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109-1078, USA. dhkohn@ 123456umich.edu
                Article
                Publisher ID: S2352-1872(20)30022-X Publisher ID: 100262
                DOI: 10.1016/j.bonr.2020.100262
                PMC ID: 7125315
                PubMed ID: 32258252
                SO-VID: 76529a91-efc6-46ef-9cc8-bb0b577bdd05
                Copyright © © 2020 The Author(s)
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 8 December 2019
                Date revision received : 25 March 2020
                Date accepted : 26 March 2020
                Categories
                Subject: Article

                Keywords: post-irradiation,mouse model,raman spectroscopy,bone quality,cortical bone,bone composition
                Data availability:
                Keywords: post-irradiation, mouse model, raman spectroscopy, bone quality, cortical bone, bone composition

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