TY - JOUR
T1 - Altered collagen chemical compositional structure in osteopenic women with past fractures
T2 - A case-control Raman spectroscopic study
AU - Mandair, Gurjit S.
AU - Akhter, Mohammed P.
AU - Esmonde-White, Francis W.L.
AU - Lappe, Joan M.
AU - Bare, Susan P.
AU - Lloyd, William R.
AU - Long, Jason P.
AU - Lopez, Jessica
AU - Kozloff, Kenneth M.
AU - Recker, Robert R.
AU - Morris, Michael D.
N1 - Funding Information:
This study was supported by grant R01-AR054496 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). GSM also acknowledges partial support by NIH grant P30 AR069620 (Karl J. Jepsen, PI; David H. Kohn, Core Director of the Michigan Integrative Musculoskeletal Health Core Center or MiMHC). All authors thank Dr. Patrice A. Watson (Creighton University) for her statistical support. GSM and MDM also thank Center for Statistical Consultation and Research (CSCAR) of the University of Michigan for statistical support. GSM and MDM thank Dr. Steven Goldstein (University of Michigan) for useful discussions. The authors thank all the study participants who provided bone biopsies for this study.
Funding Information:
GSM, MPA, FWLEW, JML, SPB, WRL, JPL, and JL declare that they have no conflict of interest. MDM, RRR, and PAW have reported grants from National Institutes of Health, during the conduct of this study. MDM reports potential benefit as a result of the content being related to licensed technology to BioMatrix Photonics. KMK has received consultant fees from Mereo Biopharma and Ultragenyx Pharmaceuticals. KMK has received research funding from Cayman Chemical and Mereo Biopharma, and has received research supplies (sclerostin antibody) from Amgen Inc. and UCB.
Funding Information:
This study was supported by grant R01-AR054496 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). GSM also acknowledges partial support by NIH grant P30 AR069620 (Karl J. Jepsen, PI; David H. Kohn, Core Director of the Michigan Integrative Musculoskeletal Health Core Center or MiMHC). All authors thank Dr. Patrice A. Watson (Creighton University) for her statistical support. GSM and MDM also thank Center for Statistical Consultation and Research (CSCAR) of the University of Michigan for statistical support. GSM and MDM thank Dr. Steven Goldstein (University of Michigan) for useful discussions. The authors thank all the study participants who provided bone biopsies for this study.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/7
Y1 - 2021/7
N2 - Incidences of low-trauma fractures among osteopenic women may be related to changes in bone quality. In this blinded, prospective-controlled study, compositional and heterogeneity contributors of bone quality to fracture risk were examined. We hypothesize that Raman spectroscopy can differentiate between osteopenic women with one or more fractures (cases) from women without fractures (controls). This study involved the Raman spectroscopic analysis of cortical and cancellous bone composition using iliac crest biopsies obtained from 59-cases and 59-controls, matched for age (62.0 ± 7.5 and 61.7 ± 7.3 years, respectively, p = 0.38) and hip bone mineral density (BMD, 0.827 ± 0.083 and 0.823 ± 0.072 g/cm3, respectively, p = 0.57). Based on aggregate univariate case-control and odds ratio based logistic regression analyses, we discovered two Raman ratiometric parameters that were predictive of past fracture risk. Specifically, 1244/1268 and 1044/959 cm−1 ratios, were identified as the most differential aspects of bone quality in cortical cases with odds ratios of 0.617 (0.406–0.938 95% CI, p = 0.024) and 1.656 (1.083–2.534 95% CI, p = 0.020), respectively. Both 1244/1268 and 1044/959 cm−1 ratios exhibited moderate sensitivity (59.3–64.4%) but low specificity (49.2–52.5%). These results suggest that the organization of mineralized collagen fibrils were significantly altered in cortical cases compared to controls. In contrast, compositional and heterogeneity parameters related to mineral/matrix ratios, B-type carbonate substitutions, and mineral crystallinity, were not significantly different between cases and controls. In conclusion, a key outcome of this study is the significant odds ratios obtained for two Raman parameters (1244/1268 and 1044/959 cm−1 ratios), which from a diagnostic perspective, may assist in the screening of osteopenic women with suspected low-trauma fractures. One important implication of these findings includes considering the possibility that changes in the organization of collagen compositional structure plays a far greater role in postmenopausal women with osteopenic fractures.
AB - Incidences of low-trauma fractures among osteopenic women may be related to changes in bone quality. In this blinded, prospective-controlled study, compositional and heterogeneity contributors of bone quality to fracture risk were examined. We hypothesize that Raman spectroscopy can differentiate between osteopenic women with one or more fractures (cases) from women without fractures (controls). This study involved the Raman spectroscopic analysis of cortical and cancellous bone composition using iliac crest biopsies obtained from 59-cases and 59-controls, matched for age (62.0 ± 7.5 and 61.7 ± 7.3 years, respectively, p = 0.38) and hip bone mineral density (BMD, 0.827 ± 0.083 and 0.823 ± 0.072 g/cm3, respectively, p = 0.57). Based on aggregate univariate case-control and odds ratio based logistic regression analyses, we discovered two Raman ratiometric parameters that were predictive of past fracture risk. Specifically, 1244/1268 and 1044/959 cm−1 ratios, were identified as the most differential aspects of bone quality in cortical cases with odds ratios of 0.617 (0.406–0.938 95% CI, p = 0.024) and 1.656 (1.083–2.534 95% CI, p = 0.020), respectively. Both 1244/1268 and 1044/959 cm−1 ratios exhibited moderate sensitivity (59.3–64.4%) but low specificity (49.2–52.5%). These results suggest that the organization of mineralized collagen fibrils were significantly altered in cortical cases compared to controls. In contrast, compositional and heterogeneity parameters related to mineral/matrix ratios, B-type carbonate substitutions, and mineral crystallinity, were not significantly different between cases and controls. In conclusion, a key outcome of this study is the significant odds ratios obtained for two Raman parameters (1244/1268 and 1044/959 cm−1 ratios), which from a diagnostic perspective, may assist in the screening of osteopenic women with suspected low-trauma fractures. One important implication of these findings includes considering the possibility that changes in the organization of collagen compositional structure plays a far greater role in postmenopausal women with osteopenic fractures.
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U2 - 10.1016/j.bone.2021.115962
DO - 10.1016/j.bone.2021.115962
M3 - Article
C2 - 33862262
AN - SCOPUS:85104295139
SN - 8756-3282
VL - 148
JO - Bone
JF - Bone
M1 - 115962
ER -