TY - JOUR
T1 - Effect of cachexia on bone turnover in cancer patients
T2 - a case-control study
AU - Zwickl, Hannes
AU - Zwickl-Traxler, Elisabeth
AU - Haushofer, Alexander
AU - Seier, Josef
AU - Podar, Klaus
AU - Weber, Michael
AU - Hackner, Klaus
AU - Jacobi, Nico
AU - Pecherstorfer, Martin
AU - Vallet, Sonia
N1 - Funding Information:
The authors want to appreciate the contribution of NÖ Landesgesundheitsagentur, legal entity of University Hospitals in Lower Austria, for providing the organizational framework to conduct this research. They also would like to acknowledge support by Open Access Publishing Fund of Karl Landsteiner University of Health Sciences, Krems, Austria.
Funding Information:
The authors want to appreciate the contribution of N? Landesgesundheitsagentur, legal entity of University Hospitals in Lower Austria, for providing the organizational framework to conduct this research. They also would like to acknowledge support by Open Access Publishing Fund of Karl Landsteiner University of Health Sciences, Krems, Austria. HZ designed the study and analyzed the data; EZT and KH collected data; AH and JS performed experiments; MP supervised and obtained research funding for the study; SV analyzed and interpreted the data, wrote the manuscript with editing from KP, MW and NJ. All authors read and approved the final manuscript.
Funding Information:
This work was supported by the Lower Austria Research Promotion Agency (Gesellschaft fuer Forschungsfoerderung Niederoesterreich) (grant number LSC14–021). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - BACKGROUND: Increased bone turnover is frequently observed in advanced cancer and predominantly related to bone metastases or therapy. Cachexia represents an important cause of morbidity and mortality in cancer patients. Key features are weight loss, muscle wasting and chronic inflammation, which induce profound metabolic changes in several organs, including the bone. However, whether cachexia contributes to abnormal bone metabolism in cancer patients is unknown. Aim of the present study was to determine the potential correlation of bone turnover markers with body composition and laboratory parameters in treatment-naïve cancer patients.METHODS: In this cross-sectional study we measured the levels of carboxy terminal telopeptide of collagen (CTX), an indicator of bone resorption, as well as osteocalcin (Ocn) and procollagen type I N-terminal propeptide (PINP), indicators of bone formation, in 52 cancer patients and correlated with body composition and laboratory parameters. Univariate and multivariate logistic analysis were performed to identify determinants of negative bone remodeling balance, estimated by CTX/Ocn and CTX/PINP ratio.RESULTS: Based on weight loss, body mass index and muscle mass, patients were divided into a cachectic (59.6%) and a control (40.4%) group. After correcting for the presence of bone metastases, our results showed a significant upregulation of CTX in cachectic patients compared to non-cachectic cancer patients (median 0.38 vs 0.27 ng/mL, p < 0.05), with no difference in Ocn and PINP levels (mean 14 vs. 16 ng/ml, p = 0.2 and median 32 vs. 26 μg/L, p = 0.5, respectively). In addition, the CTX/Ocn and the CTX/PINP ratio were indicative of bone resorption in 68% and 60% of cachexia patients, respectively (vs. 20% and 31% in the control group, p = 0.002 and p = 0.06). The main determinants of the unbalanced bone turnover were hypoalbuminemia for the CTX/Ocn ratio (OR 19.8, p < 0.01) and high CRP for the CTX/PINP ratio (OR 5.3, p < 0.01) in the multivariate regression analysis.CONCLUSIONS: CTX is substantially higher in cachectic patients compared to non-cachectic oncological patients and hypoalbuminemia as well as elevated CRP concentrations are independent predictors of a negative bone remodeling balance in cancer patients. These results strongly indicate that cachexia correlates with exacerbated bone turnover in cancer.
AB - BACKGROUND: Increased bone turnover is frequently observed in advanced cancer and predominantly related to bone metastases or therapy. Cachexia represents an important cause of morbidity and mortality in cancer patients. Key features are weight loss, muscle wasting and chronic inflammation, which induce profound metabolic changes in several organs, including the bone. However, whether cachexia contributes to abnormal bone metabolism in cancer patients is unknown. Aim of the present study was to determine the potential correlation of bone turnover markers with body composition and laboratory parameters in treatment-naïve cancer patients.METHODS: In this cross-sectional study we measured the levels of carboxy terminal telopeptide of collagen (CTX), an indicator of bone resorption, as well as osteocalcin (Ocn) and procollagen type I N-terminal propeptide (PINP), indicators of bone formation, in 52 cancer patients and correlated with body composition and laboratory parameters. Univariate and multivariate logistic analysis were performed to identify determinants of negative bone remodeling balance, estimated by CTX/Ocn and CTX/PINP ratio.RESULTS: Based on weight loss, body mass index and muscle mass, patients were divided into a cachectic (59.6%) and a control (40.4%) group. After correcting for the presence of bone metastases, our results showed a significant upregulation of CTX in cachectic patients compared to non-cachectic cancer patients (median 0.38 vs 0.27 ng/mL, p < 0.05), with no difference in Ocn and PINP levels (mean 14 vs. 16 ng/ml, p = 0.2 and median 32 vs. 26 μg/L, p = 0.5, respectively). In addition, the CTX/Ocn and the CTX/PINP ratio were indicative of bone resorption in 68% and 60% of cachexia patients, respectively (vs. 20% and 31% in the control group, p = 0.002 and p = 0.06). The main determinants of the unbalanced bone turnover were hypoalbuminemia for the CTX/Ocn ratio (OR 19.8, p < 0.01) and high CRP for the CTX/PINP ratio (OR 5.3, p < 0.01) in the multivariate regression analysis.CONCLUSIONS: CTX is substantially higher in cachectic patients compared to non-cachectic oncological patients and hypoalbuminemia as well as elevated CRP concentrations are independent predictors of a negative bone remodeling balance in cancer patients. These results strongly indicate that cachexia correlates with exacerbated bone turnover in cancer.
KW - Bone Remodeling/physiology
KW - Cachexia/complications
KW - Case-Control Studies
KW - Cross-Sectional Studies
KW - Humans
KW - Male
KW - Middle Aged
KW - Neoplasms/complications
KW - CRP
KW - Cachexia
KW - Bone turnover
KW - Procollagen type I N-terminal propeptide (PINP)
KW - Hypoalbuminemia
KW - Osteocalcin (Ocn)
KW - Carboxy terminal telopeptide of collagen type I (CTX)
UR - http://www.scopus.com/inward/record.url?scp=85108847696&partnerID=8YFLogxK
U2 - 10.1186/s12885-021-08518-9
DO - 10.1186/s12885-021-08518-9
M3 - Journal article
C2 - 34182958
SN - 1471-2407
VL - 21
SP - 744
JO - BMC Cancer
JF - BMC Cancer
IS - 1
M1 - 744
ER -