Effect of cachexia on bone turnover in cancer patients: a case-control study
Tóm tắt
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.
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.
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,
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.
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von Haehling S, Anker MS, Anker SD. Prevalence and clinical impact of cachexia in chronic illness in Europe, USA, and Japan: facts and numbers update 2016. J Cachexia Sarcopenia Muscle. 2016;7(5):507–9. https://doi.org/10.1002/jcsm.12167.
Argiles JM, Stemmler B, Lopez-Soriano FJ, Busquets S. Inter-tissue communication in cancer cachexia. Nat Rev Endocrinol. 2018;15(1):9–20. https://doi.org/10.1038/s41574-018-0123-0.
Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem. 2010;285(33):25103–8. https://doi.org/10.1074/jbc.R109.041087.
Seibel MJ. Biochemical markers of bone turnover: part I: biochemistry and variability. Clin Biochem Rev. 2005;26(4):97–122.
Massera D, Xu S, Walker MD, Valderrabano RJ, Mukamal KJ, Ix JH, et al. Biochemical markers of bone turnover and risk of incident hip fracture in older women: the cardiovascular health study. Osteoporos Int. 2019;30(9):1755–65. https://doi.org/10.1007/s00198-019-05043-1.
Civitelli R, Armamento-Villareal R, Napoli N. Bone turnover markers: understanding their value in clinical trials and clinical practice. Osteoporos Int. 2009;20(6):843–51. https://doi.org/10.1007/s00198-009-0838-9.
Coleman R, Body JJ, Aapro M, Hadji P, Herrstedt J, Group EGW. Bone health in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2014;25(Suppl 3):iii124–37.
Dumanskiy YV, Syniachenko OV, Stepko PA, Taktashov GS, Chernyshova OY, Stoliarova OY. The state of bone metabolism in lung cancer patients. Exp Oncol. 2018;40(2):136–9. https://doi.org/10.31768/2312-8852.2018.40(2):136-139.
Lassemillante AC, Doi SA, Hooper JD, Prins JB, Wright OR. Prevalence of osteoporosis in prostate cancer survivors II: a meta-analysis of men not on androgen deprivation therapy. Endocrine. 2015;50(2):344–54. https://doi.org/10.1007/s12020-015-0536-7.
El Maghraoui A, Ebo'o FB, Sadni S, Majjad A, Hamza T, Mounach A. Is there a relation between pre-sarcopenia, sarcopenia, cachexia and osteoporosis in patients with ankylosing spondylitis? BMC Musculoskelet Disord. 2016;17(1):268. https://doi.org/10.1186/s12891-016-1155-z.
Choi E, Carruthers K, Zhang L, Thomas N, Battaglino RA, Morse LR, et al. Concurrent muscle and bone deterioration in a murine model of cancer cachexia. Phys Rep. 2013;1(6):e00144. https://doi.org/10.1002/phy2.144.
Pin F, Barreto R, Kitase Y, Mitra S, Erne CE, Novinger LJ, et al. Growth of ovarian cancer xenografts causes loss of muscle and bone mass: a new model for the study of cancer cachexia. J Cachexia Sarcopenia Muscle. 2018;9(4):685–700. https://doi.org/10.1002/jcsm.12311.
Zwickl H, Hackner K, Kofeler H, Krzizek EC, Muqaku B, Pils D, et al. Reduced LDL-cholesterol and reduced Total cholesterol as potential indicators of early Cancer in male treatment-naive Cancer patients with pre-cachexia and Cachexia. Front Oncol. 2020;10:1262. https://doi.org/10.3389/fonc.2020.01262.
Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489–95. https://doi.org/10.1016/S1470-2045(10)70218-7.
Yoon SL, Grundmann O, Williams JJ, Gordan L, George TJ Jr. Body composition changes differ by gender in stomach, colorectal, and biliary cancer patients with cachexia: results from a pilot study. Cancer Med. 2018;7(8):3695–703. https://doi.org/10.1002/cam4.1665.
Grundmann O, Yoon SL, Williams JJ. The value of bioelectrical impedance analysis and phase angle in the evaluation of malnutrition and quality of life in cancer patients--a comprehensive review. Eur J Clin Nutr. 2015;69(12):1290–7. https://doi.org/10.1038/ejcn.2015.126.
Janssen I, Heymsfield SB, Ross R. Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. J Am Geriatr Soc. 2002;50(5):889–96. https://doi.org/10.1046/j.1532-5415.2002.50216.x.
Melton LJ 3rd, Atkinson EJ, Achenbach SJ, Kanis JA, Therneau TM, Johansson H, et al. Potential extensions of the US FRAX algorithm. J Osteoporos. 2012;2012:528790.
Fisher A, Fisher L, Srikusalanukul W, Smith PN. Bone turnover status: classification model and clinical implications. Int J Med Sci. 2018;15(4):323–38. https://doi.org/10.7150/ijms.22747.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. https://doi.org/10.1210/jc.2011-0385.
Forrest LM, McMillan DC, McArdle CS, Angerson WJ, Dunlop DJ. Evaluation of cumulative prognostic scores based on the systemic inflammatory response in patients with inoperable non-small-cell lung cancer. Br J Cancer. 2003;89(6):1028–30. https://doi.org/10.1038/sj.bjc.6601242.
D'Andrea D, Soria F, Abufaraj M, Gust K, Foerster B, Vartolomei MD, et al. Clinical value of cholinesterase in the prediction of biochemical recurrence after radical prostatectomy. Urol Oncol. 2018;36(12):528 e527–13.
Heymsfield SB, Gonzalez MC, Lu J, Jia G, Zheng J. Skeletal muscle mass and quality: evolution of modern measurement concepts in the context of sarcopenia. Proc Nutr Soc. 2015;74(4):355–66. https://doi.org/10.1017/S0029665115000129.
Evans WJ, Morley JE, Argiles J, Bales C, Baracos V, Guttridge D, et al. Cachexia: a new definition. Clin Nutr. 2008;27(6):793–9. https://doi.org/10.1016/j.clnu.2008.06.013.
Thibaut MM, Sboarina M, Roumain M, Potgens SA, Neyrinck AM, Destree F, et al. Inflammation-induced cholestasis in cancer cachexia. J Cachexia Sarcopenia Muscle. 2021;12(1):70–90. https://doi.org/10.1002/jcsm.12652.
Schwarz S, Prokopchuk O, Esefeld K, Groschel S, Bachmann J, Lorenzen S, et al. The clinical picture of cachexia: a mosaic of different parameters (experience of 503 patients). BMC Cancer. 2017;17(1):130. https://doi.org/10.1186/s12885-017-3116-9.
Liu JM, Zhao HY, Zhao L, Chen Y, Zhang LZ, Tao B, et al. An independent positive relationship between the serum total osteocalcin level and fat-free mass in healthy premenopausal women. J Clin Endocrinol Metab. 2013;98(5):2146–52. https://doi.org/10.1210/jc.2013-1112.
Taxel P, Faircloth E, Idrees S, Van Poznak C. Cancer treatment-induced bone loss in women with breast Cancer and men with prostate Cancer. J Endocr Soc. 2018;2(7):574–88. https://doi.org/10.1210/js.2018-00052.
Vallet S, Smith MR, Raje N. Novel bone-targeted strategies in oncology. Clin Cancer Res. 2010;16(16):4084–93. https://doi.org/10.1158/1078-0432.CCR-10-0600.
De Waele E, Demol J, Caccialanza R, Cotogni P, Spapen H, Malbrain ML, et al. Unidentified cachexia patients in the oncologic setting: Cachexia UFOs do exist. Nutrition. 2019;63-64:200–4. https://doi.org/10.1016/j.nut.2019.02.015.
Lopez-Gomez JJ, Izaola-Jauregui O, Primo-Martin D, Torres-Torres B, Gomez-Hoyos E, Ortola-Buigues A, et al. Effect of weight loss on bone metabolism in postmenopausal obese women with osteoarthritis. Obes Res Clin Pract. 2019;13(4):378–84. https://doi.org/10.1016/j.orcp.2019.03.002.
Redlich K, Smolen JS. Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat Rev Drug Discov. 2012;11(3):234–50. https://doi.org/10.1038/nrd3669.
Ng K, Sargent DJ, Goldberg RM, Meyerhardt JA, Green EM, Pitot HC, et al. Vitamin D status in patients with stage IV colorectal cancer: findings from intergroup trial N9741. J Clin Oncol. 2011;29(12):1599–606. https://doi.org/10.1200/JCO.2010.31.7255.
Crew KD, Shane E, Cremers S, McMahon DJ, Irani D, Hershman DL. High prevalence of vitamin D deficiency despite supplementation in premenopausal women with breast cancer undergoing adjuvant chemotherapy. J Clin Oncol. 2009;27(13):2151–6. https://doi.org/10.1200/JCO.2008.19.6162.
Lips P, van Schoor NM. The effect of vitamin D on bone and osteoporosis. Best Pract Res Clin Endocrinol Metab. 2011;25(4):585–91. https://doi.org/10.1016/j.beem.2011.05.002.
Stewart AF, Vignery A, Silverglate A, Ravin ND, LiVolsi V, Broadus AE, et al. Quantitative bone histomorphometry in humoral hypercalcemia of malignancy: uncoupling of bone cell activity. J Clin Endocrinol Metab. 1982;55(2):219–27. https://doi.org/10.1210/jcem-55-2-219.
Kir S, White JP, Kleiner S, Kazak L, Cohen P, Baracos VE, et al. Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature. 2014;513(7516):100–4. https://doi.org/10.1038/nature13528.
Graat-Verboom L, Spruit MA, van den Borne BE, Smeenk FW, Martens EJ, Lunde R, et al. Correlates of osteoporosis in chronic obstructive pulmonary disease: an underestimated systemic component. Respir Med. 2009;103(8):1143–51. https://doi.org/10.1016/j.rmed.2009.02.014.
Bozic B, Loncar G, Prodanovic N, Radojicic Z, Cvorovic V, Dimkovic S, et al. Relationship between high circulating adiponectin with bone mineral density and bone metabolism in elderly males with chronic heart failure. J Card Fail. 2010;16(4):301–7. https://doi.org/10.1016/j.cardfail.2009.12.015.
Tsukamoto M, Mori T, Nakamura E, Okada Y, Fukuda H, Yamanaka Y, et al. Chronic obstructive pulmonary disease severity in middle-aged and older men with osteoporosis associates with decreased bone formation. Osteoporos Sarcopenia. 2020;6(4):179–84. https://doi.org/10.1016/j.afos.2020.11.003.
Demirelli B, Babacan NA, Ercelep O, Ozturk MA, Kaya S, Tanrikulu E, et al. Modified Glasgow prognostic score, prognostic nutritional index and ECOG performance score predicts survival better than sarcopenia, Cachexia and some inflammatory indices in metastatic gastric Cancer. Nutr Cancer. 2021;73(2):230–8. https://doi.org/10.1080/01635581.2020.1749290.
Afshinnia F, Wong KK, Sundaram B, Ackermann RJ, Pennathur S. Hypoalbuminemia and osteoporosis: reappraisal of a controversy. J Clin Endocrinol Metab. 2016;101(1):167–75. https://doi.org/10.1210/jc.2015-3212.
Fisher A, Srikusalanukul W, Fisher L, Smith PN. Lower serum P1NP/betaCTX ratio and hypoalbuminemia are independently associated with osteoporotic nonvertebral fractures in older adults. Clin Interv Aging. 2017;12:1131–40. https://doi.org/10.2147/CIA.S141097.
Bellafronte NT, Batistuti MR, Dos Santos NZ, Holland H, Romao EA, P GC. Estimation of Body composition and water data depends on the bioelectrical impedance device. J Electr Bioimpedance. 2018;9(1):96–105. https://doi.org/10.2478/joeb-2018-0014.
Kyle UG, Bosaeus I, De Lorenzo AD, Deurenberg P, Elia M, Manuel Gomez J, et al. Bioelectrical impedance analysis-part II: utilization in clinical practice. Clin Nutr. 2004;23(6):1430–53. https://doi.org/10.1016/j.clnu.2004.09.012.
Khosla S, Melton LJ 3rd, Atkinson EJ, O'Fallon WM, Klee GG, Riggs BL. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab. 1998;83(7):2266–74. https://doi.org/10.1210/jcem.83.7.4924.
Hain BA, Jude B, Xu H, Smuin DM, Fox EJ, Elfar JC, et al. Zoledronic acid improves muscle function in healthy mice treated with chemotherapy. J Bone Miner Res. 2020;35(2):368–81. https://doi.org/10.1002/jbmr.3890.
Essex AL, Pin F, Huot JR, Bonewald LF, Plotkin LI, Bonetto A. Bisphosphonate treatment ameliorates chemotherapy-induced bone and muscle abnormalities in young mice. Front Endocrinol (Lausanne). 2019;10:809. https://doi.org/10.3389/fendo.2019.00809.
Bonetto A, Kays JK, Parker VA, Matthews RR, Barreto R, Puppa MJ, et al. Differential bone loss in mouse models of Colon Cancer Cachexia. Front Physiol. 2016;7:679.