nach oben

Erschienen in:

06.07.2023 | Original Article

Negative impact on bone homeostasis in postmenopausal women with non-metastatic breast cancer during cytotoxic chemotherapy

verfasst von: Yadav Nisha, Biswajit Dubashi, Zachariah Bobby, Jaya Prakash Sahoo, Smita Kayal, Ramesh Ananthakrishnan, Vijay Bhaskar Reddy, Charles L, Prasanth Ganesan

Erschienen in: Journal of Bone and Mineral Metabolism | Ausgabe 5/2023

Einloggen, um Zugang zu erhalten

Abstract

Introduction

The burden and mechanisms of endocrine therapy-related bone loss are well known, while there are limited data on chemotherapy-induced bone resorption. The study aimed to evaluate the effect of cytotoxic chemotherapy on bone homeostasis among postmenopausal women with non-metastatic breast cancer.

Materials and methods

Early and locally advanced postmenopausal non-metastatic breast cancer patients aged 45 to 65 planned for three cycles of anthracycline and four cycles of taxane chemotherapy administered along with dexamethasone (cumulative dose—256 mg) as an antiemetic from June 2018 to December 2021 were included. Bone mineral density (BMD), bone turnover markers, calciotropic hormones, pro-inflammatory cytokines, oxidative stress, and total antioxidant levels (TAS) were measured.

Results

We recruited 109 patients, with early 34 (31.2%) and locally advanced breast cancer 75 (68.8%) with median age 53 (45–65) years. There was a significant decrease in the % BMD at the lumbar spine, neck of the femur, and total hip post-chemotherapy. There was a significant increase in serum C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) levels post-chemotherapy. PINP/CTX ratio significantly decreased post-chemotherapy. Serum 25-OH vitamin D was significantly reduced with a compensatory increase in plasma iPTH levels. The change in CTX, PINP/CTX ratio, 25-OH vitamin D, iPTH, and oxidative stress index was more pronounced during anthracycline as taxane chemotherapy. There were no significant changes in pro-inflammatory cytokine levels.

Conclusion

Chemotherapy and dexamethasone as antiemetic resulted in significant bone loss, as evidenced by bone turnover markers. Further studies are required to understand the mechanism of chemotherapy-induced bone loss and the need for bone-strengthening agents during chemotherapy.

Nur mit Berechtigung zugänglich

Coleman RE, Rathbone E, Brown JE (2013) Management of cancer treatment-induced bone loss. Nat Rev Rheumatol 9:365–374. https://doi.org/10.1038/nrrheum.2013.36CrossRefPubMed

Khachidze N, Giorgadze E, Tsagareli M (2017) adjuvant (hormonal) therapy as a cause of bone loss in patients with breast cancer (review of literature). Georgian Med News 2:39–42

Weitzmann MN, Pacifici R (2006) Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest 116:1186–1194. https://doi.org/10.1172/JCI28550CrossRefPubMedPubMedCentral

Ewertz M, Jensen AB (2011) Late effects of breast cancer treatment and potentials for rehabilitation. Acta Oncol 50:187–193. https://doi.org/10.3109/0284186X.2010.533190CrossRefPubMed

Rosen CJ, Tenenhouse A (1998) Biochemical markers of bone turnover. A look at laboratory tests that reflect bone status. Postgrad Med 104:101–102. https://doi.org/10.3810/pgm.1998.10.447CrossRefPubMed

Delmas PD, Eastell R, Garnero P et al (2000) The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int 11:S2-17. https://doi.org/10.1007/s001980070002CrossRefPubMed

Jung K, Lein M (2014) Bone turnover markers in serum and urine as diagnostic, prognostic and monitoring biomarkers of bone metastasis. Biochim Biophys Acta 1846:425–438. https://doi.org/10.1016/j.bbcan.2014.09.001CrossRefPubMed

Bauer DC, Black DM, Bouxsein ML et al (2018) Treatment-related changes in bone turnover and fracture risk reduction in clinical trials of anti-resorptive drugs: a meta-regression. J Bone Miner Res 33:634–642. https://doi.org/10.1002/jbmr.3355CrossRefPubMed

Eastell R, Pigott T, Gossiel F et al (2018) DIAGNOSIS OF ENDOCRINE DISEASE: Bone turnover markers: are they clinically useful? Eur J Endocrinol 178:R19–R31. https://doi.org/10.1530/EJE-17-0585CrossRefPubMed

10.

Kailajärvi MEH, Salminen EK, Paija OMM et al (2004) Serum bone markers in breast cancer patients during 5-fluorouracil, epirubicin and cyclophosphamide (FEC) therapy. Anticancer Res 24:25

11.

Oostra DR, Lustberg MB, Reinbolt RE et al (2015) Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer. Mol Cell Endocrinol 402:51–56. https://doi.org/10.1016/j.mce.2014.12.028CrossRefPubMedPubMedCentral

12.

Rodríguez-Rodríguez LM, Rodríguez-Rodríguez EM, Oramas-Rodríguez JM et al (2005) Changes on bone mineral density after adjuvant treatment in women with non-metastatic breast cancer. Breast Cancer Res Treat. https://doi.org/10.1007/s10549-005-3803-0CrossRefPubMed

13.

Chen Y, Xu G, Yang F (2015) Effect of neoadjuvant chemotherapy on the serum levels of bone turnover markers in women with early-stage breast cancer. PLoS ONE 10:e0126053. https://doi.org/10.1371/journal.pone.0126053CrossRefPubMedPubMedCentral

14.

Jacot W, Pouderoux S, Thezenas S et al (2012) Increased prevalence of vitamin D insufficiency in patients with breast cancer after neoadjuvant chemotherapy. Breast Cancer Res Treat 134:709–717. https://doi.org/10.1007/s10549-012-2084-7CrossRefPubMed

15.

Manolagas SC (1995) Role of cytokines in bone resorption. Bone 17:63S-67S. https://doi.org/10.1016/8756-3282(95)00180-lCrossRefPubMed

16.

Kinder M, Chislock E, Bussard KM et al (2008) Metastatic breast cancer induces an osteoblast inflammatory response. Exp Cell Res 314:173–183. https://doi.org/10.1016/j.yexcr.2007.09.021CrossRefPubMed

17.

Abdollahi M, Larijani B, Rahimi R, Salari P (2005) Role of oxidative stress in osteoporosis. Therapy 2:787–796. https://doi.org/10.2217/14750708.2.5.787CrossRef

18.

Hadji P, Aapro MS, Body J-J et al (2017) Management of aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: joint position statement of the IOF, CABS, ECTS, IEG, ESCEO, IMS, and SIOG. J Bone Oncol 7:1–12. https://doi.org/10.1016/j.jbo.2017.03.001CrossRefPubMedPubMedCentral

19.

Mukherjee T (2016) Interpretation of ER and Her2neu hormonal receptor in breast cancer. Med J Armed Forces India 72:99. https://doi.org/10.1016/j.mjafi.2015.11.007CrossRefPubMed

20.

Fitzgibbons PL, Dillon DA, Alsabeh R et al (2014) Template for reporting results of biomarker testing of specimens from patients with carcinoma of the breast. Arch Pathol Lab Med 138:595–601. https://doi.org/10.5858/arpa.2013-0566-CPCrossRefPubMed

21.

Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421. https://doi.org/10.1016/0076-6879(90)86134-hCrossRefPubMed

22.

Yoshioka T, Kawada K, Shimada T, Mori M (1979) Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood. Am J Obstet Gynecol 135:372–376. https://doi.org/10.1016/0002-9378(79)90708-7CrossRefPubMed

23.

Benzie IFF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 239:70–76. https://doi.org/10.1006/abio.1996.0292CrossRefPubMed

24.

Vrieling A, Hein R, Abbas S et al (2011) Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study. Breast Cancer Res 13:R74. https://doi.org/10.1186/bcr2920CrossRefPubMedPubMedCentral

25.

Kitaura H, Marahleh A, Ohori F et al (2020) Osteocyte-related cytokines regulate osteoclast formation and bone resorption. Int J Mol Sci 21:5169. https://doi.org/10.3390/ijms21145169CrossRefPubMedPubMedCentral

26.

Steeve KT, Marc P, Sandrine T et al (2004) IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev 15:49–60. https://doi.org/10.1016/j.cytogfr.2003.10.005CrossRef

27.

Fan C, Georgiou KR, McKinnon RA et al (2016) Combination chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil causes trabecular bone loss, bone marrow cell depletion and marrow adiposity in female rats. J Bone Miner Metab 34:277–290. https://doi.org/10.1007/s00774-015-0679-xCrossRefPubMed

28.

Feng W, Liu H, Luo T et al (2017) Combination of IL-6 and sIL-6R differentially regulate varying levels of RANKL-induced osteoclastogenesis through NF-κB, ERK and JNK signaling pathways. Sci Rep 7:41411. https://doi.org/10.1038/srep41411CrossRefPubMedPubMedCentral

29.

Kobayashi K, Takahashi N, Jimi E et al (2000) Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med 191:275–286. https://doi.org/10.1084/jem.191.2.275CrossRefPubMedPubMedCentral

30.

Zha L, He L, Liang Y et al (2018) TNF-α contributes to postmenopausal osteoporosis by synergistically promoting RANKL-induced osteoclast formation. Biomed Pharmacother 102:369–374. https://doi.org/10.1016/j.biopha.2018.03.080CrossRefPubMed

31.

Numazawa S, Sugihara K, Miyake S et al (2011) Possible involvement of oxidative stress in 5-fluorouracil-mediated myelosuppression in mice. Basic Clin Pharmacol Toxicol 108:40–45. https://doi.org/10.1111/j.1742-7843.2010.00621.xCrossRefPubMed

32.

Domazetovic V, Marcucci G, Iantomasi T et al (2017) Oxidative stress in bone remodeling: role of antioxidants. Clin Cases Miner Bone Metab 14:209–216. https://doi.org/10.11138/ccmbm/2017.14.1.209CrossRefPubMedPubMedCentral

33.

Bai X, Lu D, Liu A et al (2005) Reactive oxygen species stimulates receptor activator of NF-kappaB ligand expression in osteoblast. J Biol Chem 280:17497–17506. https://doi.org/10.1074/jbc.M409332200CrossRefPubMed

34.

Anderson PH, Sawyer RK, Moore AJ et al (2008) Vitamin D depletion induces RANKL-mediated osteoclastogenesis and bone loss in a rodent model. J Bone Miner Res 23:1789–1797. https://doi.org/10.1359/jbmr.080616CrossRefPubMed

35.

Kaji H, Sugimoto T, Kanatani M et al (1997) Dexamethasone stimulates osteoclast-like cell formation by directly acting on hemopoietic blast cells and enhances osteoclast-like cell formation stimulated by parathyroid hormone and prostaglandin E2. J Bone Miner Res 12:734–741. https://doi.org/10.1359/jbmr.1997.12.5.734CrossRefPubMed

36.

Takuma A, Kaneda T, Sato T et al (2003) Dexamethasone enhances osteoclast formation synergistically with transforming growth factor-beta by stimulating the priming of osteoclast progenitors for differentiation into osteoclasts. J Biol Chem 278:44667–44674. https://doi.org/10.1074/jbc.M300213200CrossRefPubMed

37.

Kim YH, Jun J-H, Woo KM et al (2006) Dexamethasone inhibits the formation of multinucleated osteoclasts via down-regulation of beta3 integrin expression. Arch Pharm Res 29:691–698. https://doi.org/10.1007/BF02968254CrossRefPubMed

Titel: Negative impact on bone homeostasis in postmenopausal women with non-metastatic breast cancer during cytotoxic chemotherapy
verfasst von: Yadav Nisha
Biswajit Dubashi
Zachariah Bobby
Jaya Prakash Sahoo
Smita Kayal
Ramesh Ananthakrishnan
Vijay Bhaskar Reddy
Charles L
Prasanth Ganesan
Publikationsdatum: 06.07.2023
Verlag: Springer Nature Singapore
Erschienen in: Journal of Bone and Mineral Metabolism / Ausgabe 5/2023
Print ISSN: 0914-8779
Elektronische ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-023-01444-9

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Negative impact on bone homeostasis in postmenopausal women with non-metastatic breast cancer during cytotoxic chemotherapy