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

J Bone Miner Metab. 2023 Sep;41(5):682-692. doi: 10.1007/s00774-023-01444-9. Epub 2023 Jul 6.

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.

Keywords: Bone homeostasis; Bone mineral density; Bone resorption; Cytotoxic chemotherapy.

MeSH terms

  • Antiemetics*
  • Antineoplastic Agents* / adverse effects
  • Biomarkers
  • Bone Density
  • Bone Diseases, Metabolic*
  • Bone Remodeling
  • Breast Neoplasms* / drug therapy
  • Collagen Type I
  • Dexamethasone
  • Female
  • Humans
  • Lumbar Vertebrae
  • Middle Aged
  • Osteoporosis, Postmenopausal*
  • Peptides
  • Postmenopause
  • Procollagen
  • Vitamin D
  • Vitamins

Substances

  • Peptides
  • Procollagen Type I
  • Antiemetics
  • Biomarkers
  • Collagen Type I
  • Procollagen
  • Vitamin D
  • Vitamins
  • Antineoplastic Agents
  • Dexamethasone