Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer

Drew R. Oostra, Maryam B. Lustberg, Raquel E. Reinbolt, Xueliang Pan, Robert Wesolowski, Charles L. Shapiro

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Purpose: Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss. Receptor Activator of Nuclear Factor Kappa-B (RANK)-RANK ligand (RANK-L) signaling balances bone resorption and formation. Osteoprotegerin (OPG) acts as a decoy receptor for RANK, interrupting osteoclast activation and bone resorption. This study examined the relationship between OPG and bone loss in women with CIOF. Methods: Premenopausal women with stage I/II breast cancers receiving adjuvant chemotherapy were evaluated at chemotherapy initiation, 6 and 12 months. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), follicle stimulating hormone (FSH), ionized calcium, osteocalcin, and OPG were serially measured. CIOF was defined as a negative pregnancy test, FSH levels >30 MIU/mL, and ≥3 months of amenorrhea. Results: Forty women were enrolled; 31 (77.5%) met CIOF criteria. BMD significantly decreased (p < 0.001) in the CIOF group at both time points: LS BMD decreased from a median of 0.993 g/cm2 to 0.976 g/cm2 and 0.937 g/cm2 at 6 and 12 months, respectively. OPG was significantly elevated at 6 months (median increase 0.30 pmol/L, p = 0.015) and then decreased at 12 months to levels still above baseline (median difference 0.2 pmol/L, p = 0.70). Conclusions: In what was likely a compensatory response to rapid bone loss, CIOF patients' OPG levels increased at 6 months and then decreased at 12 months to values greater than baseline assessments. This phenomenon is described in other diseases, but never before in CIOF.

Original languageEnglish (US)
Pages (from-to)51-56
Number of pages6
JournalMolecular and Cellular Endocrinology
Volume402
DOIs
StatePublished - Feb 5 2015

Bibliographical note

Funding Information:
This work was supported in part by National Cancer Institute grant number R29 CA60050 (CLS). X Pan is supported in part by the National Center for Advancing Translational Sciences (grant 8UL1TR000090-05 ). M B Lustberg and R Wesolowski are supported in part by K12 NIH funding.

Publisher Copyright:
© 2014 Elsevier Ireland Ltd.

Keywords

  • Bone loss
  • Breast cancer
  • Chemotherapy
  • Osteoprotegerin
  • Ovarian failure

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