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

10 Scopus citations


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
StatePublished - Feb 5 2015

Bibliographical note

Publisher Copyright:
© 2014 Elsevier Ireland Ltd.


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


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