title: Association of osteoprotegerin and bone loss after adjuvant chemotherapy in early-stage breast cancer.
abstract: OBJECTIVE
  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/cm(2) to 0.976 g/cm(2) and 0.937 g/cm(2) 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.
authors.affiliation: The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Drew R
authors.initials: DR
authors.lastname: Oostra
authors.affiliation: The Breast Program, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; Stefanie Spielman Comprehensive Breast Center, Columbus, OH, USA. Electronic address: Maryam.lustberg@osumc.edu.
authors.forename: Maryam B
authors.initials: MB
authors.lastname: Lustberg
authors.affiliation: The Breast Program, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; Stefanie Spielman Comprehensive Breast Center, Columbus, OH, USA.
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Reinbolt
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Pan
authors.affiliation: The Breast Program, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; Stefanie Spielman Comprehensive Breast Center, Columbus, OH, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Wesolowski
authors.affiliation: The Breast Program, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA; Stefanie Spielman Comprehensive Breast Center, Columbus, OH, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shapiro
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000139:chemically induced*; D053244:Osteoprotegerin / Q000097:blood*; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000139:chemically induced
chemical_list: D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate
keywords: Bone loss; Breast cancer; Chemotherapy; Osteoprotegerin; Ovarian failure