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

• Published in: Molecular and cellular endocrinology 2015-02, Vol.402, p.51-56
• Main Authors: Oostra, Drew R., Lustberg, Maryam B., Reinbolt, Raquel E., Pan, Xueliang, Wesolowski, Robert, Shapiro, Charles L.
• Format: Article
• Language: English
• Subjects: Adjuvants; Adult; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biocompatibility; Biomedical materials; bone density; Bone loss; bone resorption; Bones; Breast; Breast cancer; breast neoplasms; Breast Neoplasms - blood; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; calcium; Cancer; Chemotherapy; Chemotherapy, Adjuvant; Cyclophosphamide - administration & dosage; Doxorubicin - administration & dosage; drug therapy; Female; femur; Fluorouracil - administration & dosage; follicle-stimulating hormone; Humans; ligands; lumbar spine; Methotrexate - administration & dosage; Middle Aged; osteocalcin; osteoclasts; Osteoporosis - blood; Osteoporosis - chemically induced; Osteoprotegerin; Osteoprotegerin - blood; Ovarian failure; patients; pregnancy; Primary Ovarian Insufficiency - blood; Primary Ovarian Insufficiency - chemically induced; Receptors; women
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2014.12.028

•Chemotherapy induced ovarian failure (CIOF) results in rapid bone loss.•Osteoprotegerin (OPG) interrupts osteoclast activation and bone resorption.•We studied the relationship between bone loss in women with CIOF and OPG.•OPG levels initially increased, then decreased to values greater than baseline.•This phenomenon is described in other diseases, but never before in CIOF. 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. 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. Forty women were enrolled; 31 (77.5%) met CIOF criteria. BMD significantly decreased (p