title: Effects of zoledronic acid on bone mineral density in premenopausal women receiving neoadjuvant or adjuvant therapies for HR+ breast cancer: the ProBONE II study.
abstract: The effects of bisphosphonates on altered bone turnover marker (BTM) levels associated with adjuvant endocrine or chemotherapy in early breast cancer have not been systematically investigated. In ProBONE II, zoledronic acid decreased these elevated BTM levels and increased bone mineral density (BMD) during adjuvant therapy, consistent with its antiresorptive effects.
  
  
  BACKGROUND
  Adjuvant chemotherapy or endocrine therapy for early hormone receptor-positive breast cancer (HR(+) BC) is associated with rapid BMD loss and altered BTM levels. Adjuvant bisphosphonate studies demonstrated BMD increases, but did not investigate BTM effects. The randomized, double-blind, ProBONE II study investigated the effect of adjuvant zoledronic acid (ZOL) on BMD and BTM in premenopausal women with early HR(+) BC.
  
  
  METHODS
  Seventy premenopausal women with early HR(+) BC received adjuvant chemotherapy and/or endocrine therapy plus ZOL (4 mg IV every 3 months) or placebo for 24 months. Primary endpoint was change in lumbar spine BMD at 24 months versus baseline. Secondary endpoints included femoral neck and total femoral BMD changes, changes in BTM, and safety.
  
  
  RESULTS
  Lumbar spine BMD increased 3.14% from baseline to 24 months in ZOL-treated participants versus a 6.43% decrease in placebo-treated participants (P < 0.0001). Mean changes in T- and Z-scores, and femoral neck and total femoral BMD, showed similar results. Bone resorption marker levels decreased ∼ 55% in ZOL-treated participants versus increases up to 65% in placebo-treated participants (P < 0.0001 for between-group differences). Bone formation marker (procollagen I N-terminal propeptide) levels decreased ∼ 57% in ZOL-treated participants versus increases up to 45% in placebo-treated participants (P < 0.0001 for between-group differences). Adverse events were consistent with the established ZOL safety profile and included one case of osteonecrosis of the jaw after a tooth extraction.
  
  
  CONCLUSIONS
  Adding ZOL to adjuvant therapy improved BMD, reduced BTM levels, and was well tolerated in premenopausal women with early HR(+) BC receiving adjuvant chemotherapy and/or endocrine therapy.
authors: Department of Obstetrics and Gynecology, Philipps-University of Marburg, Baldingerstrasse, 35033, Marburg, Germany, hadji@med.uni-marburg.de.
authors: P
authors: P
authors: Hadji
authors: A
authors: A
authors: Kauka
authors: M
authors: M
authors: Ziller
authors: K
authors: K
authors: Birkholz
authors: M
authors: M
authors: Baier
authors: M
authors: M
authors: Muth
authors: M
authors: M
authors: Bauer
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005269:Femur / Q000503:physiopathology; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D017697:Premenopause / Q000502:physiology; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016896:Treatment Outcome; D055815:Young Adult; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000077211:Zoledronic Acid