title: Bone Marker-Directed Dosing of Zoledronic Acid for the Prevention of Skeletal Complications in Patients with Multiple Myeloma: Results of the Z-MARK Study.
abstract: OBJECTIVE
  Zoledronic acid (ZOL) given every 3 to 4 weeks can reduce skeletal-related events (SRE) in patients with bone lesions from multiple myeloma. This study evaluated efficacy and safety of less-frequent ZOL dosing based on bone turnover markers in patients with 1 to 2 years of prior bisphosphonate therapy.
  
  
  METHODS
  Patients received ZOL (4 mg) every 4 or 12 weeks based on urinary N-telopeptide of type 1 collagen (uNTX) levels (every 4 weeks if uNTX ≥50 nmol/mmol creatinine, every 12 weeks if uNTX < 50).
  
  
  RESULTS
  Of 121 patients enrolled (mean age, 63.8 years; median follow-up, 21 months), 4 patients started ZOL every 4 weeks and 117 received ZOL every 12 weeks based on uNTX at study entry. All 4 patients who initiated ZOL every 4 weeks switched to every 12 weeks due to decreased uNTX. Thirty-eight of 117 patients who initiated ZOL every 12 weeks switched to ZOL every 4 weeks due to disease progression (n = 20), increased uNTX (n = 14), and SREs (n = 4). Overall SRE incidence was low; 7 (5.8%) and 5 (4.9%) patients experienced an SRE during years 1 and 2, respectively. Mean (SD) SRE rate at year 2 was 0.01 (0.03) per person-year. The 2-year incidence rate for osteonecrosis of jaw was 3.3%. Four deaths were reported, none related to ZOL.
  
  
  CONCLUSIONS
  Less frequent ZOL dosing (every 12 weeks over 2 years) maintains a low SRE rate and can be safely administered for up to 4 years.
authors.affiliation: Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts. NRAJE@mgh.harvard.edu.
authors.forename: Noopur
authors.initials: N
authors.lastname: Raje
authors.affiliation: Cedars-Sinai Samuel Oschin Comprehensive Cancer Center, Los Angeles, California.
authors.forename: Robert
authors.initials: R
authors.lastname: Vescio
authors.affiliation: Hematology and Oncology Associates, Tupelo, Mississippi.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Montgomery
authors.affiliation: University of Maryland - Baltimore, Marlene and Stewart Greenebaum Cancer Center, Blood and Marrow Transplant Program, Baltimore, Maryland.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Badros
authors.affiliation: Boston Veterans' Administration Healthcare System, Boston, Massachusetts.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Munshi
authors.affiliation: Carolina Oncology Specialists, Hickory, North Carolina.
authors.forename: Richard
authors.initials: R
authors.lastname: Orlowski
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Hadala
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Warsi
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Eliza
authors.initials: E
authors.lastname: Argonza-Aviles
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Solveig G
authors.initials: SG
authors.lastname: Ericson
authors.affiliation: Dana-Farber/Partners Cancer Care Institute, Boston, Massachusetts.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001847:Bone Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D024042:Collagen Type I / Q000652:urine; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D009367:Neoplasm Staging; D010014:Osteolysis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D010455:Peptides / Q000652:urine; D000077211:Zoledronic Acid
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid