title: Prospective observational study of treatment pattern, effectiveness and safety of zoledronic acid therapy beyond 24 months in patients with multiple myeloma or bone metastases from solid tumors.
abstract: OBJECTIVE
  To study the treatment patterns, effectiveness and safety of zoledronic acid (ZOL) beyond 2 years of therapy, given the paucity of data on long-term treatment in daily clinical practice.
  
  
  METHODS
  Patients with multiple myeloma (MM) or solid tumor bone metastases (STM) and at least 24 months of regular q3-4w ZOL therapy were followed prospectively for an additional 18 months beyond the 24 months required for study entry. End-points included ZOL exposure, incidence of skeletal related events (SRE), and safety.
  
  
  RESULTS
  In all, 298 evaluable patients were enrolled. The mean continuation rate of ZOL was 90.6%. Exposure to ZOL decreased with time in all patients, but was lower (50.0% vs. 67.6%; p<0.001) and with higher discontinuation rates (incidence rate ratio [IRR]=1.95; p=0.002) in MM compared to the STM group. ZOL suppressed the rate of SREs similarly during the study as compared to before inclusion (0.12 vs. 0.13 events per person-year; p=0.7). At 18 months, 84.5% remained SRE-free. In STM patients, persistent ZOL therapy was associated with lower SRE risk (hazard ratio [HR]=0.42; p=0.01), but not in MM. Renal deterioration occurred in 3.7% and osteonecrosis of the jaw (ONJ) developed in 6.0%, with dental trauma increasing ONJ risk (HR=4.67; p=0.002).
  
  
  CONCLUSIONS
  Beyond 2 years of therapy, treatment patterns of ZOL were heterogeneous and SRE rates were low. The safety profile of ZOL was acceptable, and interrupting ZOL in patients with solid tumors was associated with a higher risk of SREs.
authors: Department of Nuclear Medicine, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium, tim.van.den.wyngaert@skynet.be.
authors: T
authors: T
authors: Van den Wyngaert
authors: M
authors: M
authors: Delforge
authors: C
authors: C
authors: Doyen
authors: L
authors: L
authors: Duck
authors: K
authors: K
authors: Wouters
authors: I
authors: I
authors: Delabaye
authors: C
authors: C
authors: Wouters
authors: H
authors: H
authors: Wildiers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D009101:Multiple Myeloma / Q000188:drug therapy; D011446:Prospective Studies; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
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