Data From the Health Outcomes and Reduced Incidence With Zoledronic Acid
Once Yearly Clinical Trials Program
Grbic, DMD, MS,MMedSc,Dennis M. Black, PhD, Kenneth W. Lyles, MD, David M.
Reid, MD, Eric Orwoll, MD, Michael McClung, MD, Christina Bucci-Rechtweg, MD and
Guoqin Su, PhD
Background. The Health
Outcomes and Reduced Incidence with Zoledronic Acid Once
Yearly-Pivotal Fracture Trial found one case of osteonecrosis of the
jaw (ONJ) in a patient with postmenopausal osteoporosis (OP) treated
with 5 milligrams of zoledronic acid (ZOL) once yearly and one case
in a patient receiving a placebo. The authors examined ONJ incidence
in four additional clinical trials involving patients with osteopenia
or OP who were treated with ZOL, and they analyzed levels of the bone
resorption marker serum â C-telopeptide (S-CTx) to assess its
usefulness in predicting the risk of developing ONJ.
Methods. To determine ONJ prevalence, an independent committee
conducted a masked review of the clinical trials’ adverse
events databases for cases meeting predefined criteria for ONJ.
The committee collected S-CTx level data for subsets of patients
from these trials.
Results. The results of the four additional clinical trials
revealed no further cases of ONJ. The S-CTx levels commonly
were lower than 0.15 nanograms per milliliter, with no correlation
to the incidence of ONJ.
Conclusions. In the clinically diverse group of 5,903 patients
who received ZOL in five clinical trials, ONJ incidence was
less than one in 14,200 patient treatment-years. Data from four
clinical trials indicated that S-CTx levels lower than 0.15 ng/mL
were common among patients receiving ZOL for treatment of OP and were
not associated with ONJ.
Clinical Implications. Occurrences of ONJ have been rare in
patients with OP who are receiving ZOL. Whereas low S-CTx values
may be common in patients receiving bisphosphonates for OP therapy,
they are not associated necessarily with an increased risk of