genetics in predicting risk of bisphosphonate-related osteonecrosis of the jaw in patients with cancer receiving zoledronic acid

Conditions: Malignant Neoplasm; Musculoskeletal Complications

Summary: this randomized clinical trial studies genetics in predicting risk of bisphosphonate-related osteonecrosis of the jaw in patients with cancer receiving zoledronic acid. zoledronic acid is an anti-resorptive drug used as part of cancer treatment. a serious side effect of these drugs is death of the jawbone, commonly called bisphosphonate-related osteonecrosis of the jaw (bronj). genetic research may help doctors understand risk factors for bronj or who is more likely to get bronj and why.

primary objectives: i. to develop a pharmacometric model to predict jawbone zoledronic acid (zol) concentrations in oncologic patients by conducting a prospective cohort study of zol pharmacometrics in bronj patients, measuring drug in plasma, urine, and jawbone tissue obtained during surgical treatment for bronj. secondary objectives: i. to clinically assess and validate our predictive pharmacometric model, and develop a risk model for bronj in oncologic patients receiving intravenous zol. outline: patients are randomized to 1 of 2 treatment arms. arm i: patients receive zoledronic acid intravenously (iv) over 15 minutes on day 1. arm ii: patients receive zoledronic acid iv over 30 minutes on day 1. after completion of study treatment, patients are followed up for 1 month.

Eligibility criteria:
inclusion criteria: * patients with bronj: * all cancer patients \> 18 years of any ethnicity who have been treated with intravenous zoledronate (zoledronic acid) for \>=1 year duration * clinical diagnosis of bronj subsequent to oral surgery as established by standard clinical protocol per american association of oral and maxillofacial surgeons (aaoms) diagnostic criteria * willingness to have photographs taken to document lesions * consent for sample collection for urine, hematology, histopathology and microbial profiling * cognitively able and willing to provide consent * have a world health organization (who)/eastern cooperative oncology group (ecog) performance score =\ 6 months * patients without bronj: * cancer patients without bronj who have been treated with intravenous zoledronate for \>= 1 year duration * no signs or symptoms of bronj * willingness to provide consent for sample collection for blood, urine and saliva exclusion criteria: * who/ecog performance score \> 2 and life expectancy of \< 6 months * coagulopathy * active systemic infection or autoimmune disease * currently pregnant or within 3 months post-partum, or unwilling to undergo pregnancy testing or report possible pregnancy promptly * severe cardiovascular, pulmonary or other systemic conditions that prevent participation in the study * salivary gland hypofunction regardless of underlying pathology * neutropenia (serum absolute neutrophil count \[anc\] \< 1,000/ul) * cognitive, language or hearing problems * renal disease, and we will use a calculated serum creatinine clearance over 30 ml/min at the screening appointment as an exclusion criteria * participation in another research project that might interfere with completion of this study * patients undergoing active antibiotic therapy