Table 3. Toxicity and HRQOL outcomes.

Study	Reporting measure	Outcomes
Smith 2012 [13]	CTCAEv3	Increased toxicity with denosumab; osteonecrosis of the jaw (33 vs. 0) and hypocalcemia (12 vs. 2)
ZEUS [21]	Unclear; no measure reported	Increased toxicity with ZA; influenza-like symptoms of general low severity such as muscle/bone pain, arthralgia, fever, nausea and dizziness; osteonecrosis of the jaw in 10 patients (9 vs. 1); hypocalcemia in five patients (4 vs. 1); femoral head osteonecrosis in one patient not considered ZA related (1 vs. 0).
TROG 03.04 RADAR [20, 23]	CTCAEv2; EORTC QLQC30 and PR25	The use of ZA for 18 months did not appear to be associated with any independent effects on patient reported outcomes and HRQOL. Nine participants had serious adverse events potentially related to ZA (osteonecrosis jaw (2), urticaria (1), syncope during infusion (1), hypotension after infusion (1), renal pain related to hydronephrosis (1), pyrexia and chest pain (1).
MRC PR04 [19]	Non-standardized measure*	Increased toxicity with clodronate (gastrointestinal symptoms and increased lactate dehydrogenase levels)
STAMPEDE [22]	CTCAEv3.0	Thirty cases of osteonecrosis of the jaw in ZA arms of trial (10 in SOC + ZA; 20 in SOC + ZA + docetaxel)

Abbreviations: ZA, zoledronic acid; SOC, standard of care; CTCAE, common terminology criteria for adverse events; HRQOL, health related quality of life; EORTC, European Organisation for Research and Treatment of Cancer; QLQC30, quality of life questionnaire—core questionnaire; PR25, prostate cancer questionnaire

* adverse events defined as events leading to alteration in trial medication, hospitalization, prolongation of hospitalization or death.