Table 6.

Adverse events (safety population)

			Intensive pathway			Non-intensive pathway			Overall p value*
			Zoledronic acid (n=555)	Clodronic acid (n=556)	p value	Zoledronic acid (n=428)†	Clodronic acid (n=423)	p value
Acute renal failure			29 (5%)	33 (6%)	0·70	28 (7%)	27 (6%)	1·0	0·78
Osteonecrosis of the jaw			21 (4%)	2 (<1%)	<0·0001	14 (3%)	1 (<1%)	0·0009	<0·0001
Thromboembolic events			104 (19%)	82 (15%)	0·08	53 (12%)	35 (8%)	0·06	0·01
Any serious adverse event‡			327 (59%)	280 (50%)	0·0046	212 (50%)	198 (47%)	0·45	<0·0001
	No suspected association with study drugs		245 (44%)	214 (38%)	0·059	155 (36%)	161 (38%)	0·62	0·30
	Any treatment-emergent serious adverse events§		158 (28%)	141 (25%)	0·25	90 (21%)	85 (20%)	0·80	0·27
		Blood and lymphatic system disorders (haematological disorders)	30 (5%)	26 (5%)	0·59	10 (2%)	8 (2%)	0·81	0·55
		Cardiovascular disorders	40 (7%)	42 (8%)	0·91	33 (8%)	24 (6%)	0·27	0·60
		Endocrine, metabolism, and nutrition disorders	6 (1%)	2 (<1%)	0·18	2 (<1%)	1 (<1%)	1·0	0·23
		Gastrointestinal disorders	15 (3%)	12 (2%)	0·57	9 (2%)	18 (4%)	0·081	0·41
		Infection	52 (9%)	62 (11%)	0·37	16 (4%)	28 (7%)	0·06	0·07
		Musculoskeletal, connective tissue, and bone disorders	6 (1%)	2 (<1%)	0·18	11 (3%)	0	0·0009	0·0007
		Nervous system disorders	10 (2%)	8 (1%)	0·64	8 (2%)	7 (2%)	1·0	0·73
		Renal and urinary disorders	7 (1%)	8 (1%)	1·0	4 (1%)	6 (1%)	0·54	0·55
		Skin and subcutaneous disorders	6 (1%)	3 (1%)	0·34	4 (1%)	6 (1%)	0·54	1·0

^*p value for comparison of zoledronic acid (n=983) versus clodronic acid (n=979).

^†Two patients on zoledronic acid who were excluded from the non-intensive pathway because no consent was received were included in the safety population.

^‡Irrespective of suspected association with study drugs; patients who had more than one type of adverse event have been listed against all relevant types of events, but patients who had more than one occurrence of the same type of event are recorded only once.

^§Suspected association with study drugs.