6 89 33.7c 121 46.2 Severe symptoms (reported at least once) Feeling feverish 36 13.5 20 7.6b 38 find more 14.5 Headache 42 15.7 18 6.8c 42 16.0 Aches and pains 81 30.3 56 21.2b 79 30.2 ACET acetaminophen, FLUV fluvastatin, PLAC click here placebo a1°C

or more from baseline and 38.5°C or more overall b p < 0.05 vs. placebo c p ≤ 0.001 vs. placebo Compared with patients in the fluvastatin and placebo groups, patients in the acetaminophen group had a lower peak increase in body temperature and an earlier return to baseline levels (Fig. 2a). For each treatment group, the largest mean increase in temperature occurred between 24 and 48 h following ZOL infusion, and the peak value was recorded at the Day 2 evening measurement. The symptom VAS (recorded once each evening) followed a similar pattern (Fig. 2b), with peak values on Day 2, and the mean difference between placebo and acetaminophen was statistically significant

this website at all time points (p < 0.05). In contrast, no significant differences were observed between placebo and fluvastatin. Fig. 2 Change from baseline in a mean body temperature and b VAS scores following IV zoledronic acid infusion in patients who received pretreatment with fluvastatin (fluv), acetaminophen four times daily over 3 days (acet), or placebo (plac) Inflammatory biomarkers Serum levels of inflammatory biomarkers were evaluated in 96 patients at baseline, 24 h, and 72 h. Baseline concentrations of IL-6, IFN-gamma, TNF-alpha, and hs-CRP were generally comparable across treatment groups (Table 2). The pattern of elevations of all four inflammatory biomarkers showed an increase in levels by 24 h after infusion (Day 2, morning; Table 2; Fig. 3a–d); elevations in body temperature were also reported on the morning of Day 2 (Fig. 2a). Levels of all three cytokines (IL-6, TNF-alpha, and IFN-gamma) returned to near baseline by 72 h, by which point most of the temperature Protein tyrosine phosphatase elevations had declined. The biomarker, CRP, continued to rise from baseline to 72 h. Table 2

Serum levels of inflammatory biomarkers   PLAC (N = 33) ACET (N = 33) FLUV (N = 30) IL-6 (pg/ml): median (min, max)a Baseline 2.0 (1, 61) 2.1 (0, 31) 2.5 (0, 8) 24 h 14.5 (2, 154) 9.7 (2, 73) 14.8 (2, 79) 72 h 3.9 (1, 160) 2.8 (1, 56) 3.5 (2, 79) TNF-alpha (pg/ml): median (min, max)b Baseline 1.9 (1, 5) 1.9 (1, 9) 1.8 (1, 7) 24 h 3.8 (1, 9) 3.7 (2, 11) 4.1 (2, 12) 72 h 2.6 (1, 7) 2.2 (0, 12) 3.8 (1, 9) IFN-gamma (pg/ml): median (min, max)c Baseline 0.6 (1, 4) 0.6 (1, 4) 0.6 (1, 2) 24 h 75.5 (1, 363) 40.7 (1, 872) 98.2 (4, 3479) 72 h 2.0 (1, 24) 1.6 (1, 12) 3.1 (1, 10) hs-CRP (mg/l): median (min, max)d Baseline 2.3 (0, 13) 2.3 (1, 8) 1.8 (0, 49) 24 h 8.0 (0, 81) 4.7 (1, 45) 7.8 (0, 77) 72 h 25.1 (0, 89) 19.3 (1, 133) 20.2 (0, 71) ACET acetaminophen, FLUV fluvastatin, hs-CRP highly sensitive C-reactive protein, PLAC placebo aIL-6 (pg/ml) normal reference range: 0.51–4.92 bTNF-alpha (pg/ml) normal reference range: less than 1.86 cIFN-gamma (pg/ml) normal reference range: less than 1.