Bone Abstracts

Background: Zoledronic acid (ZA) for the treatment of osteoporosis (OP) is associated with a transient post-infusional acute phase reaction (APR) due to ZA-mediated activation of γ-δ TCR lymphocytes (γ-δTCR) and production of cytokines.

Primary objective: To investigate if OP patients developing APR (APR+) after ZA infusion have lower 25-OH vitamin D (25-OHvD) levels and a higher percentage of γ-δTCR compared to patients without APR (APR−). Secondary objectives: to identify 25-OHvD level associated with a lower risk of APR; to investigate if there is an inverse correlation between 25-OHvD levels and γ-δTCR.

Methods: We enrolled 38 OP patients treated with 5 mg i.v. ZA. Before the first drug infusion, serum 25-OHvD levels were recorded and peripheral blood were drawn for T lymphocyte subpopulations FACS analysis (FACS Cytofluorimeter La Fortessa, BD). APR occurrence was recorded by phone call 1 week after the infusion.

Results: 19/38 (50%) patients developed APR. APR+ patients had significantly lower 25-OHvD levels compared to APR− patients (mean 22.1± S.D 8.2 ng/ml vs mean 35.4± S.D 17 ng/ml, P=0.0028). γ-δTCR were higher in APR+ patients compared to APR− patients (0.6±0.5 vs 0.38±0.3%, P=0.13). Patients with 25-OHvD levels >30 ng/ml had a significantly lower frequency of APR (2/19, 11 vs 12/19, 63%, P=0.0008; OR=14.57, CI 95% 2.57–82.73), and significantly higher γ-δTCR percentage (1.60±0 vs 0.56±0%, P=0.024). 25-OHvD levels did not correlate with γ-δTCR percentage (r=−0.24, P=0.14). The lower APR frequency in patients previously treated with oral aminobisphosphonates vs naive patients (21 vs 63.2%) was dependent on 25-OHvD levels on logistic regression.

Conclusion: APR+ after ZA infusion have lower serum 25-OHvD levels, those with levels <30 ng/ml had a 25-fold higher risk for APR, suggesting that this concentration should be obtained before ZA infusion by supplementation. The possible correlation between γ-δTCR, 25-OHvD levels and APR should further investigated in a larger population.