30th ASBMR 2008
[M364] Acute Phase Response and Bone Metabolism Marker after Intravenous Bisphosphonate in Osteoporotic Patients with Rheumatism
Won Park, Mie Jin Lim, Seong-Ryul Kwon, Sang Gu Kim, Seong Bin Hong.. IN-HA University Hospital.
The side effects typically associated with the intermittent large dose bisphosphonate are myalgia and transient fever. Increase of cytokines in acute phase response was reported mostly in treatment for cancer and only few studies were reported for osteoporosis. The aim of this study is to evaluate cytokine change in acute phase response and bone metabolism shortly after single dose of intravenous pamidronate.
Nineteen patients with osteoporosis and rheumatism without prior bisphosphonate or immunosuppressant use were selected. They were given 30 mg of IV pamidronate and the venous blood samples were taken before and 48 hours after the infusion. Serum level of IL-6, TNF-α and C-telopeptide (CTX) were measured with an immunoenzymetric assay (serum IL-6 and TNF- α: R&D Systems, Minneapolis, Minn., USA; serum CTX: Nordic Bioscience Diagnostics, Bolden, UK). The real-time RT-PCR quantified the expression of the interferon (IFN)-γ from peripheral blood mononuclear cells. Leukocyte count and serum calcium level were also determined at the same time. Acute phase reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured for three consecutive days.
At baseline, mean level of CRP was 0.14 mg/dL which rose to 0.30 mg/dL, 0.61 mg/dL and 1.58 mg/dL at 24hours, 48 hours and 72 hours, respectively. Their rise were all significant at all times comparing to baseline (p=0.049, 0.002, 0.004, respectively). ESR seemed to increase at 72 hours but it was not significant (p = 0.413). The WBC count and serum calcium level tend to decreased after the treatment. Serum TNF- α increased significantly (p = 0.031). Both serum IL-6 and IFN-γ did not increase significantly but increment of IL-6 after treatment strongly correlated with that of CRP (p=0.023). Serum CTX decreased markedly after the treatment (p = 0.009).The dose of bisphosphonate used in this study was smaller than previous studies. The marked decrease of serum CTX implies that osteoclastic activity is suppressed as early as 48 hours after the treatment. As inflammation occurs even with 30mg of intravenous pamidronate, we recommend smaller dose frequent therapy or slower infusion of bisphosphonate in contrary to the current trend of large dose intermittent therapy.
| Before treatment | 48 hours after treatment | P value | |
| WBC ( /μl) | 6763 ± 1778 | 6352 ± 2212 | 0.31 |
| CRP (mg/dL) | 0.14 | 0.61 | 0.002 |
| IL-6 (pg/mL) | 1.76 ± 1.03 | 2.54 ± 1.51 | 0.084 |
| TNF-α (pg/mL) | 1.11 ± 0.91 | 1.96 ± 2.11 | 0.031 |
| IFN-γ | 1.0 ± 0 | 2.23 ± 2.37 | 0.38 |
| Serum CTX (ng/ml) | 0.49 ± 0.40 | 0.14 ± 0.14 | 0.009 |
W. Park, None.
Date: Monday, September 15, 2008
Session Info: Poster: Osteoporosis Treatment (Clinical): Bisphosphonates (11:30 AM-2:30 PM)
Presentation Time: 11:30 AM