Modification of serum apolipoprotein A-I, apolipoprotein B and lipoprotein(a) levels after bisphosphonates-induced acute phase response

Lipoprotein(a) (Lp(a)) is a low density lipoprotein-like particle displaying strong atherothrombotic properties. Although the concentration of Lp(a) in plasma is under strong genetic regulation, there are emerging evidences that several other factors, such as hormonal disorders, acute phase, liver and renal failure may affect its metabolism. The aim of the present study was to investigate whether bisphosphonates, an effectual drug in the treatment of malignant hypercalcemia and Paget's disease of bone, known to induce a concomitant acute phase, may have a significant influence on Lp(a) concentrations. Nine subjects (four men and five women), with plasma Lp(a) concentrations in the range between 6.4 and 17.7 mg/dl, were subjected to a single intravenous infusion of bisphosphonates (7.5 mg of aminohydroxybutylidene and 5.0 mg of aminohydroxylidene), previously dissolved in 250 ml of saline. Lp(a), apo A-I, apo B, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured at the baseline and after days one, two, four and seven. CRP, ESR and Lp(a) started to increase after two days from the treatment, reaching statistical significance after days two, four and seven, respectively. Apo B and apo A-I decreased significantly after days one and two, respectively. Although patterns and relative amounts of the increase of CRP were substantially different among the subjects studied, the increase of Lp(a) was more homogeneous; the peak of Lp(a) concentrations was reached only seven days after treatment in the group as a whole, in agreement with previous observations. In univariate regression analysis, significant correlations were found only between apo A-I and ESR, and apo A-I and Lp(a). The present study suggest that Lp(a) behaves as an acute phase protein. Besides, we observed a slight but significant decrease of apo A-I and apo B after administration of bisphosphonates. (C) 1998 Elsevier Science B.V.