by intravenous infusion. The antifracture efficacy of zoledronic SB 216763 acid has been demonstrated in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial and the HORIZON Recurrent Fracture Trial , which showed that zoledronic acid 5 mg significantly reduced fracture risk in postmenopausal women with osteoporosis and in men and women with prior low trauma hip fracture. However, neither of these studies investigated the time to onset or the year by year antifracture effect of zoledronic acid. This analysis pooled data from all female patients in the HORIZON PFT and RFT to examine the time to onset of antifracture efficacy with zoledronic acid and to evaluate the persistence of this effect, by analyzing the incidence of clinical fractures within each year of treatment.
The acute phase response is a frequent occurrence after Bcr-Abl Inhibitors infusion of zoledronic acid and is caused by activation of cd T cells. Vitamin D receptor is expressed in immune cells, and vitamin D has immunomodulatory properties. The aim of this prospective study was to test the effect of vitamin D on the incidence of APR and intensity of pain in women undergoing infusion of zoledronic acid for postmenopausal osteoporosis. 60 women were enrolled and randomized into two groups. At baseline, 30 women received an oral bolus of cholecalciferol , while another 30 women received placebo. On day 5 both groups were treated with a single infusion of zoledronic acid and received a daily supplementation of calcium and vitamin D .
Patients were clinically evaluated and inflammatory markers were assayed before zoledronic acid administration and every 24 h for the following 2 days. The onset of APR has been defined by the occurrence of fever or at least one of pericardium the typical symptoms, such as musculoskeletal pain after zoledronic acid infusion. Intensity of pain was measured by a one dimensional scale . APR developed in 66.6% of patients, with no significant difference between groups. The vitamin group experienced less musculoskeletal pain and exhibited lower inflammatory markers . Our data demonstrate that cholecalciferol at a dose of 30 IU reduces the intensity of musculoskeletal pain after infusion of zoledronic acid for postmenopausal osteoporosis.
Keywords Acute phase response Zoledronic acid Vitamin D Postmenopausal osteoporosis Flu like syndrome Aminobisphosphonates are widely used drugs for the treatment of osteoporosis and other metabolic bone diseases ; N BPs inhibit bone resorption and reduce the risk of fracture . Among intravenously administered N BPs, zoledronic acid has recently been approved for the treatment of osteoporosis: it requires a single annual infusion due to its high affinity for hydroxyapatite crystals and power of action. Zoledronic acid significantly reduces the risk of vertebral, hip, and other fractures as demonstrated by the HORIZON Pivotal Fracture Trial . Unfortunately, administration of zoledronic acid is often followed by an acute phase response , which is a nonspecific, immune driven reaction to systemic challenge, clinically manifested as a flu like syndrome observed also with other N BPs . Some evidence suggests that intravenously administered N BPs are internalized by monocytes and dendritic cells, resulting in inhibition of farnesyl pyrophosphate synthase: it implies an accumulation of intracellular metabolites upstream of FPP synthase in the mevalonate pathway, such as isopentenyl pyrophosphate.