at sites of active bone remodeling, bind to the bone matrix, and are ingested during osteolysis by osteoclasts, wherein they inhibit the transduction of osteolysis Sorafenib stimulating signals and can induce apoptosis . Among the bisphosphonates evaluated, oral clodronate and intravenous pamidronate and zoledronic acid have demonstrated significant reduction of pain and SREs in patients with MM and bone disease . In the United States, both PAM and ZOL are available for the treatment of bone disease from MM . In a 24 month clinical study comparing intravenous PAM with ZOL that included patients with MM and bone disease, SREs were reduced with similar efficacy, and the time to first SRE was similar between treatment groups . Additionally, the safety profiles of the two treatments at 25 months were comparable.
The majority of reported PS-341 179324-69-7 adverse events was mild to moderate and consisted of bone pain, nausea, and fatigue . Fever, myalgia, renal function impairment, hypocalcemia, and osteonecrosis of the jaw have also been reported in patients with advanced cancers receiving complex treatment regimens including bisphosphonates . Patients in this study had established bone lesions . However, clinical evidence suggests that there may be a benefit to administering ZOL earlier in the disease course than after the establishment of bone lesions. An early study showed that patients with asymptomatic MM treated with ZOL had significantly fewer SREs at progression than patients who did not receive bisphosphonate treatment .
Recently, ZOL was compared with clodronate in patients with newly diagnosed MM initiating intensive buy Ramelteon or nonintensive induction chemotherapy . After a median follow up of 3.7 years, patients in the ZOL group had a 16% reduced risk of death compared with the clodronate group . These benefits were observed within a few months of treatment initiation, and the differences between the two treatments continued to favor ZOL throughout the study. Moreover, ZOL significantly reduced SRE risk versus clodronate in each of the first 3 years of the study, after which time differences remained evident, although statistical power was insufficient to achieve significance . Although clinical trial data support early and continued use of ZOL in patients with newly diagnosed MM, current guidelines do not provide consistent direction on the optimal duration of bisphosphonate treatment for patients with MM .
The majority of the bisphosphonate registration clinical studies in patients with MM was limited to treatment durations purchase clomifene of 2 years or less and did not directly address whether patients who have long term persistency with treatment experience greater benefit than patients with shorter treatment periods. The current study assessed the benefit of long term ZOL use in reducing the risk of pericardium SREs, fractures, and death in patients with MM using data over a period of 7.5 years from two large health care plan databases. Methods Data sources. This was a retrospective study using medical data, pharmacy data, and patient enrollment information collected between July 1, 2000 and December 31, 2007 from two large managed care databases. Medical claims were collected from health care sites for provided services. Medical claims included multiple diagnosis codes recorded with the International Classification of Diseases, Ninth Revision diagnosis codes; procedures recorded with ICD 9 CM procedure codes, current procedural terminology.