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Presents cases of alpha fetoprotein in patients with liver disease or neoplastic disorders. Methodology of the study; Analysis of the presence of alpha fetoprotein in serum samples; Results of the study.

Introduction: Recent studies suggest that multiple myeloma (MM) triggers osteoclastogenesis by disrupting the balance between the receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG), its natural antagonist., Material/methods: Determinations of bone marrow (BM) and serum OPG and sRANKL concentrations were performed in 133 MM patients and 42 healthy subjects by the ELISA method using Osteoprotegerin ELISA and sRANKL ELISA kits., Results: MM patients had elevated serum levels of OPG compared with controls (p<0.0001) and OPG levels were higher in patients with renal failure and patients with hipercalcemia (p<0.001 and p=0.04, respectively). Serum OPG levels correlated with age, serum beta 2-microglobulin, and BM OPG concentrations and did not correlate with the presence of osteolysis or with stage of disease. sRANKL serum levels in MM patients and in controls were not statistically different (p=0.42). In MM patients, serum OPG and sRANKL levels were similar at diagnosis and in the plateau phase of disease. There was a correlation between BM and serum sRANKL concentrations (p<0.001). Median values of the sRANKL/OPG ratio for BM and serum of MM patients were 0.14 and 0.11, respectively. The median value of the sRANKL/OPG ratio for the serum of controls was 0.11., Conclusions: In 20% of MM patients, serum OPG levels are elevated, and this may be a compensative reaction related to increased bone destruction. There is not statistically significant relationship between sRANKL serum and BM levels and the main clinical and laboratory parameters of the disease. Determination of BM and the serum sRANKL/OPG ratio seems to have no clinical value.

Osteolytic bone destruction, caused by the aberrant production and activation of osteoclasts, results in significant morbidity for patients with multiple myeloma (MM). Pamidronate [(3-amino-1-hydroxypropylidene)-1,1-bis-phosphonate] inhibits osteoclastic activity and reduces bone resorption. A potency of zoledronic acid (2-[imidazol-1-yl]-1-hydroxyethylidene-1,1-bisphosphonic acid, a new third generation bisphosphonate, as inhibitor of resorption was 850-fold greater than pamidronate, as was shown in preclinical models of bone resorption. Randomized, double-blind study was conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating myeloma bone disease. Since March 1999 the efficacy and safety of pamidronate and zoledronic acid is evaluated in MM patients all receiving anti-myeloma chemotherapy acc. to VMCP/VBAP alternating regimen. Nine patients with stage III myeloma and osteolytic lesions (3 female, 6 male, median age 57 years, range 52-67, with monoclonal protein: IgG-7, IgA-2) were randomly assigned (1:1:1 ratio) to treatment with either 4 or 8 mg of zoledronic acid via 15-minute intravenous infusion or 90 mg of pamidronate via 2-hour intravenous infusion every 3 to 4 weeks for 12 months. All patients have received 500 mg of calcium supplements and 500 IU of vit.D, orally, once daily, for the duration of administration of study medication. In extension phase of the study (June 2000-April 2002) patients did not received bisphosphonates. In 7 patients 18 cycles of assessed treatment was administered to each of them and one patient received 16 cycles. One patient died after receiving of 12 pamidronate therapy cycles at 11 month of the trial duration (and at 49 month since MM diagnosis and anti-tumour treatment). The patient's death occurred during the progression of plasma cell proliferation due to acute left ventricle cardiac failure. During the 12-month-period of bisphosphonate treatment skeletal related events (SRE) and progression of osteolysis occurred with the same frequency in 3 treatment groups. One patient experienced spinal cord compression and received radiation to bone and 2 patients experienced vertebral fracture. Time from study entry to the first SRE was 304 days in pamidronate and 366 and 392 days in 4 and 8 mg zoledronic acid group, respectively. The skeletal morbidity rate was identical in all treatment groups. Single hypocalcemic events occurred in 2 patients, mild hypertransaminasemia was observed in 3, worsening of renal function parameters in 2 patients (transient in one of them). Muscular pain and fever up to 39 degrees C (transient and self-limiting "flu-like" symptoms) occurred in 6 patients after several or some dozens of hours from study drug administration. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate and were experienced by a similar proportion of patients in each treatment group. Median time of patient's observation duration after completing of administered treatment with zoledronic acid and pamidronate amounts to 20 months. At present actual median survival time of analysed patients since MM diagnosis is 42 months, since the beginning of treatment with pamidronate and zoledronic acid--33 months, and since completing treatment--20 months and is similar in 3 treatment groups. As was shown in our single center study in MM patients the safety and efficacy of pamidronate 90 mg and zoledronic acid 4 mg and 8 mg in monthly i.v. infusion are comparable. Thus the recommended dosage of zoledronic acid is 4 mg administered as a 15 minute i.v. infusion at intervals of 3 to 4 weeks.