Disease relevance of Ibandronic Acid

• Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2 [1].
• To inhibit bone resorption, a potent bisphosphonate, ibandronate (4 microg/mouse) was daily administered subcutaneously [1].
• We determined the effects of the potent bisphosphonate ibandronate in a murine model of human myeloma bone disease [2].
• In contrast, ibandronate failed to inhibit MDA-231 tumor formation with no effects on apoptosis in MDA-231 breast cancer cells in the orthotopic mammary fat pads [3].
• PURPOSE: To evaluate the hypocalcemic effect and safety of three different doses of the bisphosphonate ibandronate in tumor-associated hypercalcemia, and to identify factors predicting response [4].

Psychiatry related information on Ibandronic Acid

• Once-monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3-year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis [5].

High impact information on Ibandronic Acid

• There was no significant effect of ibandronate on total myeloma cell burden, as assessed by morphometric measurements of myeloma cells in the bone marrow, liver, and spleen, or by measurement of serum IgG2b levels [2].
• However, ibandronate did not prevent the mice from developing hindlimb paralysis and did not produce a detectable effect on survival [2].
• Consistent with this notion, inhibition of bone resorption by the bisphosphonate ibandronate reduced COX-2 expression in MDA-MB-231 cells in bone [6].
• This open-label pilot study investigated the effects of short-term intensive treatment with intravenous (i.v.) ibandronate on opioid-resistant bone pain in patients with skeletal metastases [7].
• Ibandronate was well tolerated, with no evidence of renal toxicity [7].

Chemical compound and disease context of Ibandronic Acid

• By 7 days after the infusion of ibandronate, a decrease in pCa of 0.69 +/- 0.03 mmol/L (20.0 +/- 0.7%; P < 0.001) and in bone resorption [mean change in fasting urinary Ca, 0.09 +/- 0.04 mmol/L GFR (47.6 +/- 8.6%; P < 0.001) and 14.4 +/- 1.7 nmol/mmol (27.6 +/- 10.6%; P < 0.01) in deoxypyridinoline] was observed [8].
• Several bisphosphonates (e.g., etidronate, clodronate, pamidronate, alendronate, tiludronate, risedronate, and ibandronate) are established as effective treatments in clinical disorders such as Paget's disease of bone, myeloma, and bone metastases [9].
• Therapy of osteoporosis in patients with Crohn's disease: a randomized study comparing sodium fluoride and ibandronate [10].
• METHODS: Eighty-four patients with Crohn's disease and pathological bone mineral density findings were randomized to receive either vitamin D3 (1000 IU) and calcium citrate (800 mg) daily (group A) or sodium fluoride (25 mg b.d., group B) or intravenous ibandronate (1 mg every 3 months, group C) in addition to daily calcium/vitamin D substitution [10].
• OBJECTIVE: The aim of this study was to compare the cost-effectiveness of oral ibandronate with zoledronic acid and generic pamidronate (both administered by IV) for the treatment of bone metastases in patients with breast cancer receiving oral hormonal therapy in the United Kingdom [11].

Biological context of Ibandronic Acid

• Consistent with these in vivo results, a relatively high concentration of ibandronate (100 microM) increased caspase-3 activity and induced DNA fragmentation in MDA-231 breast cancer cells in culture [3].
• Changes of bone mineral density (ibandronate versus controls) were as follows: lumbar spine, -0.9 +/- 6.1% versus -6.5 +/- 5.4% (P < 0.0001); femoral neck, +0.5 +/- 5.2% versus -7.7 +/- 6.5% (P < 0.0001); and midfemoral shaft, +2.7 +/- 12.2% versus -4.0 +/- 10.9% (P = 0.024) [12].
• As in osteoclasts, the inhibition of protein prenylation in J774 cells caused by alendronate or ibandronate treatment was dose-dependently prevented by cotreatment with clodronate [13].
• We have found that, in J774 macrophages, nitrogen-containing bisphosphonates (such as alendronate, ibandronate, and risedronate) inhibit post-translational modification (prenylation) of proteins, including the GTP-binding protein Ras, with farnesyl or geranylgeranyl isoprenoid groups [14].
• Ibandronate treatment did not affect median body temperature, and it was associated at the 10-hour measurement with maximum increases in total lymphocyte count, B cells, T cells, and CD4+ and CD8+ T-cell subsets [15].

Anatomical context of Ibandronic Acid

• Histological and histomorphometrical examination revealed that ibandronate reduced osteoclastic bone resorption, with increased apoptosis in osteoclasts [3].
• Blood vessel immunostaining on prostate tissue sections revealed that both ibandronate and zoledronic acid induced a 50% reduction of the revascularization of the prostate gland [16].
• RESULTS AND CONCLUSIONS: After 2 years, oral daily ibandronate produced a dose-related and sustained maintenance or increase in BMD at the lumbar spine and hip (total hip, femoral neck, trochanter), together with a dose-related reduction in the rate of bone turnover [17].
• Effect of first treatment with aminobisphosphonates pamidronate and ibandronate on circulating lymphocyte subpopulations [15].
• Lifelong administration of high doses of ibandronate increases bone mass and maintains bone quality of lumbar vertebrae in rats [18].

Associations of Ibandronic Acid with other chemical compounds

• Histologic sections of ibandronate-treated bone explants showed further rescue of functioning osteoclasts during concomitant treatment with geranylgeraniol [19].
• Both sodium fluoride and ibandronate resulted in significant decreases in the serum concentration of osteoprotegerin after 9 months (P < 0.001) [10].
• In common with other nitrogen-containing bisphosphonates, ibandronate is a strong inhibitor of farnesyl pyrophosphate synthase, which probably accounts for its major effects on osteoclast activity [20].
• Thus in rats, dogs, and monkeys with estrogen depletion, and in minipigs with glucocorticoid-induced bone loss, ibandronate administered s.c. or i.v. with extended intervals between doses reduces bone turnover, increases bone mineral density, and maintains bone quality in a dose-dependent manner [21].
• Activation by lipopolysaccharide (LPS) of PBMC previously incubated with ibandronate led to enhanced levels of tumour necrosis factor alpha (TNF-alpha) secretion, and this could be partially inhibited by neutralizing antibodies to IFN-gamma [22].

Gene context of Ibandronic Acid

• Geranylgeraniol antagonized the stimulation of ABCA1 expression by ibandronate [23].
• The antibody against human BSP II was significantly more active than all ASOs used and was equally active or even surpassed the activity of ibandronate and ErPC3 in all three assays [24].
• RESULTS: In both groups, the combination of chemotherapy with either pamidronate or ibandronate produced a reduction in bone resorption and tumour burden as measured by NTX, IL-6, paraprotein, CRP, and beta 2-microglobulin from the second month of treatment, having no effect on bone formation [25].
• Ibandronate stimulated the production of interferon gamma (IFN-gamma) in adherent PBMC, and increased the surface expression of FcgammaRI and HLA DP, DQ, DR on the adherent monocyte population [22].
• CONCLUSIONS: The enhanced production of TNF-alpha by ibandronate-treated PBMC in vitro involves stimulation of adherent monocytes by IFN-gamma prior to LPS-induced activation [22].

Analytical, diagnostic and therapeutic context of Ibandronic Acid

• Ibandronate reduces osteolytic lesions but not tumor burden in a murine model of myeloma bone disease [2].
• Here we examined the effects of the BP ibandronate on MDA-231 human breast cancer cells in bone metastases in a well-characterized animal model of bone metastasis [3].
• Because the incidence of drug-associated AEs was low, a dose escalation of ibandronate can be recommended for further clinical trials [4].
• PATIENTS AND METHODS: Patients with multiple myeloma stage II or III were randomly assigned to receive either ibandronate 2 mg or placebo as a monthly intravenous (IV) bolus injection for 12 to 24 months in addition to conventional chemotherapy [26].
• CONCLUSION: As assessed by BMD, intravenous injections of ibandronate (2 mg every 2 months or 3 mg every 3 months) are at least as effective as the regimen of 2.5 mg orally daily, which has proven antifracture efficacy, and are well tolerated [27].

References