Disease relevance of Me2-APD

• Four bone matrix-bound nitrogen-containing bisphosphonates (pamidronate, olpadronate, alendronate, and ibandronate) inhibited adhesion and spreading of breast cancer cells to bone dose-dependently, whereas etidronate and clodronate had little or no effect [1].
• Short-term therapy with oral olpadronate in active Paget's disease of bone [2].
• The data in this report suggest that olpadronate has potential as an effective inhibitor of the skeletal progression of clinical prostate cancer [3].
• We studied clinical and biochemical responses 5 days and 3 months after administration of the new, potent bisphosphonate, olpadronate, in 28 patients with prostate cancer and bone metastases [4].
• Modulation of cytosolic calcium levels in osteoblast-like osteosarcoma cells by olpadronate and its amino-derivative IG-9402 [5].

High impact information on Me2-APD

• Etidronate, alendronate, pamidronate, olpadronate, or amino-olpadronate (IG9402, a bisphosphonate that lacks antiresorptive activity) at 10(-9) to 10(-6) M prevented apoptosis of murine osteocytic MLO-Y4 cells, whether it was induced by etoposide, TNF-alpha, or the synthetic glucocorticoid dexamethasone [6].
• Relationships between pharmacokinetics and rate of bone turnover after intravenous bisphosphonate (olpadronate) in patients with Paget's disease of bone [7].
• To address this issue, we examined the pharmacokinetics and pharmacodynamics of the bisphosphonate olpadronate given intravenously to 75 patients with Paget's disease, using a specific assay for olpadronate concentrations in serum and urine [7].
• Replacing the hydroxyl group in the bone-binding site of three clinically useful bisphosphonates (etidronate, pamidronate, and olpadronate) by an amino group resulted in great differences in their antiresorptive potencies in vitro [8].
• Whereas olpadronate was a potent inhibitor of axenic growth of Dictyostelium amebae, the aminosubstitution reduced its potency drastically (IC50 12 microM and 700 microM, respectively) [8].

Chemical compound and disease context of Me2-APD

• Strontium-89 (Metastron) and the bisphosphonate olpadronate reduce the incidence of spinal cord compression in patients with hormone-refractory prostate cancer metastatic to the skeleton [9].

Biological context of Me2-APD

• Moreover, the mechanism of action of the NBp olpadronate, but not clodronate, on early tartrate-resistant acid phosphatase-negative osteoclast precursors involves inhibition of protein geranylgeranylation, indicating a molecular mechanism similar to that established for mature osteoclasts [10].
• Olpadronate reduced fractures in children with osteogenesis imperfecta [11].
• In conclusion, the kinetic profile of 99mTc-labelled olpadronate, mainly AUC and WBR, showed a dependence upon bone metabolism and seemed unrelated to body size variables [12].
• Serum kinetics, bioavailability and bone scanning of 99mTc-labelled sodium olpadronate in patients with different rates of bone turnover [12].
• Olpadronate: a new amino-bisphosphonate for the treatment of medical osteopathies [13].

Anatomical context of Me2-APD

• Bending fracture load of femur diaphyses, reduced in OXc, was recovered by olpadronate [14].

Analytical, diagnostic and therapeutic context of Me2-APD

• We showed that 3,3-dimethylaminopropane-1-hydroxy-1,1-diphosphonic acid (olpadronate) was the most effective bisphosphonate treatment in reducing tumor burden as assessed by GFP imaging and radiography [3].
• We addressed these issues in a longitudinal study of 157 patients with biochemically active disease (serum alkaline phosphatase activity >120 U/L) treated with the bisphosphonate olpadronate and followed for a median period of 37 months (range 3-162, mean 46 +/- 30) [15].
• We treated three boys with severe OI type III and vertebral deformities for 5-7 years with continuous oral administration of the bisphosphonate, olpadronate [16].
• Effect of topical administration of monosodium olpadronate on experimental periodontitis in rats [17].
• None of the patients treated with local radiotherapy, only 4% of patients receiving 89Sr and 21% of patients given olpadronate developed this complication [9].

References