title: High bone-binding capacity of ibandronate in hemodialysis patients.
abstract: Bisphosphonates are a potential therapy for osteoclast-mediated bone disease, such as renal osteodystrophy. This study evaluated ibandronate bone-binding in patients with secondary hyperparathyroidism and renal osteodystrophy and examined whether there is a correlation with bone metabolism parameters. Sixteen patients with end-stage renal disease and secondary hyperparathyroidism receiving regular hemodialysis were recruited to this 12-week trial. Intravenous ibandronate 2 mg was administered for 5 min every 4 weeks directly after hemodialysis. Ibandronate levels were measured 15 min after infusion and at trough levels before the next hemodialysis. Serological markers of bone metabolism were also measured. After the first infusion, the peak ibandronate level was 154 +/- 75.1 ng/ml and the trough level was 2.7 +/- 1.7 ng/ml. At week 12, peak and trough ibandronate levels were 164.8 +/- 89.9 ng/ml and 3.2 +/- 2.6 ng/ml, respectively. Ibandronate bone uptake was 98.0% at first application and 98.4% at week 12. In patients with remaining diuresis, ibandronate urine excretion was < 0.001% of the administered dose. There was no correlation of ibandronate bone-binding with parameters of osteoclast activity or parathyroid hormone (PTH). The correlation with markers of osteoblast activity was significant but weak. Ibandronate had a bone-binding capacity of approximately 98% in hemodialysis patients. After repeated dosing ibandronate bone-uptake remained stable and was independent of osteoclast activity or PTH levels. Due to the high bone-binding of ibandronate in these patients, a 2 mg dose of intravenous ibandronate is equivalent to a 4-5 mg dose of ibandronate in patients with normal renal function.
authors.affiliation: Medizinische Klinik A, Klinikum der Stadt Ludwigshafen GmbH, Ludwigshafen am Rhein, Germany. bergnerr@klilu.de
authors.forename: R
authors.initials: R
authors.lastname: Bergner
authors.forename: D
authors.initials: D
authors.lastname: Henrich
authors.forename: M
authors.initials: M
authors.lastname: Hoffmann
authors.forename: T
authors.initials: T
authors.lastname: Lenz
authors.forename: G
authors.initials: G
authors.lastname: Bals
authors.forename: M
authors.initials: M
authors.lastname: Ullmann
authors.forename: M
authors.initials: M
authors.lastname: Uppenkamp
mesh_terms: D000328:Adult; D000368:Aged; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001862:Bone Resorption / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D004164:Diphosphonates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000378:metabolism; D000077557:Ibandronic Acid; D007676:Kidney Failure, Chronic / Q000628:therapy; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000077557:Ibandronic Acid