title: Elimination and biochemical responses to intravenous alendronate in postmenopausal osteoporosis.
abstract: Postmenopausal women with established vertebral osteoporosis were studied for 2 years to determine the terminal elimination half-life and the duration of response to treatment with intravenous alendronate (30 mg) given over 4 days. The urinary excretion of alendronate followed a multiexponential decline. Approximately 50% of the total dose was excreted over the first 5 days, and a further 17% was excreted in the succeeding 6 months. Thereafter, there was a much slower elimination phase with an estimated mean terminal half-life of greater than 10 years (n = 11). Urinary excretion of hydroxyproline and calcium decreased significantly from pretreatment values by day 3, reaching a nadir by 1 week (40% and 67% decrease, respectively). Thereafter, hydroxyproline remained suppressed for the following 2 years. In contrast, urinary calcium excretion returned gradually toward pretreatment values over the first year and during the second year was comparable to pretreatment values. Serum activity of alkaline phosphatase activity decreased over 3 months (23% reduction), increased gradually thereafter, and returned to pretreatment values at month 24. Bone mineral density measured at the spine increased by approximately 5% during the first year and remained significantly higher than pretreatment values at 2 years. We conclude that a short course of high doses of intravenous alendronate is associated with a prolonged skeletal retention of the agent. This open study also suggests that this regimen has a sustained effect on bone turnover persisting for at least 1 year.
authors.affiliation: Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, United Kingdom.
authors.forename: S A
authors.initials: SA
authors.lastname: Khan
authors.forename: J A
authors.initials: JA
authors.lastname: Kanis
authors.forename: S
authors.initials: S
authors.lastname: Vasikaran
authors.forename: W F
authors.initials: WF
authors.lastname: Kline
authors.forename: B K
authors.initials: BK
authors.lastname: Matuszewski
authors.forename: E V
authors.initials: EV
authors.lastname: McCloskey
authors.forename: M N
authors.initials: MN
authors.lastname: Beneton
authors.forename: B J
authors.initials: BJ
authors.lastname: Gertz
authors.forename: D G
authors.initials: DG
authors.lastname: Sciberras
authors.forename: S D
authors.initials: SD
authors.lastname: Holland
authors.forename: J
authors.initials: J
authors.lastname: Orgee
authors.forename: G M
authors.initials: GM
authors.lastname: Coombes
authors.forename: S R
authors.initials: SR
authors.lastname: Rogers
authors.forename: A G
authors.initials: AG
authors.lastname: Porras
mesh_terms: D000368:Aged; D019386:Alendronate / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000469:Alkaline Phosphatase / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D002118:Calcium / Q000652:urine; D005260:Female; D006207:Half-Life; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D007275:Injections, Intravenous; D008159:Lumbar Vertebrae; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D010281:Parathyroid Hormone / Q000097:blood
chemical_list: D010281:Parathyroid Hormone; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D006909:Hydroxyproline; D002118:Calcium; D019386:Alendronate