Elimination and biochemical responses to intravenous alendronate in postmenopausal osteoporosis.
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.
Khan
S A
SA
Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, United Kingdom.
Kanis
J A
JA
Vasikaran
S
S
Kline
W F
WF
Matuszewski
B K
BK
McCloskey
E V
EV
Beneton
M N
MN
Gertz
B J
BJ
Sciberras
D G
DG
Holland
S D
SD
Orgee
J
J
Coombes
G M
GM
Rogers
S R
SR
Porras
A G
AG
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
D010281:Parathyroid Hormone; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D006909:Hydroxyproline; D002118:Calcium; D019386:Alendronate