Short term whole body retention in relation to rate of bone resorption and cartilage degradation after intravenous bisphosphonate (pamidronate) in rheumatoid arthritis.
OBJECTIVE
Bisphosphonates (BP) inhibit osteoclast-mediated bone resorption, and have been reported to decrease the rate of cartilage degradation. The anti-resorptive effect of BP is determined by the amount of BP retained by the skeleton. In rheumatoid arthritis (RA) the uptake is not confined only to the skeleton, but BP is also retained in joints, which could have implications for dose regimens. We investigated the whole body retention (WBR) of pamidronate and its relationship to bone resorption and cartilage degradation in patients with active RA.


METHODS
Twenty-six patients received placebo, 45 mg, or 90 mg intravenous pamidronate. Serum and urine samples were collected before and for 12 days after drug administration. Rate of bone resorption was assessed by the biochemical markers: serum carboxy terminal cross-linked telopeptide of type I collagen, urinary carboxy terminal cross-linked telopeptide of type I collagen normalized to creatinine and urinary amino-terminal telopeptide of type I collagen normalized to creatinine; and rate of cartilage degradation by urinary carboxy terminal telopeptide of type II collagen normalized to creatinine. WBR was derived from urinary excretion of pamidronate data.


RESULTS
Pamidronate induced a rapid and sustained decrease in the level of biochemical markers of bone resorption and cartilage degradation. The mean WBR of pamidronate was 69% of the administered dose, and showed a remarkably wide range (41-96%). The decrease in rate of bone resorption, but also rate of cartilage degradation appeared to be related to the WBR of pamidronate.


CONCLUSIONS
This is the first study in which the effect of BP treatment has been studied in relation to the amount of BP retained by the body in patients with active RA. The total amount of BP retained by the body shows a remarkably wide range and is comparable with literature on patients with osteoporosis. The apparent relationships between the amount of BP retained by the body and the effect could have implications for therapeutic regimens in patients with RA.
Cremers
Serge C L M
SC
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands. S.C.L.M.Cremers@lumc.nl
Lodder
Mariëtte C
MC
Den Hartigh
Jan
J
Vermeij
Pieter
P
Van Pelt
Philomena
P
Lems
Willem F
WF
Papapoulos
Socrates E
SE
Dijkmans
Ben A C
BA
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D015415:Biomarkers; D001862:Bone Resorption / Q000188:drug therapy* / Q000473:pathology; D002356:Cartilage / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D000077268:Pamidronate
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D004164:Diphosphonates; D000077268:Pamidronate