RESEARCH - Short term whole body retention in relation to rate of bone resorption and cartilage degradation after IV pamidronate in RA

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J Rheumatol. 2004 Sep;31(9):1732-7.

Short term whole body retention in relation to rate of bone resorption

and cartilage degradation after intravenous bisphosphonate (pamidronate)

in rheumatoid arthritis.

Cremers SC, Lodder MC, Den Hartigh J, Vermeij P, Van Pelt P, Lems WF,

Papapoulos SE, Dijkmans BA.

Department of Clinical Pharmacy and Toxicology and the Department of

Endocrinology and Metabolic Diseases, Leiden University Medical Center,

Leiden, The Netherlands.

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.

CONCLUSION: 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.

PMID: 15338492

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5338492 & dopt=Abstract

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