Single infusion of neridronate (6-amino-1-hydroxyhexylidene-1,1-bisphosphonate) in patients with active rheumatoid arthritis: effects on disease activity and bone resorption markers.
OBJECTIVE
The aim of this study was to assess the effects of a single infusion of the bisphosphonate neridronate (N) on parameters of inflammation and bone resorption in rheumatoid arthritis (RA).


METHODS
Forty-five patients with active RA were randomly allocated on a double blind basis to receive a single intravenous infusion of either N 25 mg (15 patients), N 50 mg (15 patients), or placebo (15 patients). At baseline and after 7 and 21 days, we assessed the following: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and Ritchie's articular index as indices of disease activity; and urinary free deoxypyridinoline (DPyr), N-telopeptide of type I collagen (NTx) and hydroxyproline (OHP) as indices of bone resorption.


RESULTS
At day 7, N 25 mg significantly decreased ESR compared to N 50 mg (p=0.002), and CRP compared to placebo (p=0.036). With regard to bone resorption markers, at day 7, both N 25 mg and 50 mg compared to placebo significantly decreased NTx (p<0.0005 and p=0.003, respectively) and OHP (p=0.001 and p=0.004, respectively). At day 21, N 50 mg significantly decreased OHP compared to placebo (p=0.017). DPyr levels remained unchanged in the three groups.


CONCLUSIONS
N 25 mg and 50 mg exerted different effects on RA activity parameters, since only the lower dose significantly decreased ESR and CRP. Both doses of N inhibited bone resorption, with a transient, significant reduction in urinary NTx and OHP, but without any effect on DPyr.
Mazzantini
Maurizio
M
Department of Internal Medicine, University of Pisa, Italy. mmazzant@int.med.unipi.it
Di Munno
Ombretta
O
Metelli
Maria Rita
MR
Bulleri
Marco
M
Giordani
Roberto
R
D000368:Aged; D000596:Amino Acids / Q000652:urine; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015415:Biomarkers; D001799:Blood Sedimentation; D001862:Bone Resorption / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000378:metabolism; D003094:Collagen / Q000652:urine; D024042:Collagen Type I; D004164:Diphosphonates / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000652:urine
D000596:Amino Acids; D015415:Biomarkers; D024042:Collagen Type I; D004164:Diphosphonates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C053389:6-amino-1-hydroxyhexane-1,1-diphosphonate; C036020:deoxypyridinoline; D003094:Collagen; D002097:C-Reactive Protein; D006909:Hydroxyproline