Disease modifying effects of N-butyryl glucosamine in a streptococcal cell wall induced arthritis model in rats.
OBJECTIVE
To evaluate the effect of different doses of N-butyryl glucosamine (GlcNBu) on joint preservation and subchondral bone density and quality in a streptococcal cell wall (SCW) induced arthritis model in Lewis rats.


METHODS
Chronic arthritis was induced in 36 female Lewis rats by a single intraperitoneal injection of SCW antigen. The 4 groups studied were: (1) no arthritis, no drug treatment; (2) arthritis, no drug treatment; (3) arthritis, oral GlcNBu 20 mg/kg/day; and (4) arthritis, oral GlcNBu 200 mg/kg/day. Inflammation (ankle swelling) was quantified throughout the clinical course; bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry on dissected distal femurs and proximal tibiae, in user defined regions of interest. Qualitative and quantitative 3-D bone architecture changes were determined using microcomputerized tomography on the left tibiae. Subchondral plate thickness and trabecular bone connectivity were studied on the proximal tibia epiphyses from the central coronal sections of each scanned tibia.


RESULTS
GlcNBu inhibited inflammatory ankle swelling at both 20 and 200 mg/kg/day, the latter being statistically significant, with an average reduction of 33%. GlcNBu preserved or enhanced BMD and bone connectivity and prevented further bone loss at both the high and the low dose. Comparisons of the isosurfaces and the architectural measures in the different groups showed that GlcNBu effectively protected the joint surfaces from further erosion in this model of chronic inflammatory arthritis. For some of the bone measurements, increasing doses of GlcNBu showed increasing protective effects, while for other measurements, effects were maximal at the lower dose.


CONCLUSIONS
These data indicate that GlcNBu provides antiinflammatory and antierosive effects by preserving BMD, joint integrity, and bone architecture in involved joints of the SCW model.
Wang
Susanne X
SX
Department of Laboratory Medicine and Pathobiology, University of Toronto, and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
Cherian
Annie
A
Dumitriu
Mircea
M
Grynpas
Marc D
MD
Carran
John
J
Wainman
Dan
D
Anastassiades
Tassos
T
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D015519:Bone Density / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D005944:Glucosamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013291:Streptococcus / Q000166:cytology / Q000276:immunology; D013977:Tibia / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; C502362:N-butyrylglucosamine; D005944:Glucosamine