Short-term low dose methotrexate ameliorates abnormal bone metabolism and bone loss in adjuvant induced arthritis.
OBJECTIVE
To clarify whether short term weekly methotrexate (MTX) therapy aggravates bone abnormalities in adjuvant induced arthritis (AIA) or improves them through its antiarthritic effect.


METHODS
Bone metabolism and bone mineral density (BMD) were studied in 6 groups of Lewis rats: (1) normal controls, (2) rats given MTX 0.3 mg/kg weekly, (3) rats given MTX 3 mg/kg weekly, (4) AIA rats, (5) AIA rats given MTX 0.3 mg/kg weekly, and (6) AIA rats given MTX 3 mg/kg weekly. Osteogenic activity was determined from serum osteocalcin levels and number of marrow fibroblast colony forming units (osteogenic precursor cells). Bone resorptive activity was assayed by detecting osteoclast-like cells and pit formation in bone marrow cultures.


RESULTS
In control rats, MTX (3 mg/kg weekly) suppressed osteogenic activity, as shown by low serum osteocalcin levels and decreased growth of marrow fibroblast colony forming units. Osteoclast-like cells and pit formation in bone marrow cultures from control rats were increased by MTX, but BMD was unchanged. In rats with AIA, MTX (3 mg/kg) suppressed arthritis and restored the decreased osteogenic activity of bone marrow cells, and reduced their increased bone resorptive activity. These changes resulted in a significant increase of periarticular BMD in the femur.


CONCLUSIONS
Low dose weekly MTX therapy had a favorable effect on abnormal bone metabolism and osteopenia in rats with AIA.
Suzuki
Y
Y
Department of Drug Delivery System, St. Marianna University School of Medicine, Kawasaki, Japan.
Nakagawa
M
M
Masuda
C
C
Ide
M
M
Uehara
R
R
Ichikawa
Y
Y
Mizushima
Y
Y
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D005260:Female; D008727:Methotrexate / Q000008:administration & dosage*; D015675:Osteocalcin / Q000097:blood / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew
D015675:Osteocalcin; D008727:Methotrexate