Glucocorticoid-induced osteopenia in the mouse as assessed by histomorphometry, microcomputed tomography, and biochemical markers.
Glucocorticoids are potent anti-inflammatory molecules used in the treatment of asthma, rheumatoid arthritis, inflammatory bowel disease, and other inflammatory and dermatological diseases, as well as in posttransplantation immunotherapy. Although glucocorticoids have been prescribed for many years, their potential side effects, when administered orally, can prevent their long-term use. The most serious side effect observed in the clinic is glucocorticoid-induced osteoporosis (GIOP). To develop a small animal model to characterize glucocorticoid-induced bone loss, we carried out a series of experiments using BALB/c mice given daily intraperitoneal doses of the synthetic glucocorticoid, dexamethasone. Following dexamethasone treatment, the mice became osteopenic, with highly significant decreases in bone formation rate and mineral apposition rate, as assessed by standard histomorphometry. Moreover, 3 week treatment with dexamethasone resulted in a decrease in trabecular thickness and trabecular number with an increase in surface-to-volume ratio of trabeculae in the distal femur, as measured using microcomputed tomography (micro-CT). The serum bone formation marker, osteocalcin, was dose-dependently decreased in all mice treated with dexamethasone and showed a parallel extent of regulation to the bone formation rate changes. In addition, serum levels of leptin, recently identified as playing a role in the regulation of bone mass, increased following dexamethasone treatment. BALB/c mice therefore represent a useful model system in which the detrimental effects of glucocorticoids on bone can be studied.
McLaughlin
F
F
Department of Asthma Cell Biology, GlaxoSmithKline, Stevenage, UK.
Mackintosh
J
J
Hayes
B P
BP
McLaren
A
A
Uings
I J
IJ
Salmon
P
P
Humphreys
J
J
Meldrum
E
E
Farrow
S N
SN
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000139:chemically induced* / Q000000981:diagnostic imaging*; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000000981:diagnostic imaging; D005938:Glucocorticoids / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008838:Microcomputers; D014057:Tomography, X-Ray Computed / Q000379:methods*
D015415:Biomarkers; D005938:Glucocorticoids