Monophasic dose-response curves of betamethasone on geometric and mechanical properties of femur diaphyses in growing rats.
The biomechanical repercussion of the corticoid-induced osteopenia (a severe consequence of long-term glucocorticoid therapy) was studied in cortical bone of small rodents. Growing rats receiving 12.5-3200 micrograms/kg/d of betamethasone (BMS) s.c. for 20 days suffered a log-dose related impairment in body weight gain and in mechanical (fracture load, bending stiffness) and cross-sectional properties (area, moment of inertia) of femur diaphyses. No changes in bone material properties (ability to stand stress, elastic modulus, energy absorption per unit volume) were observed. At variance with the biphasic dose-response curves (positive effects at low-medium doses, negative at high doses) previously obtained with cortisol in a similar model, only negative effects on every variable studied were observed in this experiment. Results suggest that BMS effects on cortical bone biomechanics derived mainly or completely from those induced on bone geometry (biomechanical correlate of corticoid-induced osteopenia) in the assayed conditions. Data are compatible with a BMS-induced change in the setpoint of bone mechanostat. Correlation of bone geometric and biomechanical data with body weight gain showed that the anti-anabolic effects of BMS on bone were proportionally less intense than those exerted on the whole biomass.
Ferretti
J L
JL
Centro de Estudios de Metabolismo Fosfocálcico (CEMFoC), Consejo de Investigaciones, U.N.R., Facultad de Medicina, Universidad Nacional de Rosario, Argentina.
Capozza
R F
RF
Cointry
G R
GR
Delgado
C J
CJ
Zanchetta
J R
JR
D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D018483:Diaphyses / Q000187:drug effects / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000187:drug effects* / Q000254:growth & development; D008297:Male; D051381:Rats
D001623:Betamethasone