Effects of continuous glucocorticoid infusion on bone metabolism in the rat.
The effects of continuous administration of supraphysiologic doses of dexamethasone (DEX) on bone metabolism were examined in rats. Adult, male, Sprague Dawley rats were infused with DEX at a constant rate of 16.25 microg/day for 19 days. Despite soft tissue catabolism, DEX treatment led to a significant increase in bone volume in all experiments. This was accompanied by a significant gain in femoral weight and calcium content. These findings were also observed in DEX-treated parathyroidectomized animals indicating that intact parathyroid function was not required for this effect. DEX treatment did not affect mean levels of serum calcium or phosphorus but led to significant declines in circulating levels of PTH and 1,25(OH)2D and in the urinary calcium/creatinine ratio. This latter finding was also observed in PTX animals in which 1,25(OH)2D levels did not change. Serum concentrations of osteocalcin and tartrate-resistant acid phosphatase both declined in a time-dependent manner with DEX treatment suggesting a slowing of bone turnover with the net effect favoring formation. However, histomorphometric findings were variable. Two of three experiments demonstrated a decrease in cellular parameters of formation and resorption and in one experiment, these indices increased. Mineralized surface increased with DEX treatment. We conclude that, in marked contrast to the findings in man and certain other species, DEX treatment increases bone mass in rats. This may in part relate to a relatively greater suppression of resorption vis à vis formation.
King
C S
CS
Section of Comparative Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Weir
E C
EC
Gundberg
C W
CW
Fox
J
J
Insogna
K L
KL
D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000652:urine; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004100:Dihydroxycholecalciferols / Q000097:blood; D004195:Disease Models, Animal; D005269:Femur / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D015918:Infusion Pumps, Implantable; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000097:blood / Q000503:physiopathology / Q000652:urine; D010281:Parathyroid Hormone / Q000097:blood; D016105:Parathyroidectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D004100:Dihydroxycholecalciferols; D005938:Glucocorticoids; D010281:Parathyroid Hormone; D015675:Osteocalcin; D003907:Dexamethasone; D002118:Calcium