Prostaglandin E2 restores cancellous bone to immobilized limb and adds bone to overloaded limb in right hindlimb immobilization rats.
The purpose of this study was to determine whether prostaglandin E2 (PGE2) can restore cancellous bone mass and architecture to osteopenic, continuously immobilized (IM), proximal tibial metaphysis (PTM) in female rats. The right hindlimb of three and one-half-month-old Sprague-Dawley female rats were immobilized by right hindlimb immobilization (RHLI) in which the right hindlimb was underloaded and the contralateral left limb was overloaded during ambulation. After 4 or 12 weeks of RHLI, the rats were treated with 3 or 6 mg PGE2/kg/day and RHLI for 8 or 16 weeks. Bone histomorphometry was performed on microradiographs of PTM. Immobilization (IM) induced a transient cancellous bone loss and decreased trabecular thickness, number and node density, and increased free end density that established a new steady state after 4 weeks of IM. Three or 6 mg PGE2/kg/d for 8 weeks beginning at 4 or 12 weeks of IM completely restored cancellous bone mass (+127% to +188%) and structure to the age-related control levels in spite of continuous IM. Another 8 weeks of treatment maintained bone mass and architecture at these levels. No differences in cancellous bone mass and architecture were found between the overloaded PTM or RHLI rats and the age-related controls. However, 3 and 6 mg/kg/d of PGE2 treatment started at 4 or 12 weeks for 8 weeks significantly increased cancellous bone mass in the overloaded PTM (+45 to +74% of untreated controls), and another 8 weeks of treatment maintained bone mass at these levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Li
M
M
Division of Radiobiology, University of Utah, School of Medicine, Salt Lake City 84112.
Jee
W S
WS
Ke
H Z
HZ
Liang
X G
XG
Lin
B Y
BY
Ma
Y F
YF
Setterberg
R B
RB
D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000503:physiopathology; D001842:Bone and Bones / Q000187:drug effects* / Q000503:physiopathology; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D006614:Hindlimb; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical
D015232:Dinoprostone