Estrogen and diphosphonate treatment provide long-term protection against osteopenia in ovariectomized rats.
The goal of this study is to determine whether the previously observed, short-term protective effect of estrogen and diphosphonate compounds against osteopenia in ovariectomized (OVX) rats can be maintained for an entire year. Sham-operated control and OVX rats were treated intermittently with vehicle alone, estrogen, or the diphosphonate compounds etidronate disodium (EHDP) and risedronate (NE-58095) for 360 days after surgery. Their proximal tibiae and first lumbar vertebrae were processed undecalcified for quantitative bone histomorphometry. Both skeletal sites in vehicle-treated OVX rats were characterized by decreased cancellous bone volume and increases in most cellular and fluorochrome-based indices of bone formation and resorption. Treatment of OVX rats with estrogen or diphosphonate compounds depressed bone turnover and provided nearly complete protection against cancellous bone loss. Long-term EHDP treatment induced a moderate mineralization defect, as indicated by increased absolute osteoid volume and a high proportion of osteoid surfaces devoid of adjacent osteoblasts. In contrast, NE-58095 had minimal effects on bone mineralization. These findings indicate that diphosphonate compounds and estrogen provide long-term protection against tibial and vertebral osteopenia in OVX rats. They further indicate that diphosphonate compounds merit consideration as an alternative to estrogen for the prevention of postmenopausal bone loss.
Wronski
T J
TJ
Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610.
Yen
C F
CF
Scott
K S
KS
D000818:Animals; D001851:Bone Diseases, Metabolic / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D015914:Estrogen Replacement Therapy; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005260:Female; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
C060493:NE 58095; D012968:Etidronic Acid