CHANGES IN BONE-MINERAL DENSITY AND BONE-SPECIFIC ALKALINE-PHOSPHATASE IN OVARIECTOMIZED EWES

An animal model of human osteoporosis which adequately meets many of t he criteria needed to test new therapeutic agents is currently unavail able. The old ewe may serve this purpose, as changes in bone remodelin g occur within 3 months, and a difference in bone mass has been indica ted 6 months after ovariectomy. In the current study, we have measured longitudinal changes in bone mass and bone-specific alkaline phosphat ase (BSAP) for six months in 7-9 year old ovariectomized (OVX) ewes. T hirty ewes were divided into three groups: sham-treated (n = 9), OVX ( n = 12) and OVX with estrogen implants (OVXE, n = 9). Bone mineral den sity (BMD) was determined at 0, 3 and 6 months in the vertebrae (L4-L6 /L5-L7), calcaneus (GAL) and distal radius (DR) using dual-energy X-ra y absorptiometry (DEXA). Bone-Specific Alkaline Phosphatase (Tandem(R) -R Ostase(TM); Hybritech) was determined at monthly intervals. Body we ight did not significantly change in any group during treatment compar ed to sham, although a trend of increasing body weight at 3 and 6 mont hs was apparent in both OVX groups. Luteinizing hormone increased in a ll OVX ewes as a function of time as expected, demonstrating successfu l ovariectomies. Uterine weight was significantly increased (p < 0.01) in the OVXE animals compared to Sham and OVX groups. BMD did not chan ge significantly during the 6-month treatment period in the CAL or DR. BMD in the vertebrae (L4-L6/L5-L7) was significantly lower in the OVX group compared to sham (p < 0.08). Estrogen significantly increased B MD (L4-L6/L5-L7) compared to both the sham (p = 0.056) and OVX (p < 0. 01) groups. Estrogen treatment did not change BSAP at any time point c ompared to sham, however OVX significantly increased BSAP at both 3 an d 6 months compared to sham and estrogen groups (p < 0.05). The result s confirm earlier studies indicating an increase in bone remodeling ra tes by 3 months in OVX ewes and demonstrated a change in bone mass bet ween the sham and OVX groups six months after OVX. The mechanisms lead ing to the increase in BMD following estrogen treatment are not clear. This study in old ewes suggests that this may be a useful model for l ongterm studies investigating estrogen-deficiency induced bone loss in a remodeling species.