Changes in bone mineral density and bone-specific alkaline phosphatase in ovariectomized ewes

An animal model of human osteoporosis which adequately meets many of the criteria needed to test new therapeutic agents is currently unavailable. The old ewe may serve this purpose, as changes in bone remodeling occur within 3 months, and a difference in bone mass has been indicated 6 months after ovariectomy. In the current study, we have measured longitudinal changes in bone mass and bone-specific alkaline phosphatase (BSAP) for six months in 7–9 year old ovariectomized (OVX) ewes. Thirty ewes were divided into three groups: sham-treated (n = 9), OVX (n = 12) and OVX with estrogen implants (OVXE, n = 9). Bone mineral density (BMD) was determined at 0, 3 and 6 months in the vertebrae (L4-L6/L5-L7), calcaneus (CAL) and distal radius (DR) using dual-energy X-ray absorptiometry (DEXA). Bone-Specific Alkaline Phosphatase (Tandem ®-R Ostase™; Hybritech) was determined at monthly intervals. Body weight did not significantly change in any group during treatment compared to sham, although a trend of increasing body weight at 3 and 6 months was apparent in both OVX groups. Luteinizing hormone increased in all OVX ewes as a function of time as expected, demonstrating successful ovariectomies. Uterine weight was significantly increased (p < 0.01) in the OVXE animals compared to Sham and OVX groups. BMD did not change 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 BMD (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 compared to sham, however OVX significantly increased BSAP at both 3 and 6 months compared to sham and estrogen groups (p < 0.05). The results confirm earlier studies indicating an increase in bone remodeling rates by 3 months in OVX ewes and demonstrated a change in bone mass between the sham and OVX groups six months after OVX. The mechanisms leading 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 long-term studies investigating estrogen-deficiency induced boen loss in a remodeling species.