Thirty male adult Wistar rats (300-/+10 g
body weight) underwent either 5/6
nephrectomy (Nx, n=20) or
sham operation (
SHAM, n=10) to determine
olpadronate effects in an experimental model of uremic
bone disease. For a 38-day period, 10 rats received
olpadronate (16microg/100g bw) once a week (Nx+OPD) and the other vehicle (Nx).
SHAM received vehicle. At baseline, treatment onset (t=7 days) and end of study (t=45 days)
calcium,
phosphorus,
creatinine, bone
alkaline phosphatase (b-ALP) and
deoxypyridinoline crosslinks (DPyr) were determined. At t=0 and t=45 bone mineral density (BMD) was measured by DXA. At t=45 the right tibia was removed for bone histology. There were no differences in serum
calcium.
Phosphorus increased in Nx and Nx+OPD compared to
SHAM (p<lt 0.05). The b-ALP increased from t=0 to t=7 in Nx and Nx+OPD (p<0.05) and decreased thereafter to
SHAM levels. DPyr/creat increased in Nx compared to
SHAM (p<0.05) and Nx+OPD (p<0.001). Nx+OPD presented lower DPyr excretion than
SHAM rats (p<0.01). At t=45, tibia BMD of Nx was 20% and 26% lower than in
SHAM (p<0.005) and Nx+OPD, respectively, (p<0.001). BMD was higher Nx+OPD than in
SHAM (p<0.05). OPD prevented the loss of bone volume, the increment in osteoid volume and erosion surface observed in Nx group (p<0.05). OPD also prevent the increment in the number of osteoclasts (OC) and the active OC surface and decreases the number of TRAP(+)-OC (p<0.05). In summary, OLP may be beneficial in
osteopenia associated to high turnover bone disease of CRF. However, the use of
bisphosphonate therapy for
renal insufficiency must be further investigated in order to clarify essential aspects of treatment as the patient selection and several aspects of treatment, such as optimum dose, frequency, and safe period of administration.