Changes in bone volume and bone resorption by olpadronate treatment in an experimental model of uremic bone disease.
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.
Tomat
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A
Sección Osteopatías Medicas, Hospital de Clínicas Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Gamba
C A
CA
Mandalunis
P
P
De Grandi
M C
MC
Somoza
J
J
Friedman
S
S
Zeni
S
S
D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects; D000596:Amino Acids; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000209:etiology; D001862:Bone Resorption / Q000378:metabolism*; D001842:Bone and Bones / Q000187:drug effects*; D002118:Calcium / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000652:urine; D004164:Diphosphonates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007668:Kidney / Q000601:surgery; D008297:Male; D010758:Phosphorus / Q000097:blood; D051381:Rats; D014511:Uremia / Q000150:complications*
D000596:Amino Acids; D004164:Diphosphonates; D010758:Phosphorus; C055774:olpadronic acid; C036020:deoxypyridinoline; D003404:Creatinine; D000469:Alkaline Phosphatase; D002118:Calcium