Effect of sevelamer hydrochloride on bone in experimental uremic rats.
Hyperphosphatemia in dialysis patients is known to cause secondary hyperparathyroidism and high-turnover bone disease. Sevelamer hydrochloride (sevelamer) is a nonabsorbed, calcium-free phosphate-binder. We determined the effect of sevelamer on parathyroid hormone (PTH)-induced high bone turnover. Rats were sham-operated or 5/6-nephrectomized (Nx) and fed a phosphate loading diet for 16 weeks or 5/6-nephrectomized and fed a phosphate loading diet for 8 weeks and then fed the same diet containing 3% sevelamer for the subsequent 8 weeks (Nx-S). Sevelamer significantly reduced serum PTH. The relative osteoid volume (OV/BV), osteoid surface (OS/BS), eroded surface (ES/BS), mineral appositional rate (MAR), volume-referent bone formation rate (BFR/TV), and bone-referent bone formation rate (BFR/BV) were measured for vertebral bone histomorphometric analysis. All parameters were statistically higher in the Nx rats than in the sham-operated control rats. The administration of sevelamer attenuated increases in OV/BV, ES/BS, BFR/TV, and BFR/BV. For femur histomorphometric analysis, the porosity area (%) (PoAr/CtAr), osteoid surface on the periosteal surface, osteoid surface on the endocortical surface (OS/Es), mineral appositional rate on the periosteal surface, mineral appositional rate on the endocortical surface, bone formation rate on the periosteal surface, and bone formation rate on the endocortical surface (Es BFR) were calculated. All parameters were higher in the Nx group than in the control group. Sevelamer inhibited the elevation of PoAr/CtAr, OS/Es, and Es BFR. Our findings suggest that the decrease in PTH by sevelamer may be beneficial in the treatment of high PTH-induced bone disease.
Kuwahara
Michio
M
Department of Nephrology, Shuwa General Hospital, Kasukabe, Japan. kuwaharam@shuwa.or.jp
Inoshita
Seiji
S
Terada
Yoshio
Y
Sasaki
Sei
S
D000818:Animals; D001847:Bone Diseases / Q000209:etiology / Q000517:prevention & control*; D016723:Bone Remodeling / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D006962:Hyperparathyroidism, Secondary / Q000150:complications / Q000209:etiology; D054559:Hyperphosphatemia / Q000150:complications / Q000209:etiology; D008297:Male; D010012:Osteogenesis / Q000187:drug effects; D010281:Parathyroid Hormone / Q000097:blood* / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D006435:Renal Dialysis / Q000009:adverse effects; D000069603:Sevelamer; D014511:Uremia / Q000503:physiopathology
D002614:Chelating Agents; D010281:Parathyroid Hormone; D011073:Polyamines; D000069603:Sevelamer