engleski

Sevelamer restores bone quality in ovariectomized rats

Sevelamer hydrochloride (Renagel® ; ), a non-calcium phosphate binder, is capable of reducing progressive coronary artery and aortic calcification. We have recently reported that sevelamer could also prevent and restore bone loss that follows ovariectomy in rats (Vukicevic et al., J Bone Miner Res 2005, S289). In the present study our aim was to determine the biomechanical properties of bones from rats treated with sevelamer. Sprague Dawley rats were ovariectomized (OVX) at 6 months and the sevelamer therapy started immediately in following groups: (1) Sham ; (2) Sham + sevelamer 3% ; (3) OVX ; (4) OVX + sevelamer 1% ; (5) OVX + sevelamer 3% and continued for 25 weeks in the prevention mode. In the restoration mode sevelamer treatment started 3 months after ovariectomy in these groups: (1) Sham ; (2) OVX ; (3) OVX + sevelamer HCl 3% ; (4) OVX + sevelamer calcium carbonate 1%, (5) OVX + sevelamer calcium carbonate 3%, (6) OVX + calcium carbonate 3%. Therapy continued for 12 weeks. In order to evaluate the biomechanical properties of rat bones we used the three-point bending and indentation tests. The intrinsic properties, stress, elastic modulus and toughness were calculated from the maximum load, stiffness, energy absorbed, anterior-posterior diameter, and the moment of inertia. In the restoration mode, rats treated with sevelamer HCl 3% had increased maximum load for 14.75% and stiffness for 12, 85% as compared to OVX animals. The cancellous bone was tested by using the indentation test in the marrow cavity of the distal femoral metaphysis. Sham animals treated with sevelamer 3% increased the maximum load for 26.5%, energy absorbed for 25, 3% and the ultimate strength for 25.9% as compared to sham rats. Sevelamer 3% in OVX rats also increased the maximum load for 69, 2%, stiffness for 70, 1% , energy absorbed for 57% and the ultimate strength for 75% as compared to OVX control animals. In the restoration mode sevelamer hydrochloride 3% had better effect on the biomechanical parameters than other treatment groups. It increased maximum load for 91, 5%, stiffness for 74, 2%, energy absorbed for 91, 4% and the ultimate strength for 89, 5% as compared to OVX animals. These results suggest that sevelamer strongly effects bone strength with a particular reference to the trabecular bone in OVX rats, and could have a positive effect on bone parameters, not only in patients on dialysis, but also in patients with osteoporosis.

Sevelamer hydrochloride ; biomechanical properties

nije evidentirano