Does the Phosphate Binder Lanthanum Carbonate Affect Bone in Rats with Chronic Renal Failure?

Abstract

Abstract. Adequate control of phosphate levels remains an important issue in patients with chronic renal failure (CRF). Lanthanum carbonate has been proposed as a new phosphate binder. Previous studies have shown a high phosphate binding capacity (Ͼ97%) and low gastrointestinal absorption of lanthanum, without serious toxic side effects in the presence of a normal renal function (NRF). Because of lanthanum's physicochemical resemblance to calcium, the possible effects of it on bone have to be considered. The aim of this study was to investigate the effects of lanthanum carbonate on bone histology in NRF and CRF rats after oral administration of the compound with doses of 100, 500, or 1000 mg/kg per d for 12 wk. Bone histomorphometry showed that CRF animals that received vehicle developed secondary hyperparathyroidism. Urinalysis of lanthanum-loaded CRF animals showed a dosedependent decrease in urinary phosphorus excretion, which was clearly more pronounced in the CRF groups compared with NRF animals. Phosphatemia, however, remained normal. Lanthanum carbonate administration induced a dose-dependent decrease in bone formation rate and increase in osteoid area in CRF animals. Three of seven animals in the CRF-1000 group and one of eight animals in the NRF-100 group were classified as having a mineralization defect. The number of cuboidal osteoblasts, however, was not affected, indicating that bone changes were not due to a toxic effect of lanthanum on the osteoblast. Furthermore, lanthanum concentrations in the femur remained low and did not correlate with histomorphometric parameters. These findings suggest that the administration of high doses of phosphate binder (1000 mg/kg per d lanthanum carbonate), in combination with decreased 25-(OH) vitamin D 3 in the uremic state, resulted in phosphate depletion and followed by an increased mobilization of phosphorus out of bone and/or reduced incorporation into bone. There was no evidence that lanthanum had a direct toxic effect on osteoblasts.

Adequate phosphate binding with lanthanum carbonate attenuates arterial calcification in chronic renal failure rats

“…The lanthanum concentration in serum, aorta and kidney samples was only slightly increased with a factor 2-3 after 8 weeks of 2% La treatment compared to untreated CRF rats. However, serum and tissue lanthanum levels remained low and were comparable to those found in other experimental studies [21][22][23].…”

Control of Hyperphosphatemia among Patients with ESRD

“…In two different rat models of CKD, the oral administration of lanthanum led to more than a 10-fold increase of tissue content in the liver, lung, and kidney (61). Furthermore, rats that were administered large doses of lanthanum for 12 wk showed a dose-dependent decrease in bone formation rate and osteomalacia (62). However, this may have been related to phosphorus depletion rather than lanthanum toxicity (63).…”

Evaluation of short-term effects of rare earth and other elements used in magnesium alloys on primary cells and cell lines☆

“…REE in magnesium alloying are predominantly used for strengthening and to improve corrosion resistance 19 . neodymium is used in magnetic prosthetic devices 21 , lanthanum is administered as a phosphate binder ("Fosrenol") in chronic renal failure 22 and gadolinium based contrast agents are widely used in Magnetic resonance imaging (MRI) 23 .…”