Effects of Phosphate Binders on Bone
Hyperphosphatemia is the harbinger of numerous complications in patients with CKD, and these complications become most evident in patients who require dialysis. Elevated phosphate levels in the blood are central to the development of CKD-mineral bone disorder (CKD-MBD).
As CKD progresses, a decrease in renal excretion results in phosphate retention, which triggers the development of hyperparathyroidism, decreased production of calcitriol, and increased production of fibroblastic growth factor-23 (FGF-23).
Eventually hyperphosphatemia ensues and contributes to diffuse extra-osseous calcification and renal osteodystrophy. Hyperphosphatemia has also been identified as an important independent predictor of mortality in patients with CKD.
Prevention and treatment of phosphate retention and hyperphosphatemia are critical to averting the complications associated with CKD-MBD. Therapy includes dietary phosphorous restriction; adequate dialysis; and the use of phosphate binders, which prevent the intestinal absorption of dietary phosphate.
Over the years, evolving phosphate binder therapy has resulted in successful phosphorus control with variable side-effect profiles. This review focuses on the current evidence regarding phosphate binders and their effects on bone.
In the 1970s and '80s, aluminum-containing phosphate binders were widely and effectively used, but recognition that aluminum caused encephalopathy, bone disease, refractory anemia, and myopathy led to the demise of those agents.
They were followed, in the 1990s, by almost exclusive use of calcium salts for phosphate-binding therapy, but development of low-turnover bone disease, hypercalcemia, and metastatic calcification raised concerns about long-term outcomes.
Since then, alternative non-calcium-containing phosphate binders have been developed. Sevelamer is a nonabsorbed cationic polyallylamine polymer that binds phosphate anions through ion exchange and hydrogen binding. Use of sevelamer has been shown to decrease the risk of hypercalcemia and both coronary and aortic calcifications, but it has also been associated with development of metabolic acidosis.
Thus sevelamer carbonate was recently brought to market; however, its effectiveness as a phosphate binder has yet to be well-established. An additional alternative emerged with the introduction of lanthanum carbonate; lanthanum is a rare earth element with a high affinity for phosphate.
Most recently, trivalent iron compounds appear to be potent phosphate binders and are now in clinical development. While all these agents have the capability to reduce serum phosphorus in patients with CKD, the effect of these binders on bone may differ.