Preclinical studies have shown that
lanthanum has a very high
phosphate-binding capacity at gastrointestinal pH, while clinical trials have shown
lanthanum carbonate to be an effective, well-tolerated
phosphate binder for the treatment of hyperphosphataemia in patients with
end-stage renal disease. Optimization of bone health is an important issue in these patients, and, based on theoretical grounds, there have been concerns that
lanthanum will have toxic effects on bone similar to those of
aluminium. However, compared with
aluminium, absorption of
lanthanum is extremely low and
lanthanum treatment is not associated with systemic toxicity. In addition, unlike
aluminium, elimination of
lanthanum is not through the kidney, but mainly takes place via the biliary route and is, therefore, independent of renal function. This implies that patients with
chronic renal failure are not at an increased risk for accumulation of the
element, compared with patients with normal renal function. In animal studies, no adverse effects on bone were seen in healthy animals receiving
lanthanum carbonate. In 5/6th nephrectomized rats, very high doses of
lanthanum (1000-2000 mg/kg) affected bone mineralization. This was not due to a direct toxic effect on bone, but was secondary to
phosphate depletion induced by
lanthanum and, as with any gastro-intestinal
phosphate-binding agent, can be reversed with a
phosphate-supplemented diet. In a phase III clinical trial, bone biopsies were taken from dialysis patients at baseline and after 1 year of treatment with either
lanthanum carbonate (median dose, 1250 mg/day) or
calcium carbonate (median dose, 2000 mg/day). Patients treated with
lanthanum carbonate for 1 year did not experience any of the
aluminium-like toxic effects on bone expressed as either
osteomalacia or adynamic
bone disease.