Source: J Indian Med Assoc  |  Posted 7 years ago

By W. A. Thomasson, PhD

CHICAGO, IL -- May 4, 2004 --The new dietary-phosphate binder lanthanum carbonate may produce more favorable results on several measures of bone dynamics in dialysis patients than does calcium carbonate, according to research presented here at the National Kidney Foundation 2004 Clinical Meeting.

The research -- presented by Anthony Freemont, MD, FRCP, FRCPath, and John Denton, University of Manchester, United Kingdom -- used a randomized open-label design with medication administered for a 4-week titration phase and a 46-week maintenance phase.

Tetracycline double-labeled iliac-crest biopsies were obtained at the start and conclusion of treatment, with paired biopsies being obtained from 63 patients who completed at least 6 months of therapy. All patients had been on dialysis for less than 12 weeks at the time of recruitment.

Since dialysis is only about 70% efficient in removing phosphate, normal dietary phosphorus intake can lead to hyperphosphatemia, hyperparathyroidism, and rapid-turnover osteodystrophy. Phosphate binders such as calcium carbonate and sometimes aluminum hydroxide are used to minimize phosphate absorption with less stringent dietary restriction. Aluminum has significant toxic effects on bone, however, while elevated dietary calcium can result in hypercalcemia that, especially in the presence of continuing hyperphosphatemia, can lead to calcification of soft tissues, including the arterial wall.

Analysis of the biopsies showed that the ratio of bone formation rate to bone surface (a measure of osteoblast activity) was below normal at baseline. This value increased (+5 mcm3/mcm2/year) with lanthanum-carbonate treatment and decreased (-1.6 mcm2/mcm2/year) with calcium-carbonate treatment because of high variability. The difference between treatments, however, did not reach statistical significance.

On the other primary end points -- mineralization lag time, percent osteoid surface, percent osteoid volume, percent osteoblast surface, percent osteoclast surface, and mean erosion depth -- there was little difference between treatments. No patient in either group developed the osteomalacia that can occur with aluminum-containing phosphate binders.

More notable results were reported on the 2 secondary endpoints. On the activation frequency (a measure of overall bone activity), 51.5% of the lanthanum-carbonate patients improved and 21.2% worsened, while 23.3% of the calcium-carbonate patients improved and 40.0% worsened. This led the authors to conclude that, "patients [on lanthanum carbonate] may be less likely to develop osteopenia."

Overall, 54.5% of lanthanum-carbonate patients improved and 33.3% worsened in terms of changes in percent osteoclast surface / bone-formation rate, while results in the calcium-carbonate group were almost the reverse: 33.3% improved and 50.0% worsened. In this case, improvement represents a movement toward normal from a state of either hyperparathyroidism or adynamic bone.

[Presentation Title: The Effects of Lanthanum Carbonate and Calcium Carbonate on Bone in Patients With Chronic Kidney Disease.]