Correspondence

Renal Osteodystrophy

N Engl J Med 1995; 333:1428November 23, 1995

Article

To the Editor:

In their otherwise comprehensive review of the mechanisms of renal osteodystrophy, Hruska and Teitelbaum (July 20 issue)1 do not mention the role of acidosis. The high-phosphate diet of the average adult American generates approximately 100 mmol of hydrogen ions daily. The inability of the failing kidney to excrete this endogenously produced acid results in metabolic acidosis, which stimulates osteoclastic bone resorption.2,3 Thus, the skeleton, the principal source of alkali buffer, is slowly consumed in the defense against metabolic acidosis. This acid-induced bone resorption is present from the earlier stages of chronic renal failure but is overshadowed late in the course of the disease by secondary hyperparathyroidism, deficiency of 1,25-dihydroxyvitamin D, and the other processes discussed in the review.

As Hruska and Teitelbaum state, a low-phosphate diet and the administration of calcium carbonate or calcium acetate are useful in maintaining normal serum phosphate concentrations in patients with chronic renal failure. However, these measures also have a direct effect on acidosis-mediated bone resorption. A low-phosphate diet generates less endogenous acid and thus causes less bone resorption, and calcium carbonate and calcium acetate provide, in their carbonate and acetate moieties, a buffer that further reduces the effect of the endogenously generated acid on the skeleton.

Uriel S. Barzel, M.D.
Montefiore Medical Center, Bronx, NY 10467

3 References

1. 1

   Hruska KA, Teitelbaum SL. Renal osteodystrophy. N Engl J Med 1995;333:166-174
   Full Text | Web of Science | Medline

2. 2

   Arnett TR, Boyde A, Jones SJ, Taylor ML. Effects of medium acidification by alteration of carbon dioxide or bicarbonate concentrations on the resorptive activity of rat osteoclasts. J Bone Miner Res 1994;9:375-379
   CrossRef | Web of Science | Medline

3. 3

   Rabadjija L, Brown EM, Swartz SL, Chen CJ, Goldhaber P. H(+)-stimulated release of prostaglandin E2 and cyclic adenosine 3',5'-monophosphoric acid and their relationship to bone resorption in neonatal mouse calvaria cultures. Bone Miner 1990;11:295-304
   CrossRef | Medline

Author/Editor Response

Dr. Hruska replies:

To the Editor: We did not mention the effect of metabolic acidosis on the skeleton because of the difficulty in quantitating the role of metabolic acidosis in renal osteodystrophy. As Dr. Barzel notes, metabolic acidosis stimulates bone resorption through osteoclast activation. We have found that hydrogen ions directly stimulate organization of the osteoclast clear zone, cytoskeletal organization, and resorptive activity.1 These actions are especially important in children, in whom acidosis decreases skeletal growth.2 In adults, however, the osteopenia predicted from hydrogen ion–mediated resorption has not been quantifiable.

We also agree that therapy in the form of dietary modification and the use of alkali — either calcium carbonate or calcium acetate — will diminish the effects of metabolic acidosis on the skeleton. Because this is so clear, we will probably never be able to quantitate accurately the role of acidosis in renal osteodystrophy.

Thank you, Dr. Barzel.

Keith A. Hruska, M.D.
Washington University School of Medicine, St. Louis, MO 63110

2 References

1. 1

   Teti A, Blair HC, Schlesinger P, et al. Extracellular protons acidify osteoclasts, reduce cytosolic calcium, and promote expression of cell-matrix attachment structures. J Clin Invest 1989;84:773-780
   CrossRef | Web of Science | Medline

2. 2

   McSherry E, Morris RC Jr. Attainment and maintenance of normal stature with alkali therapy in infants and children with classic renal tubular acidosis. J Clin Invest 1978;61:509-527
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Wojciech Cichoń, Stanisław Cichoń. (2008) What do we Know about Secondary Hyperparathyroidism. Polish Journal of Surgery 80:9, 495-505
   CrossRef

2. 2

   Curt D. Furberg, Bruce M. Psaty. (1996) Should calcium antagonists be first-line agents in the treatment of cardiovascular disease? The public health perspective. Cardiovascular Drugs and Therapy 10:4, 463-466
   CrossRef