Skip to main content
California Medicine logoLink to California Medicine
. 1969 May;110(5):397–409.

Metabolic Bone Disease Secondary to Renal and Intestinal Disorders

Francis P Muldowney
PMCID: PMC1503496  PMID: 4890532

Abstract

Metabolic bone disease occurring in renal or intestinal disorders has been reviewed with particular reference to etiological factors.

Hyperparathyroidism is seen as a recurring cycle of renal damage—hyperphosphatemia—hypocalcemia—parathyroid stimulation—mobilization of bone calcium and phosphate—renal tubular phosphate rejection. In intestinal cases, the initial stimulus is presumably hypocalcemia.

Osteomalacia is seen as resulting from phosphate depletion for the following reasons:

1. Experimentally, rickets results from dietary phosphate restriction in rats.

2. Such rickets is not prevented by the presence of normally adequate amounts of dietary vitamin D, and may therefore be termed “resistant” in the clinical sense.

3. Osteomalacia or rickets in intestinal malabsorption and renal tubular disorders is associated with hypophosphatemia due to excessive fecal or urinary loss.

4. Renal tubular rickets has been healed by oral phosphate loading in some studies.

5. Acidosis may induce osteomalacic changes, experimentally and clinically (for example, in uretero-sigmoidostomy). Reversal of systemic acidosis with oral bicarbonate has resulted in phosphate retention and a rising serum phosphate in one such case.

6. Preliminary data from analysis of full-thickness bone biopsy in two osteomalacic patients shows a significant reduction in calcium and phosphate content.

7. Despite the hyperphosphatemia of azotemic renal failure, over-all phosphate depletion may be present in this situation also due to: • Diminished dietary phosphate in low protein diets • Nausea and vomiting • Occasional diarrhea • The use of oral phosphatebinding antacids • Perpetuation of urinary phosphate losses by reduction in proportion of tubular reabsorbed phosphate (secondary hyperparathyroidism) and possibly high filtered load per nephron • Repeated losses of phosphate to bath fluid during dialysis.

Full text

PDF
397

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnstein A. R., Frame B., Frost H. M. Recent progress in osteomalacia and rickets. Ann Intern Med. 1967 Dec;67(6):1296–1330. doi: 10.7326/0003-4819-67-6-1296. [DOI] [PubMed] [Google Scholar]
  2. Avioli L. V., Birge S., Lee S. W., Slatopolsky E. The metabolic fate of vitamin D3-3H in chronic renal failure. J Clin Invest. 1968 Oct;47(10):2239–2252. doi: 10.1172/JCI105909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Avioli L. V., Williams T. F., Lund J., DeLuca H. F. Metabolism of vitamin D3-3H in vitamin D-resistant rickets and familial hypophosphatemia. J Clin Invest. 1967 Dec;46(12):1907–1915. doi: 10.1172/JCI105680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BADENOCH J., FOURMAN P. Osteomalacia in steatorrhoea. Q J Med. 1954 Apr;23(90):165–176. [PubMed] [Google Scholar]
  5. Ball J., Garner A. Mineralisation of woven bone in osteomalacia. J Pathol Bacteriol. 1966 Apr;91(2):563–567. doi: 10.1002/path.1700910232. [DOI] [PubMed] [Google Scholar]
  6. Berson S. A., Yalow R. S. Parathyroid hormone in plasma in adenomatous hyperparathyroidism, uremia, and bronchogenic carcinoma. Science. 1966 Nov 18;154(3751):907–909. doi: 10.1126/science.154.3751.907. [DOI] [PubMed] [Google Scholar]
  7. COLEMAN R. D., BECKS H., KOHL F. V., COPP D. H. Skeletal changes in severe phosphorus deficiency of the rat. Arch Pathol (Chic) 1950 Aug;50(2):209–232. [PubMed] [Google Scholar]
  8. Care A. D., Sherwood L. M., Potts J. T., Jr, Aurbach G. D. Perfusion of the isolated parathyroid gland of the goat and sheep. Nature. 1966 Jan 1;209(5018):55–57. doi: 10.1038/209055a0. [DOI] [PubMed] [Google Scholar]
  9. DAVIES D. R., DENT C. E., WILLCOX A. Hyperparathyroidism and steatorrhoea. Br Med J. 1956 Nov 17;2(5002):1133–1137. doi: 10.1136/bmj.2.5002.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DENT C. E., HARRIS H. Hereditary forms of rickets and osteomalacia. J Bone Joint Surg Br. 1956 Feb;38-B(1):204–226. doi: 10.1302/0301-620X.38B1.204. [DOI] [PubMed] [Google Scholar]
  11. DeLuca H. F., Lund J., Rosenbloom A., Lobeck C. C. Metabolism of tritiated vitamin D3 in familial vitamin D-resistant rickets with hypophosphatemia. J Pediatr. 1967 May;70(5):828–832. doi: 10.1016/s0022-3476(67)80342-1. [DOI] [PubMed] [Google Scholar]
  12. Epstein F. H. Calcium and the kidney. Am J Med. 1968 Nov;45(5):700–714. doi: 10.1016/0002-9343(68)90206-4. [DOI] [PubMed] [Google Scholar]
  13. FERGUSON H. W., HARTLES R. L. The effect of vitamin D on the bones of young rats receiving diets low in calcium or phosphorus. Arch Oral Biol. 1963 May-Jun;8:407–418. doi: 10.1016/0003-9969(63)90031-1. [DOI] [PubMed] [Google Scholar]
  14. Falls W. F., Jr, Carter N. W., Rector F. C., Jr, Seldin D. W. Familial vitamin D-resistant rickets. Study of six cases with evaluation of the pathogenetic role of secondary hyperparathyroidism. Ann Intern Med. 1968 Mar;68(3):553–560. doi: 10.7326/0003-4819-68-3-553. [DOI] [PubMed] [Google Scholar]
  15. GOLDMAN R., BASSETT S. H. Phosphorus excretion in renal failure. J Clin Invest. 1954 Dec;33(12):1623–1628. doi: 10.1172/JCI103042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Garner A., Ball J. Quantitative observations on mineralised and unmineralised bone in chronic renal azotaemia and intestinal malabsorption syndrome. J Pathol Bacteriol. 1966 Apr;91(2):545–561. doi: 10.1002/path.1700910231. [DOI] [PubMed] [Google Scholar]
  17. HARRISON A. R. Clinical and metabolic observations on osteomalacia following ureterosigmoidostomy. Br J Urol. 1958 Dec;30(4):455–462. doi: 10.1111/j.1464-410x.1958.tb03546.x. [DOI] [PubMed] [Google Scholar]
  18. KAYE M. MINERAL ANALYSIS OF THE FOURTH LUMBAR VERTEBRA IN HEALTH AND RENAL FAILURE. J Clin Invest. 1964 Jul;43:1367–1371. doi: 10.1172/JCI105012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kleeman C. R., Better O., Massry S. G., Maxwell M. H. Divalent ion metabolism and osteodystrophy in chronic renal failure. Yale J Biol Med. 1967 Aug 1;40(1):1–45. [PMC free article] [PubMed] [Google Scholar]
  20. LOTZ M., NEY R., BARTTER F. C. OSTEOMALACIA AND DEBILITY RESULTING FROM PHOSPHORUS DEPLETION. Trans Assoc Am Physicians. 1964;77:281–295. [PubMed] [Google Scholar]
  21. Lemann J., Jr, Litzow J. R., Lennon E. J. The effects of chronic acid loads in normal man: further evidence for the participation of bone mineral in the defense against chronic metabolic acidosis. J Clin Invest. 1966 Oct;45(10):1608–1614. doi: 10.1172/JCI105467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lotz M., Zisman E., Bartter F. C. Evidence for a phosphorus-depletion syndrome in man. N Engl J Med. 1968 Feb 22;278(8):409–415. doi: 10.1056/NEJM196802222780802. [DOI] [PubMed] [Google Scholar]
  23. Morgan D. B., Paterson C. R., Woods C. G., Pulvertaft C. N., Fourman P. Osteomalacia after gastrectomy. A response to very small doses of vitamin D. Lancet. 1965 Nov 27;2(7422):1089–1091. doi: 10.1016/s0140-6736(65)90061-9. [DOI] [PubMed] [Google Scholar]
  24. Mortimer P. E., Stewart J. S., Norman A. P., Booth C. C. Follow-up study of coeliac disease. Br Med J. 1968 Jul 6;3(5609):7–9. doi: 10.1136/bmj.3.5609.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Muldowney F. P., Freaney R., Brennan P. A case of osteomalacia and renal tubular acidosis associated with occult idiopathic steatorrhoea: the effect of vitamin D on renal tubular hydrion transport. Ir J Med Sci. 1965 Dec;6(480):435–448. doi: 10.1007/BF02976590. [DOI] [PubMed] [Google Scholar]
  26. Muldowney F. P., Freaney R., McGeeney D. Renal tubular acidosis and amino-aciduria in osteomalacia of dietary or intestinal origin. Q J Med. 1968 Oct;37(148):517–539. [PubMed] [Google Scholar]
  27. Pellegrino E. D., Biltz R. M. The composition of human bone in uremia. Observations on the reservoir functions of bone and demonstration of a labile fraction of bone carbonate. Medicine (Baltimore) 1965 Sep;44(5):397–418. doi: 10.1097/00005792-196509000-00002. [DOI] [PubMed] [Google Scholar]
  28. RELMAN A. S., LENNON E. J., LEMANN J., Jr Endogenous production of fixed acid and the measurement of the net balance of acid in normal subjects. J Clin Invest. 1961 Sep;40:1621–1630. doi: 10.1172/JCI104384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. STANBURY S. W. Azotaemic renal osteodystrophy. Br Med Bull. 1957 Jan;13(1):57–60. doi: 10.1093/oxfordjournals.bmb.a069572. [DOI] [PubMed] [Google Scholar]
  30. STANBURY S. W., LUMB G. A. Metabolic studies of renal osteodystrophy. I. Calcium, phosphorus and nitrogen metabolism in rickets, osteomalacia and hyperparathyroidism complicating chronic uremia and in the osteomalacia of the adult Fanconi syndrome. Medicine (Baltimore) 1962 Feb;41:1–34. [PubMed] [Google Scholar]
  31. STANBURY S. W., LUMB G. A., NICHOLSON W. F. Elective subtotal parathyroidectomy for renal hyperparathyroidism. Lancet. 1960 Apr 9;1(7128):793–799. doi: 10.1016/s0140-6736(60)90678-4. [DOI] [PubMed] [Google Scholar]
  32. Slatopolsky E., Gradowska L., Kashemsant C., Keltner R., Manley C., Bricker N. S. The control of phosphate excretion in uremia. J Clin Invest. 1966 May;45(5):672–677. doi: 10.1172/JCI105382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Slatopolsky E., Robson A. M., Elkan I., Bricker N. S. Control of phosphate excretion in uremic man. J Clin Invest. 1968 Aug;47(8):1865–1874. doi: 10.1172/JCI105877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Thompson G. R., Lewis B., Booth C. C. Absorption of vitamin D3-3H in control subjects and patients with intestinal malabsorption. J Clin Invest. 1966 Jan;45(1):94–102. doi: 10.1172/JCI105327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Thompson G. R., Neale G., Watts J. M., Booth C. C. Detection of vitamin-d deficiency after partial gastrectomy. Lancet. 1966 Mar 19;1(7438):623–626. doi: 10.1016/s0140-6736(66)90823-3. [DOI] [PubMed] [Google Scholar]

Articles from California Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES