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. 1984 Jun;73(6):1668–1672. doi: 10.1172/JCI111373

Impaired vitamin D metabolism with aging in women. Possible role in pathogenesis of senile osteoporosis.

K S Tsai, H Heath 3rd, R Kumar, B L Riggs
PMCID: PMC437077  PMID: 6327768

Abstract

Calcium absorption decreases with aging, particularly after age 70 yr. We investigated the possibility that this was due to abnormal vitamin D metabolism by studying 10 normal premenopausal women (group A), 8 normal postmenopausal women within 20 yr of menopause (group B), 10 normal elderly women (group C), and 8 elderly women with hip fracture (group D) whose ages (mean +/- SD) were 37 +/- 4, 61 +/- 6, 78 +/- 4, and 78 +/- 4 yr, respectively. For all subjects, serum 25-hydroxyvitamin D [25(OH)D] did not decrease with age, but serum 1,25-dihydroxyvitamin D [1,25(OH)2D], the physiologically active vitamin D metabolite, was lower (P = 0.01) in the elderly (groups C and D; 20 +/- 3 pg/ml) than in the nonelderly (groups A and B; 35 +/- 4 pg/ml). The increase of serum 1,25(OH)D after a 24-h infusion of bovine parathyroid hormone fragment 1-34, a tropic agent for the enzyme 25(OH)D 1 alpha-hydroxylase, correlated inversely with age (r = -0.58; P less than 0.001) and directly with glomerular filtration rate (r = 0.64; P less than 0.001). The response was more blunted (P = 0.01) in elderly patients with hip fracture (13 +/- 3 pg/ml) than in elderly controls (25 +/- 3 pg/ml). We conclude that an impaired ability of the aging kidney to synthesize 1,25(OH)2D could contribute to the pathogenesis of senile osteoporosis.

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Selected References

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  1. Alevizaki C. C., Ikkos D. G., Singhelakis P. Progressive decrease of true intestinal calcium absorption with age in normal man. J Nucl Med. 1973 Oct;14(10):760–762. [PubMed] [Google Scholar]
  2. Armbrecht H. J., Zenser T. V., Davis B. B. Effect of vitamin D metabolites on intestinal calcium absorption and calcium-binding protein in young and adult rats. Endocrinology. 1980 Feb;106(2):469–475. doi: 10.1210/endo-106-2-469. [DOI] [PubMed] [Google Scholar]
  3. Arnaud C. D., Tsao H. S., Littledike T. Radioimmunoassay of human parathyroid hormone in serum. J Clin Invest. 1971 Jan;50(1):21–34. doi: 10.1172/JCI106476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Avioli L. V., McDonald J. E., Lee S. W. The influence of age on the intestinal absorption of 47-Ca absorption in post-menopausal osteoporosis. J Clin Invest. 1965 Dec;44(12):1960–1967. doi: 10.1172/JCI105302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bullamore J. R., Wilkinson R., Gallagher J. C., Nordin B. E., Marshall D. H. Effect of age on calcium absorption. Lancet. 1970 Sep 12;2(7672):535–537. doi: 10.1016/s0140-6736(70)91344-9. [DOI] [PubMed] [Google Scholar]
  6. DAVIES D. F., SHOCK N. W. Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest. 1950 May;29(5):496–507. doi: 10.1172/JCI102286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DeLuca H. F. Parathyroid hormone as a trophic hormone for 1,25-dihydroxyvitamin D3, the metabolically active form of vitamin D. N Engl J Med. 1972 Aug 3;287(5):250–251. doi: 10.1056/NEJM197208032870511. [DOI] [PubMed] [Google Scholar]
  8. Delmas P. D., Stenner D., Wahner H. W., Mann K. G., Riggs B. L. Increase in serum bone gamma-carboxyglutamic acid protein with aging in women. Implications for the mechanism of age-related bone loss. J Clin Invest. 1983 May;71(5):1316–1321. doi: 10.1172/JCI110882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eisman J. A., Hamstra A. J., Kream B. E., DeLuca H. F. A sensitive, precise, and convenient method for determination of 1,25-dihydroxyvitamin D in human plasma. Arch Biochem Biophys. 1976 Sep;176(1):235–243. doi: 10.1016/0003-9861(76)90161-2. [DOI] [PubMed] [Google Scholar]
  10. Eisman J. A., Shepard R. M., DeLuca H. F. Determination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in human plasma using high-pressure liquid chromatography. Anal Biochem. 1977 May 15;80(1):298–305. doi: 10.1016/0003-2697(77)90648-0. [DOI] [PubMed] [Google Scholar]
  11. Gallagher J. C., Jerpbak C. M., Jee W. S., Johnson K. A., DeLuca H. F., Riggs B. L. 1,25-Dihydroxyvitamin D3: short- and long-term effects on bone and calcium metabolism in patients with postmenopausal osteoporosis. Proc Natl Acad Sci U S A. 1982 May;79(10):3325–3329. doi: 10.1073/pnas.79.10.3325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gallagher J. C., Riggs B. L., Eisman J., Hamstra A., Arnaud S. B., DeLuca H. F. Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients: effect of age and dietary calcium. J Clin Invest. 1979 Sep;64(3):729–736. doi: 10.1172/JCI109516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gallagher J. C., Riggs B. L., Jerpbak C. M., Arnaud C. D. The effect of age on serum immunoreactive parathyroid hormone in normal and osteoporotic women. J Lab Clin Med. 1980 Mar;95(3):373–385. [PubMed] [Google Scholar]
  14. Insogna K. L., Lewis A. M., Lipinski B. A., Bryant C., Baran D. T. Effect of age on serum immunoreactive parathyroid hormone and its biological effects. J Clin Endocrinol Metab. 1981 Nov;53(5):1072–1075. doi: 10.1210/jcem-53-5-1072. [DOI] [PubMed] [Google Scholar]
  15. Kumar R., Cohen W. R., Silva P., Epstein F. H. Elevated 1,25-dihydroxyvitamin D plasma levels in normal human pregnancy and lactation. J Clin Invest. 1979 Feb;63(2):342–344. doi: 10.1172/JCI109308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lips P., Courpron P., Meunier P. J. Mean wall thickness of trabecular bone packets in the human iliac crest: changes with age. Calcif Tissue Res. 1978 Nov 10;26(1):13–17. doi: 10.1007/BF02013227. [DOI] [PubMed] [Google Scholar]
  17. Manolagas S. C., Culler F. L., Howard J. E., Brickman A. S., Deftos L. J. The cytoreceptor assay for 1,25-dihydroxyvitamin D and its application to clinical studies. J Clin Endocrinol Metab. 1983 Apr;56(4):751–760. doi: 10.1210/jcem-56-4-751. [DOI] [PubMed] [Google Scholar]
  18. Mazess R. B. On aging bone loss. Clin Orthop Relat Res. 1982 May;(165):239–252. [PubMed] [Google Scholar]
  19. Riggs B. L., Hamstra A., DeLuca H. F. Assessment of 25-hydroxyvitamin D 1 alpha-hydroxylase reserve in postmenopausal osteoporosis by administration of parathyroid extract. J Clin Endocrinol Metab. 1981 Oct;53(4):833–835. doi: 10.1210/jcem-53-4-833. [DOI] [PubMed] [Google Scholar]
  20. Riggs B. L., Melton L. J., 3rd Evidence for two distinct syndromes of involutional osteoporosis. Am J Med. 1983 Dec;75(6):899–901. doi: 10.1016/0002-9343(83)90860-4. [DOI] [PubMed] [Google Scholar]
  21. Riggs B. L., Wahner H. W., Dunn W. L., Mazess R. B., Offord K. P., Melton L. J., 3rd Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis. J Clin Invest. 1981 Feb;67(2):328–335. doi: 10.1172/JCI110039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Slovik D. M., Adams J. S., Neer R. M., Holick M. F., Potts J. T., Jr Deficient production of 1,25-dihydroxyvitamin D in elderly osteoporotic patients. N Engl J Med. 1981 Aug 13;305(7):372–374. doi: 10.1056/NEJM198108133050704. [DOI] [PubMed] [Google Scholar]
  23. Sørensen O. H., Lumholtz B., Lund B., Lund B., Hjelmstrand I. L., Mosekilde L., Melsen F., Bishop J. E., Norman A. W. Acute effects of parathyroid hormone on vitamin D metabolism in patients with the bone loss of aging. J Clin Endocrinol Metab. 1982 Jun;54(6):1258–1261. doi: 10.1210/jcem-54-6-1258. [DOI] [PubMed] [Google Scholar]
  24. Wiske P. S., Epstein S., Bell N. H., Queener S. F., Edmondson J., Johnston C. C., Jr Increases in immunoreactive parathyroid hormone with age. N Engl J Med. 1979 Jun 21;300(25):1419–1421. doi: 10.1056/NEJM197906213002506. [DOI] [PubMed] [Google Scholar]

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