Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Mechanism for bone disease found in inhabitants environmentally exposed to cadmium: decreased serum 1α, 25-dihydroxyvitamin D level


To investigate the mechanism for bone disease caused by exposure to cadmium serum samples were collected from 5 itai-itai disease patients, 36 Cd-exposed residents with renal tubular damage and 17 non-exposed individuals and analyzed for 1α,25-dihydroxyvitamin D[1α, 25(OH)2D], parathyroid hormone, β2-microglobulin, calcium and inorganic phosphorus. Measurement of percentage tubular reabsorption of phosphate (%TRP) were performed only on the Cd-exposed subjects. Serum 1α, 25(OH)2D], levels were lower in itai-itai disease patients and cadmium-exposed subjects with renal damage than in non-exposed subjects. Parathyroid hormone and β2-microglobulin concentrations in serum were higher in the Cd-exposed subjects. Decrease in serum 1α,25(OH)2D levels were closely related to serum concentrations of parathyroid hormone, β2-microglobulin and %TRP. This study suggests that cadmium-induced bone effects were mainly due to a disturbance in vitamin D and parathyroid hormone metabolism, which was caused by the cadmium-induced kidney damage.

This is a preview of subscription content, log in to check access.


  1. 1.

    Akiba T, Endou H, Koseki C, Sakai F (1980) Localization of 25-hydroxyvitamin D3-1α-hydroxylase activity in the mammalian kidney. Biochem Biophys Res Commun 94:313–318

  2. 2.

    Ando M, Shimizu M, Sayato Y, Tanimura A, Tobe M (1981) The inhibition of vitamin D-stimulated intestinal calcium transport in rats after continuous oral administration of cadmium. Toxicol Appl Pharmacol 61:297–301

  3. 3.

    Chesney TW, Rosen JF, Hamstra AJ, Deluca HF (1980) Serum 1,25-dihydroxyvitamin D levels in normal children and in vitamin D disorders. Am J Dis Child 134:135–139

  4. 4.

    Eisman JA, Hamstra AJ, Kream BE, Deluca HF (1976) A sensitive, precise and convenient method for determination of 1,25-dihydroxyvitamin D in human plasma. Arch Biochem Biophys 176:235–243

  5. 5.

    Feldman SL, Cousins RJ (1973) Influence of cadmium on the metabolism of 25-hydroxycholecalciferol in chicks. Nutr Rep Int 8:251–259

  6. 6.

    Friberg L, Piscator M, Nordberg GF, Kjellström T (1974) Cadmium in the environment, 2nd ed. CRC Press, Cleveland, Ohio

  7. 7.

    Fullmer CS, Oku T, Wasserman RH (1980) Effect of cadmium administration on intestinal absorption and vitamin D-dependent calcium-binding protein. Environ Res 22:386–399

  8. 8.

    Iguchi H, Sano S (1982) Effect of cadmium on the collagen metabolism of rat. Toxicol Appl Pharmacol 62:126–136

  9. 9.

    Ishizaki A, Fukushima M (1968) Studies on itai-itai disease (review). Jpn J Hyg 23:271–285 (in Japanese)

  10. 10.

    Kajikawa K, Kitagawa M, Nakanishi I, Ueshima H, Katsuda S, Kuroda K (1974) A pathological study of itai-itai disease. J Juzen Med Soc 83:309–347 (in Japanese)

  11. 11.

    Kawamura J, Yoshida O, Nishio K, Itokawa Y (1978) Disturbances in kidney functions and calcium and phosphate metabolism in cadmium-poisoned rats. Nephron 20:101–110

  12. 12.

    Kimura M, Otaki N, Yoshiki S, Suzuki M, Horiuchi N, Suda T (1974) The isolation of metallothionein and its protective role in cadmium poisoning. Arch Biochem Biophys 165:340–348

  13. 13.

    Larsson SE, Piscator M (1971) Effect of cadmium on skeletal tissue in normal and calcium-deficient rats. Isr J Med Sci 7:495–497

  14. 14.

    Lorentzon R, Larsson SE (1977) Vitamin D metabolism in adult rats at low and normal calcium intake and the effect of cadmium exposure. Clin Sci Mol Med 30:559–562

  15. 15.

    Maehara T (1978) Studies on the calcium metabolism of rat bone after long-term administration of heavy metal (cadmium). J Japan Orthopaedic Assoc 42:287–300 (in Japanese)

  16. 16.

    Merali Z, Singhal RL (1975) Influence of chronic exposure to cadmium on hepatic and renal cyclic AMP-protein kinase system. Toxicology 4:207–214

  17. 17.

    Miyahara T, Komurasaki T, Kozuka H (1980) Inhibitory effect of cadmium on collagenous peptide synthesis of embryonic chick bone in tissue culture. Toxicol Lett 6:137–139

  18. 18.

    Mukawa A, Nogawa K, Hagino N (1980) Bone biopsy performed on women living in the cadmium-polluted Jinzu River basin. Jpn J Hyg 35:761–773 (in Japanese)

  19. 19.

    Nakagawa S (1960) A study of osteomalacia in Toyama Prefecture (so-called itai-itai disease). J Radiol Phys Ther Univ Kanazawa 56:1–51 (in Japanese)

  20. 20.

    Nishi Y, Nanjo M (1981) Method for assay of vitamin D; 3. Multiple assay of vitamin D and its metabolites. Vitamins (Japan) 55:595–605 (in Japanese)

  21. 21.

    Nogawa K (1981) Itai-itai disease and follow-up studies. In: Nriagu JO (ed) Cadmium in the environment. John Wiley & Son Inc, New York, pp 1–37

  22. 22.

    Nogawa K, Yamada Y, Honda R, Ishizaki M, Tsuritani I, Kawano S, Kato T (1983) The relationship between itai-itai disease among inhabitants of the Jinzu River basin and cadmium in rice. Toxicol Lett 17:263–266

  23. 23.

    Nogawa K, Kobayashi E, Yamada Y, Honda R, Kido T, Tsuritani I, Ishizaki M (1984) Parathyroid hormone concentration in the serum of people with cadmium-induced renal damage. Int Arch Occup Environ Health 54:187–193

  24. 24.

    Saito H, Shitomi K (1979) Chronic cadmium poisoning, Fanconi syndrome and osteomalacia. In: Cadmium-induced osteopathy. Shigematsu I, Nomiyama K (eds) Tokyo: Japan Public Health Association, pp 139–143

  25. 25.

    Shepard RM, Horst RL, Hamstra AJ (1979) Determination of vitamin D and its metabolites in plasma from normal and anephric man. Biochem J 182:55–69

  26. 26.

    Shimura F, Tamura M (1978) Application of normal hen intestinal cytosol for the radioreceptor assay of serum 1α,25-dihydroxycholecalciferol concentration. Vitamins (Japan) 52:173–181 (in Japanese)

  27. 27.

    Suda R, Shiina Y, Abe E (1984) The influence of nutritional factors and cadmium exposure on monkeys; 5. Plasma concentrations of vitamin D metabolites. Kankyo Hoken Report No 50:67–72 (in Japanese)

  28. 28.

    Suda T, Ogata E, Ogura Y, Nishii Y (1982) Vitamin D. Tokyo, Kodansha (in Japanese)

  29. 29.

    Sugawara Ch, Sugawara N (1974) Cadmium toxicity for rat intestine specially on the absorption of calcium and phosphorus. Jpn J Hyg 28:511–516 (in Japanese)

  30. 30.

    Sugimura Y, Higaki M (1985) Measurement of 1α,25-dihydroxyvitamin D in serum of healthy people using Amersham assay system. J Bone and Mineral Metab (Proceedings of the Third Conference of Japanese Society of Bone Metabolism Research) 3:63 (in Japanese)

  31. 31.

    Takebayashi S (1979) First autopsy case, suspicious of cadmium intoxication, from the cadmium-polluted area in Tsushima, Nagasaki Prefecture. In: Shigematsu I, Nomiyama K (eds) Cadmium-induced osteopathy. Japan Public Health Association, Tokyo, pp 124–138

  32. 32.

    Takebayashi S (1983) Second case of osteomalacia found in women requiring observation in a cadmium-polluted area in Tsushima. Clinical and pathological findings. Kankyo Hoken Report No 49:207–211 (in Japanese)

  33. 33.

    Takebayashi S (1984) Third case of osteomalacia found in women requiring observation in a cadmium-polluted area in Tsushima. Clinical and pathological findings. Kankyo Hoken Report No 50:238–241 (in Japanese)

  34. 34.

    Yamamoto Y (1972) Present status of environmental cadmium pollution. Kankyo Hoken Report No 11:7–12 (in Japanese)

  35. 35.

    Yoneda M Tomita A, Uchikawa A, Takatsuki K (1983) Basic and clinical studies on human parathyroid hormone using the homologous radioimmunoassay kit “Eiken”. Clin Endocrinol 4:117–121 (in Japanese)

  36. 36.

    Yumita S, Son T, Miura R, Furukawa Y (1983) The fundamental and clinical studies on human parathyroid hormone radioimmunoassay kit. Clin Endocrinol 41:41–46 (in Japanese)

Download references

Author information

Correspondence to Kôji Nogawa.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Nogawa, K., Tsuritani, I., Kido, T. et al. Mechanism for bone disease found in inhabitants environmentally exposed to cadmium: decreased serum 1α, 25-dihydroxyvitamin D level. Int. Arch Occup Environ Heath 59, 21–30 (1987). https://doi.org/10.1007/BF00377675

Download citation

Key words

  • Cadmium
  • Bone change
  • 1α,25(OH)2D
  • Renal damage