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Does iron affect osteoblast function? StudiesIn vitro and in patients with chronic liver disease

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Summary

In order to study the role of trace elements as potential osteoblastic toxins, we measured bone aluminum, copper, and iron in 106 ambulant patients with histologically proven liver disease. We used analytical and histochemical methods and we correlated our results with serum biochemistry, forearm and spinal bone density, and dynamic bone histomorphometry. Patients with chronic liver disease had higher iron-stained perimeters than control subjects (P<0.001). However, the mean ironstained perimeter was no greater than 5% of the total mineralized bone perimeter and did not correlate significantly with either the osteoblast perimeters or bone formation rates. The mean concentration of bone iron were 2.5 times (P<0.01) greater in the patients than in the controls although 80% of the patients fell within the normal range. There was a weak negative correlation between bone iron and the osteoblast perimeters (R=−0.18,P=ns) and between bone iron and bone formation (R=−0.30,P<0.05). There were 57 patients (56% of the total) with diminished bone formation, but only 16 had elevated bone iron concentrations. In a regression analysis, age, hypogonadism, and serum albumin concentrations were the most important predictors of osteoblast perimeters and bone formation rates.In vitro experiments using rat osteoblast-like osteosarcoma cells showed that an iron concentration of 400 μmol/liter was required to diminish cellular proliferation and function. Iron concentrations are elevated in the bones of patients with chronic liver disease. However, there is at present insufficient evidence that this metal is responsible for the osteoblast dysfunction seen in these patients. Bone aluminum and bone copper concentrations were within the relevant reference ranges in all patients.

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References

  1. Hodgson SF, Dickson ER, Wahner HW, Johnson KA, Mann KG, Riggs BL (1985) Bone loss and reduced osteoblast function in primary biliary cirrhosis. Ann Intern Med 103:855–860

    PubMed  CAS  Google Scholar 

  2. Stellon AJ, Webb A, Compston J, Williams R (1987) Low turnover state in primary biliary cirrhosis. Hepatology 7:137–142

    PubMed  CAS  Google Scholar 

  3. Bikle DD, Genant HK, Cann C, Recker RR, Halloran BP, Strewler GJ (1985) Bone disease in alcohol abuse. Ann Intern Med 103:42–48

    PubMed  CAS  Google Scholar 

  4. Diamond T, Stiel D, Lunzer M, Wilkinson M, Posen S (1989) Ethanol reduces bone formation and may cause osteoporosis. Am J Med 86:282–288

    Article  PubMed  CAS  Google Scholar 

  5. Stellon AJ, Webb A, Compston JE (1988) Bone histomorphometry and structure in corticosteroid-treated chronic active hepatitis. Gut 29:378–384

    PubMed  CAS  Google Scholar 

  6. Diamond TH, Stiel D, Lunzer M, McDowell D, Eckstein RP, Posen S (1989) Hepatic osteodystrophy: static and dynamic bone histomorphometry and serum bone Gla-protein in 80 patients with chronic liver disease. Gastroenterology 96:213–221

    PubMed  CAS  Google Scholar 

  7. Diamond T, Stiel D, Posen S (1989) Osteoporosis in hemochromatosis: iron excess, gonadal deficiency, or other factors. Ann Intern Med 110:430–436

    PubMed  CAS  Google Scholar 

  8. Williams JW, Vera SR, Peters TG, Luther RW, Bhattacharya S, Spears H, Graham A, Pitcock JA, Crawford AJ (1986) Biliary excretion of aluminum in aluminum osteodystrophy with liver disease. Ann Intern Med 104:782–785

    PubMed  CAS  Google Scholar 

  9. de Vernejoul MC, Belenguer R, Halkidou H, Buisine A, Bielakoff J, Miravet L (1985) Histomorphometric evidence of deleterious effect of aluminum on osteoblasts. Bone 6:15–20

    Article  PubMed  Google Scholar 

  10. Charhon SA, Chavassieux PM, Chapuy MC, Boivin GY, Meunier P (1985) Low rate of bone formation with or without histologic appearance of osteomalacia in patients with aluminum intoxication. J Lab Clin Med 106:123–131

    PubMed  CAS  Google Scholar 

  11. Andress DL, Maloney NA, Coburn JW, Endres DB, Sherrard DJ (1987) Osteomalacia and aplastic bone disease in aluminum-related osteodystrophy. J Clin Endocrinol Metab 65:11–17

    PubMed  CAS  Google Scholar 

  12. Van de Vyver FL, Visser WJ, D'Haese PC, DeBroe ME (1988) Iron overload and bone disease in chronic dialysis patients. Contrib Nephrol 64:134–143

    PubMed  Google Scholar 

  13. Diamond T, Stiel D, Lunzer M, Wilkinson M, Roche J, Posen S (1990) Osteoporosis and skeletal fractures in chronic liver disease. Gut 31:82–87

    PubMed  CAS  Google Scholar 

  14. Diamond T, Stiel D, Mason R, Lissner D, Bikle D, Wilson S, Posen P (1990) Serum vitamin D metabolites are not responsible for low turnover osteoporosis in chronic liver disease. J Clin Endocrinol Metab 69:1234–1239

    Article  Google Scholar 

  15. Addison GM, Beamish MR, Hales CN, Hodgkins M, Jacobs A, Llewellin P (1972) An immunoradiometric assay for ferritin in the serum of normal subjects and patients with iron deficiency and iron overload. J Clin Pathol 25:326–329

    PubMed  CAS  Google Scholar 

  16. Kleerekoper M, Ingham JP, McCarthy SW, Posen S (1974) Parathyroid hormone assay in primary hyperparathyroidism. Experience with radioimmunoassay based on commercially available reagents. Clin Chem 20:269–375

    Google Scholar 

  17. Seshadri MS, Frankel TL, Lissner D, Mason RS, Posen S (1985) Bioactive parathyroid hormone in the rat: effects of calcium and calcitriol. Endocrinology 17:2417–2423

    Google Scholar 

  18. Legendre GR, Alfrey AC (1976) Measuring picogram amounts of aluminum in biological tissue by flameless atomic absorption analysis of chelate. Clin Chem 22:53–56

    PubMed  CAS  Google Scholar 

  19. Buchanan MRC, Ihle BU, Dunn CM (1981) Haemodialysis-related osteomalacia: a staining method to demonstrate aluminum. J Clin Pathol 34:1352–1354

    PubMed  CAS  Google Scholar 

  20. Lindquist RR (1969) Studies on the pathogenesis of hepatolenticular degeneration. Cytochemical methods for the localization of copper. Arch Pathol 87:370–379

    PubMed  CAS  Google Scholar 

  21. Cooperberg AA, Rosenberg A, Schwartz JP (1977) Diagnostic value of bone marrow iron deposits in idiopathic hemochromatosis. Arch Intern Med 137:748–751

    Article  PubMed  CAS  Google Scholar 

  22. Maloney NA, Ott SM, Alfrey AC, Miller NL, Coburn JW, Sherrard DJ (1982) Histological quantitation of aluminum in iliac bone from patients with renal failure. J Lab Clin Med 99:206–216

    PubMed  CAS  Google Scholar 

  23. Hickman JL, McElduff A (1989) Insulin promotes growth of cultured rat osteosarcoma cell line UMR 106-01: an osteoblast-like cell. Endocrinology 124:701–706

    PubMed  CAS  Google Scholar 

  24. Lescoat G, Loreal R, Moirand R, Dezier JF, Pasdeloup N, Deugnier Y, Brissot P (1989) Iron induction of ferritin synthesis and secretion in human hepatoma cell (Hep G2) cultures. Liver 9:179–185

    PubMed  CAS  Google Scholar 

  25. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:284

    Article  Google Scholar 

  26. Seymour CA, Peters TJ (1977) Enzyme activities in human liver biopsies: assay methods and activities of some lysosomal and membrane-bound enzymes in control tissue and serum. Clin Sci Mol Med 52:229–239

    PubMed  CAS  Google Scholar 

  27. Godfrey K (1985) Statistics in practice: comparing the means of several groups. N Engl J Med 313:1450–1456

    Article  PubMed  CAS  Google Scholar 

  28. Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols and units. J Bone Min Res 6:595–610

    Article  Google Scholar 

  29. de Vernejoul MC, Girot R, Gueris J, Cancela L, Bang S, Bielakoff J, Mantalen C, Goldberg D, Miravet L (1982) Calcium phosphate metabolism and bone disease in patients with homozygous thalassaemia. J Clin Endocrinol Metab 54:276–281

    Article  PubMed  Google Scholar 

  30. Laeng H, Egger T, Roethlisberger C, Cottier H (1988) Stainable bone iron in undecalcified, plastic-embedded sections. Am J Pathol 131:344–350

    PubMed  CAS  Google Scholar 

  31. Gawlik D, Behne D, Bratter P, Gatschke W, Gessner H, Kraft D (1982) The suitability of the iliac crest biopsy in the element analysis of bone and marrow. J Clin Chem Clin Biochem 20:499–507

    PubMed  CAS  Google Scholar 

  32. McLaren GD, Muir WA, Kellermeyer RW (1983) Iron over-load disorders: natural history, pathogenesis, diagnosis and therapy. CRC Crit Rev Clin Lab Sci 19:205–266

    Article  CAS  Google Scholar 

  33. Mazzanti R, Srai KS, Debnam ES, Boss AM, Gentilini P (1987) The effect of chronic ethanol consumption on iron absorption in rats. Alcohol 22:47–52

    CAS  Google Scholar 

  34. Mendelson RA, Huber AM (1980) The effect of duration of alcohol administration on the deposition of trace elements in the fetal rat. Adv Exp Med Biol 132:295–304

    PubMed  CAS  Google Scholar 

  35. Christoffersen MR, Thyregod HC, Christofersen J (1987) Effects of aluminum, chromium and iron on the rate of dissolution of calcium hydroxyapatite crystals in the absence and presence of the chelating agent desferrioxamine. Calcif Tissue Int 41:27–30

    Article  PubMed  CAS  Google Scholar 

  36. Huser H, Gerber L, Eichenberger P, Waelti E, Cottier H (1988) Short-lasting accumulation in osteoid bone seams of radioactive iron injected as citrate into mice. Am J Pathol 131:339–343

    PubMed  CAS  Google Scholar 

  37. Lieberherr M, Grosse B, Cournot-Witmer G, Thil CL, Balsan S (1982) In vitro effects of aluminum on bone phosphatases: a possible interaction with bPTH and vitamin D3 metabolites. Calcif Tissue Int 34:280–284

    Article  PubMed  CAS  Google Scholar 

  38. Lieberherr M, Grosse B, Cournot-Witmer G, Hermann-Erlee MPM, Balsan S (1987) Aluminum action on mouse bone cell metabolism and response to PTH and 1,25(OH)2 D3. Kidney Int 31:736–743

    PubMed  CAS  Google Scholar 

  39. de Vernejoul MC, Pointillart A, Golenzer CC, Morieux C, Bielakoff J, Modrowski D, Miravet L (1984) Effects of iron overload on bone remodeling in pigs. Am J Pathol 116:377–384

    PubMed  Google Scholar 

  40. Lappalainen R, Knuuttila M, Lammi S, Alhava EM, Olkkonen H (1982) Zn and Cu content in human cancellous bone. Acta Orthop Scand 53:51–55

    PubMed  CAS  Google Scholar 

  41. Malluche HM, Faugere ML, Friedler RM, Matthews C, Fanti P (1987) Calcitriol, parathyroid hormone, and accumulation of aluminum in bone in dogs with renal failure. J Clin Invest 79:754–761

    Article  PubMed  CAS  Google Scholar 

  42. Sedman AB, Alfrey AC, Miller NC, Goodman WG (1987) Tissue and cellular basis for impaired bone formation in aluminum-related osteomalacia in pigs. J Clin Invest 79:86–92

    PubMed  CAS  Google Scholar 

  43. Halliwell B (1987) Oxygen radicals and human disease. Ann Intern Med 107:526–545

    PubMed  Google Scholar 

  44. Nordman R, Ribiere C, Rouach H (1987) Involvement of iron and iron-catalyzed free radical production in ehtanol metabolism and toxicity. Enzyme 37:57–69

    Google Scholar 

  45. Pawlotsky Y, Lacien Y, Roudier G, Hany Y, Louboutin JY, Ferrand B, Bourel M (1979) Histomorphometric osseuse et manifestations osteo-articulaires de l'hemochromatose idiopathique. Revue Rhum 46:91–99

    CAS  Google Scholar 

  46. Sherman LA, Pfeferbaum A, Brown EB (1970) Hypoparathyroidism in a patient with long-standing iron storage disease. Ann Intern Med 73:259–261

    PubMed  CAS  Google Scholar 

  47. Terao N, Yamamoto K, Nakamur R, Honma S, Asano Y, Hosoda S (1986) Suppression of parathyroid hormone secretion by iron. Kidney Int 29(A):164

    Google Scholar 

  48. Wapnick AA, Lynch SR, Seftel HC, Charlton RW, Bothwell TH, Jowsey J (1971) The effect of siderosis and ascorbic acid depletion in bone metabolism, with special reference to osteoporosis in the Bantu. Br J Nutr 25:367–376

    Article  PubMed  CAS  Google Scholar 

  49. Sternlieb I (1989) Hepatic copper toxicosis. J Gastroenterol Hepatol 4:175–181

    PubMed  CAS  Google Scholar 

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Diamond, T., Pojer, R., Stiel, D. et al. Does iron affect osteoblast function? StudiesIn vitro and in patients with chronic liver disease. Calcif Tissue Int 48, 373–379 (1991). https://doi.org/10.1007/BF02556449

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