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Calcium Malabsorption Does Not Cause Secondary Hyperparathyroidism

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Abstract

We challenge the widespread assumption that malabsorption of calcium per se causes secondary hyperparathyroidism. Serum parathyroid hormone (PTH) does not rise at the menopause despite the fall in calcium absorption, nor is it raised in osteoporotic women with vertebral fractures despite their low calcium absorption. The age-related rise in serum PTH can be accounted for by the age-related fall in serum 25(OH)D and/or decline in renal function with consequent loss of the calcemic action of vitamin D on bone. The reference interval for serum PTH is established in the fasting state when it is at the top of its diurnal cycle and is maintaining serum ionized calcium at the expense of bone to meet the calcium being lost through skin, bowel, and kidneys. There is no evidence that the fasting PTH is influenced by the previous day’s intake or absorption of calcium, although it can be lowered by a large evening calcium supplement. Malabsorption of calcium—like dietary calcium deficiency—is a risk factor for osteoporosis because it reduces or prevents the normal food-related daytime fall in PTH and bone resorption, not because it causes secondary hyperparathyroidism.

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References

  1. Heaney RP (2003) Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr 78:912–919

    PubMed  CAS  Google Scholar 

  2. Seeman E (2002) Pathogenesis of bone fragility in women and men. Lancet 359:1841–1850

    Article  PubMed  Google Scholar 

  3. Reginster J-Y (2007) Calcium and vitamin D for osteoporotic fracture risk. Lancet 370:632–634

    Article  PubMed  Google Scholar 

  4. Bouillon R, Bischoff-Ferrari H, Willett W (2008) Vitamin D and health: perspectives from mice and men. J Bone Miner Res 23:974–979

    Article  PubMed  CAS  Google Scholar 

  5. Bates CJ, Carter GD, Mishra GD, O’Shea D, Jones J, Prentice A (2003) In a population study, can parathyroid hormone aid the definition of adequate vitamin D status? A study of people aged 65 years and over from the British National Diet and Nutrition Survey. Osteoporos Int 14:152–159

    PubMed  CAS  Google Scholar 

  6. Sahota O, Mundey MK, San P, Godber IM, Lawson N, Hosking D (2004) The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis. Bone 35:312–319

    Article  PubMed  CAS  Google Scholar 

  7. Need AG, Horowitz M, Morris HA, Nordin BEC (2000) Vitamin D status: effects on parathyroid hormone and 1,25 dihydroxyvitamin D in postmenopausal women. Am J Clin Nutr 71:1577–1581

    PubMed  CAS  Google Scholar 

  8. Lemann J, Favus MJ (2002) Intestinal absorption of calcium, magnesium, and phosphate. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 5th edn. ASBMR, Washington, DC, pp 93–97

    Google Scholar 

  9. Need AG, Nordin BEC (2008) Misconceptions—vitamin D insufficiency causes malabsorption of calcium. Bone 42:1021–1024

    Article  PubMed  CAS  Google Scholar 

  10. Carlsson A, Lindquist BN (1955) A comparison of the intestinal and skeletal effect of vitamin D in relation to dosage. Acta Physiol Scand 35:53–55

    Article  PubMed  CAS  Google Scholar 

  11. Jones G, Strugnell SA, DeLuca H (1998) Current understanding of the molecular actions of vitamin D. Physiol Rev 78:1193–1231

    PubMed  CAS  Google Scholar 

  12. Tsuki K, Shima N, Mochizuki S, Yamaguchi K, Kinosaki M, Yano K et al (1998) Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1,25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone. Biochem Biophys Res Commun 246:337–341

    Article  Google Scholar 

  13. Nordin BEC, Morris HA, Wishart JM, Scopacasa F, Horowitz M, Need AG, Clifton PM (1998) Modification and validation of a single-isotope radiocalcium absorption test. J Nucl Med 39:108–113

    PubMed  CAS  Google Scholar 

  14. Nordin BEC, Need AG, Morris HA, Horowitz M (1999) Biochemical variables in pre- and postmenopausal women: reconciling the calcium and estrogen hypotheses. Osteoporos Int 9:351–357

    Article  PubMed  CAS  Google Scholar 

  15. Black DM, Palermo L, Nevitt MC, Genant HK, Epstein R, San Valentin R, Cummings SR (1995) Comparison of methods for defining prevalent vertebral deformities: the Study of Osteoporotic Fractures. J Bone Miner Res 10:890–902

    Article  PubMed  CAS  Google Scholar 

  16. Favus MJ, Bushinsky DA, Lemann J (2006) Regulation of calcium, magnesium, and phosphate metabolism. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 6th edn. ASBMR, Washington, DC, pp 76–83

    Google Scholar 

  17. Marshall DH, Nordin BEC (1969) Kinetic analysis of plasma radioactivity after oral ingestion of radiocalcium. Nature 222:797

    Article  PubMed  CAS  Google Scholar 

  18. Nordin BEC, Horsman A, Aaron J (1976) Diagnostic procedures. In: Nordin BEC (ed) Calcium, phosphate and magnesium metabolism. Churchill Livingston, Edinburgh, pp 1–35

    Google Scholar 

  19. Marshall DH, Nordin BEC (1981) A comparison of radioactive calcium absorption tests with net calcium absorption. Clin Sci 61:477–481

    PubMed  CAS  Google Scholar 

  20. Bullamore JR, Gallagher JC, Wilkinson R, Nordin BEC (1970) Effect of age on calcium absorption. Lancet 2:535–537

    Article  PubMed  CAS  Google Scholar 

  21. Crilly RG, Francis RM, Nordin BEC (1981) Steroid hormones, ageing and bone. Clin Endocrinol Metab 10:115–139

    PubMed  CAS  Google Scholar 

  22. Nordin BEC, Wilkinson R, Marshall DH, Gallagher JC, Williams A, Peacock M (1976) Calcium absorption in the elderly. Calcif Tissue Int 21(Suppl):442–451

    Google Scholar 

  23. Peacock M, Nordin BEC, Gallagher JC, Varnavides C (1975) Action of 1α-hydroxyvitamin D3 in man. In: Norman AW, Schaefer K, Grigoleit H-G, Herrath DV (eds) Vitamin D and problems to uremic bone disease. deGruyter, Berlin, pp 611–617

    Google Scholar 

  24. Nordin BEC, Peacock M, Crilly RG, Marshall DH (1979) Calcium absorption and plasma 1,25(OH)2D levels in postmenopausal osteoporosis. In: Norman AW, Schaefer K, Grigoleit H-G, Herrath DV (eds) Vitamin D: basic research and its clinical application. deGruyter, Berlin, pp 96–106

    Google Scholar 

  25. Nordin BEC, Peacock M, Crilly RG, Taylor G, Marshall DH (1979) Plasma 25 hydroxy and 1,25 dihydroxyvitamin D levels and calcium absorption in postmenopausal women. In: MacIntyre I, Szelke M (eds) Molecular endocrinology. Elsevier, Amsterdam, pp 363–373

    Google Scholar 

  26. Francis RM, Peacock M, Barkworth SA, Marshall DH (1986) A comparison of the effect of sorbitol and glucose on calcium absorption in postmenopausal women. Am J Clin Nutr 43:72–76

    PubMed  CAS  Google Scholar 

  27. Wishart JM, Horowitz M, Need AG, Scopacasa F, Morris HA, Clifton PM, Nordin BEC (1997) Relations between calcium intake, calcitriol, polymorphisms of the vitamin D receptor gene, and calcium absorption in premenopausal women. Am J Clin Nutr 65:798–802

    PubMed  CAS  Google Scholar 

  28. Need AG, Horowitz M, Philcox JC, Nordin BEC (1985) 1,25-dihydroxycalciferol and calcium therapy in osteoporosis with calcium malabsorption. Miner Electrolyte Metab 11:35–40

    PubMed  CAS  Google Scholar 

  29. Nordin BEC, Need AG, Morris HA, O’Loughlin PD, Horowitz M (2004) Effect of age on calcium absorption in postmenopausal women. Am J Clin Nutr 80:998–1002

    PubMed  CAS  Google Scholar 

  30. Wood RJ, Fleet JC, Cashman K, Bruns ME, DeLuca HF (1998) Intestinal calcium absorption in the aged rat: evidence of intestinal resistance to 1,25(OH)2 vitamin D. Endocrinology 139:3843–3848

    Article  PubMed  CAS  Google Scholar 

  31. Need AG, Morris HA, Horowitz M, Nordin BEC (1997) The response to calcitriol therapy in postmenopausal osteoporotic women is a function of initial calcium absorptive status. Calcif Tissue Int 61:6–9

    Article  PubMed  CAS  Google Scholar 

  32. Anderson PH, O’Loughlin PD, May BK, Morris HA (2005) Modulation of CYP27B1 and CYP24 mRNA expression in bone is independent of circulating 1,25(OH)2D3 levels. Bone 36:654–662

    Article  PubMed  CAS  Google Scholar 

  33. Anderson PH, Sawyer RK, Moore AJ, May BK, O’Loughlin PD, Morris HA (2008) Vitamin D depletion induces RANKL-mediated osteoclastogenesis and bone loss in a rodent model. J Bone Miner Res 23:1789–1797

    Article  PubMed  CAS  Google Scholar 

  34. Markowitz S, Arnaud S, Rosen JF, Thorpy M, Laximinarayan S (1988) Temporal interrelationships between the circadian rhythms of serum parathyroid hormone and calcium concentrations. J Clin Endocrinol Metab 67:1068–1073

    Article  PubMed  CAS  Google Scholar 

  35. Scopacasa F, Need AG, Horowitz M, Wishart JM, Morris HA, Nordin BEC (2000) Inhibition of bone resorption by divided-dose calcium supplementation in early postmenopausal women. Calcif Tissue Int 67:440–442

    Article  PubMed  CAS  Google Scholar 

  36. Blumsohn A, Herrington K, Hannon RA, Shao P, Eyre DR, Eastell R (1994) The effect of calcium supplementation on the circadian rhythm of bone resorption. J Clin Endocrinol Metab 79:730–735

    Article  PubMed  CAS  Google Scholar 

  37. Joseph F, Chan BY, Durham BH, Ahmad AM, Vinjamuri S, Gallagher JA, Vora JP, Fraser WD (2007) The circadian rhythm of osteoprotegerin and its association with parathyroid hormone secretion. J Clin Endocrinol Metab 92:3230–3238

    Article  PubMed  CAS  Google Scholar 

  38. Morris HA, Chatterton BE, Ross PD, Durbridge TC (1993) Diagnostic procedures. In: Nordin BEC, Need AG, Morris HA (eds) Metabolic bone and stone disease, 3rd edn. Churchill Livingstone, Edinburgh, pp 339–379

    Google Scholar 

  39. Talbot JR, Guardo P, Seccia S, Gear L, Lubary DR, Saad G et al (1999) Calcium bioavailability and parathyroid hormone acute changes after oral intake of dairy and nondairy products in healthy volunteers. Osteoporos Int 10:137–142

    Article  PubMed  CAS  Google Scholar 

  40. Heller HJ, Greer LG, Haynes SD, Poindexter JR, Pak CY (2000) Pharmacokinetic and pharmacodynamic comparison of two supplements in postmenopausal women. J Clin Pharmacol 40:1237–1244

    PubMed  CAS  Google Scholar 

  41. Need AG, Horowitz M, Philcox JC, Nordin BEC (1987) Biochemical effects of a calcium supplement in osteoporotic postmenopausal women with normal absorption and malabsorption of calcium. Miner Electrolyte Metab 13:112–116

    PubMed  CAS  Google Scholar 

  42. Scopacasa F, Horowitz M, Wishart JM, Need AG, Morris HA, Wittert G, Nordin BEC (1998) Calcium supplementation suppresses bone resorption in early postmenopausal women. Calcif Tissue Int 62:8–12

    Article  PubMed  CAS  Google Scholar 

  43. Reginster J-Y, Zegels B, Lejeune E, Micheletti MC, Kvsaz A, Seidel L, Sarlet N (2002) Influence of daily regimen calcium and vitamin D supplementation on parathyroid hormone secretion. Calcif Tissue Int 70:78–82

    Article  PubMed  CAS  Google Scholar 

  44. Heaney RP, Dowell MS, Hale CA, Bendich A (2003) Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 22:142–146

    PubMed  CAS  Google Scholar 

  45. Devine A, Wilson SG, Dick IM, Prince RL (2002) Effects of vitamin D metabolites on intestinal calcium absorption and bone turnover in elderly women. Am J Clin Nutr 75:283–288

    PubMed  CAS  Google Scholar 

  46. Zhu K, Bruce D, Austin N, Devine A, Ebeling PR, Prince RL (2008) Randomized controlled trial of the effects of calcium with or without vitamin D on bone structure and bone-related chemistry in elderly women with vitamin D insufficiency. J Bone Miner Res 23:1343–1348

    Article  PubMed  CAS  Google Scholar 

  47. Need AG, O’Loughlin PD, Morris HA, Horowitz M, Nordin BEC (2004) The effects of age and other variables on serum parathyroid hormone in postmenopausal women attending an osteoporosis center. J Clin Endocrinol Metab 89:1646–1649

    Article  PubMed  CAS  Google Scholar 

  48. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281

    Article  PubMed  CAS  Google Scholar 

  49. Francis RM, Peacock M, Taylor GA, Storer JH, Nordin BEC (1984) Calcium malabsorption in elderly women with vertebral fractures: evidence for resistance to the action of vitamin D metabolites on the bowel. Clin Sci 66:103–107

    PubMed  CAS  Google Scholar 

  50. Morris HA, Need AG, Horowitz M, O’Loughlin PD, Nordin BEC (1991) Calcium absorption in normal and osteoporotic postmenopausal women. Calcif Tissue Int 49:240–243

    Article  PubMed  CAS  Google Scholar 

  51. Nordin BEC, O’Loughlin PD, Need AG, Horowitz M, Morris HA (2004) Radiocalcium absorption is reduced in postmenopausal women with vertebral and most types of peripheral fractures. Osteporos Int 15:27–31

    Article  CAS  Google Scholar 

  52. Francis RM, Peacock M, Storer JH, Davies AEJ, Brown WB, Nordin BEC (1983) Calcium malabsorption in the elderly: the effect of treatment with oral 25-hydroxyvitamin D3. Eur J Clin Invest 13:391–396

    Article  PubMed  CAS  Google Scholar 

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Correspondence to B. E. Christopher Nordin.

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Nordin, B.E.C., Morris, H.A., Horowitz, M. et al. Calcium Malabsorption Does Not Cause Secondary Hyperparathyroidism. Calcif Tissue Int 85, 31–36 (2009). https://doi.org/10.1007/s00223-009-9258-2

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  • DOI: https://doi.org/10.1007/s00223-009-9258-2

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