Osteoporosis International

, Volume 6, Issue 6, pp 453–461

Magnesium deficiency: Possible role in osteoporosis associated with gluten-sensitive enteropathy

  • R. K. Rude
  • M. Olerich
Original Article

Abstract

Osteoporosis and magnesium (Mg) deficiency often occur in malabsorption syndromes such as gluten-sensitive enteropathy (GSE). Mg deficiency is known to impair parathyroid hormone (PTH) secretion and action in humans and will result in osteopenia and increased skeletal fragility in animal models. We hypothesize that Mg depletion may contribute to the osteoporosis associated with malabsorption. It was our objective to determine Mg status and bone mass in GSE patients who were clinically asymptomatic and on a stable gluten-free diet, as well as their response to Mg therapy. Twenty-three patients with biopsy-proven GSE on a gluten-free diet were assessed for Mg deficiency by determination of the serum Mg, red blood cell (RBC) and lymphocyte free Mg2+, and total lymphocyte Mg. Fourteen subjects completed a 3-month treatment period in which they were given 504−576 mg MgCl2 or Mg lactate daily. Serum PTH, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and osteocalcin were measured at baseline and monthly thereafter. Eight patients who had documented Mg depletion (RBC Mg2+<150 µM) underwent bone density measurements of the lumbar spine and proximal femur, and 5 of these patients were followed for 2 years on Mg therapy. The mean serum Mg, calcium, phosphorus and alkaline phosphatase concentrations were in the normal range. Most serum calcium values fell below mean normal and the baseline serum PTH was high normal or slightly elevated in 7 of the 14 subjects who completed the 3-month treatment period. No correlation with the serum calcium was noted, however. Mean serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and osteocalcin concentrations were also normal. Despite only 1 patient having hypomagnesemia, the RBC Mg2+ (153±6.2 µM; mean ± SEM) and lymphocyte Mg2+ (182±5.5 µM) were significantly lower than normal (202±6.0 µM,p<0.001, and 198±6.8 µM,p<0.05, respectively). Bone densitometry revealed that 4 of 8 patients had osteoporosis of the lumbar spine and 5 of 8 had osteoporosis of the proximal femur (T-scores ≥−2.5). Mg therapy resulted in a significant rise in the mean serum PTH concentration from 44.6±3.6 pg/ml to 55.9±5.6 pg/ml (p<0.05). In the 5 patients given Mg supplements for 2 years, a significant increased in bone mineral density was observed in the femoral neck and total proximal femur. This increase in bone mineral density correlated positively with a rise in RBC Mg2+. This study demonstrates that GSE patients have reduction in intracellular free Mg2+, despite being clinically asymptomatic on a gluten-free diet. Bone mass also appears to be reduced. Mg therapy resulted in a rise in PTH, suggesting that the intracellular Mg deficit was impairing PTH secretion in these patients. The increase in bone density in response to Mg therapy suggests that Mg depletion may be one factor contributing to osteoporosis in GSE.

Keywords

Gluten-sensitive enteropathy Magnesium Malabsorption Osteoporosis Sprue 

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References

  1. 1.
    Salvesen HA, Boe J. Osteomalacia in sprue. Acta Med Scand 1953;146:290–9.Google Scholar
  2. 2.
    Melvin KEW, Hepner GW, Bordier P, et al. Calcium metabolism and bone pathology in adult coeliac disease. Q J Med 1970;39:83–113.Google Scholar
  3. 3.
    Kruse HP, Ringe JD, Tomforde-Brunckhorst R. Die einheimische Sprue, oft verkannte ursache hochgradiger generalisierter Osteopathien. Dtsch Med Wochenschr 1987;112:115–9.Google Scholar
  4. 4.
    Caraceni MP, Molteni N, Bardella MT, et al. Bone and mineral metabolism in adult celiac disease. Am J Gastroenterol 1988;83:274–7.Google Scholar
  5. 5.
    Molteni N, Caraceni MP, Bardella MT, et al. Bone mineral density in adult celiac patients and the effect of gluten-free diet from childhood. Am J Gastroenterol 1990;85:51–3.Google Scholar
  6. 6.
    Mora S, Weber G, Barera G, et al. Effect of gluten-free diet on bone mineral content in growing patients with celiac disease. Am J Clin Nutr 1993;57:224–8.Google Scholar
  7. 7.
    Burkholder PK, DuBoff EA, Filmanowicz EV. Nontropical sprue with secondary hyperparathyroidism. Am J Dig Dis 1965;10:75–85.Google Scholar
  8. 8.
    Booth CC, Hanna S, Babouris N, et al. Incidence of hypomagnesaemia in intestinal malabsorption. BMJ 1963;2:141–4.Google Scholar
  9. 9.
    Arnaud SB, Newcomer AD, Go VLW. Hypomagnesemia and vitamin D deficiency in patients with non-tropical sprue. Clin Res 1976;24:564A.Google Scholar
  10. 10.
    Nadler JL, Malayan S, Luong H, et al. Intracellular free magnesium deficiency plays a key role in increased platelet reactivity in type II diabetes mellitus. Diabetes Care 1992;15:835–41.Google Scholar
  11. 11.
    Ryzen E, Nelson TA, Rude RK. Low blood mononuclear cell magnesium content and hypocalcemia in normomagnesemic patients. West J Med 1987;147:549–53.Google Scholar
  12. 12.
    Rude RK, Oldham SB, Singer FR. Functional hypoparathyroidism and parathyroid hormone end-organ resistance in human Mg deficiency. Clin Endocrinol 1976;5:209–24.Google Scholar
  13. 13.
    Estep H, Shaw WA, Watlington C, et al. Hypocalcemia due to hypomagnesemia and reversible parathyroid hormone unrespon-siveness. J Clin Endocrinol Metab 1969;29:842–8.Google Scholar
  14. 14.
    Rude RK, Adams JS, Ryzen E. Low serum concentrations of 1,25-dihydroxy-vitamin D in human magnesium deficiency. J Clin Endocrinol Metab 1985;61:933–40.Google Scholar
  15. 15.
    Medalle R, Waterhouse C, Hahn TJ. Vitamin D resistance in magnesium deficiency. Am J Clin Nutr 1976;29:854–8.Google Scholar
  16. 16.
    Kenney MA, McCoy H, Williams L. Effects of magnesium deficiency on strength, mass and composition of rat femur. Calcif Tissue Int 1994;54:44–9.Google Scholar
  17. 27.
    Carpenter TO, Mackowiak SJ, Troiano N, et al. Osteocalcin and its meassage: relationship to bone histology in magnesium-derpived rats. Am J PHysiol 1992;263:E107–14.Google Scholar
  18. 18.
    Boskey AL, Rimnac CM, Bansal M, et al. Effect of short-term hypomagnesemia on the chemical and mechanical properties of rat bone. J Orthop Res 1992;10:774–83.Google Scholar
  19. 19.
    Food and Nutrient Board, National Research Council. Recommended dietary allowance. Washington, DC: National Academy Press, 1989.Google Scholar
  20. 20.
    Seelig MS. Magnesium requirements in human nutrition. Magnesium Bull 1981;3:26–47.Google Scholar
  21. 21.
    Endres DB, Villanueva R, Sharp CF Jr, Singer FR. Immunochemiluminometric and immunoradiometric determinations of intact and total immunoreactive parathyrin: performance in the differential diagnosis of hypercalcemia and hypoparathyroidism. Clin Chem 1991;37:162–8.Google Scholar
  22. 22.
    Hollis BW, Napoli JL. Improved radioimmunoassay for vitamin D and its use in assessing vitamin D status. Clin Chem 1985;31:1815–9.Google Scholar
  23. 23.
    Hollis BW. Assay of circulating 1,25-dihydroxyvitamin D involving a novel single-cartridge extraction and purification procedure. Clin Chem 1986;32:2060–3.Google Scholar
  24. 24.
    Ryzen E, Servis KL, DeRusso P, et al. Determination of intracellular free magnesium by nuclear magnetic resonance in human magnesium deficiency. J Am Coll Nutr 1989:580–7.Google Scholar
  25. 25.
    Raju B, Murphy E, Levy LA, et al. A fluorescent indicator for measuring cystosolic free magnesium. Am J Physiol 1989;256:C540–8.Google Scholar
  26. 26.
    Lowry OH, Rosebrough NJ, Farr AL, et al. Protein measurement with the folin, phenol reagent. J Biol Chem 1951;193:265–75.Google Scholar
  27. 27.
    Spicer DV, Pike MC, Pike A, et al. Pilot trial of gonadotropin hromone agonist with replacement hormone as a prototype contraceptive to prevent breast cancer. Contraception 1993;44:427–44.Google Scholar
  28. 28.
    Kanis JA, Melton JH, Christiansen C, et al. The diagnosis of osteoporosis. J Bone Miner Res 1994;9:1137–41.Google Scholar
  29. 29.
    Kluge F, Koch HK, Grosse-Wilde H, et al. Follow-up of treated adult celiac disease: clinical and morphological studies. Hepatogastroenterology 1982;29:17–23.Google Scholar
  30. 30.
    Rude RK, Oldham SB, Sharp CF Jr, et al. Parathyroid hormone secretion in magnesium deficiency. J Clin Endocrinol Metab 1978;47:800–6.Google Scholar
  31. 31.
    Saggese G, Federico G, Bertelloni S, et al. Hypomagnesemia and the parathryoid hormone-vitamin D endocrine system in children with insulin-dependent diabetes mellitus: effects of magnesium administration. J Pediatr 1991;118:220–5.Google Scholar
  32. 32.
    Riggs BL, Melton LJM. The prevention and treatment of osteoporosis. N Engl J Med 1992;327:620–7.Google Scholar
  33. 33.
    Francheschi RT, Romano PR, Park K-H, et al. Regulation of fibronectin and collagen synthesis by 1,25-dihydroxyvitamin D3. In: Norman AW, Schaefer K, Grigoleit HG, Herrath DV (eds) Vitamin D: molecular cellular and clinical endocrinology. Berlin: W. de Gruyter, 1988:624–5.Google Scholar
  34. 34.
    Hodsman AB, Fraher LJ, Ostbye T, Adachi JD, Steer BM. An evaluation of several biochemical markers for bone formation and resorption in a protocol utilizing cyclical parathyroid hormone and calcitonin therapy for osteoporosis. J Clin Invest 1993;91:1138–48.Google Scholar
  35. 35.
    Reeve J. PTH: a future role in the management of osteoporosis. J Bone Miner Res 1996;11:440–5.Google Scholar
  36. 36.
    Liu CC, Yeh JK, Aloia JF. Magnesium directly stimulates osteoblast proliferation. J Bone Miner Res 1988;3:S104.Google Scholar
  37. 37.
    Stendig-Lindberg G, Tepper R, Leichter I. Trabecular bone density in a two-year controlled trial of peroral magnesium in osteoporosis. Magnesium Res 1993;6:155–63.Google Scholar

Copyright information

© European Foundation for Osteoporosis 1996

Authors and Affiliations

  • R. K. Rude
    • 1
  • M. Olerich
    • 1
  1. 1.Department of MedicineUniversity of Southern California School of Medicine and the Endocrine Research Laboratory, Orthopedic HospitalLos AngelesUSA

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