Top

Published in:

01-12-2012 | Epidemiology and Pathophysiology (RA Adler, Section Editor)

Idiopathic Hypercalciuria and Bone Health

Authors: Laura E. Ryan, Steven W. Ing

Published in: Current Osteoporosis Reports | Issue 4/2012

Abstract

Calcium is an important participant in many physiologic processes including coagulation, cell membrane transfer, hormone release, neuromuscular activation, and myocardial contraction. The body cooperates in a sophisticated web of hormonally mediated interactions to maintain stable extracellular calcium levels. Calcium is vital for skeletal mineralization, and perturbations in extracellular calcium may be corrected at the expense of bone strength and integrity. The aim of this review is to delineate our current understanding of idiopathic hypercalciuria in the context of bone health, specifically its definition, etiology, epidemiology, laboratory evaluation, and potential therapeutic management.

Albright F, Henneman P, Benedict PH, Forbes AP. Idiopathic hypercalciuria: a preliminary report. Proc R Soc Med. 1953;46(12):1077–81.PubMed

Pak CY, Oata M, Lawrence EC, Snyder W. The hypercalciurias. Causes, parathyroid functions, and diagnostic criteria. J Clin Invest. 1974;54(2):387–400.PubMedCrossRef

Pacifici R, Filipponi P, Mannarelli C, Vespasiani G, et al. Classification of idiopathic hypercalciuric patients by isotopic calcium absorption: a comparison with oral calcium tolerance test. Calcif Tissue Int. 1985;37(5):467–73.PubMedCrossRef

Pak CY. Pathophysiology of calcium nephrolithiasis. In: Seldin DW, Giebiscg G, editors. The Kidney: Physiology and Pathophysiology. New York, NY: Raven Press; 1992. p. 2461–80.

Frick KK, Bushinsky DA. Molecular mechanisms of primary hypercalciuria. J Am Soc Nephrol. 2003;14:1082–95.PubMedCrossRef

Pacifici R, Rothstein M, Rifas L, et al. Increased monocyte interleukin-1 activity and decreased vertebral bone density in patients with fasting idiopathic hypercalciuria. J Clin Endocrinol Metab. 1990;71(1):138–45.PubMedCrossRef

Messa P, Mioni G, Montanaro D, et al. About a primitive osseous origin of the so-called ‘renal hypercalciuria’. Contrib Nephrol. 1987;58:106–10.PubMed

•• Zerwekh JE. Bone disease and idiopathic hypercalciuria. Clinic Rev Bone Miner Metab. 2008;6:82–94. Review specifically highlights the relationship between IH and bone health.CrossRef

Coe FL. Treated and untreated recurrent calcium nephrolithiasis in patients with idiopathic hypercalciuria, hyperuricosuria, or no metabolic disorder. Ann Intern Med. 1977;87(4):404–10.PubMed

10.

Lemann Jr J. Pathogenesis of idiopathic hypercalciuria and nephrolithiasis. In: Coe FL, Favus MJ, editors. Disorders of Bone and Mineral Metabolism. New York, NY: Raven Press; 1992. p. 685–706.

11.

• Coe FL, Parks JH, Moore ES. Familial idiopathic hypercalciuria. N Engl J Med. 1979;300(7):337–40. Study of 9 families that clearly illustrates an autosomal dominant transmission of some types of hypercalciuria.PubMedCrossRef

12.

Giannini S, Nobile M, Dalle Carbonare L, et al. Hypercalciuria is a common and important finding in postmenopausal women with osteoporosis. Eur J Endocrinol. 2003;149(3):209–13.PubMedCrossRef

13.

Tannenbaum C, Clark J, Schwartzman K, et al. Yield of laboratory testing to identify secondary contributors to osteoporosis in otherwise healthy women. J Clin Endocrinol Metab. 2002;87(10):4431–7.PubMedCrossRef

14.

Cerda Gabaroi D, Peris P, Monegal A, et al. Search for hidden secondary causes in postmenopausal women with osteoporosis. Menopause. 2010;17(1):135–9.PubMedCrossRef

15.

Hodgkinson A, Pyrah LN. The urinary excretion of calcium and inorganic phosphate in 344 patients with calcium stone of renal origin. Br J Surg. 1958;46(195):10–8.PubMedCrossRef

16.

Ettinger B, Insogna KL. Nephrolithiasis. In: Felig P, Baxter JD, Frohman LA, editors. Endocrinology and Metabolism. McGraw-Hill, Inc; 1995. p. 1565–1615.

17.

Walser M. Creatinine excretion as a measure of protein nutrition in adults of varying age. J Parenter Enteral Nutr. 1987;11 Suppl 5:73S–8S.CrossRef

18.

Heaney RP, Recker RR, Ryan RA. Urinary calcium in perimenopausal women: normative values. Osteoporos Int. 1999;9(1):13–8.PubMedCrossRef

19.

Bleich HL, Moore MJ, Lemann Jr J, et al. Urinary calcium excretion in human beings. N Engl J Med. 1979;301(10):535–41.PubMedCrossRef

20.

Breslau NA, Brinkley L, Hill KD, Pak CY. Relationship of animal protein-rich diet to kidney stone formation and calcium metabolism. J Clin Endocrinol Metab. 1988;66(1):140–6.PubMedCrossRef

21.

Li XQ, Tembe V, Horwitz GM, et al. Increased intestinal vitamin D receptor in genetic hypercalciuric rats. A cause of intestinal calcium hyperabsorption. J Clin Invest. 1993;91(2):661–7.PubMedCrossRef

22.

Yao J, Kathpalia P, Bushinsky DA, Favus MJ. Hyperresponsiveness of vitamin D receptor gene expression to 1,25-dihydroxyvitamin D3. A new characteristic of genetic hypercalciuric stone-forming rats. J Clin Invest. 1998;101(10):2223–32.PubMedCrossRef

23.

Pietschmann F, Breslau NA, Pak CY. Reduced vertebral bone density in hypercalciuric nephrolithiasis. J Bone Miner Res. 1992;7(12):1383–8.PubMedCrossRef

24.

Jaeger P, Lippuner K, Casez JP, et al. Low bone mass in idiopathic renal stone formers: magnitude and significance. J Bone Miner Res. 1994;9(10):1525–32.PubMedCrossRef

25.

Vezzoli G, Soldati L, Arcidiacono T, et al. Urinary calcium is a determinant of bone mineral density in elderly men participating in the InCHIANTI study. Kidney Int. 2005;67:2006–14.PubMedCrossRef

26.

Lemann Jr J, Worcester EM, Gray RW. Hypercalciuria and stones. Am J Kidney Dis. 1991;17(4):386–91.PubMed

27.

Gokce C, Gokce O, Baydinc C, et al. Use of random urine samples to estimate total urinary calcium and phosphate excretion. Arch Intern Med. 1991;151(8):1587–8.PubMedCrossRef

28.

Jones AN, Shafer MM, Keuler NS, et al. Fasting and postprandial spot urine calcium-to-creatinine ratios do not detect hypercalciuria. Osteoporos Int. 2012;23(2):553–62.PubMedCrossRef

29.

Frick KK, Bushinsky DA. Metabolic acidosis stimulates RANKL RNA expression in bone through a cyclo-oxygenase-dependent mechanism. J Bone Miner Res. 2003;18(7):1317–25.PubMedCrossRef

30.

• Borghi L, Schianchi T, Meschi T, et al. Comparison of 2 diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med. 2002;346(2):77–84. Study highlights the importance of dietary modification in reducing hypercalciuria, especially diets low in salt and low in animal-protein.PubMedCrossRef

31.

• Ghazali A, Fuentes V, Desaint C, et al. Low bone mineral density and peripheral blood monocyte activation profile in calcium stone formers with idiopathic hypercalciuria. J Clin Endocrinol Metab. 1997;82(1):32–8. Reports on likely pathogenetic mechanism separating idiopathic hypercalciuria from other classifications.PubMedCrossRef

32.

Gomes SA, dos Reis LM, Noronha IL, et al. RANKL is a mediator of bone resorption in idiopathic hypercalciuria. Clin J Am Soc Nephrol. 2008;3(5):1446–52.PubMedCrossRef

33.

Sakhaee K, Maalouf NM, Kumar R, et al. Nephrolithiasis-associated bone disease: pathogenesis and treatment options. Kidney Int. 2011;79:393–403.PubMedCrossRef

34.

Broadus AE, Insogna KL, Lang R, et al. Evidence for disordered control of 1,25-dihydroxyvitamin D production in absorptive hypercalciuria. N Engl J Med. 1984;311(2):73–8.PubMedCrossRef

35.

Tasca A, Cacciola A, Ferrarese P, et al. Bone alterations in patients with idiopathic hypercalciuria and calcium nephrolithiasis. Urology. 2002;59(6):865–9.PubMedCrossRef

36.

Melton III LJ, Crowson CS, Khosla S, et al. Fracture risk among patients with urolithiasis: a population-based cohort study. Kidney Int. 1998;53:459–64.PubMedCrossRef

37.

Lauderdale DS, Thisted RA, Wen M, Favus MJ. Bone mineral density and fracture among prevalent kidney stone cases in the Third National Health and Nutrition Examination Survey. J Bone Miner Res. 2001;16(10):1893–8.PubMedCrossRef

38.

Cauley JA, Fullman RL, Stone KL, et al. Factors associated with the lumbar spine and proximal femur bone mineral density in older men. Osteoporos Int. 2005;16(12):1525–37.PubMedCrossRef

39.

Sowers MR, Jannausch M, Wood C, et al. Prevalence of renal stones in a population-based study with dietary calcium, oxalate and medication exposures. Am J Epidemiol. 1998;147(10):914–20.PubMedCrossRef

40.

Asplin JR, Bauer KA, Kinder J, et al. Bone mineral density and urine calcium excretion among subjects with and without nephrolithiasis. Kidney Int. 2003;63(2):662–9.PubMedCrossRef

41.

Letavernier E, Traxer O, Daudon M, et al. Determinants of osteopenia in male renal-stone-disease patients with idiopathic hypercalciuria. Clin J Am Soc Nephrol. 2011;6(5):1149–54.PubMedCrossRef

42.

Bataille P, Achard JM, Fournier A, et al. Diet, vitamin D and vertebral mineral density in hypercalciuric calcium stone formers. Kidney Int. 1991;39(6):1193–205.PubMedCrossRef

43.

Asplin JR, Donahue S, Kinder J, Coe FL. Urine calcium excretion predicts bone loss in idiopathic hypercalciuria. Kidney Int. 2006;70(8):1463–7.PubMedCrossRef

44.

Hunter D, De Lange M, Snieder H, et al. Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. J Bone Miner Res. 2001;16(2):371–8.PubMedCrossRef

45.

Reed BY, Heller HJ, Gitomer WL, Pak CY. Mapping a gene defect in absorptive hypercalciuria to chromosome 1q23.3-q24. J Clin Endocrinol Metab. 1999;84(11):3907–13.PubMedCrossRef

46.

Reed BY, Gitomer WL, Heller HJ, et al. Identification and characterization of a gene with base substitutions associated with the absorptive hypercalciuria phenotype and low spinal bone density. J Clin Endocrinol Metab. 2002;87(4):1476–85.PubMedCrossRef

47.

Geng W, Wang Z, Zhang J, et al. Cloning and characterization of the human soluble adenylyl cyclase. Am J Physiol Cell Physiol. 2005;288(6):C1305–16.PubMedCrossRef

48.

Geng W, Hill K, Zerwekh JE, et al. Inhibition of osteoclast formation and function by bicarbonate: role of soluble adenylyl cyclase. J Cell Physiol. 2009;220(2):332–40.PubMedCrossRef

49.

Vezzoli G, Soldati L, Gambaro G. Update on primary hypercalciuria from a genetic perspective. J Urol. 2008;179(5):1676–82.PubMedCrossRef

50.

Reid IR, Ames RW, Orr-Walker BJ, et al. Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women: a randomized controlled trial. Am J Med. 2000;109(5):362–70.PubMedCrossRef

51.

Bolland MJ, Ames RW, Horne AM, et al. The effect of treatment with a thiazide diuretic for 4 years on bone density in normal postmenopausal women. Osteoporos Int. 2007;18(4):479–86.PubMedCrossRef

52.

LaCroix AZ, Ott SM, Ichikawa L, et al. Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. Ann Intern Med. 2000;133:516–26.PubMed

53.

Wasnich RD, Davis JW, He Y-F, et al. A randomized, double-masked, placebo-controlled trial of chlorthalidone and bone loss in elderly women. Osteoporos Int. 1995;5:247–51.PubMedCrossRef

54.

Adams JS, Song CF, Kantorovich V. Rapid recovery of bone mass in hypercalciuric, osteoporotic men treated with hydrochlorothiazide. Ann Intern Med. 1999;130:658–60.PubMed

55.

Feskanich D, Willett WC, Stampfer MJ, Colditz GA. A prospective study of thiazide use and fractures in women. Osteoporos Int. 1997;7(1):79–84.PubMedCrossRef

56.

Lamberg BA, Kuhlback B. Effect of chlorothiazide and hydrochlorothiazide on the excretion of calcium in the urine. Scand J Clin Lab Invest. 1959;11:351–7.PubMedCrossRef

57.

Lajeunesse D, Delalandre A, Guggino SE. Thiazide diuretics affect osteocalcin production in human osteoblasts at the transcription level without affecting vitamin D3 receptors. J Bone Miner Res. 2000;15(5):894–901.PubMedCrossRef

58.

• Garcia-Nieto V, Monge-Zamorano M, Gonzalez-Garcia M, et al. Effect of thiazides on bone mineral density in children with idiopathic hypercalciuria. Pediatr Nephrol. 2012;27:261–8. A provocative paper challenging commonly held beliefs about the impact of thiazides on bone.PubMedCrossRef

59.

Bushinsky DA, Favus MJ. Mechanism of hypercalciuria in genetic hypercalciuric rats. Inherited defect in intestinal calcium transport. J Clin Invest. 1988;82(5):1585–91.PubMedCrossRef

60.

Grynpas M, Waldman S, Holmyard D, Bushinsky DA. Genetic hypercalciuric stone-forming rats have a primary decrease in BMD and strength. J Bone Miner Res. 2009;24(8):1420–6.PubMedCrossRef

61.

•• Bushinsky DA, Willett T, Asplin JR, et al. Chlorthalidone improves vertebral bone quality in genetic hypercalciuric stone-forming rats. J Bone Miner Res. 2011;26(8):1904–12. Uses genetic hypercalciuric rats to study thiazide impact on bone mineralization and architecture in a population known to have idiopathic hypercalciuria.PubMedCrossRef

62.

Pak CY, Heller HJ, Pearle MS, et al. Prevention of stone formation and bone loss in absorptive hypercalciuria by combined dietary and pharmacological interventions. J Urol. 2003;169(2):465–9.PubMedCrossRef

63.

Vescini F, Buffa A, LaManna G, et al. Long-term potassium citrate therapy and bone mineral density in idiopathic calcium stone formers. J Endocrinol Invest. 2005;28(3):218–22.PubMed

64.

Ruml LA, Dubois SK, Roberts ML, et al. Prevention of hypercalciuria and stone-forming propensity during prolonged bedrest by alendronate. J Bone Miner Res. 1995;10(4):655–62.PubMedCrossRef

65.

Alonzo E, Bellorin-Font E, Carlini R, et al. Role of the bone in the pathogenesis of idiopathic hypercalciuria: effect of aminobisphosphonate alendronate. Medicina. 1997;57 Suppl 1:45–8.PubMed

66.

Heilberg IP, Martini LA, Teixeira SH, et al. Effect of etidronate treatment on bone mass of male nephrolithiasis patients with idiopathic hypercalciuria and osteopenia. Nephron. 1998;79(4):430–7.PubMedCrossRef

67.

Bushinsky DA, Neumann KJ, Asplin J, Krieger NS. Alendronate decreases urine calcium and supersaturation in genetic hypercalciuric rats. Kidney Int. 1999;55(1):234–43.PubMedCrossRef

68.

Riccardi D, Park J, Lee WS, et al. Cloning and functional expression of a rat kidney extracellular calcium/polyvalent cation-sensing receptor. Proc Natl Acad Sci USA. 1995;92(1):131–5.PubMedCrossRef

69.

Peacock M, Bolognese MA, Borofsky M, et al. Cinacalcet treatment of primary hyperparathyroidism: biochemical and bone densitometric outcomes in a 5-year study. J Clin Endocrinol Metab. 2009;94(12):4860–7.PubMedCrossRef

70.

Bushinsky DA, LaPlante K, Asplin JR. Effect of cinacalcet on urine calcium excretion and supersaturation in genetic hypercalciuric stone-forming rats. Kidney Int. 2006;69:1586–92.PubMedCrossRef

71.

Filipponi P, Mannarelli C, Pacifici R, et al. Evidence for a prostaglandin-mediated bone resorptive mechanism in subjects with fasting hypercalciuria. Calcif Tissue Int. 1988;43:61–6.PubMedCrossRef

72.

Gomaa AA, Hassan HA, Ghaneimah SA. Effect of aspirin and indomethacin on the serum and urinary calcium, magnesium and phosphate. Pharmacol Res. 1990;22(1):59–70.PubMedCrossRef

73.

Buck AC, Davies RL, Harrison T. The protective role of eicosapentaenoic acid (EPA) in the pathogenesis of nephrolithiasis. J Urol. 1991;146(1):188–94.PubMed

74.

Ortiz-Alvarado O, Miyaoka R, Kriedberg C, et al. Omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid in the management of hypercalciuric stone formers. Urology. 2012;79(2):282–6.PubMedCrossRef

75.

Orchard TS, Pan X, Cheek F, Ing SW, Jackson RD. A systematic review of omega-3 fatty acids and osteoporosis. Br J Nutr. 2012;107 Suppl 2:S253–60.PubMedCrossRef

Title: Idiopathic Hypercalciuria and Bone Health
Authors: Laura E. Ryan
Steven W. Ing
Publication date: 01-12-2012
Publisher: Current Science Inc.
Published in: Current Osteoporosis Reports / Issue 4/2012
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI: https://doi.org/10.1007/s11914-012-0120-5

At a glance: The STEP trials

Springer Medicine

Idiopathic Hypercalciuria and Bone Health

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2012

Augmentation of Implant Fixation in Osteoporotic Bone

Heart Failure as a Risk Factor for Osteoporosis and Fractures

Osteoporosis Treatment by a New Active Vitamin D3 Compound, Eldecalcitol, in Japan

Spinal Cord Injury-Induced Osteoporosis: Pathogenesis and Emerging Therapies

Primary Arthroplasty for Management of Osteoporotic Fractures about the Knee

Co-managed Care: The Gold Standard for Geriatric Fracture Care