Abstract
Summary
A study of 959 black and white women shows that the normal range for 24-h urine calcium excretion in white women is 30–300 mg and 10–285 mg in black women. Clinical laboratories use a normal range for 24-h urine calcium excretion of 100–300 mg; there is a need for them to update their age- and race-specific ranges.
Introduction
Recommendations for a normal range for 24-h urine calcium vary from a low of 50 mg to a high of 400 mg; most “laboratory normal ranges” based on older literature are incorrect. The objective of this analysis is to define a normal range for young women age 25–45 years and older women age 55–90 years, white and black, for 24-h urine calcium and calcium/creatinine ratio, and to examine the relationship between 24-h urine calcium, calcium absorption, and vitamin D metabolites.
Methods
Data from 3 studies was collected on 959 normal black and white women, ages 25–87 years, for 24-h urine calcium, creatinine, calcium intake, serum 25-hydroxyvitamin D (25OHD),1,25 dihydroxyvitamin D (1,25(OH)2D), and calcium absorption. Urine calcium and creatinine were measured on an auto-analyzer. Calcium absorption was measured by a single isotope method. Serum 25OHD and 1,25(OH)2D were measured by competitive protein binding assay or radioimmunoassay. Because 24-h urine calcium did not fit a normal distribution, non-parametric methods were used to determine the 95% reference interval (RI) and 90% non-parametric confidence intervals (CI) calculated for groups.
Results
The 95% reference intervals for 24-h urine calcium for women were as follows: black older 7–225 mg, black younger 8–285 mg; white older 37–275 mg, and white younger 23–287 mg. In older white women, 24-h urine calcium was significantly correlated with serum 1,25(OH)2 D, r = 0.23, p < 0.001, calcium intake r = 0.12, p = 0.001, and calcium absorption r = 0.18, p = 0.003, but not serum 25OHD r = 0.07, p = 0.06.
Conclusions
The normal reference interval for 24-h urine calcium for black women is lower than white women. Twenty-four-hour urine calcium was correlated with serum 1,25(OH)2 D calcium intake and calcium absorption, but not serum 25OHD. This range will be useful clinically for defining hypercalciuria and for following patients on vitamin D and calcium treatment.
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References
Hodgkinson A, Pyrah LN (1958) The urinary excretion of calcium and inorganic phosphate in 344 patients with calcium stone of renal origin. Br J Surg 46(195):10–18. https://doi.org/10.1002/bjs.18004619504
https://www.uclahealth.org/endocrine-center/urine-calcium-test accessed4/14/2020
Watson L, Dale NE (1966) The urinary excretion of calcium, phosphorus and creatinine in normal subjects and in patients with skin cancer. Clin Sci 31(1):77–86
Nordin BEC, Hodgkinson A, Peacock M (1967) The measurement and the meaning of urinary calcium. Clin Orthop Relat Res 52:293–322. https://doi.org/10.1097/00003086-196700520-00023
Bulusu L, Hodgkinson A, Nordin BEC, Peacock M (1970) Urinary excretion of calcium and creatinine in relation to age and body weight in normal subjects and patients with renal calculus. Clin Sci 38(5):601–612. https://doi.org/10.1042/cs0380601
Blackwood AM, Sagnella GA, Cook DG, Cappuccio FP (2001) Urinary calcium excretion, sodium intake and blood pressure in a multi-ethnic population: results of the Wandsworth Heart and Stroke Study. J Hum Hypertens 15(4):229–237. https://doi.org/10.1038/sj.jhh.1001171
Davis RH, Morgan DB, Rivlin RS (1970) The excretion of calcium in the urine and its relation to calcium intake, sex and age. Clin Sci 39(1):1–12. https://doi.org/10.1042/cs0390001
Riggs BL, O’Fallon WM, Muhs J, O’Connor MK, Kumar R, Melton LJ (1998) Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. J Bone Miner Res 13(2):168–174. https://doi.org/10.1359/jbmr.1998.13.2.168
Curhan GC, Willett WC, Speizer FE, Stampfer MJ (2001) Twenty-four–hour urine chemistries and the risk of kidney stones among women and men. Kidney Int 59(6):2290–2298. https://doi.org/10.1046/j.1523-1755.2001.00746.x
Meier DE, Luckey MM, Wallenstein S, Clemens TL, Orwoll ES, Waslien CI (1991) Calcium, vitamin D, and parathyroid hormone status in young white and black women: association with racial differences in bone mass*. J Clin Endocrinol Metab 72(3):703–710. https://doi.org/10.1210/jcem-72-3-703
Meier DE, Luckey MM, Wallenstein S, Lapinski RH, Catherwood B (1992) Racial differences in pre- and postmenopausal bone homeostasis: association with bone density. J Bone Miner Res 7(10):1181–1189. https://doi.org/10.1002/jbmr.5650071010
Taylor EN, Curhan GC (2007) Differences in 24-hour urine composition between black and white women. J Am Soc Nephrol 18(2):654–659. https://doi.org/10.1681/ASN.2006080854
Aloia JF, Shieh A, Mikhail M, Islam S (2015) Urinary calcium excretion in postmenopausal African American women. Clin Nephrol 84(09):130–137. https://doi.org/10.5414/CN108548
Gallagher JC, Fowler SE, Detter JR, Sherman SS (2001) Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. J Clin Endocrinol Metab 86(8):3618–3628. https://doi.org/10.1210/jcem.86.8.7703
Gallagher JC, Sai A, Templin T, Smith L (2012) Dose response to vitamin D supplementation in postmenopausal women. Ann Intern Med 156(6):425. https://doi.org/10.7326/0003-4819-156-6-201203200-00005
Gallagher JC, Yalamanchili V, Smith LM (2012) The effect of vitamin D on calcium absorption in older women. J Clin Endocrinol Metab 97(10):3550–3556. https://doi.org/10.1210/jc.2012-2020
Gallagher JC, Peacock M, Yalamanchili V, Smith LM (2013) Effects of vitamin D supplementation in older African American women. J Clin Endocrinol Metab 98(3):1137–1146. https://doi.org/10.1210/jc.2012-3106
Gallagher JC, Jindal PS, Smith LM (2014) Vitamin D supplementation in young white and African American women. J Bone Miner Res 29(1):173–181. https://doi.org/10.1002/jbmr.2010
Geffré A, Friedrichs K, Harr K, Concordet D, Trumel C, Braun J-P (2009) Reference values: a review. Vet Clin Pathol 38(3):288–298. https://doi.org/10.1111/j.1939-165X.2009.00179.x
Gallagher JC, Jindal PS, Smith LM (2014) Vitamin D does not increase calcium absorption in young women: a randomized clinical trial. J Bone Miner Res 29(5):1081–1087. https://doi.org/10.1002/jbmr.2121
Cosman F, Morgan DC, Nieves JW, Shen V, Luckey MM, Dempster DW, Lindsay R, Parisien M (1997) Resistance to bone resorbing effects of PTH in black women. J Bone Miner Res 12(6):958–966. https://doi.org/10.1359/jbmr.1997.12.6.958
Smith LM, Gallagher JC (2019) Effect of vitamin D supplementation on total and free 25 hydroxyvitamin D and parathyroid hormone. An analysis of two randomized controlled trials. J Intern Med 286(6):651–659. https://doi.org/10.1111/joim.12950
Seeger H, Kaelin FPM, Weber D et al (2017) Changes in urinary risk profile after short-term low sodium and low calcium diet in recurrent Swiss kidney stone formers. BMC Nephrol 18(1):349, 2-9. https://doi.org/10.1186/s12882-017-0755-7
Bayomy O, Zaheer S, Williams JS, Curhan G, Vaidya A (2020) Disentangling the relationships between the renin-angiotensin-aldosterone system, calcium physiology, and risk for kidney stones. J Clin Endocrinol Metab 105(6):1937–1946. https://doi.org/10.1210/clinem/dgaa123
Sai AJ, Walters RW, Fang X, Gallagher JC (2011) Relationship between vitamin D, parathyroid hormone, and bone health. J Clin Endocrinol Metab 96(3):E436–E446. https://doi.org/10.1210/jc.2010-1886
Gallagher JC, Smith LM, Yalamanchili V (2014) Incidence of hypercalciuria and hypercalcemia during vitamin D and calcium supplementation in older women. Menopause 21(11):1173–1180. https://doi.org/10.1097/GME.0000000000000270
Jackson RD, LaCroix AZ, Gass M et al (2006) Women’s health initiative investigators. Calcium plus vitamin D and the risk of fractures. N Engl J Med 354:669–683
Bailey RL, Dodd KW, Goldman JA, Gahche JJ, Dwyer JT, Moshfegh AJ, Sempos CT, Picciano MF (2010) Estimation of total usual calcium and vitamin D intakes in the United States. J Nutr 140(4):817–822. https://doi.org/10.3945/jn.109.118539
Curhan GC, Willett WC, Speizer FE, Spiegelman D, Stampfer MJ (1997) Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med 126(7):497–504. https://doi.org/10.7326/0003-4819-126-7-199704010-00001
Acknowledgments
Dr Munro Peacock for valuable help in recruiting black women in Indiana for the study. This data was first presented as a poster in the ASBMR meeting in 2013.
Funding
This work was supported by grants from National Institute of Health grants: UO1-AG10373, RO1-AG10358, AG28168, and Department of Defense (DOD) W81XWH-07-1-201. Clinical trial registration: NCT00472823.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Smith, L.M., Gallagher, J.C. Reference range for 24-h urine calcium, calcium/creatinine ratio, and correlations with calcium absorption and serum vitamin D metabolites in normal women. Osteoporos Int 32, 539–547 (2021). https://doi.org/10.1007/s00198-020-05615-6
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DOI: https://doi.org/10.1007/s00198-020-05615-6