Abstract
Summary
Many determinants of parathyroid hormone (PTH) are unknown. In the National Health and Nutrition Examination Survey (NHANES), numerous factors not classically associated with calcium–phosphorus homeostasis, such as uric acid and smoking, are independently associated with PTH in adults without chronic kidney disease. Associations between serum phosphorus and PTH may vary by race.
Introduction
Although PTH may be an important biomarker for osteoporosis and cardiovascular disease, many determinants of PTH are unknown. We investigated associations between demographic, dietary, and serum factors and PTH level.
Methods
We studied 4,026 white, 1,792 black, and 1,834 Mexican-American adult participants without chronic kidney disease from the 2003–2004 and 2005–2006 NHANES.
Results
The mean serum PTH level was 38.3 pg/ml for whites, 42.6 pg/ml for blacks, and 41.3 pg/ml for Mexican-Americans. After adjusting for diet, body mass index, serum levels of calcium, phosphorus, 25-hydroxyvitamin D, creatinine, and other factors, smokers compared to non-smokers had lower PTH, ranging from −4.2 pg/ml (95% confidence interval (CI) −7.3 to −1.1) in Mexican-Americans to −6.1 pg/ml (95% CI −8.7 to −3.5) in blacks. After multivariate adjustment, PTH was higher in females compared to males, ranging from 1.1 pg/ml (95% CI −1.2 to 3.4) in Mexican-Americans to 4.5 pg/ml (95% CI 1.9 to 7.0) in blacks, and in older (>60 years) compared to younger participants (<30 years), ranging from 3.7 pg/ml (95% CI 1.3 to 6.1) in Mexican-Americans to 8.0 pg/ml (95% CI 5.4 to 10.7) in blacks. Higher uric acid was associated with higher PTH. In whites only, lower serum phosphorus and lower serum retinol were associated with higher PTH.
Conclusions
Numerous factors not classically associated with calcium–phosphorus homeostasis are independently associated with PTH and should be considered in future studies of PTH and chronic disease. Additional research is needed to elucidate mechanisms underlying identified associations with PTH and to explore possible racial differences in phosphorus handling.
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References
Taylor E, Curhan G, Forman J (2008) Parathyroid hormone and the risk of incident hypertension. J Hypertens 26:1390–1394
Jorde R, Sundsfjord J, Haug E, Bonaa K (2000) Relation between low calcium intake, parathyroid hormone, and blood pressure. Hypertension 35:1154–1159
Kamycheva E, Sundsfjord J, Jorde R (2004) Serum parathyroid hormone levels predict coronary heart disease: the Tromsø Study. Eur J Cardiovasc Prev Rehabil 11:69–74
Sugimoto T, Tanigawa T, Onishi K, Fujimoto N, Matsuda A, Nakamori S, Matsuoka K, Nakamura T, Koji TI M (2009) Serum intact parathyroid hormone levels predict hospitalisation for heart failure. Heart 95:395–398
Hagström E, Hellman P, Larsson T et al (2009) Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation 119:2765–2771
Khaw K, Sneyd M, Compston J (1992) Bone density parathyroid hormone and 25-hydroxyvitamin D concentrations in middle aged women. BMJ 305:273–277
Pluijm S, Visser M, Smit J, Popp-Snijders C, Roos J, Lips P (2001) Determinants of bone mineral density in older men and women: body composition as mediator. J Bone Miner Res 16:2142–2151
Paik J, Curhan G, Forman J, Taylor E (2010) Determinants of plasma parathyroid hormone levels in young women. Calcif Tissue Int 87:211–217
Gutiérrez O, Isakova T, Andress D, Levin A, Wolf M (2008) Prevalence and severity of disordered mineral metabolism in Blacks with chronic kidney disease. Kidney Int 73:956–962
Bell N, Greene A, Epstein S, Oexmann M, Shaw S, Shary J (1985) Evidence for alteration of the vitamin D-endocrine system in blacks. J Clin Invest 76:470–473
Dawson-Hughes B, Harris S, Finneran S, Rasmussen H (1995) Calcium absorption responses to calcitriol in black and white premenopausal women. J Clin Endocrinol Metab 80:3068–3072
M'Buyamba-Kabangu J, Fagard R, Lijnen P, Bouillon R, Lissens W, Amery A (1987) Calcium, vitamin D-endocrine system, and parathyroid hormone in black and white males. Calcif Tissue Int 41:70–74
El-Hajj Fuleihan G, Gundberg C, Gleason R, Brown E, Stromski M, Grant F, Conlin P (1994) Racial differences in parathyroid hormone dynamics. J Clin Endocrinol Metab 79:1642–1647
Boucher A, D'Amour P, Hamel L, Fugere P, Gascon-Barre M, Lepage R, Ste-Marie LG (1989) Estrogen replacement decreases the set point of parathyroid hormone stimulation by calcium in normal postmenopausal women. J Clin Endocrinol Metab 68:831–836
Endres D, Morgan C, Garry P, Omdahl J (1987) Age-related changes in serum immunoreactive parathyroid hormone and its biological action in healthy men and women. J Clin Endocrinol Metab 65:724–731
Chapuy M, Durr F, Chapuy P (1983) Age-related changes in parathyroid hormone and 25 hydroxycholecalciferol levels. J Gerontol 38:19–22
Portale A, Lonergan E, Tanney D, Halloran B (1997) Aging alters calcium regulation of serum concentration of parathyroid hormone in healthy men. Am J Physiol 272:E139–E146
Duarte B, Hargis G, Kukreja S (1988) Effects of estradiol and progesterone on parathyroid hormone secretion from human parathyroid tissue. J Clin Endocrinol Metab 66:584–587
Haden S, Brown E, Hurwitz S, Scott J, El-Hajj Fuleihan G (2000) The effects of age and gender on parathyroid hormone dynamics. Clin Endocrinol (Oxf) 52:329–338
Sherman S, Hollis B, Tobin J (1990) Vitamin D status and related parameters in a healthy population: the effects of age, sex, and season. J Clin Endocrinol Metab 71:405–413
Marcus R, Madvig P, Young G (1984) Age-related changes in parathyroid hormone and parathyroid hormone action in normal humans. J Clin Endocrinol Metab 58:223–230
Minisola S, Pacitti M, Scarda A, Rosso R, Romagnoli E, Carnevale V, Scarnecchia L, Mazzuoli G (1993) Serum ionized calcium, parathyroid hormone and related variables: effect of age and sex. Bone Miner 23:183–193
MacDonald P, Ritter C, Brown A, Slatopolsky E (1994) Retinoic acid suppresses parathyroid hormone (PTH) secretion and PreproPTH mRNA levels in bovine parathyroid cell culture. J Clin Invest 93:725–730
Liu W, Ridefelt P, Akerström G, Hellman P (2001) Differentiation of human parathyroid cells in culture. J Endocrinol 168:417–425
Hsu C, Patel S, Young E, Vanholder R (1991) Effects of purine derivatives on calcitriol metabolism in rats. Am J Physiol 260:F596–F601
Centers for Disease Control and Prevention (CDC). National Center for Health Statistics (NCHS) (2003–2006) National Health and Nutrition Examination Survey Data. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Hyattsville
Centers for Disease Control and Prevention (CDC). National Center for Health Statistics (NCHS). Revised analytical note for NHANES 2000–2006 and NHANES III (1988–1994) 25-hydroxyvitamin D analysis (revised November 2010). http://www.cdc.gov/nchs/data/nhanes/nhanes3/VitaminD_analyticnote.pdf. Accessed 13 May 2011
National Kidney Foundation (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39:S1–S266
Iwaniec U, Haynatzki G, Fung Y, Akhter M, Haven M, Cullen D (2002) Effects of nicotine on bone and calciotropic hormones in aged ovariectomized rats. J Musculoskelet Neuronal Interact 2:469–478
Iwaniec U, Fung Y, Akhter M, Haven M, Nespor S, Haynatzki G, Cullen D (2001) Effects of nicotine on bone mass, turnover, and strength in adult female rats. Calcif Tissue Int 68:358–364
Hoffmann D, Hoffmann I (1997) The changing cigarette, 1950–1995. J Toxicol Environ Health 50:307–364
Feig D, Kang D, Johnson R (2008) Uric acid and cardiovascular risk. N Engl J Med 359:1811–1821
Niskanen L, Laaksonen D, Nyyssönen K, Alfthan G, Lakka H, Lakka T, Salonen J (2004) Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study. Arch Intern Med 164:1546–1551
Sundström J, Sullivan L, D'Agostino R, Levy D, Kannel W, Vasan R (2005) Relations of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension 45:28–33
Mellen P, Bleyer A, Erlinger T, Evans G, Nieto F, Wagenknecht L, Wofford M, Herrington D (2006) Serum uric acid predicts incident hypertension in a biethnic cohort: the atherosclerosis risk in communities study. Hypertension 48:1037–1042
Gloth F, Gundberg C, Hollis B, Haddad JJ, Tobin J (1995) Vitamin D deficiency in homebound elderly persons. JAMA 274:1683–1686
Chapuy M, Chapuy P, Meunier P (1987) Calcium and vitamin D supplements: effects on calcium metabolism in elderly people. Am J Clin Nutr 46:324–328
Alevizaki C, Ikkos D, Singhelakis P (1973) Progressive decrease of true intestinal calcium absorption with age in normal man. J Nucl Med 14:760–762
Gallagher J, Riggs B, Eisman J, Hamstra A, Arnaud S, DeLuca H (1979) Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients: effect of age and dietary calcium. J Clin Invest 64:729–736
Bullamore J, Wilkinson R, Gallagher J, Nordin B, Marshall D (1970) Effect of age on calcium absorption. Lancet 296:535–537
Eastell R, Yergey A, Vieira N, Cedel S, Kumar R, Riggs B (1991) Interrelationship among vitamin D metabolism, true calcium absorption, parathyroid function, and age in women: evidence of an age-related intestinal resistance to 1,25-dihydroxyvitamin D action. J Bone Miner Res 6:125–132
Naveh-Many T, Almogi G, Livni N, Silver J (1992) Estrogen receptors and biologic response in rat parathyroid tissue and C cells. J Clin Invest 90:2434–2438
Cosman F, Shen V, Xie F, Seibel M, Ratcliffe A, Lindsay R (1993) Estrogen protection against bone resorbing effects of parathyroid hormone infusion. Assessment by use of biochemical markers. Ann Intern Med 118:337–343
Kärkkäinen M, Lamberg-Allardt C (1996) An acute intake of phosphate increases parathyroid hormone secretion and inhibits bone formation in young women. J Bone Miner Res 11:1905–1912
Kemi VE, Karkkainen MU, Lamberg-Allardt CJ (2006) High phosphorous intakes acutely and negatively affect Ca and bone metabolism in a dose-dependent manner in healthy young females. Br J Nutr 96:545–552
Denda M, Finch J, Slatopolsky E (1996) Phosphorus accelerates the development of parathyroid hyperplasia and secondary hyperparathyroidism in rats with renal failure. Am J Kidney Dis 28:596–602
Almaden Y, Canalejo A, Hernandez A, Ballesteros E, Garcia-Navarro S, Torres A, Rodriguez M (1996) Direct effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitro. J Bone Miner Res 11:970–976
Bergwitz C, Jüppner H (2010) Regulation of phosphate homeostasis by PTH, vitamin D, and FGF23. Annu Rev Med 61:91–104
Berndt T, Kumar R (2009) Novel mechanisms in the regulation of phosphorus homeostasis. Physiology (Bethesda) 24:17–25
Silver J, Naveh-Many T (2009) Phosphate and the parathyroid. Kidney Int 75:898–905
Gutiérrez O, Isakova T, Smith K, Epstein M, Patel N, Wolf M (2010) Racial differences in postprandial mineral ion handling in health and in chronic kidney disease. Nephrol Dial Transplant 25:3970–3977
Cosman F, Morgan D, Nieves J, Shen V, Luckey M, Dempster D, Lindsay R, Parisien M (1997) Resistance to bone resorbing effects of PTH in black women. J Bone Miner Res 12:958–966
Liu W, Hellman P, Li Q, Yu W, Juhlin C, Nordlinder H, Rollman O, Akerström G, Törmä H, Melhus H (1996) Biosynthesis and function of all-trans- and 9-cis-retinoic acid in parathyroid cells. Biochem Biophys Res Commun 229:922–929
Willett W (1998) Nutritional epidemiology. Oxford University Press, New York
Bolland MJ, Grey AB, Ames RW, Horne AM, Gamble GD, Reid IR (2006) Fat mass is an important predictor of parathyroid hormone levels in postmenopausal women. Bone 38:317–321
Pitroda A, Harris S, Dawson-Hughes B (2009) The association of adiposity with parathyroid hormone in healthy older adults. Endocrine 36:218–223
Bolland M, Grey A, Gamble G, Reid I (2005) Association between primary hyperparathyroidism and increased body weight: a meta-analysis. J Clin Endocrinol Metab 90:1525–1530
Herfarth K, Schmidt-Gayk H, Graf S, Maier A (1992) Circadian rhythm and pulsatility of parathyroid hormone secretion in man. Clinical endocrinology 37:511-519
Acknowledgments
Work on this study was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research Development. Additional research support was obtained from grants DK084707, DK007527, and R01 HL092947 from the National Institutes of Health.
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Paik, J.M., Farwell, W.R. & Taylor, E.N. Demographic, dietary, and serum factors and parathyroid hormone in the National Health and Nutrition Examination Survey. Osteoporos Int 23, 1727–1736 (2012). https://doi.org/10.1007/s00198-011-1776-x
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DOI: https://doi.org/10.1007/s00198-011-1776-x