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Published in: Osteoporosis International 5/2003

01-06-2003 | Original Article

Short-term calcitriol administration improves calcium homeostasis in adults with cystic fibrosis

Authors: S. A. Brown, D. A. Ontjes, G. E. Lester, R. K. Lark, M. B. Hensler, A. D. Blackwood, M. J. Caminiti, D. C. Backlund, R. M. Aris

Published in: Osteoporosis International | Issue 5/2003

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Abstract

Osteoporosis is a well-defined health risk in cystic fibrosis (CF) patients due to many factors. Vitamin D insufficiency, despite routine cholecalciferol supplementation in CF patients, may contribute to a relative secondary hyperparathyroidism and possibly deficient bone mineralization. An alternate form of vitamin D, calcitriol, was studied to determine short-term effects on fractional calcium absorption and other calciotropic markers in 10 adult CF subjects and in 10 age-, sex- and body mass index (BMI)-matched controls. Serum fractional absorption of 45Ca was determined after a calcium-containing meal prior to calcitriol intervention. Other measurements included serum parathyroid hormone (PTH), ionized calcium, 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D (1,25(OH)2D) and urinary calcium:creatinine and N-telopeptide (NTx) concentrations. Both groups were then given calcitriol (0.5 µg p.o. b.i.d. for 14 days) and restudied following the same protocol. Both groups increased their fractional absorption of 45Ca after calcitriol (p=0.015 CF subjects, p=0.001 controls), although calcitriol tended to be less effective in the CF group compared with the controls (p=0.055). Post-prandial serum PTH concentrations were suppressed compared with baseline in both groups (p=0.03 CF subjects, p=0.006 controls). Urinary NTx concentrations, a marker for bone resorption, decreased significantly in CF subjects after calcitriol (96.0±16.0 vs 63.9±12.7 nmol BCE/mmol Cr, p=0.01) and remained unchanged in the control group. The controls had an increase in serum 1,25(OH)2D concentrations (69.9±4.2 vs 90.7±9.6 pmol/l, p=0.02) while there was no significant change in the CF group. Oral calcitriol administration appears to improve markers of calcium balance in adults with CF by increasing fractional absorption of 45Ca and lowering PTH concentrations, similar to its known effects in healthy subjects, while also suppressing urinary NTx, a marker of bone turnover.
Literature
1.
go back to reference Aris RM, Renner JB, Winders AD, et al. Increased rate of fractures and severe kyphosis: sequelae of living into adulthood with cystic fibrosis. Ann Intern Med 1998;128:186–93.PubMed Aris RM, Renner JB, Winders AD, et al. Increased rate of fractures and severe kyphosis: sequelae of living into adulthood with cystic fibrosis. Ann Intern Med 1998;128:186–93.PubMed
2.
go back to reference Ott SM, Aitken ML. Osteoporosis in patients with cystic fibrosis. Clin Chest Med 1998;19:555–67.PubMed Ott SM, Aitken ML. Osteoporosis in patients with cystic fibrosis. Clin Chest Med 1998;19:555–67.PubMed
3.
go back to reference Haworth CS, Selby PL, Webb AK, et al. Low bone mineral density in adults with cystic fibrosis. Thorax 1999;54:961–7.PubMed Haworth CS, Selby PL, Webb AK, et al. Low bone mineral density in adults with cystic fibrosis. Thorax 1999;54:961–7.PubMed
4.
go back to reference Henderson RC, Madsen CD. Bone density in children and adolescents with cystic fibrosis. J Pediatr 1996;128:28–34.PubMed Henderson RC, Madsen CD. Bone density in children and adolescents with cystic fibrosis. J Pediatr 1996;128:28–34.PubMed
5.
go back to reference Bhudhikanok GS, Wang MC, Marcus R, Harkins A, Moss RB, Bachrach LK. Bone acquisition and loss in children and adults with cystic fibrosis: a longitudinal study. J Pediatr 1998;133:18–27.PubMed Bhudhikanok GS, Wang MC, Marcus R, Harkins A, Moss RB, Bachrach LK. Bone acquisition and loss in children and adults with cystic fibrosis: a longitudinal study. J Pediatr 1998;133:18–27.PubMed
6.
go back to reference Aris RM, Lester GE, Dingman S, Ontjes DA. Altered calcium homeostasis in adults with cystic fibrosis. Osteoporos Int 1999;10:102–8.CrossRefPubMed Aris RM, Lester GE, Dingman S, Ontjes DA. Altered calcium homeostasis in adults with cystic fibrosis. Osteoporos Int 1999;10:102–8.CrossRefPubMed
7.
go back to reference Aris RM, Ontjes DA, Buell HE, Blackwood AD, Lark RK, Caminiti M, et al. Abnormal bone turnover in cystic fibrosis adults. Osteoporos Int 2002; 13:151–7.CrossRef Aris RM, Ontjes DA, Buell HE, Blackwood AD, Lark RK, Caminiti M, et al. Abnormal bone turnover in cystic fibrosis adults. Osteoporos Int 2002; 13:151–7.CrossRef
8.
go back to reference Lark RK, Lester GE, Ontjes DA, et al. Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis patients. Am J Clin Nutr 2001;73:602–6. Lark RK, Lester GE, Ontjes DA, et al. Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis patients. Am J Clin Nutr 2001;73:602–6.
9.
go back to reference Compston JE, Merrett AL, Hammett FG, Magill P. Comparison of the appearance of radiolabelled vitamin D3 and 25-hydroxyvitamin D3 in the chylomicron fraction of plasma after oral administration in man. Clin Sci 1981; 60:241–3.PubMed Compston JE, Merrett AL, Hammett FG, Magill P. Comparison of the appearance of radiolabelled vitamin D3 and 25-hydroxyvitamin D3 in the chylomicron fraction of plasma after oral administration in man. Clin Sci 1981; 60:241–3.PubMed
10.
go back to reference Sitrin MD, Bengoa JM. Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in chronic cholestatic liver disease. Am J Clin Nutr 1987;46:1011–5.PubMed Sitrin MD, Bengoa JM. Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in chronic cholestatic liver disease. Am J Clin Nutr 1987;46:1011–5.PubMed
11.
go back to reference Maislos M, Silver J, Fainaru M. Intestinal absorption of vitamin D sterols: differential absorption into lymph and portal blood in the rat. Gastroenterology 1981;80:1528–34.PubMed Maislos M, Silver J, Fainaru M. Intestinal absorption of vitamin D sterols: differential absorption into lymph and portal blood in the rat. Gastroenterology 1981;80:1528–34.PubMed
12.
go back to reference Davies M, Mawer EB, Klass JH, Lumb GA, Berry JL, Warnes TW. Vitamin D deficiency, osteomalacia and primary biliary cirrhosis. Dig Dis Sci 1983;28:145–52.PubMed Davies M, Mawer EB, Klass JH, Lumb GA, Berry JL, Warnes TW. Vitamin D deficiency, osteomalacia and primary biliary cirrhosis. Dig Dis Sci 1983;28:145–52.PubMed
13.
go back to reference van den Berg H. Bioavailability of vitamin D. Eur J Clin Nutr 1997;51(Suppl1):S76–9. van den Berg H. Bioavailability of vitamin D. Eur J Clin Nutr 1997;51(Suppl1):S76–9.
14.
go back to reference Marshall DH, Nordin BEC. A comparison of radioactive absorption tests with net calcium absorption. Clin Sci 1981;61:477–81.PubMed Marshall DH, Nordin BEC. A comparison of radioactive absorption tests with net calcium absorption. Clin Sci 1981;61:477–81.PubMed
15.
go back to reference Dawson-Hughes B, Harris SS, Finneran S. Calcium absorption on high and low calcium intakes in relation to vitamin D receptor genotype. J Clin Endocrinol Metab 1995;80:3657–61.PubMed Dawson-Hughes B, Harris SS, Finneran S. Calcium absorption on high and low calcium intakes in relation to vitamin D receptor genotype. J Clin Endocrinol Metab 1995;80:3657–61.PubMed
16.
go back to reference Francis RM, Peacock M. Local action of oral 1,25-dihydroxycholecalciferol on calcium absorption in osteoporosis. Am J Clin Nutr 1987;46:315–8.PubMed Francis RM, Peacock M. Local action of oral 1,25-dihydroxycholecalciferol on calcium absorption in osteoporosis. Am J Clin Nutr 1987;46:315–8.PubMed
17.
go back to reference Favus M. Intestinal calcium absorption: have we absorbed enough from research to have a test for the patient? J Bone Miner Res 1989:4;461–2. Favus M. Intestinal calcium absorption: have we absorbed enough from research to have a test for the patient? J Bone Miner Res 1989:4;461–2.
18.
go back to reference Kinyamu HK, Gallagher JC, Prahl JM, Deluca HF, Petranick KM, Lanspa SJ. Association between intestinal vitamin D receptor, calcium absorption and serum 1,25-vitamin D in normal young and elderly women. J Bone Miner Res 1997;12:922–8.PubMed Kinyamu HK, Gallagher JC, Prahl JM, Deluca HF, Petranick KM, Lanspa SJ. Association between intestinal vitamin D receptor, calcium absorption and serum 1,25-vitamin D in normal young and elderly women. J Bone Miner Res 1997;12:922–8.PubMed
19.
go back to reference Heaney RP, Barger-Lux MJ, Dowell MS, Chen TC, Hollick MF. Calcium absorptive effects of vitamin D and its major metabolites. J Clin Endocrinol Metab 1997;82:4111–6. Heaney RP, Barger-Lux MJ, Dowell MS, Chen TC, Hollick MF. Calcium absorptive effects of vitamin D and its major metabolites. J Clin Endocrinol Metab 1997;82:4111–6.
20.
go back to reference Dijkgraaf-Ten Bolscher M, Netelenbos JC, Barto R, van Der Vijgh WJ. Strontium as a marker for intestinal calcium absorption: the stimulatory effect of calcitriol. Clin Chem 2000;46:248–51.PubMed Dijkgraaf-Ten Bolscher M, Netelenbos JC, Barto R, van Der Vijgh WJ. Strontium as a marker for intestinal calcium absorption: the stimulatory effect of calcitriol. Clin Chem 2000;46:248–51.PubMed
21.
go back to reference Bianchi ML. Ardissino GL, Schmitt CP, Dacco V, Barletta L, Claris-Appiani A, Mehls O. No difference in intestinal strontium absorption after an oral or an intravenous 1,25(OH)2D3 bolus in normal subjects. J Bone Miner Res 1999;14:1789–95.PubMed Bianchi ML. Ardissino GL, Schmitt CP, Dacco V, Barletta L, Claris-Appiani A, Mehls O. No difference in intestinal strontium absorption after an oral or an intravenous 1,25(OH)2D3 bolus in normal subjects. J Bone Miner Res 1999;14:1789–95.PubMed
22.
go back to reference Dawson-Hughes B, Harris SS, Finneran S, Rasmussen HM. Calcium absorption responses to calcitriol in black and white premenopausal women. J Clin Endocrinol Metab 1995;80:3068–72.PubMed Dawson-Hughes B, Harris SS, Finneran S, Rasmussen HM. Calcium absorption responses to calcitriol in black and white premenopausal women. J Clin Endocrinol Metab 1995;80:3068–72.PubMed
23.
go back to reference Colodro IH, Brickman AS, Coburn JW, Osborn TW, Norman AW. Effect of 25-hydroxy-vitamin D3 on intestinal absorption of calcium in normal man and patients with renal failure. Metabolism 1978;27:745–53. Colodro IH, Brickman AS, Coburn JW, Osborn TW, Norman AW. Effect of 25-hydroxy-vitamin D3 on intestinal absorption of calcium in normal man and patients with renal failure. Metabolism 1978;27:745–53.
24.
go back to reference Brickman AS, Coburn JW, Friedman GR, Okamura WH, Massry SG, Norman AW. Comparison of effects of 1α-hydroxy-vitamin D3 and 1,25-dihydroxy-vitamin D3 in man. J Clin Invest 1976;57:1540–7.PubMed Brickman AS, Coburn JW, Friedman GR, Okamura WH, Massry SG, Norman AW. Comparison of effects of 1α-hydroxy-vitamin D3 and 1,25-dihydroxy-vitamin D3 in man. J Clin Invest 1976;57:1540–7.PubMed
25.
go back to reference Heaney RP, Recker RR. Estimation of true calcium absorption. Ann Intern Med 1985;103:516–21.PubMed Heaney RP, Recker RR. Estimation of true calcium absorption. Ann Intern Med 1985;103:516–21.PubMed
26.
go back to reference Hanly JG, McKenna MJ, Quigley C, Freaney R, Muldowney FP, Fitzgerald MX. Hypovitaminosis D and response to supplementation in older patients with cystic fibrosis. Q J Med 1985;56:377–85.PubMed Hanly JG, McKenna MJ, Quigley C, Freaney R, Muldowney FP, Fitzgerald MX. Hypovitaminosis D and response to supplementation in older patients with cystic fibrosis. Q J Med 1985;56:377–85.PubMed
27.
go back to reference Ontjes DA, Lark RK, Lester GE, Hollis BW, Hensler MM, Aris RM. Vitamin D depletion and replacement in patients with cystic fibrosis. In: Norman AW, Bouillon R, Thomasset M, editors. Vitamin D endocrine system: structural, biological, genetic and clinical aspects. Riverside, CA: University of California, Printing and Reprographics, 2000:893–6. Ontjes DA, Lark RK, Lester GE, Hollis BW, Hensler MM, Aris RM. Vitamin D depletion and replacement in patients with cystic fibrosis. In: Norman AW, Bouillon R, Thomasset M, editors. Vitamin D endocrine system: structural, biological, genetic and clinical aspects. Riverside, CA: University of California, Printing and Reprographics, 2000:893–6.
28.
go back to reference Tilyard MW, Spears GF, Thomson J, Dovey S. Treatment of postmenopausal osteoporosis with calcitriol or calcium. N Engl J Med 1992;326:357–62. Tilyard MW, Spears GF, Thomson J, Dovey S. Treatment of postmenopausal osteoporosis with calcitriol or calcium. N Engl J Med 1992;326:357–62.
29.
go back to reference Christiansen C, Christensen MS, Rodbro P, Hagen C, Transbol I. Effect of 1,25-dihydroxy-vitamin D3, in itself or combined with hormone treatment in preventing postmenopausal osteoporosis. Eur J Clin Invest 1981;11:305–9.PubMed Christiansen C, Christensen MS, Rodbro P, Hagen C, Transbol I. Effect of 1,25-dihydroxy-vitamin D3, in itself or combined with hormone treatment in preventing postmenopausal osteoporosis. Eur J Clin Invest 1981;11:305–9.PubMed
30.
go back to reference Aloia JF, Vaswani A, Yeh JK, Ellis K, Yasumura S, Cohn SH. Calcitriol in the treatment of postmenopausal osteoporosis. Am J Med 1988; 84:401–8.PubMed Aloia JF, Vaswani A, Yeh JK, Ellis K, Yasumura S, Cohn SH. Calcitriol in the treatment of postmenopausal osteoporosis. Am J Med 1988; 84:401–8.PubMed
31.
go back to reference Ott SM, Chestnut CH. Calcitriol treatment is not effective in postmenopausal osteoporosis. Ann Intern Med 1989;110:267–74.PubMed Ott SM, Chestnut CH. Calcitriol treatment is not effective in postmenopausal osteoporosis. Ann Intern Med 1989;110:267–74.PubMed
32.
go back to reference Gallagher JC, Goldgar D. Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol: a randomized controlled study. Ann Intern Med 113:649–655. Gallagher JC, Goldgar D. Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol: a randomized controlled study. Ann Intern Med 113:649–655.
33.
go back to reference Falch JA, Ogdegaard OR, Finnanager AM, et al. Postmenopausal osteoporosis: no effect of three years treatment with 1,25-dihydroxycholecaciferol. Acta Med Scand 1987;221:199–204.PubMed Falch JA, Ogdegaard OR, Finnanager AM, et al. Postmenopausal osteoporosis: no effect of three years treatment with 1,25-dihydroxycholecaciferol. Acta Med Scand 1987;221:199–204.PubMed
34.
go back to reference Gallagher JC, Riggs BL. Action of 1,25-dihydroxyvitamin D3 on calcium balance and bone turnover and its effect on vertebral fracture rate. Metabolism 1990;39(Suppl1):30–4. Gallagher JC, Riggs BL. Action of 1,25-dihydroxyvitamin D3 on calcium balance and bone turnover and its effect on vertebral fracture rate. Metabolism 1990;39(Suppl1):30–4.
35.
go back to reference Sairanen S, Karkkainen M, Tahtela, R, Laitinen K, Makela P, Lamberg-Allardt C, Valimaki MJ. Bone mass and markers of bone and calcium metabolism in postmenopausal women treated with 1,25-dihydroxyvitamin D (calcitriol) for four years. Calcif Tissue Int 2000;67:122–7.CrossRefPubMed Sairanen S, Karkkainen M, Tahtela, R, Laitinen K, Makela P, Lamberg-Allardt C, Valimaki MJ. Bone mass and markers of bone and calcium metabolism in postmenopausal women treated with 1,25-dihydroxyvitamin D (calcitriol) for four years. Calcif Tissue Int 2000;67:122–7.CrossRefPubMed
36.
go back to reference Kanis JA, McCloskey V, de Takats D, Bernard J, Zhang ZM. Treatment of osteoporosis with vitamin D. Osteoporos Int 1997;7(Suppl 3):S140-6. Kanis JA, McCloskey V, de Takats D, Bernard J, Zhang ZM. Treatment of osteoporosis with vitamin D. Osteoporos Int 1997;7(Suppl 3):S140-6.
37.
go back to reference Gallagher JC. Metabolic effects of synthetic calcitriol (Rocaltrol) in the treatment of postmenopausal osteoporosis. Metabolism 1990;39:27–9.PubMed Gallagher JC. Metabolic effects of synthetic calcitriol (Rocaltrol) in the treatment of postmenopausal osteoporosis. Metabolism 1990;39:27–9.PubMed
38.
go back to reference Gallagher JC, Fowler SE, Detter JR, Sherman SS. Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. J Clin Endocrinol Metab 2001;86:3618–28.PubMed Gallagher JC, Fowler SE, Detter JR, Sherman SS. Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. J Clin Endocrinol Metab 2001;86:3618–28.PubMed
39.
go back to reference Ebeling PE, Wark JD, Yeung S, Poon C, Salehi N, Nicholson GC, Kotowicz MA. Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double blind, double placebo study. J Clin Endocrinol Metab 2001;86:4098–103.PubMed Ebeling PE, Wark JD, Yeung S, Poon C, Salehi N, Nicholson GC, Kotowicz MA. Effects of calcitriol or calcium on bone mineral density, bone turnover, and fractures in men with primary osteoporosis: a two-year randomized, double blind, double placebo study. J Clin Endocrinol Metab 2001;86:4098–103.PubMed
40.
go back to reference Aris RM, Lester GE, Renner JB, et al. Efficacy of pamidronate for osteoporosis in patients with cystic fibrosis following lung transplantation. Am J Resp Care 2000;162:941–6. Aris RM, Lester GE, Renner JB, et al. Efficacy of pamidronate for osteoporosis in patients with cystic fibrosis following lung transplantation. Am J Resp Care 2000;162:941–6.
41.
go back to reference Haworth CS, Selby PL, Adams JE, Mawer EB, Horrocks AW, Webb AK. Effect of intravenous pamidronate on bone mineral density in adults with cystic fibrosis. Thorax 2001; 56:314–6.CrossRefPubMed Haworth CS, Selby PL, Adams JE, Mawer EB, Horrocks AW, Webb AK. Effect of intravenous pamidronate on bone mineral density in adults with cystic fibrosis. Thorax 2001; 56:314–6.CrossRefPubMed
42.
go back to reference Haworth CS, Selby PL, Webb AK, Mawer EB, Adams JE, Fremont TJ. Severe bone pain after intravenous pamidronate in adult patients with cystic fibrosis. Lancet 1998;352:1753–4.PubMed Haworth CS, Selby PL, Webb AK, Mawer EB, Adams JE, Fremont TJ. Severe bone pain after intravenous pamidronate in adult patients with cystic fibrosis. Lancet 1998;352:1753–4.PubMed
Metadata
Title
Short-term calcitriol administration improves calcium homeostasis in adults with cystic fibrosis
Authors
S. A. Brown
D. A. Ontjes
G. E. Lester
R. K. Lark
M. B. Hensler
A. D. Blackwood
M. J. Caminiti
D. C. Backlund
R. M. Aris
Publication date
01-06-2003
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 5/2003
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-002-1331-x

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