Skip to main content
Top
Published in: Osteoporosis International 10/2006

01-10-2006 | Original Article

Calcitriol does not prevent bone loss in patients with asthma receiving corticosteroid therapy: a double-blind placebo-controlled trial

Authors: C. F. McDonald, R. M. D. Zebaze, E. Seeman

Published in: Osteoporosis International | Issue 10/2006

Login to get access

Abstract

Introduction

Oral glucocorticoid therapy reduces bone mineral density (BMD) and increases fracture risk. It is uncertain whether inhaled glucocorticoids, the most commonly used long-term therapy for asthma, have a similar effect. If bone loss does occur, it is unclear whether this is preventable by calcitriol. Patients with asthma receiving inhalational plus intermittent oral glucocorticoids lose bone, and treatment with 0.5 μg/day of calcitriol will prevent bone loss.

Methods

A 2-year randomized double-blind placebo-controlled trial. One hundred eight patients with asthma were stratified by gender, age, and inhaled glucocorticoid dose and treated with calcitriol (n=55) or placebo (n=53). There were 41 men (mean age 53.2±1.7 years) and 67 women (mean age 49.1±1 years) with moderate to severe asthma (requiring ≥800 μg/day of beclomethasone dipropionate or equivalent maintenance therapy). BMD values at the lumbar spine (LS) and femoral neck (FN) were measured at baseline and at 6, 12, and 24 months using dual x-ray absorptiometry.

Results

Changes in LS and FN BMD. Bone loss occurred in both groups at the FN (both p<0.03) and at the LS in the calcitriol (p<0.001), but not the control, group. Bone loss was not less in the calcitriol group at either site.

Conclusion

Patients with asthma receiving inhalational plus intermittent short courses of oral glucocorticoids lose bone. Calcitriol is unlikely to be appropriate therapy against this bone loss.
Literature
1.
go back to reference Lukert B (1996) Glucocorticoid-induced osteoporosis. In: Marcus R, Feldman D, Kelsey J (eds). Osteoporosis. Academic Press, San Diego, pp 801–820 Lukert B (1996) Glucocorticoid-induced osteoporosis. In: Marcus R, Feldman D, Kelsey J (eds). Osteoporosis. Academic Press, San Diego, pp 801–820
2.
go back to reference Adinoff AD, Hollister JR (1983) Steroid induced fractures and bone loss in patients with asthma. New Engl J Med 309:265–268PubMedCrossRef Adinoff AD, Hollister JR (1983) Steroid induced fractures and bone loss in patients with asthma. New Engl J Med 309:265–268PubMedCrossRef
3.
go back to reference Israel E, Banerjee TR, Fitzmaurice GM, Kotlov TV, LaHive K, LeBoff MS (2001) Effects of inhaled glucocorticoids on bone density in premenopausal women. N Engl J Med 345:941–947PubMedCrossRef Israel E, Banerjee TR, Fitzmaurice GM, Kotlov TV, LaHive K, LeBoff MS (2001) Effects of inhaled glucocorticoids on bone density in premenopausal women. N Engl J Med 345:941–947PubMedCrossRef
4.
go back to reference Suissa S, Baltzan M, Kremer R and Ernst P (2004) Inhaled and nasal corticosteroid use and the risk of fracture. Am J Respir Crit Care Med 169:83–88PubMedCrossRef Suissa S, Baltzan M, Kremer R and Ernst P (2004) Inhaled and nasal corticosteroid use and the risk of fracture. Am J Respir Crit Care Med 169:83–88PubMedCrossRef
5.
go back to reference Dykman TR, Haralson KM, Gluck OS et al (1984) Effect of oral, 1.25-dihydroxyvitamin D and calcium on glucocorticoid-induced osteopenia in patients with rheumatic diseases. Arthritis Rheum 27:1336–1343PubMedCrossRef Dykman TR, Haralson KM, Gluck OS et al (1984) Effect of oral, 1.25-dihydroxyvitamin D and calcium on glucocorticoid-induced osteopenia in patients with rheumatic diseases. Arthritis Rheum 27:1336–1343PubMedCrossRef
6.
go back to reference Braun JJ, Birkenhager-Frenkel DH, Rietveld AH, Juttman JR et al (1983) Influence of \(1_{\alpha } - {\left( {{\text{OH}}} \right)}\) D3 administration on bone and bone mineral metabolism in patients on chronic glucocorticoid treatment: a double blind controlled study. Clin Endocrinol (Oxf) 19:265–273CrossRef Braun JJ, Birkenhager-Frenkel DH, Rietveld AH, Juttman JR et al (1983) Influence of \(1_{\alpha } - {\left( {{\text{OH}}} \right)}\) D3 administration on bone and bone mineral metabolism in patients on chronic glucocorticoid treatment: a double blind controlled study. Clin Endocrinol (Oxf) 19:265–273CrossRef
7.
go back to reference U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung and Blood Institute (1997) Expert panel report 2: guidelines for the diagnosis and management of asthma. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung and Blood Institute, Bethesda U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung and Blood Institute (1997) Expert panel report 2: guidelines for the diagnosis and management of asthma. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung and Blood Institute, Bethesda
8.
go back to reference Barnes NC, Marone G, Di Maria U, Visser S, Utama I, Payne SL (1993) A comparison of fluticasone propionate 1 mg daily with beclomethasone dipropionate 2 mg daily in the treatment of severe asthma. Eur Respir J 6:877–885PubMed Barnes NC, Marone G, Di Maria U, Visser S, Utama I, Payne SL (1993) A comparison of fluticasone propionate 1 mg daily with beclomethasone dipropionate 2 mg daily in the treatment of severe asthma. Eur Respir J 6:877–885PubMed
9.
go back to reference Ayres JG, Bateman ED, Lundback B, Harris TA (1995) High dose fluticasone propionate, 1 mg daily, versus fluticasone propionate 2 mg daily, or budesonide, 1.6 mg daily, in patients with chronic severe asthma. Eur Respir J 8:579–586PubMed Ayres JG, Bateman ED, Lundback B, Harris TA (1995) High dose fluticasone propionate, 1 mg daily, versus fluticasone propionate 2 mg daily, or budesonide, 1.6 mg daily, in patients with chronic severe asthma. Eur Respir J 8:579–586PubMed
10.
go back to reference Andrew JV (2001) The use of percentage change from baseline as an outcome in controlled trial is statistically inefficient: a simulation study. BMC Med Res Methodol 1:6CrossRef Andrew JV (2001) The use of percentage change from baseline as an outcome in controlled trial is statistically inefficient: a simulation study. BMC Med Res Methodol 1:6CrossRef
11.
go back to reference Van Staa TP, Leufkens HG, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13:777–787PubMedCrossRef Van Staa TP, Leufkens HG, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13:777–787PubMedCrossRef
12.
go back to reference Hanania NA, Chapman KR, Sturtridge WC, Szalai JP, Kesten S (1995) Dose-related decreases in bone density among asthmatic patients treated with inhaled corticosteroid. J Allergy Clin Immunol 96:571–579PubMedCrossRef Hanania NA, Chapman KR, Sturtridge WC, Szalai JP, Kesten S (1995) Dose-related decreases in bone density among asthmatic patients treated with inhaled corticosteroid. J Allergy Clin Immunol 96:571–579PubMedCrossRef
13.
go back to reference Ip M, Lam K, Yam L, Kung A, Ng M (1994) Decreased bone mineral density in premenopausal asthma patients receiving long-term inhaled steroids. Chest 105:1722–1727PubMedCrossRef Ip M, Lam K, Yam L, Kung A, Ng M (1994) Decreased bone mineral density in premenopausal asthma patients receiving long-term inhaled steroids. Chest 105:1722–1727PubMedCrossRef
14.
go back to reference Packe GE, Douglas JG, McDonald AF, Robins SP, Reid DM (1992) Bone density in asthmatic patients taking high dose inhaled beclomethasone dipropionate and intermittent systemic corticosteroids. Thorax 47:414–417PubMedCrossRef Packe GE, Douglas JG, McDonald AF, Robins SP, Reid DM (1992) Bone density in asthmatic patients taking high dose inhaled beclomethasone dipropionate and intermittent systemic corticosteroids. Thorax 47:414–417PubMedCrossRef
15.
go back to reference Laatikainen AK, Kroger HPJ, Tukinainen HO, Honkanen RJ, Saarikoski SV (1999) Bone mineral density in perimenopausal women with asthma: a population-based cross-sectional study. Am J Respir Crit Care Med 159:1179–1185PubMed Laatikainen AK, Kroger HPJ, Tukinainen HO, Honkanen RJ, Saarikoski SV (1999) Bone mineral density in perimenopausal women with asthma: a population-based cross-sectional study. Am J Respir Crit Care Med 159:1179–1185PubMed
16.
go back to reference Ebeling PR, Erbas B, Hopper JL, Wark JD, Rubinfeld AR (1998) Bone mineral density and bone turnover in asthmatics treated with long-term inhaled or oral glucocorticoids. J Bone Min Res 13:1283–1289CrossRef Ebeling PR, Erbas B, Hopper JL, Wark JD, Rubinfeld AR (1998) Bone mineral density and bone turnover in asthmatics treated with long-term inhaled or oral glucocorticoids. J Bone Min Res 13:1283–1289CrossRef
17.
go back to reference Iqbal F, Michaelson J, Thaler L, Rubin J, Roman J, Nanes MS (1999) Declining bone mass in men with chronic obstructive pulmonary disease: contribution of glucocorticosteroid treatment, body mass index, and gonadal function. Chest 116:1616–1624PubMedCrossRef Iqbal F, Michaelson J, Thaler L, Rubin J, Roman J, Nanes MS (1999) Declining bone mass in men with chronic obstructive pulmonary disease: contribution of glucocorticosteroid treatment, body mass index, and gonadal function. Chest 116:1616–1624PubMedCrossRef
18.
go back to reference Hughes JA, Conry BG, Male SM, Eastell R (1999) One year prospective open study of the effect of high dose inhaled steroids, fluticasone propionate, and budesonide on bone markers and bone mineral density. Thorax 54:223–229PubMedCrossRef Hughes JA, Conry BG, Male SM, Eastell R (1999) One year prospective open study of the effect of high dose inhaled steroids, fluticasone propionate, and budesonide on bone markers and bone mineral density. Thorax 54:223–229PubMedCrossRef
19.
go back to reference Boulet LP, Giguère MC, Milot J, Brown J (1994) Effects of long-term use of high dose inhaled steroid on bone density and calcium metabolism. J Allergy Clin Immunol 94:796–803PubMedCrossRef Boulet LP, Giguère MC, Milot J, Brown J (1994) Effects of long-term use of high dose inhaled steroid on bone density and calcium metabolism. J Allergy Clin Immunol 94:796–803PubMedCrossRef
20.
go back to reference Boulet LP, Milot J, Gagnon L, Puobelle PE, Brown J (1999) Long-term influence of inhaled corticosteroids on bone metabolism and density: are biological markers predictors of bone loss? Am J Respir Crit Care Med 159:838–844PubMed Boulet LP, Milot J, Gagnon L, Puobelle PE, Brown J (1999) Long-term influence of inhaled corticosteroids on bone metabolism and density: are biological markers predictors of bone loss? Am J Respir Crit Care Med 159:838–844PubMed
21.
go back to reference Luengo M, Del Rio L, Pons F, Picado C (1997) Bone mineral density in asthmatic patients treated with inhaled corticosteroids: a case-control study. Eur Respir J 10:2110–2113PubMedCrossRef Luengo M, Del Rio L, Pons F, Picado C (1997) Bone mineral density in asthmatic patients treated with inhaled corticosteroids: a case-control study. Eur Respir J 10:2110–2113PubMedCrossRef
22.
go back to reference Jones A, Fay JK, Burr M, Stone M, Hood K, Roberts G (2002) Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease. Cochrane Database Syst Rev (1):CD003537 Jones A, Fay JK, Burr M, Stone M, Hood K, Roberts G (2002) Inhaled corticosteroid effects on bone metabolism in asthma and mild chronic obstructive pulmonary disease. Cochrane Database Syst Rev (1):CD003537
23.
go back to reference The Lung Health Study Research Group (2000) Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med 343:1902–1090CrossRef The Lung Health Study Research Group (2000) Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med 343:1902–1090CrossRef
24.
go back to reference Richy F, Bousquet J, Ehrlich GE, Meunier PJ, Israel E, Morii H, Devogelaer J-P, Peel N, Haim M et al (2003) Inhaled corticosteroid effects on bone in asthmatic and COPD patients: a quantitative systematic review. Osteoporos Int 14:179–190PubMed Richy F, Bousquet J, Ehrlich GE, Meunier PJ, Israel E, Morii H, Devogelaer J-P, Peel N, Haim M et al (2003) Inhaled corticosteroid effects on bone in asthmatic and COPD patients: a quantitative systematic review. Osteoporos Int 14:179–190PubMed
25.
go back to reference Hubbard RB, Smith CJP, Smeeth L, Harrison TW, Tattersfield AE et al (2002) Inhaled corticosteroids and hip fracture. A population-based case-control study. Am J Respir Crit Care Med 166:1563–1566PubMedCrossRef Hubbard RB, Smith CJP, Smeeth L, Harrison TW, Tattersfield AE et al (2002) Inhaled corticosteroids and hip fracture. A population-based case-control study. Am J Respir Crit Care Med 166:1563–1566PubMedCrossRef
26.
go back to reference Matsumoto H, Ishihara K, Hasegawa T, Umeda B, Niimi A, Hino M (2001) Effects of inhaled corticosteroid and short courses of oral corticosteroids on bone mineral density in asthmatic patients. Chest 120:1468–1473PubMedCrossRef Matsumoto H, Ishihara K, Hasegawa T, Umeda B, Niimi A, Hino M (2001) Effects of inhaled corticosteroid and short courses of oral corticosteroids on bone mineral density in asthmatic patients. Chest 120:1468–1473PubMedCrossRef
27.
go back to reference Sambrook P, Birmingham J, Kelly P, Kempler S, Nguyen T, Pocock N, Eisman J (1993) Prevention of corticosteroid osteoporosis-a comparison of calcium, calcitriol and calcitonin. New Engl J Med 328:1747–1752PubMedCrossRef Sambrook P, Birmingham J, Kelly P, Kempler S, Nguyen T, Pocock N, Eisman J (1993) Prevention of corticosteroid osteoporosis-a comparison of calcium, calcitriol and calcitonin. New Engl J Med 328:1747–1752PubMedCrossRef
28.
go back to reference Shane E, Addesso V, Namerow PB, McMahon DJ, Shaw-Hwa L, Staron RB, Zucker M, Pardi S, Maybaum S, Mancini D (2004) Alendronate versus calcitriol for the prevention of bone loss after cardiac transplantation. New Engl J Med 350:767–776PubMedCrossRef Shane E, Addesso V, Namerow PB, McMahon DJ, Shaw-Hwa L, Staron RB, Zucker M, Pardi S, Maybaum S, Mancini D (2004) Alendronate versus calcitriol for the prevention of bone loss after cardiac transplantation. New Engl J Med 350:767–776PubMedCrossRef
29.
go back to reference Tilyard MW, Spears GFS, Thomson J, Dovey S (1992) Treatment of postmenopausal osteoporosis with calcitriol or calcium. New Engl J Med 326:357–362PubMedCrossRef Tilyard MW, Spears GFS, Thomson J, Dovey S (1992) Treatment of postmenopausal osteoporosis with calcitriol or calcium. New Engl J Med 326:357–362PubMedCrossRef
30.
go back to reference Falch JA, Odegaard OR, Finnanger M, Matheson I (1987) Postmenopausal osteoporosis: no effect of three years treatment with 1,25-dihydroxycholecalciferol. Proc Soc Exp Biol Med 191:199–204 Falch JA, Odegaard OR, Finnanger M, Matheson I (1987) Postmenopausal osteoporosis: no effect of three years treatment with 1,25-dihydroxycholecalciferol. Proc Soc Exp Biol Med 191:199–204
31.
go back to reference Ott SM, Chestnut CH III (1989) Calcitriol treatment is not effective in postmenopausal osteoporosis. Ann Intern Med 110:267–274PubMed Ott SM, Chestnut CH III (1989) Calcitriol treatment is not effective in postmenopausal osteoporosis. Ann Intern Med 110:267–274PubMed
32.
go back to reference Christiansen C, Christensen MS, Rodbro P, Hagen C, Transbol I (1981) Effect of 1,25-dihydroxy-vitamin D3 in itself or combined with hormone treatment in preventing postmenopausal osteoporosis. Eur J Clin Invest 11:305–309PubMedCrossRef Christiansen C, Christensen MS, Rodbro P, Hagen C, Transbol I (1981) Effect of 1,25-dihydroxy-vitamin D3 in itself or combined with hormone treatment in preventing postmenopausal osteoporosis. Eur J Clin Invest 11:305–309PubMedCrossRef
33.
go back to reference Jensen GF, Christiansen C, Transbol I (1982) Treatment of postmenopausal osteoporosis. A controlled therapeutic trial comparing oestrogen/gestagen, 1,25-dihydroxy-vitaminD3 and calcium. Clin Endocrinol 16:515–524CrossRef Jensen GF, Christiansen C, Transbol I (1982) Treatment of postmenopausal osteoporosis. A controlled therapeutic trial comparing oestrogen/gestagen, 1,25-dihydroxy-vitaminD3 and calcium. Clin Endocrinol 16:515–524CrossRef
34.
go back to reference Gallagher JC, Goldgar D (1989) Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol. A randomized controlled study. Ann Intern Med 113:649–655 Gallagher JC, Goldgar D (1989) Treatment of postmenopausal osteoporosis with high doses of synthetic calcitriol. A randomized controlled study. Ann Intern Med 113:649–655
35.
go back to reference Aloia JF, Vaswani A, Yeh JK, Yasumura S, Cohn SH (1988) Calcitriol in the treatment of postmenopausal osteoporosis. Am J Med 84:401–408PubMedCrossRef Aloia JF, Vaswani A, Yeh JK, Yasumura S, Cohn SH (1988) Calcitriol in the treatment of postmenopausal osteoporosis. Am J Med 84:401–408PubMedCrossRef
36.
go back to reference Jensen GF, Meinecke B, Boesen J, Transbol I, Gallagher JC, Riggs BL, Recker RR, Goldgar D (1985) Does 1,25-(OH)2D3 accelerate spinal bone loss? Clin Orthop 192:215–221PubMed Jensen GF, Meinecke B, Boesen J, Transbol I, Gallagher JC, Riggs BL, Recker RR, Goldgar D (1985) Does 1,25-(OH)2D3 accelerate spinal bone loss? Clin Orthop 192:215–221PubMed
37.
go back to reference Ebeling PR, Wark JD, Yeung S, Poon C, Salehi N, Nicholson GC, Kotowicz MA (2001) 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 86:4098–4103PubMedCrossRef Ebeling PR, Wark JD, Yeung S, Poon C, Salehi N, Nicholson GC, Kotowicz MA (2001) 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 86:4098–4103PubMedCrossRef
38.
go back to reference Gallagher JC, Riggs BL, Recker RR, Goldgar D (1989) The effect of calcitriol on patients with postmenopausal osteoporosis with special refence to fracture frequency. Proc Soc Exp Biol Med 191:287–291PubMed Gallagher JC, Riggs BL, Recker RR, Goldgar D (1989) The effect of calcitriol on patients with postmenopausal osteoporosis with special refence to fracture frequency. Proc Soc Exp Biol Med 191:287–291PubMed
39.
go back to reference Mirzaei S, Zajicek HK, Knoll P, Hahn M, Levi M, Kohn H, Pohl W (2003) Effect of rocaltrol on bone mass in patients with pulmonary disease treated with corticosteroids. J Asthma 40:251–255PubMedCrossRef Mirzaei S, Zajicek HK, Knoll P, Hahn M, Levi M, Kohn H, Pohl W (2003) Effect of rocaltrol on bone mass in patients with pulmonary disease treated with corticosteroids. J Asthma 40:251–255PubMedCrossRef
40.
go back to reference Smith MD, Cheah SP, Taylor K, Ahern M (2001) Prevention of corticosteroid induced osteoporosis in inpatients recently discharged from a tertiary teaching hospital. J Rheumatol 28:566–570PubMed Smith MD, Cheah SP, Taylor K, Ahern M (2001) Prevention of corticosteroid induced osteoporosis in inpatients recently discharged from a tertiary teaching hospital. J Rheumatol 28:566–570PubMed
41.
go back to reference American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis (2001) Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. Arthritis Rheum 44(7):1496-1503CrossRef American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis (2001) Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis: 2001 update. Arthritis Rheum 44(7):1496-1503CrossRef
Metadata
Title
Calcitriol does not prevent bone loss in patients with asthma receiving corticosteroid therapy: a double-blind placebo-controlled trial
Authors
C. F. McDonald
R. M. D. Zebaze
E. Seeman
Publication date
01-10-2006
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 10/2006
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-006-0158-2

Other articles of this Issue 10/2006

Osteoporosis International 10/2006 Go to the issue