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Published in: Arthritis Research & Therapy 2/2014

Open Access 01-04-2014 | Research article

Bone fragility in sarcoidosis and relationships with calcium metabolism disorders: a cross sectional study on 142 patients

Authors: Nathalie Saidenberg-Kermanac’h, Luca Semerano, Hilario Nunes, Danielle Sadoun, Xavier Guillot, Marouane Boubaya, Nicolas Naggara, Dominique Valeyre, Marie-Christophe Boissier

Published in: Arthritis Research & Therapy | Issue 2/2014

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Abstract

Introduction

The prevention of fragility fractures in patients with sarcoidosis is a serious concern and the potential risk of hypercalcemia limits vitamin D and calcium supplementation. The objective of this study was to evaluate the risk factors for low bone mineral density (BMD) and fractures in sarcoidosis. In particular, we aimed to determine the link among bone fragility and calcium and vitamin D metabolism in this population.

Methods

We performed a cross-sectional analysis on 142 consecutive patients with histologically proven sarcoidosis. BMD and prevalence of vertebral fractures on X-rays were assessed and the association with potential risk factors was studied by regression analysis.

Results

Fragility fractures occurred in 23.5% of patients, despite a normal mean BMD in the study population. In a multivariate analysis, low dietary calcium, fracture, age, gender and menopause were associated with increased risk of low BMD. Low dietary calcium, high current corticosteroid dose and low creatinine clearance were associated with increased risk of fracture. Serum 25(OH)D between 10 and 20 ng/ml was significantly associated with higher BMD. Conversely, values greater than 20 ng/ml were associated with increased risk of fracture. Serum 25(OH)D level was inversely correlated with disease activity. Of note, vitamin D supplements increased serum 25(OH)D in a dose-dependent manner but had no effect on serum calcium level.

Conclusions

Sarcoidosis patients have a high risk of fracture despite not having a lowered BMD suggesting that other independent factors are involved. Current corticosteroid dose, low dietary calcium and serum 25(OH)D levels are associated with bone fragility. In sarcoidosis, calcium and vitamin D supplementation might be warranted, but desirable 25(OH)D serum levels might be lower than those advised for the general population.
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Literature
1.
go back to reference Goldring SR, Gravallese EM: Mechanisms of bone loss in inflammatory arthritis: diagnosis and therapeutic implications. Arthritis Res. 2000, 2: 33-37. 10.1186/ar67.PubMedCentralCrossRefPubMed Goldring SR, Gravallese EM: Mechanisms of bone loss in inflammatory arthritis: diagnosis and therapeutic implications. Arthritis Res. 2000, 2: 33-37. 10.1186/ar67.PubMedCentralCrossRefPubMed
2.
go back to reference Confavreux CB, Chapurlat RD: Systemic bone effects of biologic therapies in rheumatoid arthritis and ankylosing spondylitis. Osteoporos Int. 2011, 22: 1023-1036. 10.1007/s00198-010-1462-4.CrossRefPubMed Confavreux CB, Chapurlat RD: Systemic bone effects of biologic therapies in rheumatoid arthritis and ankylosing spondylitis. Osteoporos Int. 2011, 22: 1023-1036. 10.1007/s00198-010-1462-4.CrossRefPubMed
3.
go back to reference Reichel H, Koeffer H, Barbers R, Norman AW: Regulation of 1,25-dihydroxyvitamin D production by cultured alveolar macrophages from normal human donors and from patient with pulmonary sarcoidosis. J Clin Endocrinol Metab. 1987, 65: 1201-1209. 10.1210/jcem-65-6-1201.CrossRefPubMed Reichel H, Koeffer H, Barbers R, Norman AW: Regulation of 1,25-dihydroxyvitamin D production by cultured alveolar macrophages from normal human donors and from patient with pulmonary sarcoidosis. J Clin Endocrinol Metab. 1987, 65: 1201-1209. 10.1210/jcem-65-6-1201.CrossRefPubMed
5.
go back to reference Stern PH, De Olazabal J, Bell NH: Evidence for abnormal regulation of circulating 1 alpha,25-dihydroxyvitamin D in patients with sarcoidosis and normal calcium metabolism. J Clin Invest. 1980, 66: 852-855. 10.1172/JCI109924.PubMedCentralCrossRefPubMed Stern PH, De Olazabal J, Bell NH: Evidence for abnormal regulation of circulating 1 alpha,25-dihydroxyvitamin D in patients with sarcoidosis and normal calcium metabolism. J Clin Invest. 1980, 66: 852-855. 10.1172/JCI109924.PubMedCentralCrossRefPubMed
6.
go back to reference Rizzato G, Montemurro L: Reversibility of exogenous corticosteroid-induced bone loss. Eur Respir J. 1993, 6: 116-119.PubMed Rizzato G, Montemurro L: Reversibility of exogenous corticosteroid-induced bone loss. Eur Respir J. 1993, 6: 116-119.PubMed
7.
go back to reference Rizzato G, Fraioli P: Natural and corticosteroid-induced osteoporosis in sarcoidosis: prevention, treatment, follow up and reversibility. Sarcoidosis. 1990, 7: 89-92.PubMed Rizzato G, Fraioli P: Natural and corticosteroid-induced osteoporosis in sarcoidosis: prevention, treatment, follow up and reversibility. Sarcoidosis. 1990, 7: 89-92.PubMed
8.
go back to reference Rizzato G, Tosi G, Mella C, Montemurro L, Zanni D, Sisti S: Prednisone-induced bone loss in sarcoidosis: a risk especially frequent in postmenopausal women. Sarcoidosis. 1988, 5: 93-98.PubMed Rizzato G, Tosi G, Mella C, Montemurro L, Zanni D, Sisti S: Prednisone-induced bone loss in sarcoidosis: a risk especially frequent in postmenopausal women. Sarcoidosis. 1988, 5: 93-98.PubMed
9.
go back to reference Sipah S, Tuzun S, Ozaras R, Calis HT, Ozaras N, Tuzun F, Karayel T: Bone mineral density in women with sarcoidosis. J Bone Miner Metab. 2004, 22: 48-52. 10.1007/s00774-003-0448-0.CrossRef Sipah S, Tuzun S, Ozaras R, Calis HT, Ozaras N, Tuzun F, Karayel T: Bone mineral density in women with sarcoidosis. J Bone Miner Metab. 2004, 22: 48-52. 10.1007/s00774-003-0448-0.CrossRef
10.
go back to reference Adler RA, Funkhouser HL, Petkov VI, Berger MM: Glucocorticoid-induced osteoporosis in patient with sarcoidosis. Am J Med Sci. 2003, 325: 1-6. 10.1097/00000441-200301000-00001.CrossRefPubMed Adler RA, Funkhouser HL, Petkov VI, Berger MM: Glucocorticoid-induced osteoporosis in patient with sarcoidosis. Am J Med Sci. 2003, 325: 1-6. 10.1097/00000441-200301000-00001.CrossRefPubMed
11.
go back to reference Montemurro L, Fraioli P, Riboldi A, Delpiano S, Zanni D, Rizzato G: Bone loss in prednisone treated sarcoidosis: a two-year follow-up. Ann Ital Med Int. 1990, 5: 164-168.PubMed Montemurro L, Fraioli P, Riboldi A, Delpiano S, Zanni D, Rizzato G: Bone loss in prednisone treated sarcoidosis: a two-year follow-up. Ann Ital Med Int. 1990, 5: 164-168.PubMed
12.
go back to reference Rizzato G, Tosi G, Mella C, Zanni D, Sisti S, Loglisci T: Researching osteoporosis in prednisone treated sarcoid patients. Sarcoidosis. 1987, 4: 45-48.PubMed Rizzato G, Tosi G, Mella C, Zanni D, Sisti S, Loglisci T: Researching osteoporosis in prednisone treated sarcoid patients. Sarcoidosis. 1987, 4: 45-48.PubMed
13.
go back to reference Heijckmann AC, Drent M, Dumitrescu B, De Vries J, Nieuwenhuijzen Kruseman AC, Wolffenbuttel BH, Geusens P, Huijberts MS: Progressive vertebral deformities despite unchanged bone mineral density in patients with sarcoidosis: a 4-year follow-up study. Osteopors Int. 2008, 19: 839-847. 10.1007/s00198-007-0513-y.CrossRef Heijckmann AC, Drent M, Dumitrescu B, De Vries J, Nieuwenhuijzen Kruseman AC, Wolffenbuttel BH, Geusens P, Huijberts MS: Progressive vertebral deformities despite unchanged bone mineral density in patients with sarcoidosis: a 4-year follow-up study. Osteopors Int. 2008, 19: 839-847. 10.1007/s00198-007-0513-y.CrossRef
14.
go back to reference Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999, 160: 736-755. Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999, 160: 736-755.
15.
go back to reference Fardellone P, Sebert JL, Bouraya M, Bonidan O, Leclercq G, Doutrellot C, Bellony R, Dubreuil A: Evaluation of the calcium content of diet by frequential self-questionnaire. Rev Rhum Mal Osteoartic. 1991, 58: 99-103.PubMed Fardellone P, Sebert JL, Bouraya M, Bonidan O, Leclercq G, Doutrellot C, Bellony R, Dubreuil A: Evaluation of the calcium content of diet by frequential self-questionnaire. Rev Rhum Mal Osteoartic. 1991, 58: 99-103.PubMed
16.
go back to reference Genant HK, Wu CY, van Kuijk C, Nevitt MC: Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res. 1993, 8: 1137-1148.CrossRefPubMed Genant HK, Wu CY, van Kuijk C, Nevitt MC: Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res. 1993, 8: 1137-1148.CrossRefPubMed
17.
go back to reference Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA: The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011, 96: 53-58. 10.1210/jc.2010-2704.PubMedCentralCrossRefPubMed Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA: The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011, 96: 53-58. 10.1210/jc.2010-2704.PubMedCentralCrossRefPubMed
18.
go back to reference Kavathia D, Buckley JD, Rao D, Rybicki B, Burke R: Elevated 1, 25-dihydroxyvitamin D levels are associated with protracted treatment in sarcoidosis. Respir Med. 2010, 104: 564-570. 10.1016/j.rmed.2009.12.004.CrossRefPubMed Kavathia D, Buckley JD, Rao D, Rybicki B, Burke R: Elevated 1, 25-dihydroxyvitamin D levels are associated with protracted treatment in sarcoidosis. Respir Med. 2010, 104: 564-570. 10.1016/j.rmed.2009.12.004.CrossRefPubMed
19.
go back to reference Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC: Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010, 303: 815-822.CrossRef Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC: Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010, 303: 815-822.CrossRef
20.
go back to reference Grimnes G, Joakimsen R, Figenschau Y, Torjesen PA, Almås B, Jorde R: The effect of high-dose vitamin D on bone mineral density and bone turnover markers in postmenopausal. Osteoporos Int. 2012, 23: 201-211. 10.1007/s00198-011-1752-5.CrossRefPubMed Grimnes G, Joakimsen R, Figenschau Y, Torjesen PA, Almås B, Jorde R: The effect of high-dose vitamin D on bone mineral density and bone turnover markers in postmenopausal. Osteoporos Int. 2012, 23: 201-211. 10.1007/s00198-011-1752-5.CrossRefPubMed
21.
go back to reference Ensrud KE, Ewing SK, Fredman L, Hochberg MC, Cauley JA, Hillier TA, Cummings SR, Yaffe K, Cawthon PM, Study of Osteoporotic Fractures Research Group: Circulating 25-hydroxyvitamin D levels and frailty status in older women. J Clin Endocrinol Metab. 2010, 95: 5266-5273. 10.1210/jc.2010-2317.PubMedCentralCrossRefPubMed Ensrud KE, Ewing SK, Fredman L, Hochberg MC, Cauley JA, Hillier TA, Cummings SR, Yaffe K, Cawthon PM, Study of Osteoporotic Fractures Research Group: Circulating 25-hydroxyvitamin D levels and frailty status in older women. J Clin Endocrinol Metab. 2010, 95: 5266-5273. 10.1210/jc.2010-2317.PubMedCentralCrossRefPubMed
22.
go back to reference Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, Misselwitz J, Klaus G, Kuwertz-Bröking E, Fehrenbach H, Wingen AM, Güran T, Hoenderop JG, Bindels RJ, Prosser DE, Jones G, Konrad M: Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med. 2011, 365: 410-421. 10.1056/NEJMoa1103864.CrossRefPubMed Schlingmann KP, Kaufmann M, Weber S, Irwin A, Goos C, John U, Misselwitz J, Klaus G, Kuwertz-Bröking E, Fehrenbach H, Wingen AM, Güran T, Hoenderop JG, Bindels RJ, Prosser DE, Jones G, Konrad M: Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med. 2011, 365: 410-421. 10.1056/NEJMoa1103864.CrossRefPubMed
23.
go back to reference Dawson-Hughes B, Harris SS: High-dose vitamin D supplementation: too much of a good thing?. JAMA. 2010, 303: 1861-1862. 10.1001/jama.2010.598.CrossRefPubMed Dawson-Hughes B, Harris SS: High-dose vitamin D supplementation: too much of a good thing?. JAMA. 2010, 303: 1861-1862. 10.1001/jama.2010.598.CrossRefPubMed
24.
go back to reference Ueno Y, Shinki T, Nagai Y, Murayama H, Fujii K, Suda T: In vivo administration of 1,25-dihydroxyvitamin D3 suppresses the expression of RANKL mRNA in bone of thyroparathyroidectomized rats constantly infused with PTH. J Cell Biochem. 2003, 90: 267-277. 10.1002/jcb.10623.CrossRefPubMed Ueno Y, Shinki T, Nagai Y, Murayama H, Fujii K, Suda T: In vivo administration of 1,25-dihydroxyvitamin D3 suppresses the expression of RANKL mRNA in bone of thyroparathyroidectomized rats constantly infused with PTH. J Cell Biochem. 2003, 90: 267-277. 10.1002/jcb.10623.CrossRefPubMed
25.
go back to reference Anderson PH, Iida S, Tyson JH, Turner AG, Morris HA: Bone CYP27B1 gene expression is increased with high dietary calcium and in mineralising osteoblasts. J Steroid Biochem Mol Biol. 2010, 121: 71-75. 10.1016/j.jsbmb.2010.03.021.CrossRefPubMed Anderson PH, Iida S, Tyson JH, Turner AG, Morris HA: Bone CYP27B1 gene expression is increased with high dietary calcium and in mineralising osteoblasts. J Steroid Biochem Mol Biol. 2010, 121: 71-75. 10.1016/j.jsbmb.2010.03.021.CrossRefPubMed
26.
go back to reference Hamada K, Nagai S, Tsutsumi T, Izumi T: Bone mineral density and vitamin D in patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999, 16: 219-223.PubMed Hamada K, Nagai S, Tsutsumi T, Izumi T: Bone mineral density and vitamin D in patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 1999, 16: 219-223.PubMed
27.
go back to reference Lips P: Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev. 2001, 22: 477-501. 10.1210/edrv.22.4.0437.CrossRefPubMed Lips P: Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev. 2001, 22: 477-501. 10.1210/edrv.22.4.0437.CrossRefPubMed
28.
go back to reference Lips P: The relative value of 25(OH)D and 1,25(OH)2D measurements. J Bone Miner Res. 2007, 22: 1668-1671. 10.1359/jbmr.070716.CrossRefPubMed Lips P: The relative value of 25(OH)D and 1,25(OH)2D measurements. J Bone Miner Res. 2007, 22: 1668-1671. 10.1359/jbmr.070716.CrossRefPubMed
29.
go back to reference Welsh P, Peters MJ, McInnes IB, Lems WF, Lips PT, McKellar G, Knox S, Michael Wallace A, Dijkmans BA, Nurmohamed MT, Sattar N: Vitamin D deficiency is common in patients with RA and linked to disease activity, but circulating levels are unaffected by TNFα blockade: results from a prospective cohort study. Ann Rheum Dis. 2011, 70: 1165-1167. 10.1136/ard.2010.137265.CrossRefPubMed Welsh P, Peters MJ, McInnes IB, Lems WF, Lips PT, McKellar G, Knox S, Michael Wallace A, Dijkmans BA, Nurmohamed MT, Sattar N: Vitamin D deficiency is common in patients with RA and linked to disease activity, but circulating levels are unaffected by TNFα blockade: results from a prospective cohort study. Ann Rheum Dis. 2011, 70: 1165-1167. 10.1136/ard.2010.137265.CrossRefPubMed
30.
go back to reference Bouvard B, Annweiler C, Sallé A, Beauchet O, Chappard D, Audran M, Legrand E: Extraskeletal effects of vitamin D: facts, uncertainties, and controversies. Joint Bone Spine. 2011, 78: 10-16. 10.1016/j.jbspin.2010.10.011.CrossRefPubMed Bouvard B, Annweiler C, Sallé A, Beauchet O, Chappard D, Audran M, Legrand E: Extraskeletal effects of vitamin D: facts, uncertainties, and controversies. Joint Bone Spine. 2011, 78: 10-16. 10.1016/j.jbspin.2010.10.011.CrossRefPubMed
31.
go back to reference Baughman RP, Janovcik J, Ray M, Sweiss N, Lower EE: Calcium and vitamin D metabolism in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2013, 1: 113-120. Baughman RP, Janovcik J, Ray M, Sweiss N, Lower EE: Calcium and vitamin D metabolism in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2013, 1: 113-120.
32.
go back to reference van der Klift M, de Laet CE, McCloskey EV, Hofman A, Pols HA: The incidence of vertebral fractures in men and women: the Rotterdam Study. J Bone Miner Res. 2002, 17: 1051-1056. 10.1359/jbmr.2002.17.6.1051.CrossRefPubMed van der Klift M, de Laet CE, McCloskey EV, Hofman A, Pols HA: The incidence of vertebral fractures in men and women: the Rotterdam Study. J Bone Miner Res. 2002, 17: 1051-1056. 10.1359/jbmr.2002.17.6.1051.CrossRefPubMed
33.
go back to reference Siffledeen JS, Siminoski K, Jen H, Fedorak RN: Vertebral fractures and role of low bone mineral density in Crohn’s disease. Clin Gastroenterol Hepatol. 2007, 5: 721-728. 10.1016/j.cgh.2007.02.024.CrossRefPubMed Siffledeen JS, Siminoski K, Jen H, Fedorak RN: Vertebral fractures and role of low bone mineral density in Crohn’s disease. Clin Gastroenterol Hepatol. 2007, 5: 721-728. 10.1016/j.cgh.2007.02.024.CrossRefPubMed
34.
go back to reference Heijckmann AC, Huijberts MS, De Vries J, Menheere PP, Van Der Veer E, Kruseman AC, Wolffenbuttel BH, Geusens P, Drent M: Bone turnover and hip bone mineral density in patient with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2007, 24: 51-58.PubMed Heijckmann AC, Huijberts MS, De Vries J, Menheere PP, Van Der Veer E, Kruseman AC, Wolffenbuttel BH, Geusens P, Drent M: Bone turnover and hip bone mineral density in patient with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2007, 24: 51-58.PubMed
Metadata
Title
Bone fragility in sarcoidosis and relationships with calcium metabolism disorders: a cross sectional study on 142 patients
Authors
Nathalie Saidenberg-Kermanac’h
Luca Semerano
Hilario Nunes
Danielle Sadoun
Xavier Guillot
Marouane Boubaya
Nicolas Naggara
Dominique Valeyre
Marie-Christophe Boissier
Publication date
01-04-2014
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 2/2014
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4519

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