Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Osteoporosis International
Published in: Osteoporosis International 4/2016

Open Access 01-04-2016 | Original Article

Risk of vertebral and non-vertebral fractures in patients with sarcoidosis: a population-based cohort

Authors: S. Bours, F. de Vries, J. P. W. van den Bergh, A. Lalmohamed, T. P. van Staa, H. G. M. Leufkens, P. P. P. Geusens, M. Drent, N. C. Harvey

Published in: Osteoporosis International | Issue 4/2016

Login to get access

Abstract

Summary

In this retrospective cohort study using the Clinical Practice Research Datalink (CPRD), patients with sarcoidosis have an increased risk of clinical vertebral fractures and when on recent treatment with oral glucocorticoids, also an increased risk of any fractures and osteoporotic fractures.

Introduction

Sarcoidosis is a chronic inflammatory disease, in which fragility fractures have been reported despite normal BMD. The aim of this study was to assess whether patients with sarcoidosis have an increased risk of clinical fractures compared to the general population.

Methods

A retrospective cohort study was conducted using the CPRD. All patients with a CPRD code for sarcoidosis between January 1987 and September 2012 were included. Cox proportional hazards models were used to derive adjusted relative risks (RRs) of fractures in all sarcoidosis patients compared to matched controls, and within the sarcoidosis group according to use and dose of systemic glucocorticoids.

Results

Five thousand seven hundred twenty-two sarcoidosis patients (mean age 48.0 years, 51 % females, mean follow-up 6.7 years) were identified.
Compared to 28,704 matched controls, the risk of any fracture was not different in patients with sarcoidosis. However, the risk of clinical vertebral fractures was significantly increased (adj RR 1.77; 95 % CI 1.06–2.96) and the risk of non-vertebral fractures was decreased although marginally significant (adj RR 0.87; 95 % CI 0.77–0.99). Compared to sarcoidosis patients not taking glucocorticoids, recent use of systemic glucocorticoids was associated with an increased risk of any fracture (adj RR 1.50; 95 % CI 1.20–1.89) and of an osteoporotic fracture (adj RR 1.47; 95 % CI 1.07–2.02).

Conclusions

Patients with sarcoidosis have an increased risk of clinical vertebral fractures, and when using glucocorticoid therapy, an increased risk of any fractures and osteoporotic fractures. In contrast, the risk of non-vertebral fractures maybe decreased. Further investigation is needed to understand the underlying mechanisms of these contrasting effects on fracture risk.
Literature
1.
2.
Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Müller-Quernheim J (2014) Sarcoidosis. Lancet 383:1155–1167CrossRefPubMed
3.
4.
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 (1999) Statement on sarcoidosis. Am J Respir Crit Care Med 160(2):736–755CrossRef
5.
Gribbin J, Hubbard RB, Le Jeune I, Smith CJ, West J, Tata LJ (2006) Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax 61(11):980–985CrossRefPubMedPubMedCentral
6.
De Vries F, Van Staa TP, Bracke MS, Cooper C, Leufkens HG, Lammers JW (2005) Severity of obstructive airway disease and risk of osteoporotic fracture. Eur Respir J 25(5):879–884CrossRefPubMed
7.
8.
Dirven L, van den Broek M, van Groenendael JH et al (2012) Prevalence of vertebral fractures in a disease activity steered cohort of patients with early active rheumatoid arthritis. BMC Musculoskelet Disord 13:125CrossRefPubMedPubMedCentral
9.
Van Staa T, Geusens P, Bijlsma JW, Leufkens HG, Cooper C (2006) Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 54(10):3104–3112CrossRefPubMed
10.
Mohammad A, Lohan D, Bergin D et al. (2013) The prevalence of vertebral fracture on vertebral fracture assessment imaging in a large cohort of patients with rheumatoid arthritis.doi:10.​1093/​rheumatology/​ket353.
11.
Vosse D, Landewé R, Van der Heijde D et al (2009) Ankylosing spondylitis and the risk of fracture: results from a large primary care-based nested case control study. Ann Rheum Dis 68:1839–1842CrossRefPubMed
12.
Sambrook P, Geusens P (2012) The epidemiology of osteoporosis and fractures in ankylosing spondylitis. Ther Adv Musculoskel Dis 4:4CrossRef
13.
Almehed K, Hetényi, S, Ohlsson, C, et al. (2010) Prevalence and risk factors of vertebral compression fractures in female SLE patients. Arthritis Res Ther 12
14.
Vázquez A, Lopez, E, Montoya J et al. (2012) Vertebral fractures in patients with inflammatory bowel disease compared with a healthy population: a prospective case–control study. BMC Gastroenterol 12
15.
De Vries F, Bracke M, Leufkens HG, Lammers JW, Cooper C, Van Staa TP (2007) Fracture risk with intermittent high-dose oral glucocorticoid therapy. Arthritis Rheum 56(1):208–214CrossRefPubMed
16.
Van Staa T, Abenhaim L, Cooper C, Zhang B, Zhang B, Leufkens HGM (2000) The use of a large pharmacoepidemiological database to study exposure to oral corticosteroids and risk of fractures: validation of study population and results. Pharmacoepidemiol Drug Saf 9:359–366CrossRefPubMed
17.
van Staa TPLH, Abenhaim L, Zhang B, Cooper C (2000) Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford) 39(12):1383–1389CrossRef
18.
Saidenberg-Kermanac’h N, Semerano L, Nunes H, Sadoun D, Guillot X, Boubaya M, Naggara N, Valeyre D, Boissier MC (2014) Bone fragility in sarcoidosis and relationships with calcium metabolism disorders: a cross sectional study on 142 patients. Arthritis Res Ther 16:R78. doi:10.​1186/​ar4519 CrossRefPubMedPubMedCentral
19.
Heijckmann A, Huijberts MS, De Vries J, Menheere PP, Van Der Veer E, Kruseman AC, Wolffenbuttel BH, Geusens P, Drent M (2007) Bone turnover and hip bone mineral density in patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 24(1):51–58PubMed
20.
Heijckmann A, Drent M, Dumitrescu B, De Vries J, Nieuwenhuijzen Kruseman AC, Wolffenbuttel BH, Geusens P, Huijberts MS (2008) Progressive vertebral deformities despite unchanged bone mineral density in patients with sarcoidosis: a 4-year follow-up study. Osteoporos Int 19(6):839–847. doi:10.​1007/​s00198-007-0513-y CrossRefPubMedPubMedCentral
21.
Tervonen S, Karjalainen P, Valta R (1974) Bone mineral in sarcoidosis. Acta Med Scand 196(6):497–503PubMed
22.
Sipahi S, Tuzun S, Ozaras R, Calis HT, Ozaras N, Tuzun F, Karayel T (2004) Bone mineral density in women with sarcoidosis. J Bone Miner Metab 22(1):48–52CrossRefPubMed
23.
Montemurro L, Fraioli P, Rizzato G (1991) Bone loss in untreated longstanding sarcoidosis. Sarcoidosis 8(1):29–34PubMed
24.
Rottoli P, Gonnelli S, Silitro S, Zacchei F, Fabbrini D, Gennari C, Vagliasindi M (1993) Alterations in calcium metabolism and bone mineral density in relation to the activity of sarcoidosis. Sarcoidosis 10(2):161–162PubMed
25.
Bolland M, Wilsher ML, Grey A, Horne AM, Fenwick S, Gamble GD, Reid IR 2013 Randomised controlled trial of vitamin D supplementation in sarcoidosis. BMJ Open 3(10). doi: 10.​1136/​bmjopen-2013-003562.
26.
Rizzato GFP (1990) Natural and corticosteroid-induced osteoporosis in sarcoidosis: prevention, treatment, follow up and reversibility. Sarcoidosis 7:89–92PubMed
27.
Rizzato G, Montemurro L (1993) Reversibility of exogenous corticosteroid-induced bone loss. Eur Respir J 6:116–119PubMed
28.
Doherty DA, Sanders KM, Kotowicz MA, Prince RL (2001) Lifetime and five-year age-specific risks of first and subsequent osteoporotic fractures in postmenopausal women. Osteoporos Int 12:16–23CrossRefPubMed
29.
30.
Ghazi M, Kolta S, Briot K, Fechtenbaum J, Paternotte S, Roux C (2012) Prevalence of vertebral fractures in patients with rheumatoid arthritis: revisiting the role of glucocorticoids. Osteoporos Int 23(2):581–587. doi:10.​1007/​s00198-011-1584-3 CrossRefPubMed
31.
Bultink IE, Harvey NC, Lalmohamed A, Cooper C, Lems WF, van Staa TP, de Vries F (2014) Elevated risk of clinical fractures and associated risk factors in patients with systemic lupus erythematosus versus matched controls: a population-based study in the United Kingdom. Osteoporos Int 25(4):1275–1283. doi:10.​1007/​s00198-013-2587-z CrossRefPubMed
32.
33.
Jager PL, Jonkman S, Koolhaas W, Stiekema A, Wolffenbuttel BH, Slart RH (2011) Combined vertebral fracture assessment and bone mineral density measurement: a new standard in the diagnosis of osteoporosis in academic populations. Osteoporos Int 22(4):1059–1068. doi:10.​1007/​s00198-010-1293-3 CrossRefPubMed
34.
Kim SY, Schneeweiss S, Liu J, Daniel GW, Chang CL, Garneau K, Solomon DH (2010) Risk of osteoporotic fracture in a large population-based cohort of patients with rheumatoid arthritis. Arthritis Res Ther 12(4). doi: 10.​1186/​ar3107.
35.
36.
Weiss RJ, Wick MC, Ackermann PW, Montgomery SM (2010) Increased fracture risk in patients with rheumatic disorders and other inflammatory diseases—a case–control study with 53,108 patients with fracture. J Rheumatol 37(11):2247–2250. doi:10.​3899/​jrheum.​100363 CrossRefPubMed
37.
van Tuyl LH, Boers M, Lems WF, Landewé RB, Han H, van der Linden S, van de Laar M, Westhovens R, van Denderen JC, Westedt ML, Peeters AJ, Jacobs P, Huizinga TW, van de Brink H, Dijkmans BA, Voskuyl AE (2010) Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis. Ann Rheum Dis 69(5):807–812. doi:10.​1136/​ard.​2009.​108027 CrossRefPubMed
38.
Schett G, Kiechl S, Weger S, Pederiva A, Mayr A, Petrangeli M, Oberhollenzer F, Lorenzini R, Redlich K, Axmann R, Zwerina J, Willeit J (2006) High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study. Arch Intern Med 166(22):2495–2501CrossRefPubMed
39.
Oei L, Campos-Obando N, Dehghan A, Oei EH, Stolk L, van Meurs JB, Hofman A, Uitterlinden AG, Franco OH, Zillikens MC, Rivadeneira F (2014) Dissecting the relationship between high-sensitivity serum C-reactive protein and increased fracture risk: the Rotterdam Study. Osteoporos Int 25(4):1247–1254. doi:10.​1007/​s00198-013-2578-0 CrossRefPubMed
40.
Nakamura K, Saito T, Kobayashi R, Oshiki R, Oyama M, Nishiwaki T, Nashimoto M, Tsuchiya Y (2011) C-reactive protein predicts incident fracture in community-dwelling elderly Japanese women: the Muramatsu study. Osteoporos Int 22(7):2145–2150. doi:10.​1007/​s00198-010-1425-9 CrossRefPubMed
41.
42.
Ishii S, Cauley JA, Greendale GA, Crandall CJ, Danielson ME, Ouchi Y, Karlamangla AS (2013) C-reactive protein, bone strength, and nine-year fracture risk: data from the Study of Women’s Health Across the Nation (SWAN). J Bone Miner Res 28(7):1688–1698. doi:10.​1002/​jbmr.​1915 CrossRefPubMed
43.
Wu ZJ, He JL, Wei RQ, Liu B, Lin X, Guan J, Lan YB (2015) C-reactive protein and risk of fracture: a systematic review and dose–response meta-analysis of prospective cohort studies. Osteoporos Int 26(1):49–57. doi:10.​1007/​s00198-014-2826-y CrossRefPubMed
44.
Hamada K, Nagai S, Tsutsumi T, Izumi T (1999) Bone mineral density and vitamin D in patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 16(2):219–223PubMed
45.
Cremers JP, Drent M, Elfferich MD, Nelemans PJ, Wijnen PA, Witteman BJ, Schols AM (2013) Body composition profiling in a Dutch sarcoidosis population. Sarcoidosis Vasc Diffuse Lung Dis 30:289–299PubMed
46.
47.
48.
Metadata
Title
Risk of vertebral and non-vertebral fractures in patients with sarcoidosis: a population-based cohort
Authors
S. Bours
F. de Vries
J. P. W. van den Bergh
A. Lalmohamed
T. P. van Staa
H. G. M. Leufkens
P. P. P. Geusens
M. Drent
N. C. Harvey
Publication date
01-04-2016
Publisher
Springer London
Published in
Osteoporosis International / Issue 4/2016
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-015-3426-1

Other articles of this Issue 4/2016

Osteoporosis International 4/2016 Go to the issue

Original Article

A combination of low serum concentrations of vitamins K1 and D is associated with increased risk of hip fractures in elderly Norwegians: a NOREPOS study

Original Article

Once-weekly teriparatide in hemodialysis patients with hypoparathyroidism and low bone mass: a prospective study

Original Article

Bone material strength is associated with areal BMD but not with prevalent fractures in older women

Editorial

Achieving the protection of high peak bone mass

Original Article

Higher levels of s-RANKL and osteoprotegerin in children and adolescents with type 1 diabetes mellitus may indicate increased osteoclast signaling and predisposition to lower bone mass: a multivariate cross-sectional analysis

Letter

Proton pump inhibitors and fracture: they impair bone quality and increase fall risk?