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01-08-2016 | Original Article

Bone involvement in adult patients affected with Ehlers-Danlos syndrome.

Authors: C. Eller-Vainicher, A. Bassotti, A. Imeraj, E. Cairoli, F. M. Ulivieri, F. Cortini, M. Dubini, B. Marinelli, A. Spada, I. Chiodini

Published in: Osteoporosis International | Issue 8/2016

Abstract

Summary

The Ehlers-Danlos syndrome is characterized by abnormal connective tissue but bone involvement is debated. We found a reduced BMD and bone quality and increased prevalence of asymptomatic vertebral fractures in eugonadal patients with Ehlers-Danlos syndrome. These findings suggest the need of a bone health evaluation in these patients.

Introduction

The Ehlers-Danlos (EDS) syndrome is characterized by abnormalities of the connective tissue leading to ligamentous laxity and skin and tissue fragility. We evaluated the bone metabolism, bone mineral density (BMD) and bone quality (measured by trabecular bone score, TBS), and the prevalence of vertebral fractures (VFx) in a group of eugonadal adult EDS patients.

Methods

Fifty consecutive Caucasian patients, aged 30–50 years (36 females, 14 males) with classical or hypermobility EDS and 50 age-, gender-, and body mass index (BMI)-matched control subjects were enrolled. In all subjects’ calcium-phosphorous metabolism, bone turnover, BMD at the lumbar spine (LS) and femur (femoral neck, FN and total femur, FT) and TBS by dual-energy X-ray absorptiometry, and the VFx presence by spine radiograph were assessed.

Results

Patients showed reduced BMD (Z-scores LS −0.45 ± 1.00, FN −0.56 ± 1.01, FT −0.58 ± 0.92) and TBS (1.299 ± 0.111) and increased prevalence of morphometric VFx (32 %) than controls (Z-scores LS 0.09 ± 1.22, FN 0.01 ± 0.97, FT 0.08 ± 0.89; TBS 1.382 ± 0.176; VFx 8 %, p <0.05 for all comparisons), while vitamin D levels, calcium-phosphorous metabolism, and bone turnover were comparable. Fractured EDS patients showed lower TBS values than non-fractured ones (1.245 ± 0.138 vs 1.325 ± 0.086, p < 0.05), despite comparable BMD. In EDS patients, the VFx presence was significantly associated with TBS even after adjusting for sex, age, BMD, EDS type, and falls frequency.

Conclusions

EDS patients have reduced BMD and bone quality (as measured by TBS) and increased prevalence of VFx.

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Callewaert B, Malfait F, Loeys B, De Paepe A (2008) Ehlers-Danlos syndromes and Marfan syndrome. Best Pract Res Clin Rheum 22:165–189. doi:10.1016/j.berh.2007.12.005 CrossRef

De Paepe A, Malfait F (2012) The Ehlers-Danlos syndrome, a disorder with many faces. Clin Genet 82:1–11. doi:10.1111/j.1399-0004.2012.01858.x CrossRefPubMed

Deodhar AA, Woolf AD (1994) Ehlers-Danlos syndrome and osteoporosis. Ann Rheum Dis 53:841–842CrossRefPubMedPubMedCentral

Coelho PC, Santos R, Gomes JA (1994) Osteoporosis and Ehlers-Danlos syndrome. Ann Rheum Dis 53:212–213CrossRefPubMedPubMedCentral

Dolan AL, Arden NK, Grahame R, Spector TD (1998) Assessment of bone in Ehlers Danlos syndrome by ultrasound and densitometry. Ann Rheum Dis 57:630–633CrossRefPubMedPubMedCentral

Carbone L, Tylavsky FA, Bush AJ, Koo W, Orwoll E, Cheng S (2000) Bone density in Ehlers-Danlos syndrome. Osteoporos Int 11:388–392CrossRefPubMed

Thomsen JS, Ebbesen EL, Mosekilde L (2002) Predicting human vertebral bone strength by vertebral static histomorphometry. Bone 30:502–508. doi:10.1111/j.1749-6632.2011.06282.x CrossRefPubMed

Patsch JM, Burghardt AJ, Kazakia G, Majumdar S (2011) Noninvasive imaging of bone microarchitecture. Ann N Y Acad Sci 1240:77–87CrossRefPubMedPubMedCentral

Bousson V, Bergot C, Sutter B, Levitz P, Cortet B, the Scientific Committee of the GRIO (Groupe de Recherche et d’Information sur les Ostéoporoses) (2012) Trabecular bone score (TBS): available knowledge, clinical relevance, and future prospects. Osteoporos Int 23:1489–1501. doi:10.1007/s00198-011-1824-6 CrossRefPubMed

10.

Hans D, Barthe N, Boutroy S, Pothuaud L, Winzenrieth R, Krieg MA (2011) Correlations between trabecular bone score, measured using anteroposterior Dual Energy X-ray Absorptiometry acquisition and 3-dimensional parameters of bone microarchitecture: an experimental study on human cadaver vertebrae. J Clin Densitom 14:302–312. doi:10.1016/j.jocd.2011.05.005 CrossRefPubMed

11.

Pothuaud L, Carceller P, Hans D (2008) Correlations between grey-level variations in 2D projection images (TBS) and 3D microarchitecture: applications in the study of human trabecular bone microarchitecture. Bone 42:775–787. doi:10.1016/j.bone.2007.11.018 CrossRefPubMed

12.

Pothuaud L, Barthe N, Krieg MA, Mehsen N, Carceller P, Hans D (2009) Evaluation of the potential use of trabecular bone score to complement bone mineral density in the diagnosis of osteoporosis: a preliminary spine BMD-matched, case-control study. J Clin Densitom 12:170–176. doi:10.1016/j.jocd.2008.11.006 CrossRefPubMed

13.

Rabier B, Héraud A, Grand-Lenoir C, Winzenrieth R, Hans D (2010) A multicentre, retrospective case-control study assessing the role of trabecular bone score (TBS) in menopausal Caucasian women with low areal bone mineral density (BMDa): analysing the odds of vertebral fracture. Bone 46:176–181. doi:10.1016/j.bone.2009.06.032 CrossRefPubMed

14.

Winzenrieth R, Dufour R, Pothuaud L, Hans D (2010) A retrospective case-control study assessing the role of trabecular bone score in postmenopausal Caucasian women with osteopenia: analyzing the odds of vertebral fracture. Calcif Tissue Int 86:104–109. doi:10.1007/s00223-009-9322-y CrossRefPubMed

15.

Hans D, Goertzen AL, Krieg MA, Leslie WD (2001) Bone microarchitecture assessed by TBS predicts osteoporotic fractures independent of bone density; The Manitoba Study. J Bone Miner Res 26:2762–2769. doi:10.1002/jbmr.499 CrossRef

16.

Eller-Vainicher C, Filopanti M, Palmieri S, Ulivieri FM, Morelli M, Zhukouskaya VV et al (2013) Bone quality, as measured by Trabecular Bone Score (TBS), in patients with primary hyperparathyroidism. Eur J Endocrinol 169:155–162. doi:10.1530/EJE-13-0305 CrossRefPubMed

17.

Breban S, Briot K, Kolta S, Paternotte S, Ghazi M, Fechtenbaum J, Roux C (2012) Identification of rheumatoid arthritis patients with vertebral fractures using bone mineral density and trabecular bone score. J Clin Densitom 15:260–266. doi:10.1016/j.jocd.2012.01.007 CrossRefPubMed

18.

Eller-Vainicher C, Morelli V, Ulivieri FM, Palmieri S, Zhukouskaya VV, Cairoli E, Pino R, Naccarato A, Scillitani A, Beck-Peccoz P, Chiodini I (2012) Bone quality, as measured by Trabecular Bone Score (TBS), in patients with adrenal incidentalomas with and without subclinical hypercortisolism. J Bone Miner Res 27:2223–2230. doi:10.1002/jbmr.1648 CrossRefPubMed

19.

Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ (1998) Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Am J Med Genet 77:31–37CrossRefPubMed

20.

UpToDate calculator. In Calcium Correction in Hypoalbuminemia, version 18.2. Waltham, MA: Wolters Kluwer-Health (available:www.uptodate.com), 2010.

21.

Ferrari S, Bianchi ML, Eisman JA, Foldes AJ, Adami S, Wahl DA et al (2012) Osteoporosis in young adults: pathophysiology, diagnosis, and management. Osteoporos Int 23:2735–2748. doi:10.1007/s00198-012-2030-x CrossRefPubMed

22.

Genant HK, Wu CY, van Knijk C, Nevitt M (1993) Vertebral fracture assessment using a semi-quantitative technique. J Bone Miner Res 8:1137–1148CrossRefPubMed

23.

Varenna M, Binelli L, Zucchi F, Ghiringhelli D, Sinigaglia L (2001) Unbalanced diet to lower serum cholesterol level is a risk factor for postmenopausal osteoporosis and distal forearm fracture. Osteoporos Int 12:296–301CrossRefPubMed

24.

Yano H, Hamanaka R, Nakamura-Ota M, Adachi S, Zhang JJ, Matsuo N et al (2014) Sp7/Osterix induces the mouse pro-α2(I) collagen gene (Col1a2) expression via the proximal promoter in osteoblastic cells. Biochem Biophys Res Commun 452:531–536. doi:10.1016/j.bbrc.2014.08.100 CrossRefPubMed

25.

Malfait F, Symoens S, Goemans N, Gyftodimou Y, Holmberg E, López-González V et al (2013) Helical mutations in type I collagen that affect the processing of the amino-propeptide result in an Osteogenesis Imperfecta/Ehlers-Danlos Syndrome overlap syndrome. Orphanet J Rare Dis 21:8–78. doi:10.1186/1750-1172-8-78

26.

Volk SW, Shah SR, Cohen AJ, Wang Y, Brisson BK, Vogel LK et al (2014) Type III collagen regulates osteoblastogenesis and the quantity of trabecular bone. Calcif Tissue Int 94:621–631. doi:10.1007/s00223-014-9843-x CrossRefPubMedPubMedCentral

27.

Kocijan R, Muschitz C, Haschka J, Hans D, Nia A, Geroldinger A et al (2015) Bone structure assessed by HR-pQCT TBS and DXL in adult patients with different types of osteogenesis imperfecta. Osteoporos Int 26:2431–2440. doi:10.1007/s00198-015-3156-4 CrossRefPubMed

28.

Bart ZR, Hammond MA, Wallace JM (2014) Multi-scale analysis of bone chemistry, morphology and mechanics in the oim model of osteogenesis imperfecta. Connect Tissue Res 55(Suppl 1):4–8. doi:10.3109/03008207.2014.923860 CrossRefPubMed

29.

Homan EP, Lietman C, Grafe I, Lennington J, Morello R, Napierala D et al (2014) Differential effects of collagen prolyl 3-hydroxylation on skeletal tissues. PLoS Genet 10:e1004121. doi:10.1371/journal.pgen.1004121 CrossRefPubMedPubMedCentral

30.

Link TM, Majumdar S, Grampp S, Guglielmi G, van Kuijk C, Imhof H et al (1999) Imaging of trabecular bone structure in osteoporosis. Eur Radiol 9:1781–1788CrossRefPubMed

31.

Thomsen JS, Ebbesen EL, Mosekilde L (2002) Predicting human vertebral bone strength by vertebral static histomorphometry. Bone 30:502–508CrossRefPubMed

Title: Bone involvement in adult patients affected with Ehlers-Danlos syndrome.
Authors: C. Eller-Vainicher
A. Bassotti
A. Imeraj
E. Cairoli
F. M. Ulivieri
F. Cortini
M. Dubini
B. Marinelli
A. Spada
I. Chiodini
Publication date: 01-08-2016
Publisher: Springer London
Published in: Osteoporosis International / Issue 8/2016
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-016-3562-2

At a glance: The STEP trials

Springer Medicine

Bone involvement in adult patients affected with Ehlers-Danlos syndrome.

Abstract

Summary

Introduction

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

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