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Published in: Arthritis Research & Therapy 1/2019

Open Access 01-12-2019 | Systemic Sclerosis | Research article

Complex assessment of bone mineral density, fracture risk, vitamin D status, and bone metabolism in Hungarian systemic sclerosis patients

Authors: Ágnes Horváth, Edit Végh, Anita Pusztai, Zsófia Pethő, Attila Hamar, Monika Czókolyová, Harjit Pal Bhattoa, Gábor Nagy, Balázs Juhász, Katalin Hodosi, Andrea Domján, Zoltán Szekanecz, Gabriella Szücs, Szilvia Szamosi

Published in: Arthritis Research & Therapy | Issue 1/2019

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Abstract

Objective

We wished to determine bone alterations in systemic sclerosis (SSc) patients by conventional densitometry (DXA), peripheral quantitative computed tomography (pQCT), and bone biomarkers.

Methods

We included 44 SSc patients and 33 age-matched healthy controls. Lumbar spine and femoral neck bone mineral density (BMD) was assessed by DXA. Volumetric BMD was measured by pQCT at the radius. FRAX, 25-hydroxyvitamin-D3 (25-OH-D3), parathyroid hormone, osteocalcin, C-terminal collagen telopeptide, and procollagen type I amino-terminal propeptide were also assessed.

Results

SSc patients had lower L2–4 BMD (0.880 ± 0.108 vs. 0.996 ± 0.181 g/cm2; p = 0.019) and femoral neck (FN) BMD (0.786 ± 0.134 vs. 0.910 ± 0.090 g/cm2; p = 0.007) by DXA. In SSc vs. controls, pQCT indicated lower mean cortical (328.03 ± 103.32 vs. 487.06 ± 42.45 mg/cm3; p < 0.001) and trabecular density (150.93 ± 61.91 vs. 184.76 ± 33.03 mg/cm3; p = 0.037). Vitamin D3 deficiency was more common in SSc vs. controls (60.0% vs. 39.3%; p = 0.003). L2–4 (p = 0.002) and FN BMD (p = 0.015) positively correlated with BMI. pQCT assessments confirmed an inverse correlation between pulmonary manifestation and total (p = 0.024), trabecular (p = 0.035), and cortical density (p = 0.015). Anti-Scl70 positivity inversely correlated with pQCT total density (p = 0.015) and the presence of digital ulcers with cortical density (p = 0.001). We also found that vertebral and FN BMD as determined by DXA significantly correlated with pQCT total, trabecular, and cortical density (p < 0.05).

Conclusion

The results of our study suggest that bone loss in SSc patients may be associated with lower BMI, anti-Scl70 positivity, and the presence of pulmonary manifestations and digital ulcers. Both DXA and pQCT are appropriate tools to evaluate the bone alterations in SSc patients.
Literature
2.
go back to reference LeRoy EC, Medsger TA Jr. Criteria for the classification of early systemic sclerosis. J Rheumatol. 2001;28:1573–6.PubMed LeRoy EC, Medsger TA Jr. Criteria for the classification of early systemic sclerosis. J Rheumatol. 2001;28:1573–6.PubMed
3.
go back to reference Hudson M, Thombs BD, Steele R, Panopalis P, Newton E, Baron M, et al. Health-related quality of life in systemic sclerosis: a systematic review. Arthritis Rheum. 2009;61:1112–20.PubMedCrossRef Hudson M, Thombs BD, Steele R, Panopalis P, Newton E, Baron M, et al. Health-related quality of life in systemic sclerosis: a systematic review. Arthritis Rheum. 2009;61:1112–20.PubMedCrossRef
6.
go back to reference Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int. 2008;19:385–97.PubMedPubMedCentralCrossRef Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int. 2008;19:385–97.PubMedPubMedCentralCrossRef
7.
go back to reference Hoes JN, Bultink IE, Lems WF. Management of osteoporosis in rheumatoid arthritis patients. Expert Opin Pharmacother. 2015;16:559–71.PubMedCrossRef Hoes JN, Bultink IE, Lems WF. Management of osteoporosis in rheumatoid arthritis patients. Expert Opin Pharmacother. 2015;16:559–71.PubMedCrossRef
9.
go back to reference Bernstein CN. Inflammatory bowel diseases as secondary causes of osteoporosis. Curr Osteoporos Rep. 2006;4:116–23.PubMedCrossRef Bernstein CN. Inflammatory bowel diseases as secondary causes of osteoporosis. Curr Osteoporos Rep. 2006;4:116–23.PubMedCrossRef
10.
go back to reference Juhasz B, Gulyas K, Horvath A, Petho Z, Bhattoa HP, Vancsa A, et al. Comparison of peripheral quantitative computed tomography forearm bone density versus dxa in rheumatoid arthritis patients and controls. Osteoporos Int. 2017;28:1271–7.PubMedCrossRef Juhasz B, Gulyas K, Horvath A, Petho Z, Bhattoa HP, Vancsa A, et al. Comparison of peripheral quantitative computed tomography forearm bone density versus dxa in rheumatoid arthritis patients and controls. Osteoporos Int. 2017;28:1271–7.PubMedCrossRef
11.
go back to reference Rass P, Pakozdi A, Lakatos P, Zilahi E, Sipka S, Szegedi G, et al. Vitamin d receptor gene polymorphism in rheumatoid arthritis and associated osteoporosis. Rheumatol Int. 2006;26:964–71.PubMedCrossRef Rass P, Pakozdi A, Lakatos P, Zilahi E, Sipka S, Szegedi G, et al. Vitamin d receptor gene polymorphism in rheumatoid arthritis and associated osteoporosis. Rheumatol Int. 2006;26:964–71.PubMedCrossRef
12.
go back to reference Sinigaglia L, Varenna M, Girasole G, Bianchi G. Epidemiology of osteoporosis in rheumatic diseases. Rheum Dis Clin N Am. 2006;32:631–58.CrossRef Sinigaglia L, Varenna M, Girasole G, Bianchi G. Epidemiology of osteoporosis in rheumatic diseases. Rheum Dis Clin N Am. 2006;32:631–58.CrossRef
13.
go back to reference Engelke K, Adams JE, Armbrecht G, Augat P, Bogado CE, Bouxsein ML, et al. Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD official positions. J Clin Densitom. 2008;11:123–62.PubMedCrossRef Engelke K, Adams JE, Armbrecht G, Augat P, Bogado CE, Bouxsein ML, et al. Clinical use of quantitative computed tomography and peripheral quantitative computed tomography in the management of osteoporosis in adults: the 2007 ISCD official positions. J Clin Densitom. 2008;11:123–62.PubMedCrossRef
14.
go back to reference Orbach H, Zandman-Goddard G, Amital H, Barak V, Szekanecz Z, Szucs G, et al. Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann N Y Acad Sci. 2007;1109:385–400.PubMedCrossRef Orbach H, Zandman-Goddard G, Amital H, Barak V, Szekanecz Z, Szucs G, et al. Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann N Y Acad Sci. 2007;1109:385–400.PubMedCrossRef
15.
go back to reference Sun YN, Feng XY, He L, Zeng LX, Hao ZM, Lv XH, et al. Prevalence and possible risk factors of low bone mineral density in untreated female patients with systemic lupus erythematosus. Biomed Res Int. 2015;2015:510514.PubMedPubMedCentral Sun YN, Feng XY, He L, Zeng LX, Hao ZM, Lv XH, et al. Prevalence and possible risk factors of low bone mineral density in untreated female patients with systemic lupus erythematosus. Biomed Res Int. 2015;2015:510514.PubMedPubMedCentral
16.
go back to reference Amital H, Szekanecz Z, Szucs G, Danko K, Nagy E, Csepany T, et al. Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin d? Ann Rheum Dis. 2010;69:1155–7.PubMedCrossRef Amital H, Szekanecz Z, Szucs G, Danko K, Nagy E, Csepany T, et al. Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin d? Ann Rheum Dis. 2010;69:1155–7.PubMedCrossRef
17.
go back to reference Zold E, Szodoray P, Gaal J, Kappelmayer J, Csathy L, Gyimesi E, et al. Vitamin d deficiency in undifferentiated connective tissue disease. Arthritis Res Ther. 2008;10:R123.PubMedPubMedCentralCrossRef Zold E, Szodoray P, Gaal J, Kappelmayer J, Csathy L, Gyimesi E, et al. Vitamin d deficiency in undifferentiated connective tissue disease. Arthritis Res Ther. 2008;10:R123.PubMedPubMedCentralCrossRef
18.
go back to reference Takayanagi H. Osteoimmunology and the effects of the immune system on bone. Nat Rev Rheumatol. 2009;5:667–76.PubMedCrossRef Takayanagi H. Osteoimmunology and the effects of the immune system on bone. Nat Rev Rheumatol. 2009;5:667–76.PubMedCrossRef
19.
go back to reference Szentpetery A, Horvath A, Gulyas K, Petho Z, Bhattoa HP, Szanto S, et al. Effects of targeted therapies on the bone in arthritides. Autoimmun Rev. 2017;16:313–20.PubMedCrossRef Szentpetery A, Horvath A, Gulyas K, Petho Z, Bhattoa HP, Szanto S, et al. Effects of targeted therapies on the bone in arthritides. Autoimmun Rev. 2017;16:313–20.PubMedCrossRef
20.
go back to reference Omair MA, Pagnoux C, McDonald-Blumer H, Johnson SR. Low bone density in systemic sclerosis. A systematic review. J Rheumatol. 2013;40:1881–90.PubMedCrossRef Omair MA, Pagnoux C, McDonald-Blumer H, Johnson SR. Low bone density in systemic sclerosis. A systematic review. J Rheumatol. 2013;40:1881–90.PubMedCrossRef
21.
go back to reference Avouac J, Koumakis E, Toth E, Meunier M, Maury E, Kahan A, et al. Increased risk of osteoporosis and fracture in women with systemic sclerosis: a comparative study with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64:1871–8.CrossRef Avouac J, Koumakis E, Toth E, Meunier M, Maury E, Kahan A, et al. Increased risk of osteoporosis and fracture in women with systemic sclerosis: a comparative study with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64:1871–8.CrossRef
22.
go back to reference Arnson Y, Amital H, Agmon-Levin N, Alon D, Sanchez-Castanon M, Lopez-Hoyos M, et al. Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: a retrospective cohort study and review of the literature. Autoimmun Rev. 2011;10:490–4.PubMedCrossRef Arnson Y, Amital H, Agmon-Levin N, Alon D, Sanchez-Castanon M, Lopez-Hoyos M, et al. Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: a retrospective cohort study and review of the literature. Autoimmun Rev. 2011;10:490–4.PubMedCrossRef
23.
go back to reference Frediani B, Baldi F, Falsetti P, Acciai C, Filippou G, Spreafico A, et al. Bone mineral density in patients with systemic sclerosis. Ann Rheum Dis. 2004;63:326–7.PubMedPubMedCentralCrossRef Frediani B, Baldi F, Falsetti P, Acciai C, Filippou G, Spreafico A, et al. Bone mineral density in patients with systemic sclerosis. Ann Rheum Dis. 2004;63:326–7.PubMedPubMedCentralCrossRef
24.
go back to reference Sampaio-Barros PD, Costa-Paiva L, Filardi S, Sachetto Z, Samara AM, Marques-Neto JF. Prognostic factors of low bone mineral density in systemic sclerosis. Clin Exp Rheumatol. 2005;23:180–4.PubMed Sampaio-Barros PD, Costa-Paiva L, Filardi S, Sachetto Z, Samara AM, Marques-Neto JF. Prognostic factors of low bone mineral density in systemic sclerosis. Clin Exp Rheumatol. 2005;23:180–4.PubMed
25.
go back to reference Omair MA, McDonald-Blumer H, Johnson SR. Bone disease in systemic sclerosis: outcomes and associations. Clin Exp Rheumatol. 2014;32:S-28–32. Omair MA, McDonald-Blumer H, Johnson SR. Bone disease in systemic sclerosis: outcomes and associations. Clin Exp Rheumatol. 2014;32:S-28–32.
26.
go back to reference van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Ann Rheum Dis. 2013;72:1747–55.PubMedCrossRef van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Ann Rheum Dis. 2013;72:1747–55.PubMedCrossRef
27.
go back to reference Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16:713–6.PubMedCrossRef Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16:713–6.PubMedCrossRef
28.
go back to reference La Montagna G, Vatti M, Valentini G, Tirri G. Osteopenia in systemic sclerosis. Evidence of a participating role of earlier menopause. Clin Rheumatol. 1991;10:18–22.PubMedCrossRef La Montagna G, Vatti M, Valentini G, Tirri G. Osteopenia in systemic sclerosis. Evidence of a participating role of earlier menopause. Clin Rheumatol. 1991;10:18–22.PubMedCrossRef
29.
go back to reference Ibn Yacoub Y, Amine B, Laatiris A, Wafki F, Znat F, Hajjaj-Hassouni N. Bone density in Moroccan women with systemic scleroderma and its relationships with disease-related parameters and vitamin D status. Rheumatol Int. 2012;32:3143–8.PubMedCrossRef Ibn Yacoub Y, Amine B, Laatiris A, Wafki F, Znat F, Hajjaj-Hassouni N. Bone density in Moroccan women with systemic scleroderma and its relationships with disease-related parameters and vitamin D status. Rheumatol Int. 2012;32:3143–8.PubMedCrossRef
30.
go back to reference Caramaschi P, Dalla Gassa A, Ruzzenente O, Volpe A, Ravagnani V, Tinazzi I, et al. Very low levels of vitamin d in systemic sclerosis patients. Clin Rheumatol. 2010;29:1419–25.PubMedCrossRef Caramaschi P, Dalla Gassa A, Ruzzenente O, Volpe A, Ravagnani V, Tinazzi I, et al. Very low levels of vitamin d in systemic sclerosis patients. Clin Rheumatol. 2010;29:1419–25.PubMedCrossRef
31.
go back to reference Vacca A, Cormier C, Piras M, Mathieu A, Kahan A, Allanore Y. Vitamin D deficiency and insufficiency in 2 independent cohorts of patients with systemic sclerosis. J Rheumatol. 2009;36:1924–9.PubMedCrossRef Vacca A, Cormier C, Piras M, Mathieu A, Kahan A, Allanore Y. Vitamin D deficiency and insufficiency in 2 independent cohorts of patients with systemic sclerosis. J Rheumatol. 2009;36:1924–9.PubMedCrossRef
32.
go back to reference Braun-Moscovici Y, Furst DE, Markovits D, Rozin A, Clements PJ, Nahir AM, et al. Vitamin D, parathyroid hormone, and acroosteolysis in systemic sclerosis. J Rheumatol. 2008;35:2201–5.PubMedCrossRef Braun-Moscovici Y, Furst DE, Markovits D, Rozin A, Clements PJ, Nahir AM, et al. Vitamin D, parathyroid hormone, and acroosteolysis in systemic sclerosis. J Rheumatol. 2008;35:2201–5.PubMedCrossRef
33.
go back to reference Atteritano M, Sorbara S, Bagnato G, Miceli G, Sangari D, Morgante S, et al. Bone mineral density, bone turnover markers and fractures in patients with systemic sclerosis: a case control study. PLoS One. 2013;8:e66991.PubMedPubMedCentralCrossRef Atteritano M, Sorbara S, Bagnato G, Miceli G, Sangari D, Morgante S, et al. Bone mineral density, bone turnover markers and fractures in patients with systemic sclerosis: a case control study. PLoS One. 2013;8:e66991.PubMedPubMedCentralCrossRef
34.
go back to reference Yang CY, Leung PS, Adamopoulos IE, Gershwin ME. The implication of vitamin D and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol. 2013;45:217–26.PubMedPubMedCentralCrossRef Yang CY, Leung PS, Adamopoulos IE, Gershwin ME. The implication of vitamin D and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol. 2013;45:217–26.PubMedPubMedCentralCrossRef
35.
go back to reference Rosen Y, Daich J, Soliman I, Brathwaite E, Shoenfeld Y. Vitamin D and autoimmunity. Scand J Rheumatol. 2016;45:439–47.PubMedCrossRef Rosen Y, Daich J, Soliman I, Brathwaite E, Shoenfeld Y. Vitamin D and autoimmunity. Scand J Rheumatol. 2016;45:439–47.PubMedCrossRef
36.
37.
go back to reference Zerr P, Vollath S, Palumbo-Zerr K, Tomcik M, Huang J, Distler A, et al. Vitamin D receptor regulates TGF-beta signalling in systemic sclerosis. Ann Rheum Dis. 2015;74:e20.PubMedCrossRef Zerr P, Vollath S, Palumbo-Zerr K, Tomcik M, Huang J, Distler A, et al. Vitamin D receptor regulates TGF-beta signalling in systemic sclerosis. Ann Rheum Dis. 2015;74:e20.PubMedCrossRef
38.
go back to reference Vacca A, Cormier C, Mathieu A, Kahan A, Allanore Y. Vitamin D levels and potential impact in systemic sclerosis. Clin Exp Rheumatol. 2011;29:1024–31.PubMed Vacca A, Cormier C, Mathieu A, Kahan A, Allanore Y. Vitamin D levels and potential impact in systemic sclerosis. Clin Exp Rheumatol. 2011;29:1024–31.PubMed
39.
go back to reference Marot M, Valery A, Esteve E, Bens G, Muller A, Rist S, et al. Prevalence and predictive factors of osteoporosis in systemic sclerosis patients: a case-control study. Oncotarget. 2015;6:14865–73.PubMedPubMedCentralCrossRef Marot M, Valery A, Esteve E, Bens G, Muller A, Rist S, et al. Prevalence and predictive factors of osteoporosis in systemic sclerosis patients: a case-control study. Oncotarget. 2015;6:14865–73.PubMedPubMedCentralCrossRef
40.
go back to reference Alexandersson BT, Geirsson AJ, Olafsson I, Franzson L, Sigurdsson G, Gudbjornsson B. Bone mineral density and bone turnover in systemic sclerosis. Laeknabladid. 2007;93:535–41.PubMed Alexandersson BT, Geirsson AJ, Olafsson I, Franzson L, Sigurdsson G, Gudbjornsson B. Bone mineral density and bone turnover in systemic sclerosis. Laeknabladid. 2007;93:535–41.PubMed
41.
go back to reference Allanore Y, Borderie D, Lemarechal H, Cherruau B, Ekindjian OG, Kahan A. Correlation of serum collagen I carboxyterminal telopeptide concentrations with cutaneous and pulmonary involvement in systemic sclerosis. J Rheumatol. 2003;30:68–73.PubMed Allanore Y, Borderie D, Lemarechal H, Cherruau B, Ekindjian OG, Kahan A. Correlation of serum collagen I carboxyterminal telopeptide concentrations with cutaneous and pulmonary involvement in systemic sclerosis. J Rheumatol. 2003;30:68–73.PubMed
42.
go back to reference Mok CC, Chan PT, Chan KL, Ma KM. Prevalence and risk factors of low bone mineral density in Chinese patients with systemic sclerosis: a case-control study. Rheumatology (Oxford). 2013;52:296–303.CrossRef Mok CC, Chan PT, Chan KL, Ma KM. Prevalence and risk factors of low bone mineral density in Chinese patients with systemic sclerosis: a case-control study. Rheumatology (Oxford). 2013;52:296–303.CrossRef
Metadata
Title
Complex assessment of bone mineral density, fracture risk, vitamin D status, and bone metabolism in Hungarian systemic sclerosis patients
Authors
Ágnes Horváth
Edit Végh
Anita Pusztai
Zsófia Pethő
Attila Hamar
Monika Czókolyová
Harjit Pal Bhattoa
Gábor Nagy
Balázs Juhász
Katalin Hodosi
Andrea Domján
Zoltán Szekanecz
Gabriella Szücs
Szilvia Szamosi
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2019
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-019-2072-y

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