Reduced bone mass and normal calcium metabolism in systemic sclerosis with and without calcinosis

Munno, Ombretta Di; Mazzantini, M; Massei, Paola; Ferdeghini, M; Pitaro, N.; Latorraca, A; Ferri, Clodoveo

doi:10.1007/bf02207673

Cited by 45 publications

(52 citation statements)

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“…This finding is similar to previous studies in adult SSc; however, none have evaluated concomitantly the level of vitamin D [2][3][4][5]15]. Other biochemical parameters within the normal range have excluded additional causal factors for this bone metabolic disturbance such as renal and hepatic insufficiency, osteomalacia and malabsorption.…”

Section: Discussionsupporting

confidence: 88%

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Low bone mass in juvenile onset sclerosis systemic: the possible role for 25-hydroxyvitamin D insufficiency

et al. 2010

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Juvenile onset systemic sclerosis (JoSSc) is a rare disease, and there are no studies focusing in bone mineral density and biochemical bone parameters. Ten consecutive patients with JoSSc and 10 controls gender, age, menarche age, and physical activity matched were selected. Clinical data were obtained at the medical visit and chart review. Laboratorial analysis included autoantibodies, 25-hydroxyvitamin D (25OHD), intact parathyroid hormone, calcium, phosphorus, alkaline phosphatase and albumin sera levels. Bone mineral density was analyzed by dual-energy X-ray absorptiometry, and bone mineral apparent density (BMAD) was calculated. A lower BMAD in femoral neck (0.294 ± 0.060 vs. 0.395 ± 0.048 g/cm(3), P = 0.001) and total femur (0.134 ± 0.021 vs. 0.171 ± 0.022 g/cm(3), P = 0.002) was observed in JoSSc compared to controls. Likewise, a trend to lower BMAD in lumbar spine (0.117 ± 0.013 vs. 0.119 ± 0.012 g/cm(3), P = 0.06) was also found in these patients. Serum levels of 25OHD were significantly lower in JoSSc compared to controls (18.1 ± 6.4 vs. 25.1 ± 6.6 ng/mL, P = 0.04), and all patients had vitamin D insufficiency (<20 ng/mL) compared to 40% of controls (P = 0.01). All other biochemical parameters were within normal range and alike in both groups. BMAD in femoral neck and total femur was correlated with 25OHD levels in JoSSc (r = 0.82, P = 0.004; r = 0.707, P = 0.02; respectively). We have identified a remarkable high prevalence of 25OHD insufficiency in JoSSc. Its correlation with hip BMAD suggests a causal effect and reinforces the need to incorporate this hormone evaluation in this disease management.

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Section: Discussionsupporting

confidence: 88%

“…In fact, previous studies had observed a relationship between low bone density and scleroderma [3][4][5]. This risk may be even greater in JoSSc due to the longer survival of most of these patients.…”

Section: Introductionmentioning

confidence: 89%

Low bone mass in juvenile onset sclerosis systemic: the possible role for 25-hydroxyvitamin D insufficiency

et al. 2010

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“…It was found that the frequency of menopause was higher in SSc patients than in age‐matched controls . Di Munno et al . reported reduced BMD in SSc patients and observed a negative correlation between BMD and the duration of menopause.…”

Section: Discussionmentioning

confidence: 97%

The association between systemic sclerosis and bone mineral density- a meta-analysis of observational studies

et al. 2014

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Previous research has shown inconsistent effect of systemic sclerosis (SSc) on bone mineral density (BMD). The objective of this study was to perform a meta-analysis of previous articles to investigate the differences in BMD (g/cm(2) ) between SSc and non-SSc populations and to discuss potential underlying mechanisms. Twelve full-text articles (including an outlier study and two studies with identical data) with 662 SSc patients and 886 controls were identified by searching Medline prior to 10 September, 2013 using search terms 'Systemic sclerosis' OR 'scleroderma' and 'osteoporosis' OR 'bone density' OR 'bone mass'. BMD (mean and standard deviation), T-scores and Z-scores at lumbar spine, femoral neck and total hip measured by dual-energy X-ray absorptiometry were extracted. Meta-analysis showed that a lower level of BMD was found in SSc patients, with weighted mean difference of -0.343 (95% CI: -0.500 to -0.186) at femoral neck, -0.084 (95% CI: -0.110 to -0.057) at total hip and -0.104 (95% CI: -0.135 to -0.073) at the lumbar spine. We conclude that patients with SSc may have a lower BMD level than healthy controls.

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“…Multiple mouse models with deletions of bone-related genes display vascular and ectopic calcification, including targeted deletions of osteoprotegerin and fetuin-A, another inhibitor of calcification, in knockout mice [19]. A systematic review [21 ] identified calcinosis as a candidate risk factor for low bone mineral density (BMD) in SSc patients; however, the data were conflicting with two small studies (37 and 25 SSc patients, respectively) reporting lower total bone mineral content in patients with calcinosis ( p < 0.05) [22,23], while another (43 SSc females) noted no effect of calcinosis on BMD [24]. One study that included 60 SSc patients showed that circulating levels of osteoprotegerin, but not RANKL, were higher in those with calcinosis.…”

Section: Discussionmentioning

confidence: 99%

Calcinosis is associated with digital ulcers and osteoporosis in patients with systemic sclerosis: A Scleroderma Clinical Trials Consortium study

Valenzuela

Baron

Herrick

et al. 2016

Seminars in Arthritis and Rheumatism

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Objectives We sought to identify the clinical factors associated with calcinosis in an international multicenter collaborative effort with the Scleroderma Clinical Trials Consortium (SCTC). Methods This is a retrospective cohort study of 5218 patients with systemic sclerosis (SSc). Logistic regression was used to obtain odds ratios (OR) relating calcinosis to various clinical features in multivariate analyses. Results A total of 1290 patients (24.7%) had calcinosis. In univariate analyses, patients with calcinosis were older than patients without calcinosis, more likely to be female, and had longer disease duration from the first non-Raynaud phenomenon symptom. Patients with calcinosis were more likely to have digital ulcers, telangiectasias, acro-osteolysis, cardiac disease, pulmonary hypertension, gastrointestinal involvement, arthritis, and osteoporosis, but less likely to have muscle disease. Anti-Scl-70, RNA-polymerase-III, and U1-RNP autoantibodies were significantly less common in patients with calcinosis, while anticentromere (ACA), anti-PM/Scl, and anticardiolipin antibodies were more frequent. In multivariate analysis, the strongest associations with calcinosis were digital ulcers (OR = 3.9; 95% CI: 2.7–5.5; p < 0.0001) and osteoporosis (OR = 4.2; 95% CI: 2.3–7.9; p < 0.0001). Conclusion One quarter of patients with SSc have calcinosis at some time during their illness. Our data confirm a strong association of calcinosis with digital ulcers, and support a novel association with osteoporosis.

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Reduced bone mass and normal calcium metabolism in systemic sclerosis with and without calcinosis

Cited by 45 publications

References 9 publications

Low bone mass in juvenile onset sclerosis systemic: the possible role for 25-hydroxyvitamin D insufficiency

Low bone mass in juvenile onset sclerosis systemic: the possible role for 25-hydroxyvitamin D insufficiency

The association between systemic sclerosis and bone mineral density- a meta-analysis of observational studies

Calcinosis is associated with digital ulcers and osteoporosis in patients with systemic sclerosis: A Scleroderma Clinical Trials Consortium study

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