Abstract

Background:Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by self-amplifying microvascular damage sustained by autoimmune response and progressive skin and visceral fibrosis. Besides, SSc patients show higher incidence of bone micro/macroarchitectural damages and bone fractures. Emerging data demonstrate that high serum levels of homocysteine (Hcy) could modulate osteoclastogenesis and are recognized as risk factors for osteoporosis (2). Furthermore, serum levels of Hcy were found to be higher in SSc patients than in healthy controls (3).Objectives:to evaluate the bone status according to HCy serum levels in a cohort of SSc patients.Methods:20 female patients fulfilling ACR 2013 criteria for SSc underwent a dual-energy X-ray absorptiometry scan (DXA) (Lunar Prodigy) to evaluate bone status. We analysed bone quantity and quality respectively by bone mineral density (BMD) and trabecular bone score (TBS). According to the WHO criteria, osteoporosis was defined as a bone density of 2.5 standard deviations below that of a young adult (T-Score). Fasting blood samples were obtained from all patients in order to test serum Hcy level and bone turnover markers after obtaining the informed consent. All subjects underwent morphometric spine X-Ray to evaluate vertebral fractures. Statistical analysis was performed using non-parametric tests.Results:The mean age of patients was 64.15 ± 10.8 years with a mean disease duration of 9.1 ± 2.3 years. The mean modified Rodnan Skin Score (mRSS) was 10.7 ± 8.5. All patients showed a “scleroderma pattern” at nailfold Videocapillaroscopy (NVC): in particular, 7 patients showed the “Late” pattern, 9 patients the “Active” pattern and 4 patients the “Early” NVC pattern. Hyperomocisteinemia (HHcy) was found in 25% of patients. Interestingly, SSc patients with the “Late” NVC pattern showed a significantly higher serum level of Hcy compared to the “Early/Active” group (11.15 ± 4.4 vs 17.17 ± 6.4, p=0.03). No significant differences were observed in relation to the autoantibody profiles. Of note, 60% of patients with HHcy were found osteoporotic and 40% had bone fractures.Considering the bone status, patients with Hcy showed a significantly lower TBS (p=0.03); the average values of BMD on the lumbar spine (p=0.79) and femoral neck (p=0.13) were found lower compared to, but without any statistical significance. Furthermore, no significant differences were observed in bone turnover markers according to Hcy levels.Conclusion:The study demonstrates a relationship between higher levels of Hcy and lower TBS values within SSc patients, particularly in those with most severe microvascular damage al NVC (“Late” SSc pattern). Therefore it is concluded that higher serum levels of Hcy associate to both bone microarchitectural and microvascular damage in SSc.

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