Klotho and Mineral Bone Density in Systemic Sclerosis

Study Overview
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Brief Summary
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The present study recruits female patients aged 45-65 years with a diagnosis of Systemic Sclerosis according to the EULAR/ACR 2013 criteria and age and gender-matched healthy control subjects. The purpose of the study is to investigate the possible role of Klotho and other cytokines involved in the osteoimmunological control of bone turnover as a possible determinant of the microvascular damage and fibrosis observed in SSc patients

Official Title
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Klotho and Bone Mineral Density (BMD) in Systemic Sclerosis Patients: Relationship With Microvascular Damage and Fibrosis

Conditions
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Systemic Sclerosis

Intervention / Treatment
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* Other: Possible Klotho effects on SSc clinical conditions, namely skeletal, fibrotic and microangiopathic damage
* Other: Evalution in healthy patients of bone mineral density, Klotho level and key bone-related cytokines


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female gender Systemic sclerosis diagnosis Signature of the informed consent Exclusion Criteria: Chronic kidney disease Liver or thyroid disease Diabetes Ongoing diuretic treatment Estrogen replacing treatment Vitamin D or Calcium supplementation Drugs able to interfere with bone turn-over (such as bisphosphonates or glucocorticoids)

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Systemic Sclerosis patients<br> | Other: Possible Klotho effects on SSc clinical conditions, namely skeletal, fibrotic and microangiopathic damage<br>* Female patients with a diagnosis of Systemic Sclerosis ( EULAR/ACR 2013 criteria ) attending the FPG Department of Rheumatology will be recruited after exclusion criteria are ruled out and informed consent is signed. DXA bone mineral density determination (Lunar Prodigy ) will be performed and bone metabolism parameters, according to routinary clinical practice, will be collected. Immunological and SSc-related disease features will also be recorded. Fibrosis will be determined by the extent of cutaneous involvement (limited or diffuse) and modified Rodnan Skin Score. Microangiopathy will be assessed by videocapillaroscopy and presence of acral ulcers or acrosteolysis; Presence of calcinosis will also be assessed . Upon recruitment each SSc patient will undergo blood sampling, which will be centrifuged and stored at -80° until the day of the processing. Biomarkers (Klotho, OPG, DKK, and sclerostin) will be determined using commercial kit of the ELISA Immunoenzyme techniques<br>|
| Healthy subjects<br> | Other: Evalution in healthy patients of bone mineral density, Klotho level and key bone-related cytokines<br>* Healthy female control patients undergoing bone mineral density determination will be recruited upon exclusion criteria are ruled out. A detailed clinical history will be assessed and blood sempling will be processed for detection of bone-related cytokines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Klotho serum levels in a group of 63 female SSc patients aged 45-65 years compared to 63 age and sex-matched healthy controls | Klotho serum levels in each SSc and control subject will be determined by a commercial ELISA assay | 21 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Klotho serum levels in female SSc patients: relationship to microvascular damage and fibrosis | Evaluation of a possible relationship among Klotho serum levels, the extent and type of the microvascular damage assessed by videocapillaroscopy, and the extent of the cutaneous fibrotic involvement assessed by the modified Rodnan skin score (mRSS). | 21 months | 
| Klotho serum levels in female SSc patients: relationship to bone mineral density values | Detection of a possible relationship between Klotho serum levels and bone mineral density values in female SSc patients stratified according to the extent of vascular and fibrotic damage | 21 months | 
| Klotho serum levels in female SSc patients relationship to key bone-related cytokine serum levels | Assessment of a possible relationship among Klotho, DDK-1, OPG, and sclerostin serum levels | 21 months |