Klotho and Mineral Bone Density in Systemic Sclerosis

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

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

Study Overview

• Status: Completed
• Conditions: Systemic Sclerosis
• Intervention / Treatment: 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

Detailed Description

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 . For each patient demographic data, history of fractures and smoking habits will be gathered. Evaluation of bone mineral density will be performed and blood samples to dose DDK1, sclerostin, osteoprotegerin and Klotho will be collected.

• Study Type: Observational
• Enrollment (Actual): 126

Contacts and Locations

Study Locations

• Italy
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Division of Rheumatology, Fondazione Policlinico Universitario A.Gemelli IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Female patients with a diagnosis of Systemic Sclerosis according to the EULAR/ACR 2013 criteria and followed by the FPG-IRCSS Rheumatology Department will be progressively recruited, after exclusion criteria are ruled out and informed consent is signed.

Concomitantly healthy control female patients undergoing bone mineral density determination are recruited, once exclusion criteria are ruled out.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Systemic Sclerosis patients; Female patients with systemic sclerosis with an age between 45 and 65 years old and did not met the exclusion criteria. Blood sample were collected to determine DKK1, Sclerostin Klotho and Osteoprotegerin. Bone mineral density was assessed. No drug was tested during the study.	Other: Possible Klotho effects on SSc clinical conditions, namely skeletal, fibrotic and microangiopathic damage; 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
Healthy subjects; Female patients with no history of inflammatory rheumatic disease and who di not met the exclusion criteria. Blood sample were collected to determine DKK1, Sclerostin Klotho and Osteoprotegerin. Bone mineral density was assessed. No drug was tested during the study.	Other: Evalution in healthy patients of bone mineral density, Klotho level and key bone-related cytokines; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Luisa Mirone, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2022
• Primary Completion (Actual): April 30, 2024
• Study Completion (Actual): April 30, 2024

Study Registration Dates

• First Submitted: February 21, 2023
• First Submitted That Met QC Criteria: March 8, 2023
• First Posted (Actual): March 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Connective Tissue Diseases; Skin Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: 4633

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No