Osteoporosis and Fragility Fractures Among SLE Patients. (FRAIL Trial)

Study Overview
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Brief Summary
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The trial is designed to evaluate prevalence of fragility fracture, their impact on quality of life of SLE patients and disease or treatment variables such as steroids dosage or use of specific drugs like hydroxychloroquine, DMARDs or belimumab. Patients will perform DXA evaluation, blood tests and PROs questionnaires. Moreover, the investigators want to correlate those variables to bone turnover markers and bone metabolism modulators. A secondary aim is also to assess the fracture risk of those patients as described by FRAX and DEFRA tools.

Official Title
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Prevalence and Impact on Quality of Life of Osteoporosis and Fragility Fractures Among SLE Patients. (FRAIL Trial)

Conditions
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Lupus Erythematosus, Systemic

Intervention / Treatment
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* Diagnostic Test: DXA
* Diagnostic Test: serum sample
* Diagnostic Test: PROs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SLE fulfilling 2019 ACR/EULAR or 2012 SLICC criteria willing to perform DXA/ x-Ray investigation (common clinical practice) willing to donate blood sample willing to complete questionnaires the patients should be in a stable disease activity. Exclusion Criteria: Uncontrolled endocrinological disease. metabolic bone disease other than osteoporosis ( e.g. Paget disease). celiac disease, inflammatory bowel disease or pancreatic exocrine deficiency resulting in malabsorption patients lacking medication history information (SLE and bone related medications). Have any other clinically significant abnormal laboratory value in the opinion of the investigator Have any intercurrent significant medical illness that the investigator considers would make the candidate unsuitable for the study. The patients shouldn't be enrolled during a moderate to severe flare of disease requiring an escalation of therapy ( especially glucocorticoid) - no new BILAG A or B in the last 3 months. Pregnant patients or during the first year after child birth.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: DXA|bone densitometry at lumbar and femoral site+ morphometry (DXA),|
|Diagnostic Test: serum sample|serum samples for bone biomarkers ( eg. P1NP, CTX, Dkk-1, etc)|
|Diagnostic Test: PROs|questionnaires to investigate patients reported outcome on quality of life|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of osteoporosis | percentage of patient with osteoporosis defined by WHO definition with T score | 1 visit - 1 hour | 
| Prevalence of fragility fractures | percentage of patients with fragility fractures | 1 visit 1 hour | 
| EQ5D | scores at questionnaire on quality of life EQ5D = EuroQol 5 dimension 5 L; (min 1-1-1-1-1, max 5-5-5-5-5 higher score worse + EQ VAS min 0, max 100 higher score better quality of life) | 1 visit - 1 hour | 
| FACIT-F | scores in fatigue as for questionnaire FACIT-F (Functional Assessment of Chronic Illness Therapy - Fatigue; min 0 - max 52, higher score less fatigue) | 1 visit - 1 hour | 
| SF-36 v2 | scores on quality of life with SF36 v2 (Short Form 36 version 2 Health Survey; min 0 - max 100, higher score better health) | 1 visit - 1 hour | 
| HADS | scores on mood disorder scale HADS (Health Anxiety and Depression Scale; min 0 - Max 42, higher score worse anxiety) | 1 visit - 1 hour | 
| CQR5 | compliance questionnaire in rheumatoogy 5 items; adherent - not adherent to medication) | 1 visit - 1 hour | 
| PGA | Patient global assessment ( VAS scale 0-10) higher score worse health | 1 visit - 1 hour | 
| influence of SLE medication - glucocorticoid | The population will be analyzed grouping by presence or absence of fragility fracture in relation to medications variables such as difference in cumulative corticosteroid dose (mg) | 1 visit - 1 hour | 
| influence of SLE medication - hydroxychloroquine | The population will be analyzed grouping by presence or absence of fragility fracture in relation to medications variables such as difference in percentage of hydroxychloroquine users. | 1 visit - 1 hour | 
| influence of SLE medication - immunosuppressant | The population will be analyzed grouping by presence or absence of fragility fracture in relation to medications variables such as difference in percentage percentage of immunosuppressant users | 1 visit - 1 hour | 
| influence of SLE medication - biologics | The population will be analyzed grouping by presence or absence of fragility fracture in relation to medications variables such as difference in percentage of percentage of biologics ( e.g. belimumab) users. | 1 visit - 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive statistics of study population - 1 | The population will be analyzed as whole and also grouping by presence or absence of fragility fracture in relation to clinical variables - SLE disease duration | 1 visit - 1 hour | 
| Descriptive statistics of study population - 2 | The population will be analyzed as whole and also grouping by presence or absence of fragility fracture in relation to clinical variables - SDI ( SLICC Damage index - from 0, higher score higher disease damage accrual) | 1 visit - 1 hour | 
| Descriptive statistics of study population - 3 | The population will be analyzed as whole and also grouping by presence or absence of fragility fracture in relation to demographic variable - Age ( years) | 1 visit - 1 hour | 
| Descriptive statistics of study population - 4 | The population will be analyzed as whole and also grouping by presence or absence of fragility fracture in relation to demographic variable - gender ( % females) | 1 visit - 1 hour | 
| serum bone biomarkers - BAP | bone alkaline phosphatase (BAP) (ug/L) level in study population and difference by fracture status | 1 visit - 1 hour | 
| serum bone biomarkers - P1NP | N-terminal propeptide of type I procollagen - P1NP (ng/ml) level in study population and difference by fracture status | 1 visit - 1 hour | 
| serum bone biomarkers - CTX | C-terminal telopeptide of type I collagen (CTX) (ng/ml), level in study population and difference by fracture status | 1 visit - 1 hour | 
| serum bone biomarkers - PTH | parathormone (PTH) pg/ml level in study population and difference by fracture status | 1 visit - 1 hour | 
| serum bone biomarkers - vitamin D(OH) | 25OH vitamin D (ng/ml), level in study population and difference by fracture status | 1 visit - 1 hour | 
| serum bone biomarkers - Sclerostin | sclerostin (pmol/L) level in study population and difference by fracture status | 1 visit - 1 hour | 
| serum bone biomarkers - Dkk1 | Dkk1 (pmol/L) level in study population and difference by fracture status | 1 visit - 1 hour | 
| serum bone biomarkers - RANKL | RANKL (pg/ml) level in study population and difference by fracture status | 1 visit - 1 hour | 
| serum bone biomarkers - OPG | OPG (pg/ml level) in study population and difference by fracture status | 1 visit - 1 hour | 
| Fracture risk calculation by FRAX tool | FRAX fracture risk assessment ( % risk major fracture in 10 yrs) | 1 visit - 1 hour | 
| Fracture risk calculation by DEFRA tool | DEFRA fracture risk assessment ( % risk major fracture in 10 yrs) | 1 visit - 1 hour |