Radiological Biological Genetic and Micro-architectural Bone Determinants of Fractures in Men With Low Bone Mineral Density

Not Applicable

Completed

• Conditions: Osteoporosis
• Interventions: Other: Radiology; Other: Biological, biochemical and genetic samples

• Registration Number: NCT01250314
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Rational: Osteoporosis in men is responsible for one third of fragility fractures. However the definition and especially the determinants of fracture in humans are less well known than in women.

Primary Objective: To search radiologic, biochemical, genetic and micro-architecture bone factors associated to fractures in men with low bone density.

Study design: case/control study (fracture vs. no fracture) with men selected according to low bone density (Z-score\<-2).

Eligibility criteria: Included subjects will be men whose age is ³ 40 and £ 70 years with a Z-score\< -2 at least at one of the 3 measured sites (wrist, lumbar spine, femoral neck). Subjects with secondary osteoporosis will be excluded (corticosteroid treatment, hypogonadism, ...) Progress of the study: The recruitment will be over two years. The study will include two periods, an inclusion visit and a period of 3 months to achieve radiological and biological examinations. The subjects will be recruited in the 3 rheumatology departments (LARIBOISIERE, COCHIN). Subjects will be investigated at LARIBOISIERE hospital to perform radiological examinations and biological sampling for laboratory tests within 3 months of enrollment.

Evaluation criteria: Biochemistry: dosages of sexual steroids, bone remodeling markers and homocysteine; Genetic: evaluation of polymorphism of candidates genes associated to fragility fractures (collagen type I, homocysteine, LRP5); Radiology: evaluation of bone micro-architecture with a scan of lumbar spine and hip and peripheral micro-scan (XTREME sSCANCO) and bone densitometry at spine, femoral neck and wrist.

Duration of participation: there is no follow up Total duration of the study: 2 years and 3 months. Number of subjects: 100 patients with fracture and 100 controls without fracture

Detailed Description

Statistical Analysis: Relationship between computed scan parameters at different sites, bone micro-architectural parameters (peripheral scan), biological parameters, genetic markers and the occurrence of fracture will be analyzed initially by univariate analysis (screening process). This will help to reduce the number of variables analyzed at the second stage of analysis (i.e. multivariate analysis).

Expected results: This study will help to evaluate radiological, biochemical and genetic determinants of bone quality in men with decreased bone density. It will help to establish a prospective study to evaluate predictive factors of fractures in men.

Study Timeline

• Study Start: 2008-02
• Primary Completion: 2010-09
• Study First Submitted: 2010-11-27
• Study First Submitted QC: 2010-11-27
• Study First Posted: 2010-11-30
• Study Completion: 2010-12
• Status Verified: 2012-07
• Last Update Submitted: 2012-07-01
• Last Update Posted: 2012-07-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 79

Inclusion Criteria

• Subject of masculine gender
• Aged ≥ 40 years and ≤ 70 years
• Subject with Z-score < -2 at least one of 3 sites
• one of 3 sites (wrists, lumbar spine (defined on at least 2 continuous evaluable vertebrae between L1-L4) and femoral neck) discovered incidentally or not
• Subject who have signed the informed consent form

The inclusion densitometry examination, less than 6 months old, will be performed on a Lunar or Hologic system. The reference data are the French reference data included in the Lunar system and TK in the Hologic system).

Exclusion criteria:

• Patient or control subject with no affiliation at health national system (beneficiary or co-beneficiary)
• Subject who received any corticoid treatment more than 3 months along
• Subject with any known seropositivity for HIV
• Subject with a chronic inflammation disease (rheumatoid polyarthritis, ankylosing spondylarthritis, inflammatory bowel)
• Subject with secondary osteoporosis documented by clinical and biological examinations (serum calcium, serum phosphate, serum phosphatase alkaline, gamma GT, testosterone) in order to eliminate any chronic alcoholism, alcoholic cirrhosis, hypogonadism, osteomalacia, hemochromatosis, hyperthyroidism, primitive hyperparathyroidism, hypercorticism
• Subject who received treatment with bisphosphonates intravenously
• Subject who received a treatment with bisphosphonates (Actonel® or Fosamax®) for at least 5 years and stopped since less than 2 years
• Subject who received a treatment with bisphosphonates for at least 3 years and stopped since less than 1 year
• Subject who received a treatment with bisphosphonates during the 6 months before inclusion

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
With fracture	Biological, biochemical and genetic samples	Patients with fracture
Without fracture	Radiology	Patients without fracture
Without fracture	Biological, biochemical and genetic samples	Patients without fracture
With fracture	Radiology	Patients with fracture

Primary Outcome Measures

Name	Time	Method
Biochemical	up to 90 days	Sexual steroid dosages, bone remodeling markers, homocysteine, IGF1
Genetic	up to 90 days	Polymorphism evaluation of candidate genes associated to fractures of fragility (collagen type I, receptor of 25-hydroxy vitamin D, aromatase, MTHFR, LRP5)
Radiological	up to 90 days	Bone micro-architecture evaluation with a scanner examination of lumbar spine and hip, peripheral scanner (Xtreme Scanco) and bone mineral densitometry at spine, femoral neck and wrist.

Trial Locations

Locations (1)

Fédération de Rhumatologie - Hôpital LARIBOISIERE; 🇫🇷 Paris, France