Radiological Biological Genetic and Micro-architectural Bone Determinants of Fractures in Men With Low Bone Mineral Density
Condition: Osteoporosis
MeSH terms: Osteoporosis; Bone Diseases, Metabolic
Study type: Interventional

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.
    

Intervention name(s): Radiology; Biological, biochemical and genetic samples
Intervention type(s): Other; Other
Intervention description(s): Spine radiography, densitometry, evaluation of bone architecture and micro-architecture (computed tomography of lumbar spine and hip and peripheral micro-scanner (XREME SCANCO) at tibia and wrist).; *Serum calcium and phosphore evaluation, bone remodeling markers, 25-hydroxyvitamin D level assessment: Blood samples plasma (5 ml):Creatin, calcemia, phosphoremia, alkaline phosphatase, bone alkaline phosphatase, osteocalcin, CTX, 25 hydroxyvitamin D and parathormone
Urinary samples :
Deoxy-pyridinoline, creatinuria Fasting morning urine on a sample Calciuria, creatinuria, cortisoluria Day urine on a sample
*Assessment of possible determinants of fractures in man
Blood samples plasma (5 ml):
Sexual Hormones: Estradiol, Testosterone, SHBG, LH, FSH
Homocysteine
IGF1
Extraction of DNA for a genetic polymorphism study:
Sample of 10 ml of blood on EDTA for DNA extraction.
Tested polymorphisms will be: LRP5, CYP19 (Aromatase), COL1A1 (Collagen I),MHTFR, IGF-1,VDR vitamin D receptor
Globally 20 ml of blood will be taken for each subject. Every biological sample for biochemical dosages and for genetic analysis will be preserved in an anonymous way.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Keywords: osteoporosis; men; bone micro-architecture; bone markers