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

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

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

Study Overview

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 Type

Interventional

Enrollment (Actual)

79

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Paris, France, 75010
        • Fédération de Rhumatologie - Hôpital LARIBOISIERE

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: With fracture
Patients with fracture
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.

Other: Without fracture
Patients without fracture
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biochemical
Time Frame: up to 90 days
Sexual steroid dosages, bone remodeling markers, homocysteine, IGF1
up to 90 days
Genetic
Time Frame: 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)
up to 90 days
Radiological
Time Frame: 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.
up to 90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Marie-Christine De VERNEJOUL, MD,PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2008

Primary Completion (Actual)

September 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

November 27, 2010

First Submitted That Met QC Criteria

November 27, 2010

First Posted (Estimate)

November 30, 2010

Study Record Updates

Last Update Posted (Estimate)

July 3, 2012

Last Update Submitted That Met QC Criteria

July 1, 2012

Last Verified

July 1, 2012

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Osteoporosis

Clinical Trials on Radiology

3
Subscribe