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

Osteoporosis Clinical Trial

— OSTEHOM  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01250314
• Other study ID #: P070121
• Status: Completed
• Phase: N/A
• First received: November 27, 2010
• Last updated: July 1, 2012
• Start date: February 2008
• Est. completion date: December 2010

Study information

• Verified date: July 2012
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: December 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 70 Years

Eligibility

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 Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Osteoporosis

Intervention

Other:
• Radiology
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).
• Biological, biochemical and genetic samples
*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.

Locations

Country	Name	City	State
France	Fédération de Rhumatologie - Hôpital LARIBOISIERE	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biochemical	Sexual steroid dosages, bone remodeling markers, homocysteine, IGF1	up to 90 days	No
Primary	Genetic	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	No
Primary	Radiological	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	No