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

NCT01250314 | Completed

• 1 other identifier: P070121
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

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

Conditions

Osteoporosis

Keywords

osteoporosis; men; bone micro-architecture; bone markers

Outcome Measures

Primary Outcomes (3)

• Biochemical

  Sexual steroid dosages, bone remodeling markers, homocysteine, IGF1

  up to 90 days

• 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

• 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

Study Arms (2)

With fracture

OTHER

Patients with fracture

Other: Radiology; Other: Biological, biochemical and genetic samples

Without fracture

OTHER

Patients without fracture

Other: Radiology; Other: Biological, biochemical and genetic samples

Interventions

Radiology OTHER

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).

With fracture; Without fracture

Biological, biochemical and genetic samples OTHER

\*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.

With fracture; Without fracture

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Ministry of Health, France: collaborator

Study Sites (1)

Fédération de Rhumatologie - Hôpital LARIBOISIERE

Paris, 75010, France

Location

MeSH Terms

Conditions

Osteoporosis; Multiple Endocrine Neoplasia Type 1

Interventions

X-Rays; Biological Products

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Complex Mixtures

Study Officials

• Marie-Christine De VERNEJOUL, MD,PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2010
• First Posted: November 30, 2010
• Study Start: February 1, 2008
• Primary Completion: September 1, 2010
• Study Completion: December 1, 2010
• Last Updated: July 3, 2012

Record last verified: 2012-07

Locations

FR (1)