Microbiota and Bone Fragility:Study of the Relation Between Gut Microbiota and Bone Microarchitecture

NCT04265742 | Completed DMC

• 2 other identifiers: C18-042018-A01806-49
• Study Type: interventional
• Target: 440
• Locations: 1 country
• Sites: 1

Brief Summary

Gut microbiota regulate metabolism of their human host. Some diseases are associated with variations in gut microbiota diversity and higher fracture risk. Intestinal bacteria synthesize or influence synthesis of factors modulating bone metabolism. The link between gut microbiota and bone was assessed mainly in experimental animal studies. Clinical data, e.g. on the role of gut microbiota in postmenopausal osteoporosis are scarce. The investigators will compare gut microbiota composition in four groups of women aged ≥60 recruited on the basis of bone mineral density (BMD) and personal history of fracture. the participants will have diagnostic exams: clinical tests, bone densitometry (body composition, vertebral fractures), high resolution peripheral QCT (bone strength estimated by microfinite element analysis, micro-FEA), biological sample collection. Gut microbiome profiling will be performed at the INRA MetaGenoPolis laboratory. The investigators will compare gut microbiota diversity according to BMD level and to the fracture status. The investigators will analyze interactions of the gut microbiota diversity with bone status (bone turnover rate, BMD, bone microarchitecture, bone strength estimated by micro-FEA), muscle mass and strength, inflammatory cytokines and micro-RNAs modulating their expression. This study will provide new data concerning the importance of gut microbiota for the fracture risk in older women. It will help to identify the main metabolic pathways underlying the observed associations.

Conditions

Bone Loss, Age-related

Keywords

Bone microarchitecture; intestinal microbiote; post-menopausal women; bone remodeling

Outcome Measures

Primary Outcomes (1)

• Comparison of the composition of the gut microbiota according to fracture status in postmenopausal women with comparable bone mineral density.

  The composition of the intestinal microbiota will be evaluated by the ratio between the amount of proinflammatory bacteria (Prevotellaceae, E. coli, Bacteroides vulgatus, Proteus mirabili) and the amount of anti-inflammatory bacteria (Faecalibacterium, Roseburia) in postmenopausal women with mineral density comparable bone according to their fracture status.

  through study completion, an average of 3 years

Secondary Outcomes (7)

• Determine the relationship between the composition of the gut microbiota and bone microarchitecture according to fracture status in postmenopausal women with comparable bone mineral density.

  through study completion, an average of 3 years

• Determine the relationship between the composition of the gut microbiota and bone mineral density according to fracture status in postmenopausal women with comparable bone mineral density.

  through study completion, an average of 3 years

• Determine the relationship between the composition of the gut microbiota and muscle mass and strength according to fracture status in postmenopausal women with comparable bone mineral density.

  through study completion, an average of 3 years

• Determine the relationship between the composition of the gut microbiota and physical performance according to fracture status in postmenopausal women with comparable bone mineral density.

  through study completion, an average of 3 years

• Determine the relationship between the composition of the gut microbiota and bone remodeling according to fracture status in postmenopausal women with comparable bone mineral density.

  through study completion, an average of 3 years

Study Arms (4)

Group A. Normal BMD, no fracture

EXPERIMENTAL

Post-menopausal women with normal bone density (BMD t-score \>-1.5) and no history of fractures. Intervention: bone densitometry, high resolution peripheral QCT(HR-pQCT), collection of biological samples, questionnaires, clinical tests.

Radiation: bone densitometry; Radiation: High resolution peripheral QCT; Diagnostic Test: Collection of biological samples; Other: questionnaires; Other: clinical tests

Group B. Normal BMD, with fracture

EXPERIMENTAL

Post-menopausal women with normal bone density (BMD T-score \>-1.5) with history of fractures. Intervention: bone densitometry, high resolution peripheral QCT(HR-pQCT), collection of biological samples, questionnaires, clinical tests.

Radiation: bone densitometry; Radiation: High resolution peripheral QCT; Diagnostic Test: Collection of biological samples; Other: questionnaires; Other: clinical tests

Group C. osteoporotic, no fracture

EXPERIMENTAL

Post-menopausal women with low bone density (BMD T-score \<-2.5) and no history of fractures. Intervention: bone densitometry, high resolution peripheral QCT(HR-pQCT), collection of biological samples, questionnaires, clinical tests.

Radiation: bone densitometry; Radiation: High resolution peripheral QCT; Diagnostic Test: Collection of biological samples; Other: questionnaires; Other: clinical tests

Group D. osteoporotic, with fracture

EXPERIMENTAL

Post-menopausal women with low bone density (BMD T-score \<-2.5) with history of fractures. Intervention: bone densitometry, high resolution peripheral QCT(HR-pQCT), collection of biological samples, questionnaires, clinical tests.

Radiation: bone densitometry; Radiation: High resolution peripheral QCT; Diagnostic Test: Collection of biological samples; Other: questionnaires; Other: clinical tests

Interventions

bone densitometry RADIATION

Bone Mineral Density (BMD), body composition, vertebral fractures

Group A. Normal BMD, no fracture; Group B. Normal BMD, with fracture; Group C. osteoporotic, no fracture; Group D. osteoporotic, with fracture

High resolution peripheral QCT RADIATION

High resolution peripheral QCT (HR-pQCT): bone microarchitecture and bone strength

Group A. Normal BMD, no fracture; Group B. Normal BMD, with fracture; Group C. osteoporotic, no fracture; Group D. osteoporotic, with fracture

Collection of biological samples DIAGNOSTIC_TEST

Peripheral blood and urine samples to assess bone turnover markers and cytokines; and faeces to assess gut microbiota composition

Group A. Normal BMD, no fracture; Group B. Normal BMD, with fracture; Group C. osteoporotic, no fracture; Group D. osteoporotic, with fracture

questionnaires OTHER

Epidemiologic and nutritional questionnaire and physical activity scale

Group A. Normal BMD, no fracture; Group B. Normal BMD, with fracture; Group C. osteoporotic, no fracture; Group D. osteoporotic, with fracture

clinical tests OTHER

physical performance tests and grip strenght measurement

Group A. Normal BMD, no fracture; Group B. Normal BMD, with fracture; Group C. osteoporotic, no fracture; Group D. osteoporotic, with fracture

Eligibility Criteria

• Age: 60 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• post-menopausal women
• with a normal Bone Mineral Density (T-score \>-1.5) at the 3 sites (lumbar spine, total hip and femoral neck) or with osteoporosis (T-score ≤ -2.5) at least at one of the 3 sites.

You may not qualify if:

• Current antibiotherapy or in the last 6 months or repeated antibiotherapy
• Current corticotherapy or stopped for less than 6 months
• Current treatment of osteoporosis or having lasted more than 3 months in the last 5 years
• Current hormonal treatment for menopause
• Current or discontinued drugs that may affect bone metabolism (eg anti-aromatase)
• Known hepatic, cardiac or respiratory insufficiency
• Pathologies that may affect bone metabolism, particularly severe renal insufficiency
• Serious illnesses, particularly disabling and chronic diseases of the gastrointestinal tract
• Diseases characterized by substantial disorders of the gut microbiota (eg severe obesity, BMI\> 40 kg / m2, depression, poorly controlled diabetes)
• Psychiatric pathology hindering understanding
• Difficulty understanding oral French
• Person protected by law, unable to express her consent, subject to a protective measure or deprived of liberty.

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Hopital E. Herriot

Lyon, 69437, France

Location

MeSH Terms

Conditions

Osteoporosis

Interventions

Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Pawel SZULC, MD, Ph.D

  Hospital Edouard Herriot, , 69437 Lyon

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: The composition of the intestinal microbiota will be evaluated by the ratio between the amount of pro-inflammatory bacteria (Prevotellaceae, E. coli, Bacteroides vulgatus, Proteus mirabili) and the amount of anti-inflammatory bacteria (Faecalibacterium, Roseburia) in postmenopausal women with comparable bone mineral density, according to their fracture status.

Study Record Dates

• First Submitted: September 24, 2018
• First Posted: February 12, 2020
• Study Start: February 8, 2019
• Primary Completion: February 4, 2022
• Study Completion: February 4, 2022
• Last Updated: August 31, 2022

Record last verified: 2021-08

Locations

FR (1)