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

Postmenopausal osteoporosis is a major public health problem in developed countries. Despite the progress, knowledge of its pathophysiological mechanisms and identification of women at high risk of fracture in the clinical practice are not satisfactory. Gut microbiota consist of trillions of commensal bacteria playing a major role in the regulation of metabolism of their human host. Some conditions (diabetes mellitus, obesity, liver cirrhosis, inflammatory bowel disease, end stage renal disease, depression, heavy drinking, heavy smoking) are associated with variations in gut microbiota diversity and higher risk of fracture. Intestinal bacteria synthesize or influence the synthesis of factors which modulate bone metabolism, e.g. lipopolysaccharide (present in the wall of Gram-negative bacteria), inflammatory cytokines (synthesized in the gut associated lymphoid tissue), serotonin (synthesized in the colon epithelium), short-chain fatty acids, estrogens (deconjugation of sulphates and glucuronides). Data on the association between gut microbiota and bone metabolism were obtained mainly in experimental animal studies. Clinical data are limited. Data on the possible role of gut microbiota in the pathophysiology of the postmenopausal osteoporosis are scarce.

The investigators will carry out a cross-sectional comparison of gut microbiota composition in four groups of women aged 60 and over recruited on the basis of their bone mineral density (BMD) and personal history of fragility fracture. The primary statistical analyses will be focused on the comparison of gut microbiota diversity according to BMD (in women with the same fracture status) and according to the fracture status (in women with similar BMD). The investigators will analyze interactions of the gut microbiota diversity, its metabolic activity and other metabolic factors on the one hand, with bone status on the other hand. The investigators will study the association of gut microbiota composition with bone turnover rate, BMD, bone microarchitecture, bone strength estimated by microfinite element analysis (micro-FEA) and with physical performance, muscle mass and strength. The investigators will assess the impact of microRNAs modulating the expression of inflammatory cytokines on the serum levels of these cytokines according to the pattern of gut microbiota diversity and their associations with the characteristics of bone status (e.g. bone microarchitecture). The investigators will analyze the association between serum serotonin, abundance of intestinal bacteria stimulating serotonin synthesis (some Clostridia species) in the colon and the characteristics of bone status.

This study will provide new data concerning the importance of gut microbiota for the fracture risk in older women. The main limitation of this study is its cross-sectional design but this is the first clinical study exploring this subject. It will help to identify the main metabolic pathways underlying the observed associations. These data will stimulate experimental studies to elucidate biological mechanisms underlying these associations. the results will provide indications for future clinical and experimental studies. In the long run, the results will lead up to future studies permitting to develop new biological markers of fracture risk in older women and new anti-osteoporotic medications.

Inclusion criteria

• 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.

Exclusion criteria

• 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.