Abstract

Osteoporosis is a disease characterized by low bone mass and alterations of bone microarchitecture, with an increased risk of fractures. It is a multifactorial disorder that is more frequent in postmenopausal women but can be associated to other diseases (inflammatory and metabolic diseases). At present, several options are available to treat osteoporosis trying to block bone reabsorption and reduce the risk of fracture. Anyway, these drugs have safety and tolerance problems in long-term treatment. Recently, gut microbiota has been highlighted to have strong influence on bone metabolism, becoming a potential new target to modify bone mineral density. Such evidences are mainly based on mouse models, showing an involvement in modulating the interaction between the immune system and bone cells. Germ-free mice represent a basic model to understand the interaction between microbiota, immune system, and bone cells, even though data are controversial. Anyway, such models have unequivocally demonstrated a connection between such systems, even if the mechanism is unclear. Gut microbiota is a complex system that influences calcium and vitamin D absorption and modulates gut permeability, hormonal secretion, and immune response. A key role is played by the T helper 17 lymphocytes, TNF, interleukin 17, and RANK ligand system. Other important pathways include NOD1, NOD2, and Toll-like receptor 5. Prebiotics and probiotics are a wide range of substances and germs that can influence and modify microbiota. Several studies demonstrated actions by different prebiotics and probiotics in different animals, differing according to sex, age, and hormonal status. Data on the effects on humans are poor and controversial. Gut microbiota manipulation appears a possible strategy to prevent and treat osteopenia and/or osteoporosis as well as other possible bone alterations, even though further clinical studies are necessary to identify correct procedures in humans.

Highlights

  • Osteoporosis is the most common bone disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, with increased risk of fractures.Fractures severely affect patients’ quality of life and mortality, especially in case of major fractures and represent a serious public health problem due to population aging, with high impact on the health care costs

  • Scientific community is increasing interest in studying such new “organ” to deeply understand its role and potentiality to treat diseases. It is strongly involved in human development, especially of the immune system; gut microbiota (GM) is necessary for an appropriate education and evolution of the innate and adaptive immune response [13]

  • Osteoporosis is a multifactorial disorder associated with reduced bone density and high risk of fracture

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Summary

Introduction

Osteoporosis is the most common bone disorder characterized by low bone mass and microarchitectural deterioration of bone tissue, with increased risk of fractures. Several drugs are available to treat osteoporosis and reduce the risk of fracture blocking bone reabsorption (such as bisphosphonates and denosumab), by stimulating bone formation or both (such as teriparatide or abaloparatide). Such drugs have safety and tolerance problems in long-term treatment. Scientific community is increasing interest in studying such new “organ” to deeply understand its role and potentiality to treat diseases It is strongly involved in human development, especially of the immune system; GM is necessary for an appropriate education and evolution of the innate and adaptive immune response [13]. The intent of this review is to expose the mechanism underlying the interaction between GM and osteoporosis

Studies on Germ-Free Models
Role of Gut Microbiota in Vitamin D and Calcium Absorption
Role of Gut Microbiota in Bone Homeostasis
Prebiotics
Probiotics
Conclusions
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