New insights into the complex biology of osteoporosis: energy metabolism of bone cells, chemical and structural bone matrix properties and gut microbiota are involved in the etiopathogenesis

Osteoporosis (OP) is a systemic skeletal disease with a complex and multifactorial etiology, associated with aging and characterized by a low bone mass and microarchitectural deterioration of bone tissue. OP poses a significant health burden and notable economic issues due to its high incidence among the population. OP fragility fractures result in disability and even premature death. Preventing bone fragility is of great importance for both patient health and the sustainability of healthcare systems, therefore in-depth understanding of the complex etiology of this disease is urgent. Molecular and chemical modifications of bone tissue, together with other systemic factors are involved in the etiopathogenesis of OP, thus underlining its complex pathogenesis. Herein, three main aspects are explored: (i) the impact of monocarboxylate transporter MCT1 on osteocytes, focusing on the intracellular accumulation of lactate and protons that may play a role in osteocyte apoptosis and bone tissue health, (ii) chemical alterations in the inorganic and organic matrix of bone tissue may be related to bone fragility, and (iii) the imbalanced composition of gut microbiota as a possible cause of altered bone health. Molecular analyses of the energetic metabolism of osteocytes, spectroscopic analyses on bone tissue, and the characterization of the entire gut microbiota were performed on osteoporotic patients compared to healthy patients to underline potential characteristic signatures of OP. Results showed that: (i) MCT1 has a pivotal role in osteocytes survival and apoptosis; (ii) the inorganic matrix of bone tissue shows chemical alterations due to aging, being potential risk factors for bone tissue weakness, and (iii) gut microbiota composition exhibited dysbiosis in aged patients, an important task to be addressed with specific treatments. The collected data underline the importance of both prevention and treatment paying attention synergically to all the different risk factors, using a multidisciplinary approach.