Bone development and remodeling in metabolic disorders

Abstract

There are many metabolic disorders that present with bone phenotypes. In some cases, the pathological bone symptoms are the main features of the disease whereas in others they are a secondary characteristic. In general, the generation of the bone problems in these disorders is not well understood and the therapeutic options for them are scarce. Bone development occurs in the early stages of embryonic development where the bone formation, or osteogenesis, takes place. This osteogenesis can be produced through the direct transformation of the pre‐existing mesenchymal cells into bone tissue (intramembranous ossification) or by the replacement of the cartilage by bone (endochondral ossification). In contrast, bone remodeling takes place during the bone's growth, after the bone development, and continues throughout the whole life. The remodeling involves the removal of mineralized bone by osteoclasts followed by the formation of bone matrix by the osteoblasts, which subsequently becomes mineralized. In some metabolic diseases, bone pathological features are associated with bone development problems but in others they are associated with bone remodeling. Here, we describe three examples of impaired bone development or remodeling in metabolic diseases, including work by others and the results from our research. In particular, we will focus on hereditary multiple exostosis (or osteochondromatosis), Gaucher disease, and the susceptibility to atypical femoral fracture in patients treated with bisphosphonates for several years.

Coumarin Ameliorates Impaired Bone Turnover by Inhibiting the Formation of Advanced Glycation End Products in Diabetic Osteoblasts and Osteoclasts

“…Aberrant bone remodeling results in bone diseases such as osteoporosis [8,9]. Several metabolic diseases accompany pathological features in the bone due to impaired bone remodeling [8,10]. Bone turnover is reduced or disrupted in diabetes mellitus, in parallel with increased risk of bone fractures and reduced mineralization [12,16].…”

“…In several metabolic diseases, bone pathology is associated with impaired bone development or bone remodeling [8,10]. Diabetic complications and osteoporotic fracture are chronic diseases that share several features including genetic susceptibility and environmental factors [11].…”

Calcium fructoborate coating of titanium–hydroxyapatite implants by chemisorption deposition improves implant osseointegration in the femur of New Zealand White rabbit experimental model

“…Woven bone is found in different processes, such as the process of rapid ossification, during fracture development and healing, or in different tumors and some bone metabolic disorders. The isotropic mechanical characteristics of the woven bone are given by the disorientation of collagen fibers [ 26 ]. Osteocyte is considered to be the most mature or most differentiated cell of the osteoblastic line, located in lacunae and interconnected by canals.…”

Desktop-Stereolithography 3D Printing of a Polyporous Extracellular Matrix Bioink for Bone Defect Regeneration

“…MSCs proliferate intensively and differentiate into osteoblasts, forming ossification center. The ossification center acts as a primed template for subsequent osteoblast infiltration, woven bone ossification, and bone remodeling restore healthy lamellar bone architecture (Dennis et al, 2015;Serra-Vinardell et al, 2020). Further work is needed to confirm the inference of these molecular mechanisms.…”