Who Is Involved In The Remodeling Of Bones?

Bone metabolism involves two main types of cells: osteoblasts (secreting new bone) and osteoclasts (breaking down bone). The structure of bones and adequate calcium supply require close cooperation between these two cell types and other cell populations present at bone remodeling sites, such as immune cells. Bone remodeling is essential for adult bone homeostasis, consisting of two phases: bone formation and resorption. The balance between the two phases is crucial.

Bone remodeling occurs on trabecular surfaces in the form of shallow irregular Howship’s lacunae, while in cortical bone it occurs as a cylinder to form the skeleton. The bone remodelling cycle replaces old and damaged bone and is a highly regulated, lifelong process essential for preserving bone integrity and maintaining mineral content.

Osteocytes are key players in bone remodeling, regulating both osteoclastic bone resorption and osteoblastic bone formation. Osteoclasts initiate bone remodeling and perform the actual removal of old bone matrix, while osteoblasts become activated to lay down new bone. During bone remodeling, bone formation is tightly coupled to bone resorption, and direct contacts between osteoclasts and osteoblasts have been observed.

The basic multicellular unit (BMU) responsible for bone remodeling consists of osteoclasts and osteoblasts. In bone, RANKL stimulates osteoclast formation by binding RANK on osteoclast precursors and osteoclasts, which is required for bone resorption. The remodelling cycle occurs within the BMU and comprises five co-ordinated steps: activation, resorption, reversal, formation, and resorption.

What are the 5 stages of bone Remodelling?

The bone remodelling cycle is a lifelong process that replaces old and damaged bone, preserving bone integrity and maintaining mineral homeostasis. It involves five steps: activation, resorption, reversal, formation, and termination. The cycle is regulated by key signaling pathways, including receptor activator of nuclear factor-κB (RANK)/RANK ligand/osteoprotegerin and canonical Wnt signalling. Cytokines, growth factors, and prostaglandins act as paracrine regulators, while endocrine regulators include parathyroid hormone, vitamin D, calcitonin, growth hormone, glucocorticoids, sex hormones, and thyroid hormone.

Disruption of the bone remodelling cycle and imbalance between resorption and formation leads to metabolic bone disease, most commonly osteoporosis. Advances in understanding these mechanisms have provided targets for pharmacological interventions, including antiresorptive and anabolic therapies. This review discusses the remodelling process, osteoporosis, and common pharmacological interventions used in its management.

What is involved in bone remodeling?

The skeleton is a metabolically active organ that undergoes continuous remodeling throughout life. Bone remodeling involves the removal of mineralized bone by osteoclasts and the formation of bone matrix through osteoblasts. The remodeling cycle consists of three phases: resorption, reversal, and formation. It adjusts bone architecture to meet changing mechanical needs, repairs microdamages in bone matrix, and maintains plasma calcium homeostasis.

Systemic and local regulation of bone remodeling is involved, with major systemic regulators including parathyroid hormone (PTH), calcitriol, growth hormone, glucocorticoids, thyroid hormones, and sex hormones. Factors such as insulin-like growth factors (IGFs), prostaglandins, tumor growth factor-beta (TGF-beta), bone morphogenetic proteins (BMP), and cytokines are also involved. Local regulation of bone remodeling involves a large number of cytokines and growth factors that affect bone cell functions.

The RANK/receptor activator of NF-kappa B ligand (RANKL)/osteoprotegerin (OPG) system tightly couples the processes of bone resorption and formation, allowing a wave of bone formation to follow each cycle of bone resorption, thus maintaining skeletal integrity.

Are osteoclasts key players in controlling bone remodeling?

Osteoclasts are cells that degrade bone during normal bone remodeling and mediate bone loss in pathologic conditions by increasing their resorptive activity. They are derived from precursors in the myeloid/monocyte lineage that circulate in the blood after their formation in the bone marrow. These osteoclast precursors (OCPs) are attracted to sites on bone surfaces destined for resorption and fuse with one another to form multinucleated cells that resorb calcified matrixes under the influence of osteoblastic cells in bone marrow.

Recent studies have identified functions for OCPs and osteoclasts in and around bone other than bone resorption, such as regulating the differentiation of osteoblast precursors, participating in immune responses, and secreting cytokines that can affect their own functions and those of other cells in inflammatory and neoplastic processes affecting bone. These findings define new roles for osteoclasts and OCPs in the growing field of osteoimmunology and in common pathologic conditions in which bone resorption is increased. Osteoclasts form microscopic trenches on the surfaces of bone trabeculae in the spongy bone seen at the ends of long bones and inside vertebrae.

What are the 5 steps of bone regeneration?

Fracture healing is influenced by the mechanical stability at the fracture site and the strain. The amount of strain involved influences the biological behavior of the cells involved in the healing process. Primary bone healing occurs with a mechanical strain below 2, resulting in intramembranous bone healing through Haversian remodeling. Secondary bone healing occurs in non-rigid fixation modalities like braces, external fixation, plates in bridging mode, and intramedullary nailing, achieving a mechanical strain between 2-10 and resulting in endochondral bone healing.

Bone healing can involve a combination of primary and secondary processes based on the stability throughout the construct. Failed or delayed healing can affect up to 10 of all fractures and can result from factors such as comminution, infection, tumor, and disrupted vascular supply. This article will cover each of these steps in detail before discussing primary healing, factors affecting fracture healing, and methods of stimulation of fracture healing.

What are the 4 steps of bone remodeling in order?

Following a fracture, secondary healing begins, consisting of hematoma formation, granulation tissue formation, bony callus formation, and bone remodeling. The type of fracture healing depends on the mechanical stability at the fracture site and the strain. The amount of strain affects the biological behavior of cells involved in the healing process. Primary bone healing occurs with a mechanical strain below 2, while secondary bone healing occurs when the strain is between 2 and 10.

There are two main modes of bone healing: primary bone healing, which occurs through Haversian remodeling, and secondary bone healing, which occurs in non-rigid fixation modalities like braces, external fixation, plates in bridging mode, and intramedullary nailing. Bone healing can involve a combination of primary and secondary processes based on the stability throughout the construct. Failed or delayed healing can affect up to 10 of all fractures and can result from factors such as comminution, infection, tumor, and disrupted vascular supply.

What is the difference between rank and RANKL?

RANK, also known as TRANCE receptor or TNFRSF11A, is a member of the tumor necrosis factor receptor (TNFR) molecular sub-family and is involved in osteoclast differentiation and activation. It is associated with bone remodeling, immune cell function, lymph node development, thermal regulation, and mammary gland development. Osteoprotegerin (OPG) is a decoy receptor for RANKL, which competes for RANKL.

RANK is expressed in various tissues, including skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoclast, mammary gland epithelial cells, prostate, vascular cell, and pancreas.

NF-κB activation is typically mediated by RANKL, but over-expression of RANK alone is sufficient to activate the NF-κB pathway. RANKL is found on the surface of stromal cells, osteoblasts, and T cells. Mutations affecting RANK have been linked to infantile malignant osteopetrosis in humans, mice, and cats.

What directly controls bone remodeling?

Recent studies have shown that the activity of osteocytes during bone remodeling is tightly controlled by hormones secreted by other endocrine glands, such as parathyroid hormone (PTH) and gonadal estrogen. Osteocytes communicate with osteoblasts in a paracrine manner, and their ability to modulate osteoblast function is associated with the synthesis of SOST, an inhibitor of bone formation. This interaction slows down the rate of bone formation. Osteocytes can also affect osteoblasts by secreting prostaglandin E2, nitric oxide (NO), and ATP, which stimulate their activity.

During bone remodeling, osteoblasts are activated via RANKL and M-CSF, while osteoblasts are inhibited via OPG, NO, and TGFβ. Osteocytes-derived PGE2, NO, and ATP stimulate osteoblasts, while sclerostin or DKK1 decrease osteoblast activity. Osteoblasts interact with osteoclasts through RANKL, and bone-lining cells support the process of bone turnover. The role of SOST in the regulation of bone growth and remodeling is discussed in the following section.

Which two mechanisms are most responsible for controlling bone remodeling?

The binding of RANKL to OPG inhibits osteoclast differentiation and activity, regulating bone remodeling rate by the relative amounts of RANKL and OPG secreted close to the bone’s surface. This information is sourced from ScienceDirect, a website that uses cookies and holds copyright for text and data mining, AI training, and similar technologies. Open access content is licensed under Creative Commons terms.

What are the 6 processes of bone healing?

Direct healing involves fixing bony fragments with compression, without callus formation, and is facilitated by osteoclast and osteoblast activity. Indirect healing, more common than direct healing, involves both endochondral and intramembranous bone healing. It doesn’t require anatomical reduction or stable conditions, but a small amount of motion and weight-bearing at the fracture causes a soft callus to form, leading to secondary bone formation. However, too much load can cause delayed healing or non-union in 5-10% of fractures.

What are the 4 stages of bone healing and remodeling?

Following a fracture, secondary healing begins, consisting of hematoma formation, granulation tissue formation, bony callus formation, and bone remodeling. The type of fracture healing depends on the mechanical stability at the fracture site and the strain. The amount of strain affects the biological behavior of cells involved in the healing process. Primary bone healing occurs with a mechanical strain below 2, while secondary bone healing occurs when the strain is between 2 and 10.

There are two main modes of bone healing: primary bone healing, which occurs through Haversian remodeling, and secondary bone healing, which occurs in non-rigid fixation modalities like braces, external fixation, plates in bridging mode, and intramedullary nailing. Bone healing can involve a combination of primary and secondary processes based on the stability throughout the construct. Failed or delayed healing can affect up to 10 of all fractures and can result from factors such as comminution, infection, tumor, and disrupted vascular supply.

What role does estrogen play in bone remodeling?

Estrogen plays a crucial role in bone growth, maturation, and bone turnover regulation. It is necessary for proper closure of epiphyseal growth plates in both males and females during bone growth. In young skeletons, estrogen deficiency leads to increased osteoclast formation and enhanced bone resorption. In menopause, estrogen deficiency induces bone loss in cancellous and cortical bones, leading to general bone loss and destruction of local architecture.

In cortical bone, estrogen withdrawal leads to increased endocortical resorption and intracortical porosity, resulting in decreased bone mass, disturbed architecture, and reduced bone strength. Estrogen inhibits osteoclast differentiation, decreasing their number and active remodeling units. Estrogen regulates the expression of IL-6 in bone marrow cells through an unknown mechanism. It is unclear if estrogen’s effects on osteoblasts are direct or due to a coupling phenomenon between bone formation and resorption.