Do Hormones And Mechanical Stress Affect How Bones Remodel?

Bone remodeling is a lifelong process that creates a mature, dynamic bone structure through a balance between bone formation by osteoblasts and resorption by osteoclasts. Mechanical forces are essential for bone homeostasis, as they influence skeletal formation, resorption, and adaptation. Mechanical signals are transmitted to nearby osteocytes regarding bone stress, which in turn induces stress stimulation of the bone and transmits the force to bone cells.

Bone remodeling involves resorption by osteoclasts and replacement by osteoblasts, with osteoblasts and osteoclasts being considered bone remodeling units. The rate of remodelling is determined by loading and endocrine influences, with oestrogen being the most important endocrine regulator of bone turnover. Osteoblasts and osteoclasts are referred to as bone remodeling units.

Mechanical loading is a simple yet effective way to increase bone mass, decrease bone loss, and improve strength. It also acts synergistically with parathyroid hormone PTH (1-34) to regulate bone growth. GPCRs are involved in this process. A decrease in stress on the bone will cause these bone layers to weaken.

Mechanical stress to bone plays a crucial role in maintaining bone homeostasis, causing the deformation of the bone matrix and generating strain force. Apart from other factors such as genetics, nutrition, vascular, neural, and hormonal statuses, mechanical force plays a crucial role in bone remodeling. As a potent stimulus for bone cells, mechanical forces enhance bone strength and prevent bone loss with aging.

A new mechanism has been presented to explain how increased or decreased mechanical stresses applied to bone are translated into osteoblastic and/or osteoclastic structures.

What is responsible for bone remodeling?

Bone remodeling involves the resorption and deposition phases, with osteoclasts and osteoblasts being the primary cells responsible. Osteocytes also play a role in this process. The activity of these cells, particularly osteoclasts, is influenced by hormonal signals. This interaction between bone remodeling cells and hormones leads to various pathophysiological consequences. The bone remodeling cycle begins in early fetal life and relies on the interaction between two cell lineages: osteoblasts, stem cells from mesenchymal origin, and osteoclasts, stem cells from a hematopoietic lineage. The process begins when osteoblast and osteoclast precursor cells fuse to form a multinucleated osteoclastic cell.

What are the main mechanical stresses on bone?

Mechanical stimuli on bone, including shear stress, hydrostatic pressure, mechanical stretch, tension, matrix stiffness, and matrix alignment, influence the formation of osteoblasts, which constitute 85-90 percent of all adult bone cells. Osteocytes play a pivotal role in the development and maintenance of bone, cartilage, and collagenous tissue. They offer invaluable insights into the functioning of these vital organs.

What stimulates bone Remodelling?

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.

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.

What hormonal and mechanical control of bone remodeling?

Reconstruction serves both structural and metabolic functions of the skeleton, and it can be stimulated by hormones that regulate mineral metabolism and mechanical loads and local damage. Repairing local damage is an important function of remodeling, as repeated small stresses on the skeleton can produce areas of defective bone, termed micro-damage. Replacement of that damaged bone by remodeling restores bone strength.

Signals for these responses are probably developed by the network of osteocytes and osteoblasts, which can detect changes in the stress placed upon bone and in the health of the small areas of micro-damage.

Factors that affect the formation, activity, and life span of osteoclasts and osteoblasts as they develop from precursor cells can affect the remodeling cycle. Drugs have been developed to reduce bone loss or increase bone formation and maintain skeletal health.

Both genes and the environment contribute to bone health, with some elements of bone health being determined largely by genes, while external factors such as diet and physical activity are critically important to bone health throughout life and can be modified. The mechanical loading of the skeleton is essential for maintaining normal bone mass and architecture. The skeleton also requires certain nutritional elements to build tissue, including large amounts of calcium and phosphorus.

The growth of the skeleton, its response to mechanical forces, and its role as a mineral storehouse are all dependent on the proper functioning of systemic or circulating hormones produced outside the skeleton that work in concert with local regulatory factors. The system is illustrated for calcium regulation, where the amount taken in is equal to the amount excreted. When calcium and/or phosphorus are in short supply, the regulating hormones take them out of the bone to serve vital functions in other systems of the body.

Regulatory hormones also play critical roles in determining how much bone is formed at different phases of skeletal growth and how well bone strength and mass is maintained throughout life.

What is the control mechanism of bone remodeling?

Bone remodeling is a process that involves the tight coupling and regulation of osteoclasts and osteoblasts, influenced by various hormones and osteocyte products. This process occurs in the Bone Remodeling Compartment (BRC), a specialized vascular entity that provides the structural basis for cellular activity. Understanding the interplay between factors and cells surrounding the BRC could lead to better treatment options for skeletal diseases.

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What are the mechanical factors of bone remodeling?

Mechanical loading significantly impacts bone remodeling. Disuse or lack of loading accelerates bone turnover, leading to rapid loss of bone mass, as seen in astronauts in weightless environments. Overuse of bone can cause small cracks or focal damage, stimulating bone remodeling as a reparative process. Osteoclasts target microcracks within bone tissue and remove compromised tissue, replacing it with new bone tissue. If damage accumulates faster than repair, larger microcracks form stress fractures.

The increased number of bone remodeling sites with disuse or overuse is preceded by programmed cell death in osteocytes. The mechanisms causing osteocyte death (apoptosis) are not well understood, but may include direct damage to osteocytes via microcracks in the bone matrix or lack of convective fluid flow during disuse. Prolinerich tyrosine kinase 2 (Pyk2) must be activated before osteocyte apoptosis occurs.

The effects of loading on bone remodeling follow a U-shaped curve, with a physiological range where bone remodeling is minimized. Periosteal bone formation steadily increases with increased loading, indicating that the mechanisms controlling bone growth and reshaping differ from those controlling bone remodeling.

Does mechanical stress affect bone remodeling?

Bone remodeling occurs due to physical circumstances like mechanical stress, with the bone matrix receiving the most efficient load. Osteocytes act as mechanosensors in the early stage of bone remodeling, converting loaded mechanical stress into biochemical reactions that activate osteoclasts and osteoblasts, causing bone resorption and formation. Recent biochemical and molecular biological studies have identified genes that are affected by mechanical stress, such as nitric oxide (NO) and cAMP, which are secreted in response to mechanical stress.

Mechanical stress-responsive genes include GLAST, NOS, and PGHS-2. The expression of IGF-I is enhanced under the control of PTH/PTHrP, and c-fos expression is increased by loading mechanical stress. AP1, a heterodimer of c-FOS/c-JUN, functions as a transcription factor of downstream genes. The promoter region of mechanical stress-response genes contains elements like AP1 sites, cyclic AMP response elements (CRE), and shear stress response elements (SSRE). The enhanced expression of osteopontin (OPN) in osteocytes of bone resorption sites was demonstrated through in situ hybridization and immunohistochemistry.

What hormones control bone remodelling?

Hormonal regulation of bone remodeling is primarily regulated by oestrogen, with other important endocrine regulators including IGF-1, cortisol, PTH, leptin, and gut hormones also playing roles. Other sex hormones, IGF-1, cortisol, and PTH are also important. Recent research has also identified roles for leptin and gut hormones. Copyright © 2024 Elsevier B. V., its licensors, and contributors. All rights reserved.

What are the effects of mechanical stress?

Several authors report device degradation due to process-induced mechanical stress, which can cause reliability issues and affect the diffusion behavior of impurities during processing. This stress can also lead to a slip during processing. The content on this site is protected by copyright and is used by ScienceDirect, its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

What is mechanical stress on joints?

Mechanical stress is a common cause of joint breakdown due to overuse, impacting various joints in the body, including the back, feet, and hands. These joints can fail to cushion movement properly and can cause pain in various parts of the body. At Sports and Spine Orthopaedics, we investigate the various reasons for joint pain and do not ignore pain in other joints, such as the back, which can cause pain due to misalignment. Our board-certified spinal surgeon can help you with a mechanical stress injury of the back and is dedicated to helping you overcome your pain, regardless of its location.