Bone resorption

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Bone Resorption
Osteoclast.jpg
Light micrograph of an osteoclast displaying typical distinguishing characteristics: a large cell with multiple nuclei and a "foamy" cytosol.
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Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones [1] and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. [2]

Contents

The osteoclasts are multi-nucleated cells that contain numerous mitochondria and lysosomes. These are the cells responsible for the resorption of bone. Osteoblasts are generally present on the outer layer of bone, just beneath the periosteum. Attachment of the osteoclast to the osteon begins the process. The osteoclast then induces an infolding of its cell membrane and secretes collagenase and other enzymes important in the resorption process. High levels of calcium, magnesium, phosphate and products of collagen will be released into the extracellular fluid as the osteoclasts tunnel into the mineralized bone. Osteoclasts are prominent in the tissue destruction found in psoriatic arthritis and rheumatological disorders. [3]

The human body is in a constant state of bone remodeling. [4] Bone remodeling is a process which maintains bone strength and ion homeostasis by replacing discrete parts of old bone with newly synthesized packets of proteinaceous matrix. [5] Bone is resorbed by osteoclasts, and is deposited by osteoblasts in a process called ossification. [6] Osteocyte activity plays a key role in this process. Conditions that result in a decrease in bone mass can either be caused by an increase in resorption or by a decrease in ossification. During childhood, bone formation exceeds resorption. As the aging process occurs, resorption exceeds formation. [5]

Bone resorption rates are much higher in post-menopausal older women due to estrogen deficiency related with menopause. [7] Common treatments include drugs that increase bone mineral density. Bisphosphonates, RANKL inhibitors, SERMs—selective oestrogen receptor modulators, hormone replacement therapy and calcitonin are some of the common treatments. [8] Light weight bearing exercise tends to eliminate the negative effects of bone resorption. [9]

Regulation

Bone resorption is highly stimulated or inhibited by signals from other parts of the body, depending on the demand for calcium.

Calcium-sensing membrane receptors in the parathyroid gland monitor calcium levels in the extracellular fluid. Low levels of calcium stimulates the release of parathyroid hormone (PTH) from chief cells of the parathyroid gland. [4] In addition to its effects on kidney and intestine, PTH increases the number and activity of osteoclasts. The increase in activity of already existing osteoclasts is the initial effect of PTH, and begins in minutes and increases over a few hours. [4] Continued elevation of PTH levels increases the abundance of osteoclasts. This leads to a greater resorption of calcium and phosphate ions. [4]

High levels of calcium in the blood, on the other hand, leads to decreased PTH release from the parathyroid gland, decreasing the number and activity of osteoclasts, resulting in less bone resorption. Vitamin D increases absorption of calcium and phosphate in the intestinal tract, leading to elevated levels of plasma calcium, [4] and thus lower bone resorption.

Calcitriol (1,25-dihydroxycholecalciferol) is the active form of vitamin D3. [10] It has numerous functions involved in blood calcium levels. Recent research indicates that calcitriol leads to a reduction in osteoclast formation, and bone resorption. [11] [12] It follows that an increase in vitamin D3 intake should lead to a decrease in bone resorption — it has been shown that oral administration of vitamin D does not linearly correlate to increased serum levels of calcifediol, [13] the precursor to calcitriol.

Calcitonin is a hormone secreted by the thyroid in humans. Calcitonin decreases osteoclast activity, and decreases the formation of new osteoclasts, resulting in decreased resorption. [4] Calcitonin has a greater effect in young children than in adults, and plays a smaller role in bone remodeling than PTH. [4]

In some cases where bone resorption outpaces ossification, the bone is broken down much faster than it can be renewed. The bone becomes more porous and fragile, exposing people to the risk of fractures. Depending on where in the body bone resorption occurs, additional problems like tooth loss can arise. This can be caused by conditions such as hyperparathyroidism and hypovitaminosis D or even decreased hormonal production in the elderly. Some diseases with symptoms of decreased bone density are osteoporosis, and rickets.

Some people who experience increased bone resorption and decreased bone formation are astronauts. Due to the condition of being in a zero-gravity environment, astronauts do not need to work their musculoskeletal system as hard as when on earth. Ossification decreases due to a lack of stress, while resorption increases, leading to a net decrease in bone density. [14]

Alcoholism

The effects of alcohol on bone mineral density (BMD) are well-known and well-studied in animal and human populations. Through direct and indirect pathways, prolonged ethanol exposure increases fracture risk by decreasing bone mineral density and promoting osteoporosis. Indirect effects of excessive alcohol use occur via growth hormone, sex steroids, and oxidative stress.

Growth hormone is an important regulator of bone growth and remodeling in adults, and it acts via insulin-like growth factor I (IGF1) to stimulate osteoblastic differentiation. [15] Chronic alcoholism decreases the levels of IGF1, which suppresses the ability of GH to increase bone mineral density. [15]

Increasing alcohol consumption is linked with decreasing testosterone and serum estradiol levels, which in turn lead to the activation of RANK (a TNF receptor) protein that promote osteoclast formation. [16] Oxidative stress results when ethanol induces NOX expression, resulting in ROS production in osteoblasts which can ultimately result in cell senescence. [17] Direct effects of chronic alcoholism are apparent in osteoblasts, osteoclasts and osteocytes. Ethanol suppresses the activity and differentiation of osteoblasts.

At the same time, it has a direct effect on osteoclast activity. This results in an increased bone resorption rate and a decreased bone mineral density due to increased pit numbers and pit areas in the bone. [18] [19] [20] Research has shown that viable osteocytes (another type of bone cell) may prevent osteoclastogenesis, whereas apoptotic osteocytes tend to induce osteoclast stimulation. Stimulation of osteocyte apoptosis by alcohol exposure may explain decreased bone mineral density in chronic drinkers. [20] [6]

Clinical importance

Bone resorption is an integral part of both physiological and pathological processes. [21]

Pathological bone resorption could be limited (local) which is induced by local inflammation, [22] for example, trauma or infection, resorption activated local factors, including growth factors, cytokines, prostaglandins, etc., are simultaneously triggered. This bone resorption could also be observed in patients with many metabolic skeleton diseases, especially osteopenia and osteoporosis, endocrine diseases, rheumatic disorders, and other cases, as well as in patients with genetic disorders.

Physiological bone resorption is an integral part of bone functioning, while the bone is constantly growing thanks to two processes — breakdown and formation of bone tissue. [23] Locally, it could be manifested in tooth eruption when the movement of a tooth follicle is followed by an active resorption of jaw bone tissue. Resorption of old bone and formation of a new one are balanced in a well-developed skeleton. However, resorption starts taking a large part in remodeling processes with age. Dentistry sees resorption as dissolution or breakdown of a tooth structure. This could be inflammation and dentine or cement loss.

Bone tissue is a dynamic system with active metabolism. [24] Bone tissue remodelling or bone remodeling is a successive chain of old bone matrix removal and its replacement with a new one. [25] These processes make a child’s skeleton grow and extend, while childhood is characterized by bone tissue growth rather than its resorption.

See also

Related Research Articles

<span class="mw-page-title-main">Bone</span> Rigid organs that constitute part of the endoskeleton of vertebrates

A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, and enable mobility. Bones come in a variety of shapes and sizes and have complex internal and external structures. They are lightweight yet strong and hard and serve multiple functions.

<span class="mw-page-title-main">Osteoporosis</span> Skeletal disorder

Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in fracture risk.

<span class="mw-page-title-main">Parathyroid hormone</span> Mammalian protein found in humans

Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.

<span class="mw-page-title-main">Calcium metabolism</span> Movement and regulation of calcium ions in and out of the body

Calcium metabolism is the movement and regulation of calcium ions (Ca2+) in (via the gut) and out (via the gut and kidneys) of the body, and between body compartments: the blood plasma, the extracellular and intracellular fluids, and bone. Bone acts as a calcium storage center for deposits and withdrawals as needed by the blood via continual bone remodeling.

<span class="mw-page-title-main">Osteoblast</span> Cells secreting extracellular matrix

Osteoblasts are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function in groups of connected cells. Individual cells cannot make bone. A group of organized osteoblasts together with the bone made by a unit of cells is usually called the osteon.

<span class="mw-page-title-main">Calcitonin</span> Peptide hormone secreted by the thyroid

Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH).

Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemia. Those with a mild increase that has developed slowly typically have no symptoms. In those with greater levels or rapid onset, symptoms may include abdominal pain, bone pain, confusion, depression, weakness, kidney stones or an abnormal heart rhythm including cardiac arrest.

<span class="mw-page-title-main">Parathyroid hormone-related protein</span> Mammalian protein

Parathyroid hormone-related protein (PTHrP) is a proteinaceous hormone and a member of the parathyroid hormone family secreted by mesenchymal stem cells. It is occasionally secreted by cancer cells. However, it also has normal functions in bone, teeth, vascular tissues and other tissues.

<span class="mw-page-title-main">Osteoclast</span> Cell that breaks down bone tissue

An osteoclast is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption. This process also helps regulate the level of blood calcium.

<span class="mw-page-title-main">Hyperparathyroidism</span> Increase in parathyroid hormone levels in the blood

Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands or as response to external stimuli. Symptoms of hyperparathyroidism are caused by inappropriately normal or elevated blood calcium excreted from the bones and flowing into the blood stream in response to increased production of parathyroid hormone. In healthy people, when blood calcium levels are high, parathyroid hormone levels should be low. With long-standing hyperparathyroidism, the most common symptom is kidney stones. Other symptoms may include bone pain, weakness, depression, confusion, and increased urination. Both primary and secondary may result in osteoporosis.

<span class="mw-page-title-main">Osteoprotegerin</span> Mammalian protein found in Homo sapiens

Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor (OCIF) or tumour necrosis factor receptor superfamily member 11B (TNFRSF11B), is a cytokine receptor of the tumour necrosis factor (TNF) receptor superfamily encoded by the TNFRSF11B gene.

<span class="mw-page-title-main">Osteocyte</span> Mature osteoblasts which helps in communication between cells and also in molecular synthesis

An osteocyte, an oblate shaped type of bone cell with dendritic processes, is the most commonly found cell in mature bone. It can live as long as the organism itself. The adult human body has about 42 billion of them. Osteocytes do not divide and have an average half life of 25 years. They are derived from osteoprogenitor cells, some of which differentiate into active osteoblasts. Osteoblasts/osteocytes develop in mesenchyme.

<span class="mw-page-title-main">Calcitriol</span> Active form of vitamin D

Calcitriol is a hormone and the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the expression of many genes. Calcitriol increases blood calcium mainly by increasing the uptake of calcium from the intestines.

<span class="mw-page-title-main">RANKL</span> Mammalian protein found in Homo sapiens

Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene.

Senile osteoporosis has been recently recognized as a geriatric syndrome with a particular pathophysiology. There are different classification of osteoporosis: primary, in which bone loss is a result of aging and secondary, in which bone loss occurs from various clinical and lifestyle factors. Primary, or involuntary osteoporosis, can further be classified into Type I or Type II. Type I refers to postmenopausal osteoporosis and is caused by the deficiency of estrogen. While senile osteoporosis is categorized as an involuntary, Type II, and primary osteoporosis, which affects both men and women over the age of 70 years. It is accompanied by vitamin D deficiency, body's failure to absorb calcium, and increased parathyroid hormone.

<span class="mw-page-title-main">Bone remodeling</span> Continuous turnover of bone matrix and mineral

In osteology, bone remodeling or bone metabolism is a lifelong process where mature bone tissue is removed from the skeleton and new bone tissue is formed. These processes also control the reshaping or replacement of bone following injuries like fractures but also micro-damage, which occurs during normal activity. Remodeling responds also to functional demands of the mechanical loading.

An endocrine bone disease is a bone disease associated with a disorder of the endocrine system. An example is osteitis fibrosa cystica.

<span class="mw-page-title-main">Eldecalcitol</span> Chemical compound

Eldecalcitol is an analog of calcitriol, the active form of vitamin D.

The human skeletal system is a complex organ in constant equilibrium with the rest of the body. In addition to supporting and giving structure to the body, a bone is the major reservoir for many minerals and compounds essential for maintaining a healthy pH balance. The deterioration of the body with age renders the elderly particularly susceptible to and affected by poor bone health. Illnesses like osteoporosis, characterized by weakening of the bone's structural matrix, increases the risk of hip-fractures and other life-changing secondary symptoms. In 2010, over 258,000 people aged 65 and older were admitted to the hospital for hip fractures. Incidence of hip fractures is expected to rise by 12% in America, with a projected 289,000 admissions in the year 2030. Other sources estimate up to 1.5 million Americans will have an osteoporotic-related fracture each year. The cost of treating these people is also enormous, in 1991 Medicare spent an estimated $2.9 billion for treatment and out-patient care of hip fractures, this number can only be expected to rise.

A bone growth factor is a growth factor that stimulates the growth of bone tissue.

References

  1. ↑ Bone+Resorption at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
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  12. ↑ Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, et al. (March 2013). "Vitamin D receptor in osteoblasts is a negative regulator of bone mass control". Endocrinology. 154 (3): 1008–1020. doi: 10.1210/en.2012-1542 . PMID   23389957.
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  22. ↑ Epsley S, Tadros S, Farid A, Kargilis D, Mehta S, Rajapakse CS (2020). "The Effect of Inflammation on Bone". Frontiers in Physiology. 11: 511799. doi: 10.3389/fphys.2020.511799 . PMC   7874051 . PMID   33584321.
  23. ↑ Rowe P, Koller A, Sharma S (March 2023). "Physiology, Bone Remodeling". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID   29763038 . Retrieved 2023-06-07.{{cite book}}: |work= ignored (help)
  24. ↑ Wawrzyniak A, Balawender K (July 2022). "Structural and Metabolic Changes in Bone". Animals. 12 (15): 1946. doi: 10.3390/ani12151946 . PMC   9367262 . PMID   35953935.
  25. ↑ Lindsay R, Cosman F (January 2007). "Pathogenesis of osteoporosis.". Treatment of the Postmenopausal Woman (3rd ed.). pp. 323–330. doi:10.1016/B978-012369443-0/50032-6. ISBN   9780123694430. Bone remodeling describes the process whereby old bone is continuously replaced by new tissue.
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