Bone resorption

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Bone resorption is the process by which osteoclasts break down bone[1] and release

the minerals, resulting in a transfer of calcium from bone fluid to the blood.

The osteoclasts are multi-nucleated cells that contain numerous mitochondria and lysosomes.
These are the cells responsible for the resorption of bone. 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 also prominent in the
tissue destruction commonly found in psoriatic arthritis and other rheumatology related
disorders.

Bone resorption can also be the result of disuse and the lack of stimulus for bone maintenance.
Astronauts, for instance will undergo a certain amount of bone resorption due to the lack of
gravity, providing the proper stimulus for bone maintenance.

During childhood, bone formation exceeds resorption, but as the aging process occurs,
resorption exceeds formation.

[edit]Regulation

Bone resorption is highly constructable 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. In addition to its effects on kidney and intestine, PTH
also increases the number and activity of osteoclasts to release calcium from bone, and thus
stimulates bone resorption.

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.
[edit]References

1. ^ MeSH Bone+Resorption

2.Bone remodeling
3. From Wikipedia, the free encyclopedia
4.   (Redirected from Bone metabolism)

This article needs additional citations for verification.

Please help improve this article by adding reliable references. Unsourced material may
be challenged and removed. (February 2010)

5.
6.
7. Bone is broken down by osteoclasts, and rebuilt by osteoblasts, both of which communicate through
cytokine (TGF-β, IGF) signalling.
8. Bone remodeling (or bone metabolism) is a life long process where old bone is
removed from the skeleton (a sub-process called bone resorption) and new bone is
added (a sub-process called ossification or bone formation). These processes also
control the reshaping or replacement of bone duringgrowth and following injuries
like fractures but also micro-damage, which occurs during normal activity. Remodeling
responds also to functional demands of the mechanical loading. As a result bone is
added where needed and removed where it is not required.
9. In the first year of life, almost 100% of the skeleton is replaced. In adults, remodeling
proceeds at about 10% per year.[1]
10. An imbalance in the regulation of bone remodeling's two sub-processes, bone resorption
and bone formation, results in many metabolic bone diseases, such as osteoporosis.[2]
11. [edit]Physiology
12. The cells responsible for bone metabolism are known as osteoblasts, which secrete new
bone, andosteoclasts which break bone down. The structure of bones as well as
adequate supply of calciumrequires close cooperation between these two types of cells.
It relies on complex signaling pathways to achieve proper rates of growth and
differentiation. These signaling pathways include the action of several hormones,
including parathyroid hormone (PTH), vitamin D, growth hormone, steroids,
andcalcitonin, as well as several cytokines. It is in this way that the body is able to
maintain proper levels of calcium required for physiological processes.
Parathyroid hormone
From Wikipedia, the free encyclopedia

edit
Parathyroid hormone

PDB rendering based on 1bwx.

[show]Available structures

Identifiers

Symbols PTH;

External IDs OMIM: 168450 MGI: 97799 HomoloGene: 266GeneC

ards: PTH Gene

[show]Gene Ontology

RNA expression pattern

More reference expression data

Orthologs

Species Human Mouse

Entrez 5741 19226

 Ensembl ENSG00000152266 ENSMUSG00000059077

UniProt P01270 n/a

RefSeq NM_000315 NM_020623

(mRNA)

RefSeq NP_000306 NP_065648

(protein)

Location Chr 11: Chr 7:

(UCSC) 13.47 - 13.47 Mb 113.18 - 113.18 Mb

PubMedsearc [1] [2]

Parathyroid hormone (PTH), parathormone orparathyrin, is secreted by the parathyroid

glands as a polypeptide containing 84 amino acids. It acts to increase the concentration
of calcium (Ca2+) in the blood, whereas calcitonin (a hormone produced by the parafollicular
cells (C cells) of the thyroid gland) acts to decrease calcium concentration. PTH acts to increase
the concentration of calcium in the blood by acting upon parathyroid hormone receptor in three
parts of the body:[1] PTH half-life is approximately 4 minutes.[2] It has a molecular mass of 9.4
kDa.[3]

Contents
 [hide]

1 Function
o 1.1 Regulation of serum
calcium
o 1.2 Regulation of serum
phosphate
o 1.3 Vitamin D synthesis

2 Regulation of PTH secretion

o 2.1 Stimulators
o 2.2 Inhibitors
 3 Clinical significance
4 Measurement
5 See also
6 References
7 Further reading

[edit]Function

[edit]Regulation of serum calcium

Parathyroid hormone regulates serum potssium through its effects on the following tissues:[4]

Region Effect

It enhances the release of calcium from the large reservoir contained in the bones. [5] Bone
resorption is the normal destruction of bone byosteoclasts, which are indirectly stimulated
by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather,
PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates
bone
osteoblasts to increase their expression ofRANKL, which can bind to osteoclast precursors
containingRANK, a receptor for RANKL. The binding of RANKL to RANK stimulates
these precursors to fuse, forming new osteoclasts which ultimately enhances bone
resorption.

It enhances active reabsorption of calcium and magnesium from distal tubules and the thick
ascending limb. As bone is degraded both calcium and phosphate are released. It also
kidney greatly increases the excretion of phosphate, with a net loss in plasma phosphate
concentration. By increasing the calcium:phosphate ratio more calcium is therefore free in
the circulation. [6]

It enhances the absorption of calcium in the intestine by increasing the production of

activated vitamin D. Vitamin D activation occurs in the kidney. PTH up-regulates 25-
intestinevia hydroxyvitamin D31-alpha-hydroxylase, the enzyme responsible for 1-
kidney alphahydroxylation of 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-
dihydroxy vitamin D). This activated form of vitamin D increases the absorption of calcium
(as Ca2+ ions) by the intestine viacalbindin.
Calcium regulation in the human body.[7] The role of parathyroid hormone is shown in blue.

PTH was one of the first hormones to be shown to use the G-protein, adenylyl cyclase second
messenger system.

Normal total plasma calcium level ranges from 8.5 to 10.2 mg/dL (2.12 mmol/L to 2.55 mmol/L).
[8]

[edit]Regulation of serum phosphate

PTH reduces the reabsorption of phosphate from theproximal tubule of the kidney[6] which
means more phosphate is excreted through the urine.

However, PTH enhances the uptake of phosphate from the intestine and bones into the blood.
In the bone, slightly more calcium than phosphate is released from the breakdown of bone. In
the intestines, which is mediated by an increase in activated vitamin D, the absorption of
phosphate is not as dependent on vitamin D as is that of calcium. The end result is a small net
drop in the serum concentration of phosphate.

[edit]Vitamin D synthesis
PTH increases the activity of 1-α-hydroxylase enzyme, which converts 25-
hydroxycholecalciferol to 1,25-dihydroxycholecalciferol, the active form of vitamin D.

[edit]Regulation of PTH secretion

Secretion of parathyroid hormone is controlled chiefly by serum [Ca2+] through negative
feedback.calcium-sensing receptors located on parathyroid cells are activated when [Ca2+] is
low.[9] Calcium sensing receptors work by activating the phospholipase C pathway,[10][11] through
a Gqα type of G protein, which ultimately increases intracellular concentration of calcium, which
triggers vesicle fusionand exocytosis of parathyroid hormone. It also inhibits (not stimulates, as
some[12] sources state) thecAMP-dependent pathway.[11]

[edit]Stimulators

 Decreased serum [Ca2+].

 Mild decreases in serum [Mg2+].
 An increase in serum phosphate (Since increased phosphate will complex with serum
calcium to form calcium phosphate, which causes the Ca-sensitive receptors (CaSr) to think
that serum Ca has decreased, as CaSR do not sense Calcium phosphate, thereby triggering
an increase in PTH)
[edit]Inhibitors

 Increased serum [Ca2+].

 Severe decreases in serum [Mg2+], which also produces symptoms
of hypoparathyroidism (such as hypocalcemia).[12]
[edit]Clinical significance

 A high level of PTH in the blood is known as hyperparathyroidism.

 If the cause is in the parathyroid gland it is called primary hyperparathyroidism.
The causes are parathyroid adenoma, parathyroid hyperplasia and parathyroid cancer.
 If the cause is outside the gland, it is known as secondary hyperparathyroidism.
This can occur in chronic renal failure. In secondary hyperparathyroidism, serum calcium
levels are decreased, which causes the hypersecretion of PTH from the parathyroid
glands. PTH acts on the proximal tubules in the kidney to decrease reabsorption of
phosphate (increasing its excretion in urine, decreasing its serum concentration). NOTE:
in chronic renal failure, the failing kidneys are unable to excrete phosphate in the urine.
In this case of secondary hyperparathyroidism, serum calcium will be decreased, but
serum phosphate will be increased.

 A low level of PTH in the blood is known as hypoparathyroidism. Causes include

surgicalmisadventure (eg inadvertent removal during routine thyroid surgery), autoimmune
disorder, andinborn errors of metabolism.
[edit]Measurement
PTH can be measured in the blood in several different forms: intact PTH; N-terminal PTH; mid-
molecule PTH, and C-terminal PTH, and different tests are used in different clinical situations.

The average PTH level is 10-60 pg/ml.

[edit]See also

 Calcium metabolism
 Disorders of calcium metabolism
 Parathyroid hormone-related protein
[edit]References

1. ^ Physiology at MCG 5/5ch6/s5ch6_11
2. ^ Bieglmayer C, Prager G, Niederle B (October 2002). "Kinetic analyses of parathyroid hormone
clearance as measured by three rapid immunoassays during parathyroidectomy". Clin.
Chem. 48(10): 1731–8. PMID 12324490.
3. ^ Prahalad AK, Hickey RJ, Huang J, et al. (June 2006). "Serum proteome profiles identifies
parathyroid hormone physiologic response". Proteomics 6 (12): 3482–
93.doi:10.1002/pmic.200500929. PMID 16705755.
4. ^ Coetzee M, Kruger MC (May 2004). "Osteoprotegerin-receptor activator of nuclear factor-
kappaB ligand ratio: a new approach to osteoporosis treatment?". South. Med. J. 97 (5): 506–
11.doi:10.1097/00007611-200405000-00018. PMID 15180028.
5. ^ Poole K, Reeve J (2005). "Parathyroid hormone - a bone anabolic and catabolic agent". Curr
Opin Pharmacol 5 (6): 612–7. doi:10.1016/j.coph.2005.07.004. PMID 16181808.
6. ^ a b http://sprojects.mmi.mcgill.ca/nephrology/presentation/presentation5.htm
7. ^ Page 1094 (The Parathyroid Glands and Vitamin D) in: Walter F., PhD. Boron (2003). Medical
Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. pp. 1300. ISBN 1-4160-
2328-3.
8. ^ Zieve, MD, MHA, David. "MedlinePlus Medical Encyclopedia: Serum calcium". National Library
of Medicine, National Institutes of Health. Retrieved 2009-02-01.
9. ^ Physiology at MCG 5/5ch6/s5ch6_9
10. ^ InterPro: IPR000068 GPCR, family 3, extracellular calcium-sensing receptor-related Retrieved
on June 2, 2009
11. ^ a b Coburn JW, Elangovan L, Goodman WG, Frazaõ JM (December 1999). "Calcium-sensing
receptor and calcimimetic agents". Kidney Int. Suppl. 73: S52–8. PMID 10633465.
12. ^ a b Costanzo, Linda S. (2007). BRS Physiology. Lippincott, Williams, & Wilkins.
pp. 260.ISBN 978-0781773119.