Editing Bone (section)

== Structure ==

Bone is not uniformly solid, but consists of a flexible [[matrix (biology)|matrix]] (about 30%) and bound minerals (about 70%), which are intricately woven and continuously remodeled by a group of specialized bone cells. Their unique composition and design allows bones to be relatively [[Rockwell scale|hard]] and strong, while remaining lightweight.

Bone matrix is 90 to 95% composed of elastic [[collagen]] fibers, also known as ossein,<ref>{{cite web|url=http://medical-dictionary.thefreedictionary.com/ossein|title=Ossein| work = The Free Dictionary}}</ref> and the remainder is [[ground substance]].<ref name="Hall">{{cite book | vauthors = Hall J |url=https://archive.org/details/textbookofmedica00guyt_1/page/957/mode/2up |title=Textbook of Medical Physiology |date=2011 |publisher=Elsevier |isbn=978-08089-2400-5 |edition=12th |location=Philadelphia |pages=957–960 |url-access=registration}}</ref> The elasticity of [[collagen]] improves fracture resistance.<ref name="Schmidt-Nielsen">{{Cite book| vauthors = Schmidt-Nielsen K |author-link=Knut Schmidt-Nielsen|year=1984|title=Scaling: Why Is Animal Size So Important?|publisher=Cambridge University Press|page=[https://archive.org/details/scalingwhyisanim0000schm/page/6 6]|isbn=978-0-521-31987-4|place=Cambridge|url=https://archive.org/details/scalingwhyisanim0000schm/page/6}}</ref> The matrix is hardened by the binding of inorganic mineral salt, [[calcium phosphate]], in a chemical arrangement known as [[bone mineral]], a form of calcium [[apatite]].<ref>{{cite journal | doi=10.1016/j.msec.2005.01.008 | title=A mineralogical perspective on the apatite in bone | year=2005 | vauthors = Wopenka B, Pasteris JD | journal=Materials Science and Engineering: C | volume=25 | issue=2 | pages=131–143 | doi-access=free }}</ref><ref>{{cite journal | vauthors = Wang B, Zhang Z, Pan H | title = Bone Apatite Nanocrystal: Crystalline Structure, Chemical Composition, and Architecture | journal = Biomimetics | volume = 8 | issue = 1 | page = 90 | date = February 2023 | pmid = 36975320 | pmc = 10046636 | doi = 10.3390/biomimetics8010090 | doi-access = free }}</ref> It is the mineralization that gives bones rigidity.

Bone is actively constructed and remodeled throughout life by specialized bone cells known as osteoblasts and osteoclasts. Within any single bone, the tissue is woven into two main patterns: cortical and cancellous bone, each with a distinct appearance and characteristics.

===Cortex===
[[File:Illu compact spongy bone.jpg|thumb|Cross-section details of a long bone]]

The hard outer layer of bones is composed of '''cortical bone''', which is also called '''compact bone''' as it is much denser than cancellous bone. It forms the hard exterior (cortex) of bones. The cortical bone gives bone its smooth, white, and solid appearance, and accounts for 80% of the total bone mass of an adult [[human skeleton]].<ref>{{Cite web|title=Structure of Bone|publisher=CK12-Foundation|url=https://flexbooks.ck12.org/cbook/ck-12-college-human-biology-flexbook-2.0/section/13.4/primary/lesson/structure-of-bone-chumbio|website=flexbooks.ck12.org|access-date=2020-05-28}}</ref> It facilitates bone's main functions—to support the whole body, to protect organs, to provide [[lever]]s for movement, and to store and release chemical elements, mainly calcium. It consists of multiple microscopic columns, each called an [[osteon]] or Haversian system. Each column is multiple layers of [[osteoblast]]s and [[osteocyte]]s around a central canal called the [[Haversian canal|osteonic canal]]. [[Volkmann's canal]]s at right angles connect the osteons together. The columns are metabolically active, and as bone is reabsorbed and created the nature and location of the cells within the osteon will change. Cortical bone is covered by a [[periosteum]] on its outer surface, and an [[endosteum]] on its inner surface. The endosteum is the boundary between the cortical bone and the cancellous bone.{{sfn|Young|2006|p=192}} The primary anatomical and functional unit of cortical bone is the [[osteon]].

=== Trabeculae <span class="anchor" id="Cancellous bone"></span>===
{{Further|Trabecula#Bone trabecula}}
[[File:Spongy bone - trabecules.jpg|thumb|Micrograph of cancellous bone]]

'''Cancellous bone''' or '''spongy bone''',<ref name="SEER">{{cite web |title=Structure of Bone Tissue | work = SEER Training |url=https://training.seer.cancer.gov/anatomy/skeletal/tissue.html |publisher = Surveillance, Epidemiology, and End Results Program (SEER) U.S. National Cancer Institute |access-date=25 January 2023}}</ref>{{sfn|Young|2006|p=192}} also known as '''trabecular bone''', is the internal tissue of the skeletal bone and is an open cell [[Porosity|porous]] network that follows the material properties of [[biofoams]].<ref>{{Cite journal | vauthors = Meyers MA, Chen PY, Lin AY, Seki Y |date= January 2008 |title=Biological materials: Structure and mechanical properties |url=https://www.sciencedirect.com/science/article/pii/S0079642507000254 |journal=Progress in Materials Science |language=en |volume=53 |issue=1 |pages=1–206 |doi=10.1016/j.pmatsci.2007.05.002 |issn=0079-6425}}</ref><ref name="Buss_2022">{{cite journal | vauthors = Buss DJ, Kröger R, McKee MD, Reznikov N | title = Hierarchical organization of bone in three dimensions: A twist of twists | journal = Journal of Structural Biology | volume = 6 | page = 100057 | date = 2022 | pmid = 35072054 | pmc = 8762463 | doi = 10.1016/j.yjsbx.2021.100057 }}</ref> Cancellous bone has a higher [[surface-area-to-volume ratio]] than cortical bone and it is less [[dense]]. This makes it weaker and more flexible. The greater surface area also makes it suitable for metabolic activities such as the exchange of calcium ions. Cancellous bone is typically found at the ends of long bones, near joints, and in the interior of vertebrae. Cancellous bone is highly [[Blood vessel|vascular]] and often contains red [[bone marrow]] where [[hematopoiesis]], the production of blood cells, occurs. The primary anatomical and functional unit of cancellous bone is the [[trabecula]]. The trabeculae are aligned towards the mechanical load distribution that a bone experiences within long bones such as the [[femur]]. As far as short bones are concerned, trabecular alignment has been studied in the [[vertebral]] [[pedicle of vertebral arch|pedicle]].<ref>{{cite journal | vauthors = Gdyczynski CM, Manbachi A, Hashemi S, Lashkari B, Cobbold RS | title = On estimating the directionality distribution in pedicle trabecular bone from micro-CT images | journal = Physiological Measurement | volume = 35 | issue = 12 | pages = 2415–2428 | date = December 2014 | pmid = 25391037 | doi = 10.1088/0967-3334/35/12/2415 | s2cid = 206078730 | bibcode = 2014PhyM...35.2415G }}</ref> Thin formations of [[osteoblast]]s covered in endosteum create an irregular network of spaces,{{sfn|Young|2006|p=195}} known as trabeculae. Within these spaces are [[bone marrow]] and [[hematopoietic stem cell]]s that give rise to [[platelet]]s, [[red blood cell]]s and [[white blood cell]]s.{{sfn|Young|2006|p=195}} Trabecular marrow is composed of a network of rod- and plate-like elements that make the overall organ lighter and allow room for blood vessels and marrow. Trabecular bone accounts for the remaining 20% of total bone mass but has nearly ten times the surface area of compact bone.<ref>{{cite book| vauthors = Hall SJ |title=Basic Biomechanics with OLC.|date=2007|publisher=McGraw-Hill Higher Education|location=Burr Ridge|isbn=978-0-07-126041-1|page=88|edition=5th }}</ref>

The words ''cancellous'' and ''trabecular'' refer to the tiny lattice-shaped units (trabeculae) that form the tissue. It was first illustrated accurately in the engravings of [[Crisóstomo Martinez]].<ref>{{cite journal | vauthors = Gomez S | title = Crisóstomo Martinez, 1638-1694: the discoverer of trabecular bone | journal = Endocrine | volume = 17 | issue = 1 | pages = 3–4 | date = February 2002 | pmid = 12014701 | doi = 10.1385/ENDO:17:1:03 | s2cid = 46340228 }}</ref>

===Marrow===
[[Bone marrow]], also known as [[myeloid tissue]] in red bone marrow, can be found in almost any bone that holds [[cancellous tissue]]. In [[Infant|newborns]], all such bones are filled exclusively with red marrow or [[hematopoietic]] marrow, but as the child ages the hematopoietic fraction decreases in quantity and the fatty/ yellow fraction called [[marrow adipose tissue]] (MAT) increases in quantity. In adults, red marrow is mostly found in the bone marrow of the femur, the ribs, the vertebrae and [[pelvic bones]].<ref>{{cite book| vauthors = Barnes-Svarney PL, Svarney TE |title=The Handy Anatomy Answer Book: Includes Physiology|date=2016|publisher=Visible Ink Press|location=Detroit|isbn=978-1-57859-542-6|pages=90–91}}</ref>

===Vascular supply===
Bone receives about 10% of cardiac output.<ref name="pmid26273504">{{cite journal | vauthors = Marenzana M, Arnett TR | title = The Key Role of the Blood Supply to Bone | journal = Bone Research | volume = 1 | issue = 3 | pages = 203–215 | date = September 2013 | pmid = 26273504 | pmc = 4472103 | doi = 10.4248/BR201303001 }}</ref> Blood enters the [[endosteum]], flows through the marrow, and exits through small vessels in the cortex.<ref name="pmid26273504" /> In humans, [[Blood gas tension#Oxygen tension|blood oxygen tension]] in bone marrow is about 6.6%, compared to about 12% in arterial blood, and 5% in venous and capillary blood.<ref name="pmid26273504" />

===Cells===
[[File:604 Bone cells.jpg|thumb|Bone cells]]

Bone is metabolically active tissue composed of several types of cells. These cells include [[osteoblast]]s, which are involved in the creation and [[mineralized tissue|mineralization]] of bone tissue, [[osteocyte]]s, and [[osteoclast]]s, which are involved in the reabsorption of bone tissue. Osteoblasts and osteocytes are derived from [[osteoprogenitor]] cells, but [[osteoclast]]s are derived from the same cells that differentiate to form [[macrophage]]s and [[monocyte]]s.{{sfn|Young|2006|p=189}} Within the marrow of the bone there are also [[hematopoietic stem cell]]s. These cells give rise to other cells, including [[white blood cell]]s, [[red blood cell]]s, and [[platelet]]s.{{sfn|Young|2006|p=58}}

====Osteoblast====
[[File:Active osteoblasts.jpg|thumb|[[Micrograph|Light micrograph]] of [[Bone decalcification|decalcified]] cancellous bone tissue displaying osteoblasts actively synthesizing osteoid, containing two osteocytes.]]

[[Osteoblast]]s are mononucleate bone-forming cells. They are located on the surface of osteon seams and make a [[protein]] mixture known as [[osteoid]], which mineralizes to become bone.{{sfn|Young|2006|pp=189–190}} The osteoid seam is a narrow region of a newly formed organic matrix, not yet mineralized, located on the surface of a bone. Osteoid is primarily composed of Type I [[collagen]]. Osteoblasts also manufacture [[hormone]]s, such as [[prostaglandin]]s, to act on the bone itself. The osteoblast creates and repairs new bone by actually building around itself. First, the osteoblast puts up collagen fibers. These collagen fibers are used as a framework for the osteoblasts' work. The osteoblast then deposits calcium phosphate which is hardened by [[hydroxide]] and [[bicarbonate]] ions. The brand-new bone created by the osteoblast is called [[osteoid]].<ref>{{cite web | url = http://depts.washington.edu/bonebio/bonAbout/bonecells.html | archive-url = https://web.archive.org/web/20110807200120/http://depts.washington.edu/bonebio/bonAbout/bonecells.html | archive-date = 7 August 2011 | title = The O' Cells | work = Bone Cells | publisher = The University of Washington | date = 3 April 2013 }}</ref> Once the osteoblast is finished working it is actually trapped inside the bone once it hardens. When the osteoblast becomes trapped, it becomes known as an osteocyte. Other osteoblasts remain on the top of the new bone and are used to protect the underlying bone, these become known as bone lining cells.<ref>{{cite journal | vauthors = Wein MN |date=28 April 2017 |title= Bone Lining Cells: Normal Physiology and Role in Response to Anabolic Osteoporosis Treatments |journal=Current Molecular Biology Reports |volume=3 |issue= 2|pages= 79–84 |doi= 10.1007/s40610-017-0062-x|s2cid= 36473110 }}</ref>

====Osteocyte====
[[Osteocyte]]s are cells of mesenchymal origin and originate from osteoblasts that have migrated into and become trapped and surrounded by a bone matrix that they themselves produced.{{sfn|Young|2006|p=192}} The spaces the cell body of osteocytes occupy within the mineralized collagen type I matrix are known as [[lacuna (histology)|lacunae]], while the osteocyte cell processes occupy channels called canaliculi. The many processes of osteocytes reach out to meet osteoblasts, osteoclasts, bone lining cells, and other osteocytes probably for the purposes of communication.<ref>{{cite journal | vauthors = Sims NA, Vrahnas C | title = Regulation of cortical and trabecular bone mass by communication between osteoblasts, osteocytes and osteoclasts | journal = Archives of Biochemistry and Biophysics | volume = 561 | pages = 22–28 | date = November 2014 | pmid = 24875146 | doi = 10.1016/j.abb.2014.05.015 }}</ref> Osteocytes remain in contact with other osteocytes in the bone through gap junctions—coupled cell processes which pass through the canalicular channels.

====Osteoclast====
[[Osteoclast]]s are very large [[multinucleate]] cells that are responsible for the breakdown of bones by the process of [[bone resorption]]. New bone is then formed by the osteoblasts. Bone is constantly [[bone remodeling|remodeled]] by the resorption of osteoclasts and created by osteoblasts.{{sfn|Young|2006|p=189}} Osteoclasts are large cells with multiple [[Cell nucleus|nuclei]] located on bone surfaces in what are called ''Howship's lacunae'' (or ''resorption pits''). These lacunae are the result of surrounding bone tissue that has been reabsorbed.{{sfn|Young|2006|p=190}} Because the osteoclasts are derived from a [[monocyte]] [[stem cell|stem-cell]] lineage, they are equipped with [[Phagocytosis|phagocytic]]-like mechanisms similar to circulating [[macrophage]]s.{{sfn|Young|2006|p=189}} Osteoclasts mature and/or migrate to discrete bone surfaces. Upon arrival, active enzymes, such as [[tartrate-resistant acid phosphatase]], are [[Secretion|secreted]] against the mineral substrate.{{citation needed|date=September 2013}} The reabsorption of bone by osteoclasts also plays a role in [[calcium]] [[homeostasis]].{{sfn|Young|2006|p=190}}

===Composition===
{{Main|Extracellular matrix}}

Bones consist of living cells (osteoblasts and osteocytes) embedded in a mineralized organic matrix. The primary inorganic component of human bone is [[hydroxyapatite]], the dominant [[bone mineral]], having the nominal composition of Ca<sub>10</sub>(PO<sub>4</sub>)<sub>6</sub>(OH)<sub>2</sub>.<ref>[https://arxiv.org/ftp/arxiv/papers/2001/2001.11808.pdf#page=2 Enhancement of Hydroxyapatite Dissolution] Journal of Materials Science & Technology,38, 148-158</ref> The organic components of this matrix consist mainly of [[Collagen#Types|type I collagen]]—"organic" referring to materials produced as a result of the human body—and inorganic components, which alongside the dominant [[hydroxyapatite]] phase, include other compounds of [[calcium]] and [[phosphate]] including salts. Approximately 30% of the acellular component of bone consists of organic matter, while roughly 70% by mass is attributed to the inorganic phase.{{sfn|Hall|2005|p=981}} The [[collagen]] fibers give bone its [[ultimate tensile strength|tensile strength]], and the interspersed crystals of [[hydroxyapatite]] give bone its [[compressive strength]]. These effects are [[synergy|synergistic]].{{sfn|Hall|2005|p=981}} The exact composition of the matrix may be subject to change over time due to nutrition and [[biomineralization]], with the ratio of [[calcium]] to [[phosphate]] varying between 1.3 and 2.0 (per weight), and trace minerals such as [[magnesium]], [[sodium]], [[potassium]] and [[carbonate]] also be found.{{sfn|Hall|2005|p=981}}

{{anchor|Woven vs. lamellar bone}}
Type I collagen composes 90–95% of the organic matrix, with the remainder of the matrix being a homogenous liquid called [[ground substance]] consisting of [[proteoglycan]]s such as [[hyaluronic acid]] and [[chondroitin sulfate]],{{sfn|Hall|2005|p=981}} as well as non-collagenous proteins such as [[osteocalcin]], [[osteopontin]] or [[bone sialoprotein]]. Collagen consists of strands of repeating units, which give bone tensile strength, and are arranged in an overlapping fashion that prevents shear stress. The function of ground substance is not fully known.{{sfn|Hall|2005|p=981}} Two types of bone can be identified microscopically according to the arrangement of collagen: woven and lamellar.

* Woven bone (also known as ''fibrous bone''), which is characterized by a haphazard organization of collagen fibers and is mechanically weak.<ref name="Curry2006">Currey, John D. (2002). [http://press.princeton.edu/chapters/s7313.html "The Structure of Bone Tissue"] {{Webarchive|url=https://web.archive.org/web/20170425052316/http://press.princeton.edu/chapters/s7313.html |date=25 April 2017 }}, pp.  12–14 in ''Bones: Structure and Mechanics''. Princeton University Press. Princeton, NJ. {{ISBN|978-1-4008-4950-5}}</ref>
* Lamellar bone, which has a regular parallel alignment of collagen into sheets ("lamellae") and is mechanically strong.<ref name="Buss_2022" /><ref name="Curry2006"/>

[[File:Woven bone matrix.jpg|thumb|right|[[Transmission electron microscopy|Transmission]] [[electron micrograph]] of decalcified woven bone matrix displaying characteristic irregular orientation of collagen fibers]]

Woven bone is produced when osteoblasts produce osteoid rapidly, which occurs initially in all [[fetus|fetal]] bones, but is later replaced by more resilient lamellar bone. In adults, woven bone is created after [[Bone fracture|fractures]] or in [[Paget's disease of bone|Paget's disease]]. Woven bone is weaker, with a smaller number of randomly oriented collagen fibers, but forms quickly; it is for this appearance of the fibrous matrix that the bone is termed ''woven''. It is soon replaced by lamellar bone, which is highly organized in [[concentric]] sheets with a much lower proportion of osteocytes to surrounding tissue. Lamellar bone, which makes its first appearance in humans in the [[fetus]] during the third trimester,<ref name="Salentijn">Salentijn, L. ''Biology of Mineralized Tissues: Cartilage and Bone'', [[Columbia University College of Dental Medicine]] post-graduate dental lecture series, 2007</ref> is stronger and filled with many collagen fibers parallel to other fibers in the same layer (these parallel columns are called osteons). In [[cross section (geometry)|cross-section]], the fibers run in opposite directions in alternating layers, much like in [[plywood]], assisting in the bone's ability to resist [[torsion (mechanics)|torsion]] forces. After a fracture, woven bone forms initially and is gradually replaced by lamellar bone during a process known as "bony substitution". Compared to woven bone, lamellar bone formation takes place more slowly. The orderly deposition of collagen fibers restricts the formation of osteoid to about 1 to 2&nbsp;[[Micrometre|μm]] per day. Lamellar bone also requires a relatively flat surface to lay the collagen fibers in parallel or concentric layers.<ref>{{Cite book| vauthors = Royce PM, Steinmann B |url=https://books.google.com/books?id=x-Z-cXUGlL8C&q=Lamella+bone+requires+a+relatively+flat+surface&pg=PA70|title=Connective Tissue and Its Heritable Disorders: Molecular, Genetic, and Medical Aspects|date=2003-04-14|publisher=John Wiley & Sons|isbn=978-0-471-46117-3|language=en}}</ref>

====Deposition====
The extracellular matrix of bone is laid down by [[osteoblast]]s, which secrete both collagen and ground substance. These cells synthesise collagen alpha polypetpide chains and then secrete collagen molecules. The collagen molecules associate with their neighbors and crosslink via lysyl oxidase to form collagen fibrils. At this stage, they are not yet mineralized, and this zone of unmineralized collagen fibrils is called "osteoid". Around and inside collagen fibrils calcium and phosphate eventually [[Precipitation (chemistry)|precipitate]] within days to weeks becoming then fully mineralized bone with an overall carbonate substituted hydroxyapatite inorganic phase.<ref>{{cite journal | vauthors = Buss DJ, Reznikov N, McKee MD | title = Crossfibrillar mineral tessellation in normal and Hyp mouse bone as revealed by 3D FIB-SEM microscopy | journal = Journal of Structural Biology | volume = 212 | issue = 2 | page = 107603 | date = November 2020 | pmid = 32805412 | doi = 10.1016/j.jsb.2020.107603 | s2cid = 221164596 | url = https://escholarship.mcgill.ca/concern/articles/vq27zt432 }}</ref>{{sfn|Hall|2005|p=981}}

In order to mineralise the bone, the osteoblasts secrete alkaline phosphatase, some of which is carried by [[Vesicle (biology and chemistry)|vesicles]]. This cleaves the inhibitory pyrophosphate and simultaneously generates free phosphate ions for mineralization, acting as the foci for calcium and phosphate deposition. Vesicles may initiate some of the early mineralization events by rupturing and acting as a centre for crystals to grow on. Bone mineral may be formed from globular and plate structures, and via initially amorphous phases.<ref name=r1>{{cite journal| vauthors = Bertazzo S, Bertran CA |year=2006|title=Morphological and dimensional characteristics of bone mineral crystals|journal= Key Engineering Materials|volume=309-311 |pages=3–6 |doi=10.4028/www.scientific.net/kem.309-311.3|s2cid=136883011 }}</ref><ref>{{cite journal|doi=10.4028/www.scientific.net/kem.309-311.11|title=Morphological Characterization of Femur and Parietal Bone Mineral of Rats at Different Ages|year=2006| vauthors = Bertazzo S, Bertran C, Camilli J |journal=Key Engineering Materials|volume=309–311|pages=11–14|s2cid=135813389}}</ref>