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Bone

Original Editors - Candace Goh

Top Contributors - Lucinda hampton, Jess Bell, Ewa Jaraczewska, Candace Goh, Admin, Shaimaa Eldib, Kim Jackson, Wataru Okuyama, George Prudden, Robin Tacchetti, Claire Knott, Manisha Shrestha, Khloud Shreif, Stacy Schiurring, Jorge Rodríguez Palomino, Nupur Smit Shah, Sai Kripa, Joao Costa, WikiSysop, Tarina van der Stockt, Stephanie Geeurickx and Tony Lowe

Introduction

Bone is a specialised connective tissue that forms most of the skeleton, providing the structural foundation for the human body. Bone is a metabolically active connective tissue that constantly remodels and repairs.[1] It is capable of restoring itself to full function after injury.[2] [3] To support its various roles, bone must be both rigid and stiff, and flexible and elastic.[4] This article discusses the basic structure, development and function of bone and overviews bone pathologies.

Bone Composition and Structure

Bone is composed of specialised bone cells embedded within an extracellular matrix (ECM).

Bone composition
Bone cells

Cellular Components

Four main types of specialised cells make up approximately 10% of total bone volume and are responsible for bone production, maintenance, and remodelling. These cell types are osteoprogenitor cells, osteoblasts, osteocytes and osteoclasts.

Osteoprogenitor cells are stem cells that play an important role in bone repair and growth.[5] They are precursors to specialised bone cells[5] and are involved in forming bone remodelling compartments (BRC).[3]

Osteoblasts synthesise and secrete osteoids and regulate bone mineralisation. They are also involved in hormone production (e.g., prostaglandins).

Osteocytes make up 90-95% of all bone cells.[4] They form from osteoblasts. They are involved in mechanosensation (i.e. detecting mechanical loading) and bone matrix maintenance and renewal.

Osteoclasts are large multinucleated bone-resorbing cells (i.e., cells that break down bone). The two cytokines essential for osteoclast formation are RANK-ligand (RANKL) and macrophage colony-stimulating factor (M-CSF).

Extracellular Matrix (ECM)

The extracellular matrix has both inorganic and organic components. It provides bone with its integrity and elasticity.[6] The ECM makes up about 90% of bone volume.[3] Its composition changes depending on an individual's biological sex, age, and health conditions.[6]

The organic bone matrix makes up around 40% of the ECM.[6] It is predominantly Type I collagen but also includes noncollagenous proteins, glycoproteins, growth factors, and proteoglycans. It provides resistance to tensile forces.[3]

The inorganic bone matrix makes up around 60% of the ECM.[6] It is composed mainly of calcium phosphate minerals, particularly hydroxyapatite crystals, which provide strength, stiffness, and resistance to compressive forces. This component stores:

  • 99% of the body's calcium
  • 85% of the body's phosphorus
  • 40-60% of the body's magnesium and sodium

Bone Organisation and Tissue Types

Extracellular Matrix Arrangement

Depending on its collagen fibre arrangement, bone tissue can be classified as woven (primary) bone and lamellar (secondary) bone.[7]

Woven (primary) bone is an immature bone type formed during development or after fractures. Collagen fibres in woven bone are arranged randomly. Woven bone is eventually replaced by mature lamellar bone.

Lamellar (secondary) bone is a mature bone type—almost all adult bone is lamellar. In lamellar bone, collagen is arranged in organised sheets called lamellae. This organisation makes it mechanically stronger than woven bone.

Structural Classification

Mature bone can be classified into trabecular (cancellous) bone and cortical bone. All bones have a cancellous interior and a cortical exterior, but the proportion and distribution vary depending on the location and function of the bone.[4][8][9]

Trabecular (cancellous/spongy) bone makes up around 20% of total human bone. It has a larger surface-to-volume ratio than cortical bone. Trabecular bone can respond more quickly to changes in load, so it is more dynamic than cortical bone. It is common in areas that experience compressive loads (e.g. vertebrae, pelvis, and metaphyses/epiphyses of long bones).[10]

Cortical (compact) bone makes up around 80% of total human bone. It is stronger and more dense than cancellous bone and can resist bending, torsional and compressive forces. It forms an outer shell around cancellous bone and is found in the shaft of long bones (e.g., femur, tibia).[10]

Diagram of an osteon

Osteons

Osteons (also known as Haversian systems) are the functional units of cortical bones. There are two types of osteons: primary and secondary.[11]

Primary osteons are located next to primary bone. Secondary osteons form from primary osteons. They are usually cylindrical with concentric layers (lamellae) of bone tissue that surround a central canal (Haversian canal).[11] This central canal contains blood vessels and nerves.[10]

Osteons help with load transmission, bone turnover and bone remodelling.[11] This system also includes canaliculi and Volkmann canals, which "allow for communication between neighbouring osteocytes and osteons, respectively."[10]

This optional video describes the structure of osteons:

[12]

Bone Marrow

Bone marrow is located in the cancellous part of bones. Haematopoiesis, or the production/turnover of red and white blood cells and platelets, occurs in the bone marrow.[10]

Please watch this optional video if you would like to learn more about haematopoiesis:

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[13]

Bone Development and Formation

Ossification Processes

Bone formation occurs through two distinct processes: intramembranous ossification and endochondral ossification.

Various flat bones, like many of those of the skull and face, are formed through intramembranous ossification. Intramembranous ossification also occurs in primary bone healing. The process of intramembranous ossification starts with the proliferation of mesenchymal stem cells in highly vascularised parts of embryonic connective tissue, forming sheets of mesenchymal cells. These sheets create a template for the bone. These cells eventually differentiate into osteogenic cells, which then become early osteoblasts. The osteoblasts secrete osteoid, which then mineralises to produce hardened, mineralised bone. Intramembranous ossification begins during fetal development, and bones formed through this process are more developed at birth than those formed by endochondral ossification.[14]

Most axial and appendicular bones, such as the vertebral bodies and long bones, like the femur, are formed via endochondral ossification.[14] Like intramembranous ossification, endochondral ossification occurs during embryonic development and fracture healing.[15] During this process, hyaline cartilage is gradually replaced with mineralised bone tissue.[14] Endochondral ossification begins when mesenchymal cells differentiate into chondrocytes. The chondrocytes form the cartilage model that serves as the template for future bone. Calcification of the extracellular matrix leads to cell death (apoptosis), which creates spaces within the cartilage template. Blood vessels subsequently grow into and enlarge these spaces. Eventually, these spaces join and become the medullary cavity. During this process, osteoblasts create thickened areas of cortical bone in the diaphysis, where primary ossification centres form. In these centres, cartilage is replaced by bone tissue. Secondary ossification centres develop in the epiphyses, usually after birth. These centres replace most of the remaining cartilage with bone. Throughout childhood and adolescence, cartilage continues to form at the epiphyseal growth plates, which allows bones to increase in length. Finally, during late adolescence or early adulthood, longitudinal bone growth ceases as the growth plates completely ossify.[14][16]

Bone Types and Anatomy

Bones can be classified by shape into five types: long bones, short bones, flat bones, sesamoid bones, and irregular bones.[10]

Bone classification by shape

Long bones are longer than they are wide. They have thick cortical layers, especially in the diaphyseal region.[9] Examples of long bones include the femur, humerus, and tibia. Long bones develop via endochondral ossification.[17] They support weight and enable movement.

Short bones have a similar length, width and thickness. Short bones develop via endochondral ossification. They have a thin layer of cortical bone surrounding a cancellous interior. The carpal and tarsal bones are examples of short bones.[17]

Flat bones are thin, flat and often curved. They develop via intramembranous ossification.[17] They consist of two outer layers of cortical bone and an inner layer of cancellous bone. Most of the bones of the skull, sternum and ribs are flat bones. Flat bones often have a protective function.

Sesamoid bones are embedded in tendons (e.g., the patella); they protect tendons from wear and stress.

Irregular bones have complex shapes that do not fit other categories. They have a thin layer of cortical bone, which surrounds the cancellous interior. Examples include the vertebrae and pelvic bones.

Long bone structure and anatomy

Long Bone Anatomy

Long bones have three anatomical zones: (1) diaphysis, (2) metaphysis and (3) epiphysis.[17]

The diaphysis is the tubular shaft of the long bone. It has a hollow region called the medullary cavity, which is filled with yellow marrow. The "walls" of the diaphysis are made of dense cortical bone.[18]

The metaphysis is the zone between the diaphysis and epiphysis. This zone contains the epiphyseal plate in children. The epiphyseal plate enables linear bone growth; growth plates typically fuse at the end of puberty.

The epiphysis is located at the end of long bones. It is a site for articulation and the primary source of red marrow in long bones. The epiphysis and metaphysis join once the epiphyseal growth plate fuses.

Bone Coverings and Support Structures

All bones, except for sesamoid bones, have an outer covering called the periosteum. The periosteum covers the whole bone except for areas where ligaments and tendons attach and where there is articular cartilage. It is connected to bone by Sharpey’s fibres. The periosteum changes with age. It is more elastic in children. As we age, the innervation and vascularisation of the periosteum increase and become firmer.[19] It has two layers: (1) an outer fibrous layer, which is firm and filled with collagen, and (2) an inner cellular layer, which contains osteoprogenitor cells and osteoblasts. Osteoblasts in the inner cellular layer may be absent in adults but form if needed (e.g. for fracture healing).[20][19] The periosteum is essential for bone formation and resorption. It is supplied by four vascular systems and can respond "to insults in the cortical bone, such as tumours, infections, traumas, medications and arthritic diseases."[19]

The endosteum is a membrane that lines the wall of the bone marrow cavity. It also lines the central canal of osteons and the bone's internal cavities.[20]

Bone Functions

Bone has a range of functions, including:[10][17]

  • acting as the body's "physical scaffold" and providing structural support[2]
  • protecting vital organs from injury
  • movement and locomotion, as bones provide attachment sites for muscles, tendons, and ligaments
  • haematopoiesis (i.e. blood cell formation in the bone marrow)
  • mineral storage and release, including calcium and phosphorus
  • fat storage in the yellow marrow
  • releasing alkaline salts to maintain an optimal pH level
  • storage and periodic release of growth factors (e.g. insulin-like growth factor)
  • detoxification, as osteocytes can sequester harmful substances, such as toxic molecules and heavy metals
  • facilitating hearing through the temporal bone

Bone Remodelling

Bones constantly undergo remodelling to maintain strength and repair damage.[21] [22] This process involves four overlapping phases:[3]

  1. Activation: bone remodelling is initiated or activated in a specific area with the recruitment of osteoclast precursors to bone remodelling compartments (BRC)
  2. Resorption: osteoclasts resorb (break down) old bone while osteoprogenitors are recruited to the BRC
  3. Osteoblast differentiation: osteoblasts differentiate and produce osteoid to replace resorbed bone
  4. Mineralisation: osteoid mineralises, completing the remodelling cycle

The balance between osteoblast and osteoclast activity is crucial for maintaining bone integrity.

Please watch this optional video if you would like to learn more about bone remodelling:

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[23]

Fracture Healing

When fractures occur, bones are repaired through primary and secondary healing.[24]

Primary healing occurs when fracture ends are well-aligned with minimal motion. Healing proceeds through direct bone remodelling without callus formation.

Secondary healing is the most common type of fracture healing, occurring unless fractures are perfectly aligned with rigid fixation. It involves both intramembranous and endochondral ossification processes. A callus typically forms in secondary healing.[25]

Clinical Significance

Various conditions can impact bone:[10]

  • Osteoporosis: low bone mineral density is caused by altered microstructure.[26]
  • Osteomalacia: softening of the bones (rickets in children).
  • Paget's disease of the bone: occurs when there is imbalanced osteoblast/osteoclast activity resulting in weaker, larger, misshapen bones.[27] Paget's disease doesn't affect the whole body, but rather, one or more neighbouring bones.[10]
  • Achondroplasia: the most common cause of disproportionate short stature. Individuals with this developmental disorder present with short extremities due to decreased development of endochondral bone.[28]
  • Osteomyelitis: an acute or chronic infection of the bone.
  • Osteosarcoma: associated with "a malignant proliferation of osteoblasts." Osteosarcoma often affects the distal femur and proximal tibia. Individuals may experience bone pain, swelling, or pathologic fracture.
  • Hemangioma of the vertebrae: the most common benign spinal neoplasm, often occurring in women aged between 40 and 50 years.[8]
  • Avascular necrosis: tissue death from inadequate blood supply.
  • Fracture.
  • Epiphyseal plate disorders.

Additional Resources

The following optional video provides a general overview of the anatomy of the skeletal system:

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[29]


References

  1. ↑ Choi IA, Umemoto A, Mizuno M, Park-Min KH. Bone metabolism - an underappreciated player. NPJ Metab Health Dis. 2024 Jul 1;2(1):12.
  2. ↑ 2.0 2.1 Salhotra A, Shah HN, Levi B, Longaker MT. Mechanisms of bone development and repair. Nature reviews Molecular cell biology. 2020 Nov;21(11):696-711.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 El Sayed SA, Nezwek TA, Varacallo M. Physiology, Bone. InStatPearls [Internet] 2019 Jul 29. StatPearls Publishing. Available from:https://www.ncbi.nlm.nih.gov/books/NBK441968/ (last accessed 10.2.2020)
  4. ↑ 4.0 4.1 4.2 Hart NH, Newton RU, Tan J, Rantalainen T, Chivers P, Siafarikas A, Nimphius S. Biological basis of bone strength: anatomy, physiology and measurement. J Musculoskelet Neuronal Interact. 2020 Sep 1;20(3):347-71.
  5. ↑ 5.0 5.1 Nahian A, Davis DD. Histology, Osteoprogenitor Cells. [Updated 2022 Dec 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559160/
  6. ↑ 6.0 6.1 6.2 6.3 Lin X, Patil S, Gao YG, Qian A. The bone extracellular matrix in bone formation and regeneration. Front Pharmacol. 2020 May 26;11:757.
  7. ↑ Shapiro F, Wu JY. Woven bone overview: structural classification based on its integral role in developmental, repair and pathological bone formation throughout vertebrate groups. Eur Cell Mater. 2019 Oct 1;38:137-167.
  8. ↑ 8.0 8.1 Cunningham S. Clinical Overview of Bone Health and Dysfunction Course. Plus, 2024.
  9. ↑ 9.0 9.1 Osterhoff G, Morgan EF, Shefelbine SJ, Karim L, McNamara LM, Augat P. Bone mechanical properties and changes with osteoporosis. Injury. 2016 Jun;47 Suppl 2(Suppl 2):S11-20.
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 10.8 Baig MA, Bacha D. Histology, Bone. InStatPearls [Internet] 2019 May 5. StatPearls Publishing. Available from:https://www.ncbi.nlm.nih.gov/books/NBK541132/ (last accessed 10.2.2020)
  11. ↑ 11.0 11.1 11.2 Chang B, Liu X. Osteon: structure, turnover, and regeneration. Tissue Eng Part B Rev. 2022 Apr;28(2):261-78.
  12. ↑ Michele Parry. Osteon model. Available from: http://www.youtube.com/watch?v=UC1UgGLX98o [last accessed 15/08/2024]
  13. ↑ Alila Medical Media. Hematopoiesis - Formation of Blood Cells, Animation. Available from: https://www.youtube.com/watch?v=0deCbmh7PHs [last accessed 7.8.2022]
  14. ↑ 14.0 14.1 14.2 14.3 López JM. Bone Development and Growth. Int J Mol Sci. 2024 Jun 20;25(12):6767.
  15. ↑ Allen MR, Burr DB. Chapter 4 - bone modeling and remodeling. In: Burr, DB, Allen MR. Editors. Basic and Applied Bone Biology. Academic Press, 2014. p.75-90.
  16. ↑ Breeland G, Sinkler MA, Menezes RG. Embryology, Bone Ossification. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539718/
  17. ↑ 17.0 17.1 17.2 17.3 17.4 Cowan PT, Kahai P. Anatomy, Bones.[Updated 2021 Jul 26]. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2022.
  18. ↑ Hall JE. Guyton and Hall textbook of medical physiology e-Book. Elsevier Health Sciences; 2015 May 31.
  19. ↑ 19.0 19.1 19.2 Maia Ferreira Alencar CH, Sampaio Silveira CR, Cavalcante MM, Maia Vieira CG, Diógenes Teixeira MJ, Neto FA, de Abreu A, Chhabra A. "Periosteum: an imaging review". Eur J Radiol Open. 2020 Aug 27;7:100249.
  20. ↑ 20.0 20.1 Nahian A, Chauhan PR. Histology, Periosteum And Endosteum. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557584/
  21. ↑ Epsley S, Tadros S, Farid A, Kargilis D, Mehta S, Rajapakse CS. The effect of inflammation on bone. Frontiers in physiology. 2021:1695.
  22. ↑ Ofer L, Dean MN, Zaslansky P, Kult S, Shwartz Y, Zaretsky J, Griess-Fishheimer S, Monsonego-Ornan E, Zelzer E, Shahar R. A novel nonosteocytic regulatory mechanism of bone modelling. PLoS biology. 2019 Feb 1;17(2):e3000140.
  23. ↑ Physiology for Hippies . How are bones remodelled? Available from: https://www.youtube.com/watch?v=sNfY8z3CqDg [last accessed 8.8.2022]
  24. ↑ Chandran M, Akesson KE, Javaid MK, Harvey N, Blank RD, Brandi ML, et al. Impact of osteoporosis and osteoporosis medications on fracture healing: a narrative review. Osteoporos Int. 2024 Aug;35(8):1337-1358.
  25. ↑ Gao H, Huang J, Wei Q, He C. Advances in animal models for studying bone fracture healing. Bioengineering (Basel). 2023 Feb 3;10(2):201.
  26. ↑ Xu J, Yu L, Liu F, Wan L, Deng Z. The effect of cytokines on osteoblasts and osteoclasts in bone remodeling in osteoporosis: a review. Front Immunol. 2023 Jul 5;14:1222129.
  27. ↑ Šromová V, Sobola D, Kaspar P. A brief review of bone cell function and importance. Cells. 2023 Nov 5;12(21):2576.
  28. ↑ Legare JM. Achondroplasia. 1998 Oct 12 [Updated 2023 May 11]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1152/
  29. ↑ Crash Course. The Skeletal System: Crash Course Anatomy & Physiology #19. Available from: http://www.youtube.com/watch?v=dMH0bHeiRNg [last accessed 7.8.2022]
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