skeletal system function essay

The Skeletal System Essay

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Introduction

Axial portion of the skeleton, appendicular portion of the skeleton, functions of the skeleton, relationship between the skeletal system and the muscular system, sexual differences in skeletons, clinical conditions and disorders that affect the skeleton, works cited.

Movement is vital for all of you because it provides you with the opportunity to live your lives to the full. Just as other human beings, you fall and stand up to continue moving forward. But what provides you with this opportunity? It is your skeletal system. It does not only facilitate your physical activity but also supports and protects your bodies. This system consists of hundreds of bones that are full of calcium, which makes them strong enough to carry your weight. Bones are connected with the help of joints that facilitate motion. The majority of you were born with about 300 bones that fuse with the course of time so that now you have only 206 bones. They all are divided into two parts: axial and appendicular skeletons.

Your axial portion of skeleton is composed of “the skull, the vertebral column, and the thoracic cage” ( Skeletal System: Bones and Joints 120). Due to its location, it manages to protect your brain and spinal cord from injuries. In addition to that, it supports the organs in the ventral body cavity so that you do not need to carry them in your hands.

Twenty-two bones that are separated into two parts form the skull. You have 8 bones of the cranial cavity that are known as braincase. They surround your brain so that you do not hurt it when fall or receive a headnut. The rest of the bones (there are 14 of them) form your face. They are tightly connected to one another so that your nose is always in the right place. The only exception is the mandible that makes chewing possible. Otherwise, how would you eat? Minimal movement can also be observed within the middle ears. Each of them includes 3 auditory ossicles that are hidden deep in your head.

The vertebral column, or backbone, usually consists of “7 cervical vertebrae, 12 thoracic vertebrae, 5 lumbar vertebrae, 1 sacral bone, and 1 coccyx bone” ( Skeletal System: Bones and Joints 125). It is the central axis of the skeleton that has four major curvatures. Normally, the cervical and the lumbar regions curve anteriorly. The thoracic, as well as the sacral and coccygeal regions, curves posteriorly. However, considering the way you sit, abnormal curvatures are widespread.

The thoracic or the rib cage protects your organs and supports them. All in all, human beings have 24 ribs that are divided into 12 pairs, but you can recount them to make sure. They are categorized according to their attachment to the sternum. Thus, a direct attachment by costal cartilages is true (1-7); an attachment by a common cartilage is false (8-12); and the absence of attachment resorts to floating ribs (11-12). The sternum, or breastbone, consists of three parts: “the manubrium, the body, and the xiphoid process” ( Skeletal System: Bones and Joints 129).

Your appendicular skeleton consists of the bones of limbs and girdles so that you have:

• “4 bones in the shoulder girdle (clavicle and scapula each side).
• 6 bones in the arm and forearm (humerus, ulna, and radius).
• 58 bones in the hands (carpals 16, metacarpals 10, phalanges 28, and sesamoid 4).
• 2 pelvis bones.
• 8 bones in the legs (femur, tibia, patella, and fibula).
• 56 bones in the feet (tarsals, metatarsals, phalanges, and sesamoid)” (“The Axial & Appendicular Skeleton” par. 4).

What would you be without this part of skeleton? Imagine that it is a big 3D puzzle, gathering all these bones together in a right order, you will build your arms and legs with all details. These are all movable parts that allow you to run, dance, write, and even hug your nearest and dearest. Even though the axial skeleton seems to be more important because it is connected with your brain, the appendicular portion of the skeleton contains about 60% of all your bones, which means that its importance should not be undervalued.

As you have already understood, your skeleton maintains a lot of different functions. Some of them, such as movement and support, were already mentioned. But let us discuss them all in detail.

• Support. Your bodies are supported by the skeleton so that you can change your position to vertical one and stand strait. Without it, you would be able only to lie because of the gravitation. This function is provided by many bones but the long ones seem to be the leaders in this competition. For instance, those that are in legs, support the trunk. Similarly, vertebras support one another so that eventually the firs one provides support to the skull. In addition to that, they support the organs and ensure that they do not change their positions.
• Protection. The skeleton also protects you. For example, the skull prevents fatal brain injuries. The rib cage protects such vital organs as the heart and lungs. It also takes care of your abdominal organs ensuring that they develop normally.
• Movement. The function of bodily motion allowed you to come here today. However, it is critical to remember that it is maintained not only due to the bones but also with the help of the muscular system.
• Mineral and energy storage. From the outer side of your bones, there is a tissue that serves as a storage. It gathers calcium and phosphorus and withdraws them to maintain appropriate blood levels. In addition to that, mature bones store yellow marrow. It consists of fat almost totally and provides you with energy for various activities.
• Blood-cell formation. The inner core of your bones takes part in the formation of blood cell and platelet. It is known as bone marrow or red marrow. Platelet is vital for you because it ensures your ability to heal wounds while blood cells spread oxygen and destroy infectious cells (CAERT 3).

Have you ever thought of the way our movement are maintained? Even a simple nod of the head requires the cooperation between the skeletal and muscular systems. Muscles ensure movement of our body through the attachment to the bones. All in all, there are about 700 of them, which is an enormous amount that comprises about 50% of your weight.

So what happens in your body when you moves? When you want to move, your brain sends a message for the body to release energy. In medical terms, it is called adenosine triphosphate. Affecting your muscles, it makes them contract or shorten. Shortened muscles pulls bones at their insertion point. Thus, the angle between the bones connected by a joint shortens. Relaxation is maintained when the opposing muscle extends and pulls a bone to its initial position.

Human skeletons seem to be similar, as they contain the same bones. However, you should remember that their characteristics differ depending on the gender. For example, women have lighter pelvis bones that form a shorter cavity with less dimensions. It has less prominent marking for muscles and more circular pelvic brim. The sacral bones of men are longer and narrower, which makes them more massive. Their femur is also longer and heavier. Its texture is rough unlike women’s smooth.

Muscle marking is more developed and shaft is less oblique. The head of men’s femur is larger and trochanters are more prominent. The femoral neck angle in males is more than 125 and in females is less than 125. Women’s sternum is less than twice the length of manubrium and larger in men. Differences in skull include greater capacity, thicker walls, more marked muscular ridges, prominent air sinuses, smoother upper margin of orbit, less vertical forehead, and heavier cheekbones in males.

Hopefully, it will never affect any of you but the skeleton may be affected by tumours that cause bone defects. People may have skeletal developmental disorders including gigantism, dwarfism, osteogenesis imperfecta, and rickets lead to abnormal body sizes, brittle bones, and growth retardation. Bacterial infections cause inflammation and lead to bone destruction.

Decalcification, including the known to you osteoporosis, reduces bone tissue and softens bones. Joint disorders often deal with inflammation. For instance, arthritis. They are often influenced by age and physical activity. In this way, degradation of joints is observed in the elderly but can be delayed due to regular exercises. The abnormal curvatures of the spine may also cause health issues. That is why you should pay attention to your back posture and avoid kyphosis (a hunchback condition), lordosis (a swayback condition), and scoliosis (an abnormal lateral curvature).

CAERT. Structures and Functions of the Skeletal System . 2014. Web.

Skeletal System: Bones and Joints. 2012. Web.

“ The Axial & Appendicular Skeleton. ” TeachPE , 2017. Web.

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IvyPanda. (2020, September 6). The Skeletal System. https://ivypanda.com/essays/the-skeletal-system/

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6.1 The Functions of the Skeletal System

Learning objectives.

By the end of this section, you will be able to:

List and describe the functions of the skeletal system

• Attribute specific functions of the skeletal system to specific components or structures

The skeletal system is the body system composed of bones, cartilages, ligaments and other tissues that perform essential functions for the human body. Bone tissue, or osseous tissue , is a hard, dense connective tissue that forms most of the adult skeleton, the internal support structure of the body. In the areas of the skeleton where whole bones move against each other (for example, joints like the shoulder or between the bones of the spine), cartilages, a semi-rigid form of connective tissue, provide flexibility and smooth surfaces for movement. Additionally, ligaments composed of dense connective tissue surround these joints, tying skeletal elements together (a ligament is the dense connective tissue that connect bones to other bones). Together, they perform the following functions:

Support, Movement, and Protection

Some functions of the skeletal system are more readily observable than others. When you move you can feel how your bones support you, facilitate your movement, and protect the soft organs of your body. Just as the steel beams of a building provide a scaffold to support its weight, the bones and cartilages of your skeletal system compose the scaffold that supports the rest of your body. Without the skeletal system, you would be a limp mass of organs, muscle, and skin. Bones facilitate movement by serving as points of attachment for your muscles. Bones also protect internal organs from injury by covering or surrounding them. For example, your ribs protect your lungs and heart, the bones of your vertebral column (spine) protect your spinal cord, and the bones of your cranium (skull) protect your brain (see Figure 6.1.1 ).

Mineral and Fat Storage, Blood Cell Formation

On a metabolic level, bone tissue performs several critical functions. For one, the bone tissue acts as a reservoir for a number of minerals important to the functioning of the body, especially calcium, and phosphorus. These minerals, incorporated into bone tissue, can be released back into the bloodstream to maintain levels needed to support physiological processes. Calcium ions, for example, are essential for muscle contractions and are involved in the transmission of nerve impulses.

Bones also serve as a site for fat storage and blood cell production. The unique connective tissue that fills the interior of most bones is referred to as bone marrow . There are two types of bone marrow: yellow bone marrow and red bone marrow. Yellow bone marrow contains adipose tissue, and the triglycerides stored in the adipocytes of this tissue can be released to serve as a source of energy for other tissues of the body. Red bone marrow is where the production of blood cells (named hematopoiesis, hemato- = “blood”, -poiesis = “to make”) takes place. Red blood cells, white blood cells, and platelets are all produced in the red bone marrow. As we age, the distribution of red and yellow bone marrow changes as seen in the figure ( Figure 6.1.2 ).

Career Connection – Orthopedist

An orthopedist is a doctor who specializes in diagnosing and treating disorders and injuries related to the musculoskeletal system. Some orthopedic problems can be treated with medications, exercises, braces, and other devices, but others may be best treated with surgery ( Figure 6.1.3 ).

While the origin of the word “orthopedics” (ortho- = “straight”; paed- = “child”), literally means “straightening of the child,” orthopedists can have patients who range from pediatric to geriatric. In recent years, orthopedists have even performed prenatal surgery to correct spina bifida, a congenital defect in which the neural canal in the spine of the fetus fails to close completely during embryologic development.

Orthopedists commonly treat bone and joint injuries but they also treat other bone conditions including curvature of the spine. Lateral curvatures (scoliosis) can be severe enough to slip under the shoulder blade (scapula) forcing it up as a hump. Spinal curvatures can also be excessive dorsoventrally (kyphosis) causing a hunch back and thoracic compression. These curvatures often appear in preteens as the result of poor posture, abnormal growth, or indeterminate causes. Mostly, they are readily treated by orthopedists. As people age, accumulated spinal column injuries and diseases like osteoporosis can also lead to curvatures of the spine, hence the stooping you sometimes see in the elderly.

Some orthopedists sub-specialize in sports medicine, which addresses both simple injuries, such as a sprained ankle, and complex injuries, such as a torn rotator cuff in the shoulder. Treatment can range from exercise to surgery.

Section Review

The major functions of the skeletal system are body support, facilitation of movement, protection of internal organs, storage of minerals and fat, and blood cell formation.

Review Questions

Critical thinking questions.

• Suppose your red bone marrow could not be formed. What functions would your body not be able to perform?
• Suppose your osseous tissue could not store calcium. What functions would your body not be able to perform?

Answers for Critical Thinking Questions

• Without red bone marrow, you would not be able to produce blood cells. The red bone marrow is responsible for forming red and white blood cells as well as platelets. Red blood cells transport oxygen to tissues, and remove carbon dioxide. Without red blood cells, your tissues would not be able to produce ATP using oxygen. White blood cells play a role in the immune system fighting off foreign invaders in our body – without white blood cells you would not be able to recover from infection. Platelets are responsible for clotting your blood when a vessel ruptures. Without platelets you would bleed to death and die.
•  The calcium in osseous tissue provides mineral support to bones. Without this calcium, the bones are not rigid and cannot be supportive. The calcium in osseous tissue is also an important storage site, that can release calcium when needed. Other organ systems rely on this calcium for action (specifically, muscle contraction and neural signaling). Without calcium storage, blood calcium levels change dramatically and affect muscle contraction and neural signaling.

This work, Anatomy & Physiology, is adapted from Anatomy & Physiology by OpenStax , licensed under CC BY . This edition, with revised content and artwork, is licensed under CC BY-SA except where otherwise noted.

Images, from Anatomy & Physiology by OpenStax , are licensed under CC BY except where otherwise noted.

Access the original for free at https://openstax.org/books/anatomy-and-physiology/pages/1-introduction .

Anatomy & Physiology Copyright © 2019 by Lindsay M. Biga, Staci Bronson, Sierra Dawson, Amy Harwell, Robin Hopkins, Joel Kaufmann, Mike LeMaster, Philip Matern, Katie Morrison-Graham, Kristen Oja, Devon Quick, Jon Runyeon, OSU OERU, and OpenStax is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License , except where otherwise noted.

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The Skeletal System and Its Functions

The skeletal system is one of the most significant ones in the body, along with the muscular and nervous ones. This paper provides detailed information about it, addressing its anatomical location and description, cells and tissues present in it, and the functions it has. Moreover, the report features data about homeostasis and its benefits. The paper concludes that the skeletal system is crucial for the body’s well-being.

The Information About the Skeletal System

Anatomical location.

The skeletal system can be considered a framework of the body. Therefore, it is located anterior to many of the organs. Some bones of the skeletal system, for example, those positioned in the upper part of the body, serve as a protective cage for several organs, including the heart and the lungs. At the same time, the skeletal system is posterior to some of the organs, such as the intestines.

Anatomical Description

The skeletal system includes all the joints and bones in the body. Adult bodies have 206 individual bones arranged into the axial skeleton and the appendicular skeleton (Barclay, 2019). The first skeleton is located along the human body’s midline axis and involves 80 bones located in the ribs, skull, auditory ossicles, hyoid, sternum, and vertebral column. The second skeleton has 126 bones in the pelvic girdle, lower and upper limbs, and shoulder girdle (Barclay, 2019). The skeletal system includes long, short, irregular, flat, and sesamoid bones, which differ in their sizes and functions.

Cells and Tissues Present in the Skeletal System

The skeletal system has bones, which, in turn, are made of several types of tissues. They include fibrous connective tissue that makes up ligaments and the tendons and the periosteum, irregular connective tissue covering the outside of a bone (Warren, 2019). The periosteum contains nervous tissue and nerve endings, which provide the body with pain sensitivity. Moreover, the bones contain stem cells and osteoblast cells involved in the processes of the growth and repair, as well as osteocytes maintaining the strength of the bones (Warren, 2019). Living bone cells are located on the edges of the bones and in cavities inside of the bone matrix.

Functions of the Skeletal System

There are several significant functions of the skeletal system that should be noted. First, the bones belonging to the system compose the skeleton, which provides the support and structure for the body (Bailey, 2019). Second, as mentioned above, the skeletal system protects organs, blood cells, and soft tissues of the body. For instance, in addition to the rib cage protecting the lungs, the vertebral column protects the spinal cord from possible damages. The third function is mobility; the bones of the system work with skeletal muscles and other skeletal components to enable body movement (Bailey, 2019). Finally, bones can store the minerals playing a significant role for the body, including calcium, responsible for the firmness of bones.

Homeostasis

The bones of the skeletal system have several functions maintaining homeostasis in the body. First, they supply oxygen and nutrients to cells (Sivan, De Angelis, & Kusumbe, 2019). Second, as mentioned above, they store calcium and phosphorous, which are crucial for proper nerve impulse conduction and muscle contraction. Third, the skeletal system produces new red blood cells (American Society of Hematology, 2019). Moreover, the fact that the skeletal system protects organs from damage is also a significant part of homeostasis. If the system could not maintain homeostasis, it would cause severe problems in the body, which will be discussed in detail below.

As mentioned above, the skeletal system maintains homeostasis by protecting the organs of the body, which is highly significant. For instance, bones protect the brain, as any harm to this organ may result in highly adverse consequences for an individual’s well-being (Roberts, Henry, & Molenberghs, 2018). Moreover, the production of red blood cells is highly crucial for the body, as they contain hemoglobin. Without it, oxygen cannot be carried from the lungs to the rest of the body (American Society of Hematology, 2019). Thus, the skeletal system plays a significant role in maintaining homeostasis.

One of the diseases affecting the skeletal system is osteoporosis. As a result of this condition, the bones become prone to fracture and fragile (Healthline Media, 2015). The bones of an individual living with osteoporosis have abnormal tissue structure and decreased density. As a result, they may break easily; the bone breaks typically occur in the spine and the hip (Healthline Media, 2015). Thus, as a result of the condition, a person’s skeletal system becomes weakened, which means that it is crucial to prevent this disease.

The skeletal system, consisting of 206 bones, is one of the most significant systems of the body. Its functions include protecting the organs from damage, supporting the structure of the body, ensuring mobility, and storing minerals. The system maintains homeostasis by producing new blood cells and supplying oxygen and nutrients. The skeletal system may be affected by osteoporosis, which results in proneness to fracture and weakness of the bones.

American Society of Hematology. (2019). Blood basics. Web.

Bailey, R. (2019). Skeletal system and bone function . Web.

Barclay, T. (2019). Skeletal system . Web.

Healthline Media. (2015). Skeletal system . Web.

Roberts, S., Henry, J. D., & Molenberghs, P. (2018). Immoral behavior following brain damage: A review. Journal of Neuropsychology, 13 (3), 564-588.

Sivan, U., De Angelis, J., & Kusumbe, A. P. (2019). Role of angiocrine signals in bone development, homeostasis and disease. Open Biology , 9 . Web.

Warren, A. (2019). Human skeleton . Web.

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Skeletal System

Reviewed by: BD Editors

The skeletal system provides support and protection for the body’s internal organs and gives the muscles a point of attachment. Humans have an endoskeleton , where our bones lie underneath our skin and muscles. In other animals, such as insects, there is an exoskeleton on the outside of the body.

In humans, the skeletal system consists of bones, joints and associated cartilages. An adult human has 206 bones in their body and variety of different joints.

Image shows a human skeleton with the major bones labeled.

The human skeleton can be divided into two components: the axial skeleton and the appendicular skeleton. The axial skeleton is formed around the central axis of the body and thus includes the skull, spine , and ribcage. It protects the brain, spinal cord, heart, lungs, esophagus and major sense organs like the eyes, ears, nose, and tongue. The appendicular skeleton is related to the limbs and consists of the bones of the arms and legs, as well as the shoulder and hip girdles.

Skeletal System Function

The first and most apparent function of the skeletal system is to provide a framework for the body. The presence of a firm bony skeleton allows the organism to have a distinctive shape adapted towards a particular lifestyle. For instance, in a fast-moving animal like the cheetah, the skeleton contains long, thin limb bones and an extremely flexible spine. The structure of the skeleton also allows it to absorb the impact of running at high speeds.

The bones of birds are hollow, light and create a streamlined body adapted for flight. Many animals even have sexual dimorphism in their skeletons. In humans, while this dimorphism is fairly limited, there are differences in the angle of the pelvic bones, to accommodate pregnancy.

Integration with the Muscular System

The skeletal system also provides an important form of attachments to the muscular system. Bones and exoskeletons are hard and do not bend or move when muscles are flexed. This means that the contraction of muscle cells will lead to the shortening of muscles, while the bone retains its shape. This basic structure allows muscles to move different parts of the body, using forces generated while pulling on the skeletal system.

The next obvious function of the skeletal system is the role it plays protecting the fragile internal organs. In humans, this is seen in the skull, which surrounds the brain completely. It is also exhibited by the ribcage, which surrounds the lungs and heart but still allows for expansion. Even invertebrates like snails and prawns often have hard exoskeletons to protect themselves from predators.

The rigid endoskeleton allows the body to rise up above the ground or stand upright, and bears the weight of the organism, and provides the scaffolding for movement. Muscles generate the force required to move bones at joints. Muscle fibers contain actin and myosin, two protein filaments that can slide past each other to change the length of the muscle. When a nerve impulse arrives at the neuromuscular junction, it signals the muscle to contract. The force generated by the contracting muscle either pulls two bones together or apart, based on the nature of the interaction between the muscle and joint.

Blood Cell Production

The central part of a bone contains the bone marrow , the primary site for blood cell production in adult humans. There are two types of bone marrow in adults. Around 50% is red bone marrow containing hematopoietic stem cells and supportive tissue. The rest is yellow bone marrow made of fat and its proportion increases with age.

Bone marrow will revert to a higher proportion of red marrow if the body suffers an injury and needs to create more red blood cells. The bone marrow composition also changes during pregnancy and lactation in mammals. Over the course of gestation, blood volume increases by about 1.5 liters, and even the concentration of red blood cells and white blood cells increase.

Production of other Cell Types

In addition to producing red blood cells, bone marrow within the skeletal system is the production site of a number of other cells. These include lymphocytes , which are immune cells that travel the lymphatic system. In addition to providing immune functions, the skeletal system is also responsible for hosting stem cells which can differentiate into muscle cells, cartilage-producing cells, and cells that create bone (osteoblasts).

Osteoblasts in bone also have an endocrine function, secreting a hormone called osteocalcin. It requires vitamin K to be synthesized and is an anabolic hormone. It mediates an increase in insulin levels and increases the sensitivity of the body to insulin. Osteocalcin contributes to an increase in bone mass and bone mineralization.

Storing Minerals

The bones of the skeletal system act as a storehouse for calcium ions , changing the quantum of mineralized deposits within bones to maintain plasma calcium ion concentration within a narrow range. Calcium ions can affect crucial sodium ion channels in the plasma membrane of every cell, thereby affecting overall homeostasis.

For this reason, changes to the concentration of calcium ions have particularly adverse effects on excitable cells in the nervous system, and in cardiac, skeletal and smooth muscle. Different interacting hormones maintain the balance of calcium ions in the plasma and bones, especially the parathyroid hormone secreted from the parathyroid glands in the neck.

Skeletal System Parts

The anatomy of the skeletal system is complex, and it includes hundreds of bones in the human body . The anatomy of the system varies widely between organisms, as evolution has selected for various adaptations in certain species which change the structure and function of their bones.

Bones serve a variety of functions, but the most important is supporting movement of the limbs and body. Two bones or cartilages are held together at a joint through tough connective tissues called ligaments. Muscles are securely attached to bones through flexible but inelastic connective tissue called tendons. Muscles, joints, tendons, and ligaments are part of the intricate machinery that allows the movement of different bones.

Functionally, joints can be divided into three classes based on the range of movement they allow in the associated bones. Immovable joints are formed when two bones are held together by fibrous connective tissue with no synovial fluid. These kinds of joints hold the bones of the cranium together.

Partially movable joints are also called cartilaginous joints and are present in the spine and ribs. The third type of joints are called synovial joints and have a fluid-filled synovial cavity that allows the interfacing bones the largest range of movement. Based on the structure of the synovial joints, they can be classified into 6 types, including the hinge joints of the fingers and the ball and socket joints of the hips and shoulders.

Cellular Composition

Each bone is made of complex sets of cells, tissues and a specialized extracellular matrix . The two main cell types are called osteoblasts and osteoclasts with mostly opposing functions. While osteoblasts are involved in the formation of bone, osteoclasts are associated with a reduction in bone mass. The extracellular matrix of the bone consists of collagen and other organic fibers as well as the inorganic component containing calcium salts such as hydroxyapatite. In the interior of bones, a soft tissue called the bone marrow plays an important role in immunity and hematopoiesis. The bone is also richly supplied with nerves and blood vessels.

Skeletal System Structure

In general, the skeletal system is structured to provide support against gravity and protect an animal’s internal organs. While this article mainly discusses the human skeletal system, most animals have some sort of skeleton. Some animals, like sponges, can have an extremely simplified skeleton made of calcium deposits within the animal. Others, like the turtle, have drastically modified their skeletal system to provide extra protection.

While this article mostly discusses an  endoskeleton,  many animals use an  exoskeleton for the same purposes. Instead of bones being on the inside, the bones, protective plates, or chitinous skeleton actually surrounds the muscles. While this may seem completely different, the structure of the system is still very similar. The only difference is that muscles and tendons connect to the inside of the system, rather than to the surface of bones.

The structure of the skeletal system reflects an animal’s evolution, as well as the needs it has to survive. For example, humans have a tailbone. This is an evolutionary relic, from the time when our ancestors had tails and were swinging from the trees. As we became bipedal, we lost the need for a tail, and it was reduced to a single, nonfunctional bone. Likewise, all animals are constantly adapting and changing their skeletal system through evolutionary time.

Skeletal System Diseases

Diseases of the skeletal system could be confined to one section of the skeleton such as changes to the curvature of the spine, or they could be a genetic disorder affecting all bones and joints such as arthritis or osteoporosis.

The spine in healthy individuals is S-shaped, with a convex curvature for the thoracic region and the concave tilt in the cervical and lumbar regions. This shape for the spine is ideally suited for an upright walking posture. If either the thoracic or lumbar regions have a change in curvature or there is sideways bend to the spine, it can lead to back pain, difficulty with breathing, digestion, mobility, and reproduction.

Curvature of the Spine

The bulk of the weight of the upper body is transmitted along the central axis towards the legs. When the bones or muscles of the back or not functioning optimally, it can lead initially to accommodative changes in posture and thereafter to pain, injury or permanent deformity. Since the spine surrounds the spinal cord, abnormalities in the skeletal structure of the spine can affect the nervous system, either manifesting as pain, tingling or numbing in the extremities. Additionally, the spine supports the ribcage, enclosing the heart, lungs, and diaphragm. Thus, spinal deformities can also lead to shortness of breath, palpitations or even cardiac arrhythmias.

Kyphosis is the term for the convex curve of the thoracic region and excessive curvature in this region is called hyperkyphosis. Extreme hyperkyphosis presents as a hunchback. This could arise from genetic factors or poor posture due to obesity or osteoporosis or arthritis.

The normal concave structure of the lumbar region is called lordosis , and when the region is overly arched, it is called lumbar hyperlordosis. In hyperlordosis, shoulders appear to be pushed back, while the abdominal region seems to be jutting forward.

Image shows a person with hyperlordosis. In a healthy spine, the midpoint of the spine (A) would be directly above the knee (B).

Hyperlordosis can arise from genetic factors, poor posture, or even deficient muscle strength. When the spine has a sideways tilt, or a lateral bend, it is called scoliosis and could be associated with both hyperkyphosis and hyperlordosis.

Osteoporosis

Osteoporosis is a condition marked by bone resorption. This reduces bone mass and density, thereby enhancing the probability of fractures from even minor stressors such as sneezing. Although osteoporosis is commonly associated with aging, smoking, obesity, diet, some medications and alcohol consumption can contribute to the progression of the ailment.

Weight training, exercise, and a diet containing adequate calcium, iron, phosphorous as well as Vitamin D, help in enhancing bone density and bone mass. There is some evidence that the pH of blood plays a role in the release of calcium stores from bones and the extent of bone mineralization since calcium salts are often used as buffers in acidic environments in the body. A whole-foods, plant-based diet has been shown greatly reduce blood acidification. As a result, it also lowers cases of osteoporosis.

Arthritis includes a number of joint disorders that are characterized by stiffness, inflammation, and pain. While there is a range of potential causes, arthritis usually worsens with age, affecting the joints that are used most frequently – especially the joints in fingers, hips, and knees. Arthritis, therefore, causes disability, restricts movement and impairs fine motor skills.

Interesting Facts

• Three bones in the inner ear, called malleus, incus and stapes, are the smallest bones in the human body. The thigh bone, or femur, is the largest bone.
• The hyoid bone situated behind the lower jaw is also called a ‘floating’ bone because it is not part of any joint, and is not directly attached to any other bone.
• The position of the hyoid bone makes it extremely resistant to fractures. However, autopsies that reveal a broken hyoid bone indicate death from strangulation.
• Newborn babies have about 300 bones. Many of these bones fuse together to form the 206 bones of the adult.
• Teeth are part of the skeletal system. However, they are not bones.

1. Which of these is an inflammatory condition?

2. Meat, carbonated beverages, cheese, eggs and even milk have been linked to a decrease in blood pH. How might these things affect bone health?

3. Why is the hyoid bone called a floating bone?

4. Why do babies have more bones than adults?

5. Which of the following are functions of the skeletal system?

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The Skeletal System: Parts, Functions, Diagrams, & Facts

The skeletal system is the internal framework of the body which provides support and protects the soft organs of the body.

The skeletal system is the collection of bones, cartilage, ligaments, and tendons and account for 20% body weight.

The skeleton is the structure that gives us our shape and offers a supportive framework for the attachment of muscles, therefore, facilitating movement.

Functions of the Skeletal System:

The skeletal system is the body system composed of bones and cartilage and performs the following critical functions for the human body:

• supports the body
• facilitates movement
• protects internal organs
• produces blood cells
• stores and releases minerals and fat

Support, Movements & Protection

The most apparent functions of the skeletal system are the gross functions—those visible by observation.

• The bones support, facilitate movement, and protect the human body.
• Just as the steel beams of a building provide a scaffold to support its weight, the bones and cartilage of your skeletal system compose the scaffold that supports the rest of your body.
• Without the skeletal system, you would be a limp mass of organs, muscles, and skin.
• Bones also facilitate movement by serving as points of attachment for your muscles.
• While some bones only serve as a support for the muscles, others also transmit the forces produced when your muscles contract.
• From a mechanical point of view, bones act as levers and joints serve as fulcrums. Unless a muscle spans a joint and contracts, a bone is not going to move.

Mineral Storage, Energy Storage & Hematopoiesis

On a metabolic level, bone tissue performs several critical functions.

• For one, the bone matrix acts as a reservoir for a number of minerals important to the functioning of the body, especially calcium, and phosphorus.
• These minerals, incorporated into bone tissue, can be released back into the bloodstream to maintain levels needed to support physiological processes.
• Calcium ions, for example, are essential for muscle contractions and controlling the flow of other ions involved in the transmission of nerve impulses.
• Bone also serves as a site for fat storage and blood cell production. The softer connective tissue that fills the interior of most bone is referred to as bone marrow.
• There are two types of bone marrow: yellow marrow and red marrow. Yellow marrow contains adipose tissue; the triglycerides stored in the adipocytes of the tissue can serve as a source of energy.
• Red marrow is where hematopoiesis—the production of blood cells—takes place.
• Red blood cells, white blood cells, and platelets are all produced in the red marrow.

Anatomy of the skeletal system:-

The average human adult has 206 bones that are divided into two different parts, the axial and the appendicular skeleton:

Axial Skeleton:

The axial skeleton forms the axis of the human body. It consists of Skull, vertebral column, and thoracic cage .

• Skull : Skull is the most complex part of the human skeleton It consists of 22 different bones that are divided into two groups: bones of cranium and bones of the face .
• Vertebral Column : It is a flexible column of vertebrae, connecting the trunk of the human body to the skull and appendages. It is composed of 33 vertebrae which are divided into 5 regions: Cervical, Thoracic, Lumbar, Sacral, and Coccygeal .
• Rib Cage : It is a bony cage enclosing vital human organs formed by the sternum and ribs. There are 12 pairs of ribs that are divided into three groups: True ribs, False ribs, and Floating ribs .

Appendicular Skeleton:

It is the skeleton of appendages of the human body. It consists of the Shoulder girdle, Skeleton of the upper limb, Pelvic girdle and Skeleton of the lower limb .

• Shoulder Girdle : It attaches the upper limb to the body trunk and is formed by two bones: clavicle and scapula . The clavicle is a modified long bone and is subcutaneous throughout its position. It is also known as beauty bone. The scapula is a pear-shaped flat bone that contains the glenoid fossa for the formation of shoulder joint. It possesses three important processes: Spine of scapula, Acromion process, and Coracoid process .
• Skeleton of Upper limb : The skeleton of each upper limb consists of 30 bones. These bones are Humerus, Ulna, Radius, Carpals, Metacarpals, Phalanges .
• Pelvic Girdle : There are two pelvic girdles (one for each lower limb) but unlike the pectoral girdles, they are joined with each other at the symphysis pubis . Each pelvic girdle is a single bone in adults and is made up of three components: Ileum, Ischium, and Pubis .
• Skeleton of the Lower limb : The skeleton of each lower limb consists of 30 bones. These bones are Femur, Tibia, Patella, Tarsals, Metatarsals, Phalanges .

Frequently Asked Questions (FAQs)

What are the 5 primary components of the skeletal system.

The skeletal system has five main parts: bones, cartilage, ligaments, tendons, and joints. Bones provide structural support and protection, while cartilage cushions and absorbs shock. Connective tissues known as ligaments and tendons serve to attach bones to each other and to muscles. Joints allow for movement and flexibility.

What are the parts of the skeleton?

The human skeletal system consists of two primary divisions: the axial skeleton and the appendicular skeleton.

Axial skeleton: The axial skeleton is composed of the skull, vertebral column, and rib cage.It offers a safeguard and shelter for the crucial organs of the body. The skull serves to protect the brain and provide support to the face. The vertebral column, also known as the spine, offers support to the body and safeguards the spinal cord. The heart and lungs are protected from harm by the rib cage.

Appendicular skeleton: This includes the bones of the arms, legs, shoulder girdle, and pelvic girdle. The shoulder girdle supports the arms and allows for their movement. The pelvic girdle supports the legs and connects the lower limbs to the axial skeleton.

What is called a skeleton?

A skeleton is the internal framework of bones, cartilage, and other connective tissues that support and protect the body of an animal, including humans. The skeleton provides a structure for muscles to attach to and enables movement, while also protecting vital organs such as the brain, heart, and lungs. It also serves as a storehouse for minerals such as calcium and phosphorus, and plays a role in blood cell production.

Which bone protects the brain?

The skull, also known as the cranium, is the bone that protects the brain. It is a bony structure that surrounds and encloses the brain, providing it with physical protection from external forces that could cause damage. The skull is composed of several bones that are fused together, including the frontal, parietal, temporal, occipital, sphenoid, and ethmoid bones. The skull also contains several openings and cavities, such as the orbits for the eyes, the nasal cavity, and the ear canals.

What is bone made of?

Bone is a complex living tissue made up of several components. The main component of bone is a mineral called hydroxyapatite, which gives bone its hardness and strength. Hydroxyapatite is a crystalline form of calcium phosphate that is deposited in a matrix of collagen fibers.

The collagen fibers provide flexibility and resilience to bone, allowing it to withstand stress and strain. Bone also contains living cells, including osteoblasts, osteocytes, and osteoclasts, which are responsible for maintaining and remodeling bone tissue throughout life. Additionally, bone contains blood vessels, nerves, and other connective tissues that support its function and growth.

What is the main bone function?

The main function of bones is to provide support and structure to the body. Bones serve as a framework for muscles to attach to, which allows for movement and locomotion. Additionally, bones protect and support internal organs, such as the brain, heart, and lungs.

Bones also play a role in mineral storage and release, as they contain a significant amount of calcium, phosphorus, and other minerals. They serve as a reservoir for these minerals, releasing them into the bloodstream when needed to maintain proper levels in the body.

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6.1 The Functions of the Skeletal System

Learning objectives.

By the end of this section, you will be able to:

• Define bone, cartilage, and the skeletal system
• List and describe the functions of the skeletal system

Bone , or osseous tissue , is a hard, dense connective tissue that forms most of the adult skeleton, the support structure of the body. In the areas of the skeleton where bones move (for example, the ribcage and joints), cartilage , a semi-rigid form of connective tissue, provides flexibility and smooth surfaces for movement. The skeletal system is the body system composed of bones and cartilage and performs the following critical functions for the human body:

• supports the body
• facilitates movement
• protects internal organs
• produces blood cells
• stores and releases minerals and fat

Support, Movement, and Protection

The most apparent functions of the skeletal system are the gross functions—those visible by observation. Simply by looking at a person, you can see how the bones support, facilitate movement, and protect the human body.

Just as the steel beams of a building provide a scaffold to support its weight, the bones and cartilage of your skeletal system compose the scaffold that supports the rest of your body. Without the skeletal system, you would be a limp mass of organs, muscle, and skin.

Bones also facilitate movement by serving as points of attachment for your muscles. While some bones only serve as a support for the muscles, others also transmit the forces produced when your muscles contract. From a mechanical point of view, bones act as levers and joints serve as fulcrums ( Figure 6.2 ). Unless a muscle spans a joint and contracts, a bone is not going to move. For information on the interaction of the skeletal and muscular systems, that is, the musculoskeletal system, seek additional content.

Bones also protect internal organs from injury by covering or surrounding them. For example, your ribs protect your lungs and heart, the bones of your vertebral column (spine) protect your spinal cord, and the bones of your cranium (skull) protect your brain ( Figure 6.3 ).

Career Connection

Orthopedist.

An orthopedist is a doctor who specializes in diagnosing and treating disorders and injuries related to the musculoskeletal system. Some orthopedic problems can be treated with medications, exercises, braces, and other devices, but others may be best treated with surgery ( Figure 6.4 ).

While the origin of the word “orthopedics” (ortho- = “straight”; paed- = “child”), literally means “straightening of the child,” orthopedists can have patients who range from pediatric to geriatric. In recent years, orthopedists have even performed prenatal surgery to correct spina bifida, a congenital defect in which the neural canal in the spine of the fetus fails to close completely during embryologic development.

Orthopedists commonly treat bone and joint injuries but they also treat other bone conditions including curvature of the spine. Lateral curvatures (scoliosis) can be severe enough to slip under the shoulder blade (scapula) forcing it up as a hump. Spinal curvatures can also be excessive dorsoventrally (kyphosis) causing a hunch back and thoracic compression. These curvatures often appear in preteens as the result of poor posture, abnormal growth, or indeterminate causes. Mostly, they are readily treated by orthopedists. As people age, accumulated spinal column injuries and diseases like osteoporosis can also lead to curvatures of the spine, hence the stooping you sometimes see in the elderly.

Some orthopedists sub-specialize in sports medicine, which addresses both simple injuries, such as a sprained ankle, and complex injuries, such as a torn rotator cuff in the shoulder. Treatment can range from exercise to surgery.

Mineral Storage, Energy Storage, and Hematopoiesis

On a metabolic level, bone tissue performs several critical functions. For one, the bone matrix acts as a reservoir for a number of minerals important to the functioning of the body, especially calcium, and phosphorus. These minerals, incorporated into bone tissue, can be released back into the bloodstream to maintain levels needed to support physiological processes. Calcium ions, for example, are essential for muscle contractions and controlling the flow of other ions involved in the transmission of nerve impulses.

Bone also serves as a site for fat storage and blood cell production. The softer connective tissue that fills the interior of most bone is referred to as bone marrow ( Figure 6.5 ). There are two types of bone marrow: yellow marrow and red marrow. Yellow marrow contains adipose tissue; the triglycerides stored in the adipocytes of the tissue can serve as a source of energy. Red marrow is where hematopoiesis —the production of blood cells—takes place. Red blood cells, white blood cells, and platelets are all produced in the red marrow.

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skeleton summary

Learn about the parts and functions of the skeletal system.

skeleton , Bony framework of the body. It includes the skull, vertebral column , collarbone, shoulder blades, rib cage, pelvic girdle and the bone s of the hands, arms, feet, and legs. The skeleton supports the body and protects its internal organs. It is held together by ligaments and moved at the joint s by the muscle s, which are attached to it. The skeletal system includes both bones and cartilage.

• Biology Article

Skeletal System

Human skeletal system.

The skeletal system functions as the basic framework of a body and the entire body are built around the hard framework of Skeleton. It is the combination of all the bones and tissues associated with cartilages and joints. Almost all the rigid or solid parts of the body are the main components of the skeletal system. Joints play an important role in the skeletal system as it helps in permitting the different types of movements at different locations. If the skeleton were without joints, then there would be no sign of the movements in the human body.

Skeletal System Anatomy

This skeletal system can be divided into the axial and appendicular systems. In an adult body, it is mainly composed of 206 individual bones which are organized into two main divisions:

Axial skeleton

• Appendicular skeleton.

The axial skeleton runs along the body’s central axis, therefore it is called the central core of the human body. The axial skeleton is composed of 80 bones and it consists of:

• Skull Bone – It includes 8 cranial bones, 14 facial bones, 6 auditory ossicles, and the Hyoid Bone
• The bone of the Thoracic Cage – It includes 25 bones of the thorax- a breastbone and 24 ribs.
• The bone of the Vertebral column- It includes 24 vertebrae bones, the sacrum bone, and the coccyx bone.

Also check: Function of Parietal Bones

Appendicular skeleton

The appendicular skeleton is composed of 126 bones and it comprises of the-

• Pelvic girdle
• Upper Limbs
• Lower Limbs
• Shoulder Girdle or the Pectoral

Read more: Parts and Names of Human Skeleton

Skeletal System Physiology

The primary functions of the skeletal system include movement, support, protection production of blood cells , storage of minerals and endocrine regulation.

The primary function of the skeletal system is to provide a solid framework to support and safeguard the human body and its organs. This helps in maintaining the overall shape of the human body.

Also check: Function of Short Bones

The skeletal system also helps to protect our internal organs and other delicate body organs, including the brain, heart, lungs and spinal cord by acting as a buffer. Our cranium (skull) protects our brain and eyes, the ribs protect our heart and lungs and our vertebrae (spine, backbones) protect our spinal cord.

Bones provide the basic structure for muscles to attach themselves onto so that our bodies are able to move. Tendons are tough inelastic bands that attach our muscle to that particular bone.

Also read: Femur Structure and Function

The bone matrix of the skeletal system is mainly involved in storing or preserving different types of essential minerals which are required to facilitate growth and repair of the body cells and tissues. The cell-matrix acts as our calcium bank by storing and releasing calcium ions into the blood cell when required.

Regulation of Endocrine glands

The bone cells present within the skeletal system plays an important role in releasing the synthesized hormones from the respective endocrine glands for the further requirement by the body for different metabolisms . Apart from these functions, the skeletal system also contributes to the regulation of blood sugar.

To learn more about the structure and functions of the skeletal system, visit BYJU’S.

Also check:

• How Many Bones Does A Human Have?
• How many bones does a female body have?
• How many bones are present in the human face?
• What is the meaning of appendicular skeleton?
• What is the function of the cranium?

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Author: Roberto Grujičić, MD • Reviewer: Dimitrios Mytilinaios, MD, PhD Last reviewed: October 30, 2023 Reading time: 8 minutes

Bones make up the skeletal system of the human bod y. The adult human has two hundred and six bones. There are several types of bones that are grouped together due to their general features, such as shape, placement and additional properties. They are usually classified into five types of bones that include the flat, long, short, irregular, and sesamoid bones.

The human bones have a number of important functions in the body. Most importantly, they are responsible for somatic rigidity, structural outline, erect posture and movement (e.g. bipedal gait ). Due to their rigidity, bones are the main 'protectors' of the internal organs and other structures found in the body.

This article will describe all the  anatomical and important histological facts about the bones.

What is a bone?

Short bones, irregular bones, sesamoid bones, clinical aspects.

A bone is a somatic structure that is composed of calcified connective tissue . Ground substance and collagen fibers create a matrix that contains osteocytes . These cells are the most common cell found in mature bone and responsible for maintaining bone growth and density. Within the bone matrix both calcium and phosphate are abundantly stored, strengthening and densifying the structure.

Each bone is connected with one or more bones and are united via a joint (only exception: hyoid bone ). With the attached tendons and musculature, the skeleton acts as a lever that drives the force of movement. The inner core of bones ( medulla ) contains either red bone marrow (primary site of hematopoiesis) or is filled with yellow bone marrow filled with adipose tissue .

The main outcomes of bone development (e.g. skull bones development ) are endochondral and membranous forms . This particular characteristic along with the general shape of the bone are used to classify the skeletal system. The bones are mainly classified into five types that include:

Types of bones

These bones develop via endochondral ossification , a process in which the hyaline cartilage plate is slowly replaced. A shaft, or diaphysis , connects the two ends known as the epiphyses (plural for epiphysis). The marrow cavity is enclosed by the diaphysis which is thick, compact bone . The epiphysis is mainly spongy bone and is covered by a thin layer of compact bone; the articular ends participate in the joints.

The metaphysis is situated on the border of the diaphysis and the epiphysis at the neck of the bone and is the place of growth during development.

Some examples of this type of bones include:

• The humerus
• The  fibula
• The  metacarpal bones
• The metatarsal bones
• The  phalanges
• The  radius and ulna . 

The short bones are usually as long as they are wide. They are usually found in the carpus of the hand and tarsus of the foot. 

In the short bones, a thin external layer of compact bone covers vast spongy bone and marrow , making a shape that is more or less cuboid . 

The main function of the short bones is to provide stability and some degree of movement.

Some examples of these bones are:

• The scaphoid bone
• The lunate bone
• The calcaneus
• The navicular bone

In flat bones, the two layers of compact bone cover both spongy bone and bone marrow space. They grow by replacing connective tissue. Fibrocartilage covers their articular surfaces. This group includes the following bones:

• The  skull bones
• The  sternum
• The  scapulae

The prime function of flat bones is to protect internal organs such as the brain, heart, and pelvic organs. Also, due to their flat shape, these bones provide large areas for muscle attachments. 

Due to their variable and irregular shape and structure, the irregular bones do not fit into any other category. In irregular bones, the thin layer of compact bone covers a mass of mostly spongy bone .

The complex shape of these bones help them to protect internal structures. For example, the irregular pelvic bones protect the contents of the pelvis. 

Some examples of these types of bones include:

• The bones of the spine (i.e. vertebrae )
• The bones of the pelvis ( ilium , ischium and pubis )

Sesamoid bones are embedded within tendons . These bones are usually small and oval-shaped. 

The sesamoid bones are found at the end of long bones in the upper and lower limbs, where the tendons cross.

Some examples of the sesamoid bones are the patella bone in the knee  or the pisiform bone of the carpus.

The main function of the sesamoid bone is to protect the tendons from excess stress and wear by reducing friction.

Learn the basics of the skeletal system with this interactive quiz.

The bones mainly provide structural stability to the human body. Due to the development of the complex bony structures (e.g. spine) the humans are able to maintain erect posture, to walk on two feet (bipedal gait) and for all sorts of other activities not seen in animals. 

Due to their rigid structure, bones are key in the protection of internal organs and other internal structures. Some bones protect other structures by reducing stress and friction (e.g. sesamoid bones) while some bones join together to form more complex structures to surround vital organs and protect them (e.g. skull, thoracic cage, pelvis). 

Bones also harbor bone marrow which is crucial in production of blood cells in adults. In addition, the bone tissue can act as a storage for blood cells and minerals.

Common bone diseases often affect the bone density, e.g. in young children due to malnutrition. For example, rickets is a bone deformity seen in young children who lack vitamin D. Their legs are disfigured and they have trouble walking. The damage is irreversible though surgery may help. Osteomalacia and osteoporosis are diseases seen mainly in adulthood.

Osteomalacia is the improper mineralization of bone due to a lack of available calcium and phosphate. The bone density decreases and the bones become soft. Osteoporosis has been noted in all ages but mostly in postmenopausal and elderly women. A progressive decrease in bone density increases the risk of fracture. Patients who are on long-term steroid medication are in particular risk.

• Kyung Won Chung and Harold M. Chung , Gross Anatomy, Sixth Edition, Wolters Kluwer: Lippincott, Williams and Wilkins, Chapter 1, p.1-2.

Illustrators:

• Hamate bone (ventral view) - Yousun Koh
• Patella (lateral-right view) - Yousun Koh

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Bone function, dysfunction and its role in diseases including critical illness

1 Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.

Hangang Chen

2 Bone Research Program, ANZAC Research Institute, The University of Sydney, Hospital Road, Sydney, NSW 2139, Australia.

The skeleton is one of the largest organs in the human body. In addition to its conventional functions such as support, movement and protection, the skeleton also contributes to whole body homeostasis and maintenance of multiple important non-bone organs/systems (extraskeletal functions). Both conventional and extraskeletal functions of the skeleton are defined as bone function . Bone-derived factors (BDFs) are key players regulating bone function. In some pathophysiological situations, including diseases affecting bone and/or other organs/systems, the disorders of bone itself and the subsequently impaired functions of extraskeletal organs/systems caused by abnormal bone (impaired extraskeletal functions of bone) are defined as bone dysfunction . In critical illness, which is a health status characterized by the dysfunction or severe damage of one or multiple important organs or systems, the skeleton shows rapid bone loss resulting from bone hyper-resorption and impaired osteoblast function. In addition, the dysfunctions of the skeleton itself are also closely related to the severity and prognosis of critical illness. Therefore, we propose that there is bone dysfunction in critical illness. Some methods to inhibit osteoclast activity or promote osteoblast function by the treatment of bisphosphonates or PTH1-34 benefit the outcome of critical illness, which indicates that enhancing bone function may be a potential novel strategy to improve prognosis of diseases including critical illness.

Introduction

The skeleton constitutes up to approximately 15% of total body weight and is among the largest organs/systems in the human body 1 . Adult bone structure mainly includes cortical bone, cancellous bone (trabecular bone) and bone marrow cavity. Bone consists of three compartments: bone cells, extracellular organic matrix including collagen fibers and amorphous matrix, and extracellular minerals 2 , 3 . There are three major types of bone cells in bone tissue: osteoblasts, osteoclasts, and osteocytes. Osteoblasts are the major cells responsible for bone formation, whereas osteoclasts mainly resorb bone. Bone homeostasis is maintained by the coupling between bone-forming and bone-resorbing (bone turnover). Osteocytes, which make up the majority of bone cells in the adult 4 , are terminally differentiated osteolineage cells. Osteocytes are now recognized as important cells playing essential roles in skeletal development and especially homeostasis, including bone modeling and remodeling that was previously thought to be largely controlled by the osteoblasts and osteoclasts 5 .

Bone function and bone-derived factors

The conventional function of the skeleton is as a static structural organ supporting body movement, protecting the internal organs, and as a reservoir of minerals 2 .

The skeleton is an important organ for the support of the body and for the attachment of muscles and tendons, as well as body movement. The skeleton protects the organs of the cranial and thoracic cavities from injuries, and it houses and protects the bone marrow within its cavities. Additionally, the skeleton has an important role as a reservoir of minerals such as calcium and phosphate, which can be released when demands are increased in the body, and in maintaining serum homeostasis 2 . These conventional functions of skeleton depend on the homeostasis of bone itself.

Recently, increasing studies have revealed that the skeleton contributes to whole body homeostasis and the maintenance of multiple important organs/systems such as hematopoiesis, immune activity, energy metabolism, and brain function. These functions affecting non-bone tissues are called extraskeletal functions 6 , 7 .

Bone tissue and cells can generate a variety of substances such as proteins/peptides including growth factors, chemokines, cytokines etc . , as well as matrix degradation products, metallic/non-metallic elements, metabolic products, and extracellular vesicles (such as exosomes and micro vesicles) 8 , 9 , which can be collectively defined as bone-derived factors (BDFs) (Figure ​ (Figure1). 1 ). In addition to their roles in regulating bone modeling and remodeling, these BDFs are the major factors mediating the extraskeletal functions of bone 1 , 7 , 8 .

Bone-derived factors (BDFs) from bone. Bone tissue and cells can generate a variety of substances. (A) Proteins/peptides including growth factors, chemokines, cytokines, matrix protein and enzymes etc . such as FGF23, CXCL12, ILs, OC and others. (B) Matrix degradation products and metallic/non-metallic elements released during bone resorption such as CTX and lead ions. (C) Metabolic products of bone cells such as lactic acid. (D) Structural elements secreted by bone cells such as exosomes and micro vesicles.

Extraskeletal functions of bone mediated by BDFs

The effect of bone on the hematopoietic and immune systems.

Hosted by bone tissue, hematopoietic stem cells (HSCs) in bone marrow are able to differentiate into all hematopoietic lineages. The functional communication among different bone cell types and hematopoiesis in the bone marrow has been extensively studied in recent decades. Mesenchymal stem cells, osteoblasts, and other cells in the bone marrow form a special local environment termed a “niche,” which not only nests the HSCs but also helps to maintain the stemness of the resident HSCs 10 - 12 (Figure ​ (Figure2 2 A).

Schematic diagram illustrating the effects of some molecules generated by bone on systemic homeostasis. (A) Some molecules secreted by osteoblasts, osteocytes and osteoclasts such as CXCL12, CTSK, G-CSF, MMP-9, IL-7 and IL-9 play very important roles in regulating HSCs maintenance, expansion or mobilization, and thus influence the hematopoietic and immune systems such as lymphopoiesis and megakaryopoiesis. (B) FGF23 inhibits phosphate reabsorption and promotes calcium and sodium reabsorption in the kidney. (C) GluOC and LCN2 induce insulin production and improve insulin sensitivity and then regulate energy expenditure. Sclerostin secreted by osteocytes regulates insulin sensitivity and metabolism of adipocytes. (D) GluOC promotes brain development and cognitive function. (E) GluOC can regulate male fertility by promoting testosterone production and inhibiting the apoptosis of Leydig cells in testes. (F) Bone regulates muscle mass and exercise capacity through secretion of GluOC, PGE2, VEGF, and others.

Osteoblasts are indispensable for the quiescent status and self-renewal of HSCs. The absence of osteoblasts leads to decreased self-renewal of HSCs in the bone marrow 13 . Activation of parathyroid hormone (PTH) signaling in osteoblasts results in increased numbers of both osteoblasts and HSCs 10 . Spindle-shaped N-cadherin positive (N-cadherin + ) osteoblasts (known to enrich osteoprogenitors) are mainly located on the surface of cancellous/trabecular bone and are directly attached to long-term HSCs (LT-HSCs) and maintain HSC quiescence 14 , 15 . In addition to directly attaching to HSCs, some molecules secreted from osteoblasts can support HSCs. For example, Wnt11, one of the osteoblast derived Wnt ligands, activates non-canonical Wnt signaling mediated by Fmi and Fz8 in HSCs and maintains the quiescent status of HSCs in the bone marrow niche 16 . Thrombopoietin and angiopoietin-1 secreted by osteoblasts can also regulate HSC quiescence 17 , 18 . In addition, osteoblasts play an important role in lymphopoiesis, myelopoiesis and megakaryopoiesis. C-X-C motif chemokine ligand 12 (CXCL12) is a chemokine that regulates HSC maintenance and retention 19 , 20 and is required for lymphopoiesis and myelopoiesis 21 , 22 . The deletion of CXCL12 from osteoblasts led to depletion of certain early lymphoid progenitors but not HSCs, suggesting that osteoblast CXCL12 mainly promotes the maintenance of early lymphoid progenitors 19 . The deletion of interleukin 7 (IL-7) in osteoblasts led to a lymphopenic phenotype by decreasing common lymphoid progenitor number but not HSCs, indicating the important effect of osteoblast IL-7 on lymphopoiesis 23 . Furthermore, m-TORC1 signaling inhibits megakaryopoiesis through decreasing the osteoblast derived IL-9 levels 24 .

Osteoclasts are another important cells regulating hematopoiesis in bone. Engraftment of HSCs to bone marrow depends on local level of calcium ion elevated during bone resorption 25 . Cathepsin K, the major bone-resorbing proteinase secreted by osteoclasts, cleaves CXCL12 and stem cell factor (SCF) in the stem cell niche, which is associated with promoted mobilization of hematopoietic progenitor cells (HPCs) into the systemic circulation 11 . Matrix metalloproteinase 9 (MMP-9) secreted by osteoclasts induces the release of SCF from bone marrow stromal cells to promote hematopoietic reconstitution, suggesting an important role of osteoclasts in HSC niche maintenance and mobilization 26 . Administration of receptor activator of nuclear factor-κ B ligand (RANKL) increases concomitant mobilization of HSCs to the systemic circulation by promoting bone resorption 11 , while inhibition of osteoclast function by bisphosphonates treatment (clinical drugs used to treat osteoporosis) reduced HSC numbers in mice 27 . The absence of osteoclast activity results in a defective HSC niche associated with an increased proportion of mesenchymal progenitors but reduced osteoblastic differentiation, leading to impaired HSC homing to the bone marrow 28 . It is suggested that bone marrow B lymphopoiesis is also regulated by osteoclast activity. Inhibiting osteoclast activity by zoledronic acid injections caused a decrease in the number of B-cells in the bone marrow in mice, resulting from decreased expression of CXCL12 and IL-7 by stromal cells, associated with reduced osteoblastic engagement 29 .

Several studies have revealed that osteocytes also regulate the endosteal microenvironment and hematopoiesis. The ablation of osteocytes led to severe lymphopenia due to the lack of lymphoid-supporting stroma in both the bone marrow for B-cell precursors and the thymus for T-cell precursors, and a marked loss of white adipose tissues 30 . Osteocytes produce granulocyte-colony stimulating factor (G-CSF), an important factor promoting myeloid expansion in the bone marrow. The deletion of Gs alpha specifically in osteocytes resulted in enhanced G-CSF production 31 .

The effect of bone on mineral metabolism

In the last 10 years, bone has been recognized as an important endocrine organ regulating multiple metabolic processes. Mineral metabolism is very important for homeostasis. In addition to storing minerals, the skeleton also regulates systemic mineral metabolism through an endocrine manner (Figure ​ (Figure2 2 B).

Fibroblast growth factor 23 (FGF23), a member of the FGF family, is a bone-derived hormone secreted by osteoblasts and osteocytes. Mutations in FGF23 prevent its cleavage, resulting in autosomal-dominant hypophosphatemic rickets (ADHR), which is characterized by low serum phosphorus concentrations, rickets, osteomalacia, etc. 32 - 35 . The overproduction of FGF23 by tumors 36 and osteogenic cells in fibrous dysplastic lesions 37 is responsible for the hypophosphatemia in tumor-induced osteomalacia (TIO) and fibrous dysplasia. These studies help to define the critical role of FGF23 in regulating phosphate metabolism.

FGF23 inhibits phosphate reabsorption by inhibiting expression of the type IIa sodium-phosphate co-transporter (NaPi-2a) in the proximal tubules of the kidney through binding to a FGFR1-α-Klotho co-receptor complex 38 - 40 , leading to phosphate loss. FGF23 also regulates calcium and sodium reabsorption of the kidney 41 , 42 . FGF23 promotes renal calcium reabsorption through the transient receptor potential vanilloid-5 (TRPV5) channel in the distal renal tubules 41 , and FGF23 promotes sodium reabsorption through the sodium-chloride co-transporter (NCC) in the renal distal renal tubules and leads to volume expansion and hypertension 42 .

In addition, FGF23 systematically regulates serum calcium and phosphate by regulating levels of PTH and the active form of vitamin D (1,25-dihydroxyvitamin D 3 , 1,25(OH) 2 D 3 ). PTH promotes calcium release from bone by stimulating bone resorption and calcium absorption in the kidney and intestinal calcium absorption via an increase in the 1,25(OH) 2 D 3 level. PTH also inhibits phosphate reabsorption in the kidney 43 . 1,25(OH) 2 D 3 promotes calcium absorption in the small intestine and phosphate reabsorption by suppressing the PTH level in the kidney 44 .

FGF23 inhibits PTH synthesis and secretion in the parathyroid in a Klotho-dependent or independent manner 45 , 46 and suppresses the synthesis of 1,25(OH) 2 D 3 by inhibiting 25-hydroxyvitamin D-1a-hydroxylase (1a-OHase) and increasing 25-hydroxyvitamin D-24-hydroxylase (24-OHase) in the kidney 47 . These studies demonstrate that FGF23 regulates mineral metabolism locally in the kidney and systematically by regulating PTH and 1,25(OH) 2 D 3 .

The effect of bone cells on glucose and energy metabolism

As an endocrine organ, bone also regulates glucose and energy metabolism through different pathways (Figure ​ (Figure2 2 C).

Osteocalcin (OC) is another osteoblast-secreted multifunctional hormone and is embedded in the bone matrix during bone formation 5 . There are two forms of OC: uncarboxylated OC (γ-carboxylated OC, GlaOC) and undercarboxylated OC (GluOC). During bone resorption, the acidic environment in the bone resorption pits generated by osteoclasts promotes the decarboxylation of GlaOC embedded in bone matrix to GluOC, which has a lower affinity for hydroxyapatite and therefore is more easily released from bone tissue into the circulation 48 , 49 . GluOC can promote β-cell proliferation, stimulate insulin synthesis and secretion, and increase the insulin sensitivity of adipose tissue, muscle, and liver, leading to increased energy expenditure 50 .

Changing osteoblast or osteoclast activity alters glucose metabolism by affecting GluOC levels. A clinical study shows that patients treated with preotact (PTH1-84), a bone formation-promoting drug for osteoporosis by increasing osteoblastic activity, resulted in an increased serum GluOC level and decreased blood glucose level 51 . Animal experiments show similar results. Conditional deletion of the insulin receptor (IR) in osteoblasts led to impaired osteoblast differentiation and decreased OC production, and increased expression of osteoprotegerin (OPG) in IR-deficient osteoblasts hampers osteoclast differentiation and bone resorption, resulting in a reduced serum GluOC level. The decreased serum GluOC level leads to impaired glucose tolerance, insulin secretion and sensitivity 48 , 52 . It is well known that long-term glucocorticoid treatment induces insulin resistance and glucose intolerance. Interestingly, it is reported that these glucocorticoid side effects are partially mediated through osteoblasts. As a glucocorticoid target gene, the total serum OC levels can be suppressed within 3 days after glucocorticoid treatments 53 , 54 . The deletion of glucocorticoid signaling in osteoblasts attenuated the glucocorticoid suppressed OC synthesis and prevented the development of insulin resistance and glucose intolerance 53 . The deletion of OPG in mice led to an increased osteoclast number and an improved serum GluOC level, resulting in higher glucose tolerance compare to wild-type animals, suggesting that osteoclasts control glucose metabolism through the regulation of OC decarboxylation.

In addition to OC, recent studies also implicate an OC-independent influence of bone on energy metabolism. For example, ablation of osteoblasts in adult mice or conditional deletion of β-catenin or Lrp5 (a coreceptor of Wnt-β-catenin signaling) in osteoblasts/osteocytes leads to systemic metabolic alterations, which could not be fully reversed by OC treatment or explained by increased or unchanged serum OC level 55 - 57 . These results suggest that there are some other unknown factors or mechanisms involved in mediating energy metabolism by bone.

Lipocalin 2 (LCN2), a newly identified hormone secreted by osteoblasts, also regulates energy metabolism (Figure ​ (Figure2C). 2 C). LCN2 maintains glucose homeostasis by inducing insulin secretion and improving glucose tolerance and insulin sensitivity, as well as inhibiting food intake 58 . Sclerostin is a secreted glycoprotein specifically generated by osteocytes to inhibit Wnt signaling 59 and plays an endocrine function to influence body composition by regulating adipocyte metabolism 60 , 61 (Figure ​ (Figure2C). 2 C). The deletion of SOST in mice or sclerostin-neutralizing antibody treatment led to reduced mass of white adipose tissue and corresponding enhancements in insulin sensitivity and fatty acid 60 , indicating a positive role of sclerostin on anabolic metabolism in adipocytes. However, another study showed the opposite results. Enhanced sclerostin levels in mice with deficiency of Gsα in mature osteoblasts and/or osteocytes also lead to the loss of white adipose tissue 61 . These inconsistent results might be due to the different mouse models.

A recently study shows that the deletion of von Hippel-Lindau ( Vhl ), a hypoxia signaling pathway component, in osteolineage cells led to hypoglycemia and increased glucose tolerance in mice, which is caused by increased glucose uptake and glycolysis of osteoblasts, but not caused by OC because the serum OC level was decreased in these mice 62 . This result suggests that osteoblasts regulate whole-body glucose homeostasis by regulating their own cellular glucose metabolism.

Other extraskeletal functions of bone

Embryonic brain development and adult brain function are regulated by bone via GluOC 63 (Figure ​ (Figure2D). 2 D). Mouse maternal GluOC can cross the placenta and blood-brain barrier to directly promote brain development and the acquisition of cognitive function in the fetus 64 . In adult mice, GluOC can also pass through the blood-brain barrier to promote brain-derived neurotrophic factor expression and affect cognitive function of the brain. OC absence in mice resulted in deficiency of spatial learning and memory and a worsened anxiety-like behavior. Delivering GluOC can correct age-related cognitive decline and decrease anxiety-like behavior and functions 63 , 64 .

In addition, GluOC can regulate male fertility by promoting testosterone production and inhibit the apoptosis of Leydig cells in testes 65 (Figure ​ (Figure2 2 E).

Bone also has important effects on muscle. GluOC increases IL-6 production of muscle, which enhances glucose and fatty acid uptake of myofibers, and then promotes adaptation to exercise 66 . In addition, a comparatively high concentration of GluOC administered exogenously increased muscle mass in aged mice 67 . Moreover, in vitro studies have shown that bone marrow mesenchymal stromal cells stimulate myoblast proliferation through the paracrine release vascular endothelial growth factor (VEGF) 68 , and osteocytes can support myogenesis and muscle function by secreted prostaglandin E2 (PGE2) 69 . These results indicate the positive influences of bone on muscle (Figure ​ (Figure2 2 F).

Based on these data described above, in addition to the classic functions of movement and protection, the skeleton has extraskeletal functions that play important roles in the maintenance of vital organs/systems and the general health (Figure ​ (Figure2). 2 ). We, therefore, define these classic and extraskeletal functions of skeleton as BONE FUNCTION (Figure ​ (Figure3A). 3 A). The impaired bone function may lead to bone dysfunction.

Bone function and hypothesis of bone dysfunction. (A) Bone function includes conventional functions (such as movement, protection and reserve of minerals) and extraskeletal functions (regulation of the function and homeostasis of extraskeletal organs/systems such as hematopoietic and immune systems, mineral and metabolism, etc .). (B) Hypothesis of bone dysfunction. In some pathophysiological situations, including genetic/aging/injury diseases of bone and/or other organs/systems diseases, the disorders of bone itself and the subsequently impaired function of extraskeletal organs/systems caused by abnormal bone (impaired extraskeletal function of bone) are defined as BONE DYSFUNCTION.

Bone dysfunction

The body is composed of multiple organs/systems and exists and functions as a whole system. There is elegant coordination and crosstalk among different organs/systems, which makes our bodies functional in physiological situations and might also accelerate the dysfunction or failure of multiple organs/systems during severe diseases. For example, chronic renal failure can lead to heart failure.

As for the skeleton, in some pathophysiological situations including diseases affecting bone tissue (such as genetic bone diseases or osteoporosis) and/or other organs/systems (such as systemic inflammation, chronic kidney disease (CKD), diabetes, etc. ), the impaired functions of bone cells might lead to abnormal bone formation or resorption, and then result in bone disorders characterized by impaired bone microstructure and decreased bone strength, which increases bone fragility and fracture. Furthermore, the abnormalities of the skeleton might also injure the homeostasis of other organs/systems by changing the production and metabolism of BDFs, which might subsequently lead to dysregulated or impaired function of extraskeletal organs/systems (Figure ​ (Figure3 3 B).

For example, osteoporosis is the most common bone disease in humans characterized by bone loss, microarchitectural deterioration, and compromised bone strength 70 , 71 . Osteoporosis leads to increasing bone fragility and propensity for fracture, particularly in postmenopausal women 70 - 72 . Recent studies also show that there is close relationship between osteoporosis (Or low bone mass) and other system diseases or mortality. Osteoporosis is associated with an increased risk of the incidence of Alzheimer's disease dementia 73 . Low bone mass is also associated with increased all-cause mortality of the elderly, and is also an independent risk factor for mortalities of stroke, chronic lung and cardiovascular diseases 74 - 77 . Osteoporosis treatment can reduce mortality in elderly and frailer individuals with osteoporosis who are at high risk of fracture 78 .

Osteopetrosis is a kind of bone genetic diseases sharing the hallmark of a generalized increase in bone mass 79 . Many patients with osteopetrosis have more brittle bones and increased incidence of anemia and recurrent infections 79 . Activating mutation of β-catenin in osteoblasts led to osteosclerosis and the development of acute myeloid leukemia (AML) in mice, and thirty-eight percent of patients with myelodysplastic syndrome (MDS)/AML showed increased β-catenin signaling in osteoblasts 80 .

Therefore, as mentioned above, we define these disorders of bone itself, and the impaired extraskeletal functions of bone as BONE DYSFUNCTION (Figure ​ (Figure3 3 B).

Bone dysfunction in critical illness

Critical illness describes a health status with dysfunction or severe damages of one or multiple important organs/systems and includes conditions such as sepsis, shock, acute respiratory distress syndrome (ARDS), acute renal failure, heart failure, disorders of the immune and hematopoietic systems, endocrine and metabolic disturbances, and electrolyte and acid-base imbalance 81 - 84 , etc .

However, as one of the largest organs with an emerging important role in regulating multiple organs/systems, changes of the skeleton and its functional role during critical illness remain poorly understood. We previously proposed a relationship between bone and critical illness and the potential important role of bone dysfunction in critical illness 85 , which has been supported by increasing evidences.

Changes of bone in critical illness

The most significant pathological changes in bone during critical illness are accelerated bone loss and increased risk of fracture, especially in patients with osteoporosis 86 - 88 and especially following a prolonged stay in an intensive care unit (ICU) 89 , 90 . These changes in bone are ultimately due to enhanced bone resorption and impaired bone formation.

Bone resorption activity is significantly increased in critically ill patients. C-telopeptide of type I collagen (CTX) and N-telopeptide of type I collagen (NTX) are degradation products of type I collagen during bone resorption. Serum levels of CTX or urine NTX are recommended as biochemical markers of bone resorption and have been used in clinical diagnosis 9 . Patients with critical illness had obvious enhanced bone resorption activity with elevated serum CTX and urine NTX levels 90 - 94 .

In addition, bone formation is also profoundly affected by critical illness. N-terminal propeptide of type I procollagen (P1NP) is cleaved from procollagen molecules in the extracellular matrix before the assembly of type I collagen molecules into fibers 9 . P1NP, OC and serum bone alkaline phosphatase (bALP) secreted by mature osteoblasts are used as biochemical markers to assess osteoblast function and bone formation 9 . Patients with critical illness had a significant increase in P1NP and a decrease in OC levels, which suggests an increase in the activity of immature osteoblasts, with low activity of mature osteoblasts 95 . We also found that serum bALP levels were lower in infected newborns than that in the non-infected group 96 . These changes in osteoblasts might be a possible cause for bone loss and demineralization of bone in critically ill patients 88 . Our animal study also showed decreased bone mass and mRNA expression of OC in mice with systemic inflammation and sepsis caused by lipopolysaccharide (LPS) treatment 97 . Other animal experiments showed that the increased apoptosis or acute deficiency of osteoblasts might be another reason causing impaired of bone formation 23 , 98 .

In addition to the enhanced bone resorption and impaired bone formation, some molecules secreted from bone cells are also influenced by critical illness. For example, LPS stimulates osteoblasts to generate IL-1, IL-6, and tumor necrosis factor α (TNF-α), which are important cytokines regulating inflammation. Furthermore, researchers also found that pro-inflammatory factors promoted osteocyte secretion of FGF23 99 , and plasma FGF23 levels were elevated in critically ill patients 100 .

The causes of these changes in bone have not been fully elucidated but are intimately connected with extremely stressful situations such as vitamin D deficiency, glucocorticoid therapies 94 , 101 , long-term bed-rest, inflammatory environments, and disorders of metabolism such as glucose and hormones in critical illness 88 , 94 , 102 , 103 (Figure ​ (Figure4 4 ).

Schematic diagram illustrating the relationship between critical illness and bone dysfunction. Many pathological conditions such as inflammation, endocrine and metabolic disturbances, electrolyte and acid-base imbalance or vitamin D deficiency, as well as other causes such as long-term bed-rest or glucocorticoid therapies in critical illness could result in impaired osteoblast function and increased osteoclast activity, ultimately leading to acute bone loss and even bone fracture. Furthermore, the impaired osteoblast function and enhanced bone resorption could also cause increased secretion of proinflammatory factors, which might exacerbate the systemic inflammatory response. The changes of some BDFs secreted by osteoblasts such as the decreased serum levels of OC, IL-7 and CXCL12 or increased FGF23 level in critical illness may also worsen metabolic or hematopoietic disorders. We define these damages or changes in the structure and functions of bone as bone dysfunction in critical illness.

The effects of changed bone on progress and prognosis of critical illness

The important role of bone in the maintenance of vital organs and systems described above strongly suggests that bone might be a critical player in the initiation, progress and prognosis of critical illness.

Patients in the ICU who died showed a greater degree of bone loss 104 . Low osteoblast activity (characterized by decreased bALP serum levels) was inversely correlated with the scores for neonatal acute physiology-perinatal extension II (SNAPPE-II, an index assessing neonatal illness severity in the neonatal ICU population) of infected neonates 96 . Higher serum FGF23 levels are also independently associated with greater mortality in critically ill patients with or without CKD 100 , 105 . Animal experiments showed that osteoblast ablation in sepsis led to a high mortality rate in mice 23 . These studies provide important clinical and animal experimental evidences supporting the causal links between disorders of bone and the severity and outcome of critical illness.

The mechanisms underlying the important role of bone in the pathogenesis of critical illness have not been fully clarified to date. Changes of some BDFs might participate in the pathogenesis of critical illness. Decreased serum levels of OC might contribute to abnormalities of glucose metabolism, such as hyperglycemia in critical illness. Elevated serum level of FGF23 might contribute to hypophosphatemia during sepsis 99 . Meanwhile, the increased FGF23 level might be related to the impaired defense and inflammatory status of critically ill patients as FGF23 has been found to impair neutrophil activation and stimulate hepatic production of inflammatory cytokines 106 , 107 . Furthermore, pro-inflammatory factors secreted by bone cells such as high mobility group box 1 protein (HMGB1), RANKL, TNF-α, and IL-1/6 might also aggravate the systemic inflammatory response in critical illness 108 - 110 . Osteoblast-derived IL-7 regulates early lymphopoiesis, and decreased IL-7 expression in osteoblasts resulted in lymphopenia in sepsis mice 23 . However, the detailed roles and underlying mechanisms of bone in critical illness need further studies.

Briefly, the above mentioned data suggest that damage or changes in bone function are highly related to the severity and prognosis of critical illness. Therefore, we hypothesize that there is bone dysfunction in critical illness, which is likely to be involved in the pathogenesis of critical illness and that improvement of bone function might benefit the critical illness prognosis (Figure ​ (Figure4 4 ).

Improvement of bone function may benefit the prognosis of critical illness

Enhancing osteoblast function is a potential mean to improve the prognosis of patients with critical illness. Pharmacological activation of osteoblasts using teriparatide (PTH1-34), a drug for osteoporosis that promotes bone formation, improves bone mass and sepsis-induced lymphopenia, and increases the survival rate of mice by increasing IL-7 generation 23 . We found that deletion of fibroblast growth factor receptor 1 (FGFR1) in mature osteoblasts leads to increased osteoblast activity and enhances the mobilization of endothelial progenitor cells (EPCs) into the peripheral blood by promoting CXCL12 secretion from osteoblasts, resulting in increased survival rate of mice with sepsis 111 . The inhibition of bone resorption might be another way to regulate critical illness prognosis. A recent study shows that preadmission treatment with bisphosphonates is associated with improved survival among critically ill patients, possibly by inhibiting bone resorption and increasing bone mass 104 .

These studies suggest that improvement of bone mass or bone function is a potential novel strategy to improve the prognosis of critically ill patients, although the mechanisms and detailed approaches need to be further studied.

Conclusion and Perspective

As the one of the largest organs, the skeleton shows diverse important functions (bone function). Abnormalities of the skeleton will not only affect bone itself but will also profoundly influence other organs/systems. Dysfunction of bone might significantly affect the maintenance of our health. Improvement of bone function might benefit the function of vital organs and systems.

At present, the major clinical and experimental parameters used to evaluate bone status include imaging (X-ray, CT, MRI), ultrasound, mechanical properties, histology of bone and bone metabolic markers, which mainly focus on bone structure and bone turnover (bone forming and resorbing function). Few physiological parameters of bone such as intramedullary pressure, capillary permeability oxygen and water content, blood flow, PH value, etc . are evaluated in research and especially in clinics, and the effects of these physiological parameters on bone function are not clear. In addition, BDFs, the major mediators regulating bone function, are not well evaluated. Although some BDFs are known, more specific BDFs need to be further discovered using advanced techniques such as genomics, proteomics and metabonomics. Furthermore, more animal and clinical studies also should be conducted to reveal the production and metabolism of BDFs in disease states and to clarify the roles and underlying mechanisms of individual BDF in specific acute or chronic diseases.

To date, the parameters used to evaluate bone status during critical illness are mainly focused on bone mass and metabolic markers. The changes in some known and unknown BDFs, physiological parameters mentioned above, and the function of bone-related cells should be further explored during critical illness.

Previous studies indicate that bone dysfunction is closely related to the prognosis of critical illness, but more evidence is needed to further examine this relationship mechanistically. Many questions remain to be answered. For example, preadmission treatment with bisphosphonates is associated with improved survival of critically ill patients; however, it is unclear if this association is related to the blunted bone resorption due to the action of bisphosphonate itself, or to the increased bone mass, or to the molecular and cellular changes caused by bisphosphonates in other cell types. This mechanism needs to be clarified. It also remains unknown if a significantly increased serum CTX is a surrogate for the outcome of critical illness. In addition, the mechanism by which FGF23 affects the mortality of critically ill patients is not known.

Although only a few studies have shown that improvement of bone function might benefit the outcome of critical illness, considering the availability and efficacy of commonly used anti-osteoporosis drugs in the clinic, modulating bone structure and function might provide a novel strategy to improve the outcome of critical illness. In addition to the current drugs, further approaches with the potential to improve bone function, such as novel anti-resorptive drugs and rehabilitation measures (such as mechanical loading) should be studied for their potential beneficial effects on diseases including critical illness.

Acknowledgments

We thank Meng Xu for modifying the figures.

Consent for publication

All authors read and approved the final manuscript.

National Natural Science Foundation of China (No.81830075, 81870621), Independent Research Project of the State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University (No. SKLZZ(III)201601), Innovative Research Team in University (IRT1216).

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Year 7 - Living systems - L8 Skeleton

Subject: Biology

Age range: 7-11

Resource type: Lesson (complete)

Last updated

8 September 2024

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This lesson is designed for year 7, It covers the skeleton, and the function.

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