Although often thought of as a static support structure, the skeletal system is a dynamic organ with many functions, including giving us our human shape, allowing locomotion and motor function, facilitating respiration, protecting vital organs, producing marrow-derived cells, and playing a crucial role in homeostasis. [1, 2, 3, 4, 5]
Bones are dynamic structures that are undergoing constant change and remodeling in response to the ever-changing environment.  In fact, there is so much turnover that in 4 years, the skeleton of a young person will be completely new as compared with their skeleton today.  Bones can react and respond to environmental stimuli; they can get bigger or smaller, they can strengthen themselves when needed, and, when broken, they are among the few organs with the ability to regenerate without scar. 
There are 206 bones (some say 213  ) in the human body. Some variation exists, because humans may have different numbers of certain bones (eg, vertebrae and ribs). Bones vary widely in size, ranging from the tiny inner ear bones that are responsible for transmitting mechanical sound waves to the sensory organs to the large (nearly 2 ft long) femur bone that is strong enough to withstand 30 times one's body weight.
Gross Anatomy Overview
Long bones are formed from a cartilage model precursor by endochondral ossification (see the image below) and can range in size from a phalanx to a femur. They are typically tubular, have distinct anatomic zones, and are longer than they are wide. [1, 2, 4] Short bones arise from the same precursors but are not necessarily structurally similar to long bones, often taking on unique shapes (eg, carpal bones). Flat bones are formed without a precursor by intramembranous ossification  and can have unusual shapes (eg, skull or sternum).
Most bones have a thick, well-organized outer shell (cortex) and a less dense mesh of bony struts in the center (trabecular bone) (see the image below). The ratio of cortical bone to trabecular bone varies widely;  in adults, this ratio is typically 80:20. 
The only bones that lack a true cortex are the vertebrae, which are covered by a compact condensation of trabecular bone.  All bones are encased in a soft tissue envelope known as the periosteum, which is vital for perfusion and nutrient supply to the outer third of the bone (see the image below). [1, 2] The remainder of the blood supply is through nutrient vessels that pierce the cortex and supply the marrow cavity and the inner two thirds of the cortical bone. [1, 2]
Mature long bones have 3 distinct zones: epiphysis, metaphysis, and diaphysis (see the image below).  In development, the epiphysis and metaphysis are separated by a fourth zone, known as the epiphyseal plate, or physis. This segment of the bone is cartilaginous and is the region from which the bone grows longitudinally. By adulthood, all epiphyseal plates have closed down, and a bony scar is all that remains of this important structure. Long bones include the femur, tibia, fibula, humerus, radius, ulna, metacarpals, metatarsals, and phalanges.
The epiphysis is the region at the polar ends of long bones. Most commonly associated with joint surfaces, it usually comprises a thin, compact bone shell with a large amount of bony struts (trabecular bone) for support of the cortical shell. The network of bony struts below the compact shell is ideally suited for its job as a shock absorber. 
The shell or covering of compact bone is thicker just below a joint and is known as the subchondral bone; it supports the hyaline articular cartilage of the joint just above it. The subchondral bone is not true cortical bone, in that it lacks some of the organization of cortical bone. 
The epiphysis also serves as an attachment region in many bones, allowing joint capsular attachments, many ligamentous attachments, and some tendinous attachments as well. Like most sections of bone, it is strong, but it lacks the rigidity of the diaphysis.
Epiphyseal plate (physis)
An extremely important zone in human development, the epiphyseal plate is responsible for longitudinal growth of the skeleton and therefore one's height and stature. There are many diseases of the epiphyseal plate such as achondroplasia that affect the plate’s ability to grow normally and this can lead to significant change in stature and are often know as the skeletal dysplasias. The epiphyseal plate itself is broken down into distinct zones (see the image below).
There is a layer of resting cartilage that is the precursor to the process. Cells are stimulated to replicate in the zone of proliferation, and chondrocytes then hypertrophy in the zone of hypertrophy. They then undergo a process of mineralization, and eventually death, in the zone of calcification. This forms the bone precursor that will continuously be remodeled throughout life. Bones can also grow in width from direct bone formation supported by the periosteum.
The metaphysis is a transitional zone between the epiphysis and diaphysis. It is also characterized by thinner cortical walls with dense trabecular bone. It is commonly the site of tendinous attachments to bone. It is a metabolically active region and often supports a fair amount of bone marrow. The metaphysis is the region where the bone made by the epiphyseal plate is fine-tuned into its diaphyseal shape.
In the middle of long bones is the diaphysis, a segment of thick cortical bone with a minimal amount of trabecular bone. It is often smaller in diameter than metaphyseal and epiphyseal bone; because its thick cortical layer is extremely strong, it does not require a large diameter to distribute its load. The central portion is the least dense area of the bone and is known as the intramedullary canal. The area of the bone inside the cortex is continuous throughout an entire bone and is known as the endosteal area. 
Diaphyseal bone’s primary function is structural: it gives the skeleton much of its length and providing much of the surface area for muscular and tendinous attachment.
Short bones are also formed by the same cartilage precursor model as long bones; however, they tend to have unique shapes and functions. They provide less overall height than long bones. Like long bones, they have a cortical shell on the periphery and a trabecular inner portion. They vary in size and shape. Examples include the carpal bones, vertebrae, patella, and sesamoid bones.
Although similar to the previously mentioned bones in some respects, flat bones differ completely in their embryologic origin. Stemming from mesenchymal tissue sheets, flat bones never go through a cartilaginous model. The mesenchymal sheets condense and organize and are eventually ossified. They grow from membranous or periosteal growth. They consist of a cortical shell with a cancellous interior and are often broad and flat. They provide protection (eg, skull) and also offer wide, flat surfaces for muscular attachment (eg, scapula).
Gross Anatomy of Axial Skeleton
The skeleton is divided into 2 anatomic regions: axial and appendicular (see the images below). The appendicular skeleton comprises the extremities, which are paired mirror images of each other. The axial skeleton is the central structural core of the body. The auditory ossicles and the hyoid bone are nonstructural, nonextremity bones that are used in sensation, phonation, and swallowing; they do not fit well into either category.
The axial skeleton includes the bones of the skull, cervical vertebrae, thoracic vertebrae, ribs, sternum,  lumbar vertebrae,  and the sacrum and coccyx (see the image below). Some authors consider the bones of the pelvis to be axial, although they properly belong to the appendicular skeleton.
The skull is made of many interdigitating flat bones with numerous sinuses, foramina, and features; detailed discussion of these features is beyond the scope of this article. The main joints of the skull are the articulations between the mandible and skull and the articulation between C1 and the base of the skull. The skull’s primary purpose is to house the brain and sensory organs. The bones of the skull also allow mastication, swallowing, phonation, and numerous other vital functions.
The cervical spine is made up of 7 vertebrae (see the first and second images below). C1 and C2 are highly specialized and are given unique names: atlas and axis, respectively (see the third image below). C1 and C2 form a unique set of articulations that provide a great degree of mobility for the skull. C1 serves as a ring or washer that the skull rests upon the dens or odontoid process of C2. Approximately 50% of flexion extension of the neck happens between the occiput and C1; 50% of the rotation of the neck happens between C1 and C2.
C3-7 are more classic vertebrae, having a body, pedicles, lamina, spinous processes and facet joints. The cervical spine is highly mobile. The other unique feature of cervical vertebrae is that they contain transverse foramina for the vertebral arteries as they travel cephalad, encased in bone at each level.
The thoracic spine is typically made up of 12 vertebrae. These vertebrae also have a body, pedicles, laminae, spinous processes, and facet joints (see the first two images below). Additionally, they have prominent lateral processes that form the articulation with the paired 12 ribs on either side. The 12 vertebrae, 24 ribs, and sternum together form the chest cavity, allowing negative-pressure respiration and providing protection of the chest wall (see the third image below). The thoracic spine is highly immobile.
The lumbar spine is the next mobile segment of the spine, typically consisting of 5 large vertebrae with classic features, including body, pedicles, lamina, spinous processes, facet joints, and lateral processes (see the image below). The lumbar spine is mobile with all articulations, contributing to flexion-extension, bending, and rotation. The lumbar spine allows truncal mobility.
The lumbar spine connects to the sacrum through the L5-S1 articulation (see the images below). The wedge-shaped sacrum is a fused set of sacral vertebrae. Its primary purpose is to transfer the load from the spine to the pelvis. This happens through the extremely strong and immobile sacroiliac joints. The sacrum also houses the sacral nerve roots from the terminal end of the spinal canal. At the end of the sacrum is the coccyx, which is the vestigial remnant of the tail.
Gross Anatomy of Appendicular Skeleton
The upper extremities are mirrored paired structures. The upper extremity starts at the shoulder girdle and extends to the finger tips. The shoulder girdle consists of the scapula and the clavicle (see the first and second images below). The clavicle is an S-shaped bone that provides a strut on which the shoulder girdle articulates (see the third image below). It originates at the sternoclavicular joint and terminates at the acromioclavicular joint.
The scapula is a multifunctional bone. Its body (the wide and flat medial portion) is the site of origin of the rotator cuff muscles. Additionally, the scapula articulates with the chest wall to give the shoulder a greater net motion that could be achieved with just glenohumeral motion. The body of the scapula then turns into the neck and flattens into the shallow glenoid cavity.
The glenoid cavity is the socket of the ball-and-socket joint of the shoulder (the glenohumeral joint). It is a deficient socket, being very flat. Accordingly, the soft tissue labrum, ligaments, and muscular attachments are crucial in stabilizing this joint.
In addition, the scapula has a process that protrudes superiorly and another that protrudes anteriorly. These are called the acromion and the coracoid, respectively, and both serve 2 functions. The primary function is soft tissue attachment: the deltoid to the acromion and the conjoint tendon to the coracoid. The secondary function is secondary stabilization of the glenohumeral joint.
The only bone of the arm is the humerus. This bone starts with a ball-and-socket type joint at the glenohumeral articulation and terminates at the elbow in a hingelike joint (see the images below). The humerus is a long tubular bone. Its proximal portion allows highly mobile motion at the shoulder. Its shaft has numerous muscular attachments for muscles controlling shoulder motion and elbow motion. There are even muscles acting distal to forearm that attach on the humerus and cross multiple joints.
The forearm is made up of the radius and the ulna (see the images below). The ulna is the principal weight-bearing articulation at the elbow through the olecranon. The radius is the principal weight-bearing articulation at the wrist. The load is transitioned between the 2 through the syndesmotic interosseous ligament. The anatomy of the radius and ulna allow pronation and supination of the wrist.
The wrist comprises 7 bones: scaphoid, lunate, triquetrum, pisiform, trapezoid, trapezium, capitate, and hamate (see the images below). The bones are divided into 2 rows: proximal and distal.
All of the bones of the wrist are small and unique in shape. The scaphoid, lunate, triquetrum, and pisiform make up the proximal row and primarily articulate with the distal radius. This complex articulation accounts for a high proportion of wrist flexion/extension and radial/ulnar deviation. The proximal row and distal row are intimately connected and have multiple ligamentous structures to stabilize them. The metacarpals articulate with the distal row.
Hand and fingers
The hand is made up of multiple rays of bones (see the image below). Each finger starts as a metacarpal, which is a long tubular bone that articulates with the distal row of carpal bones and other metacarpals proximally. Metacarpals have a rounded articular surface at the distal end that forms the metacarpophalangeal (MP) joint. The metacarpals (except for the thumb metacarpal) are relatively immobile, owing to the numerous ligamentous connections in the palm.
The unique thumb metacarpal articulates with the trapezium through a saddle-type joint known as the carpometacarpal (CMC) joint. This highly mobile joint enables thumb opposition and is crucial to grip and hand function. The thumb also has the unique feature of possessing only having 2 phalanges, proximal and distal, and thus only 1 interphalangeal joint. The remainder of the fingers are made up of 3 phalanges, each of which is a short tubular structure joined to the others through the proximal and distal interphalangeal joints.
Lower extremity and pelvis
The lower extremities are mirrored paired structures. The lower extremity starts at the pelvis and extends to the toes.
The os coxae, or hip bone (see the images below), is occasionally (and incorrectly) considered part of the axial skeleton. It is a fusion of 3 bones bilaterally (6 total): ilium, ischium, and pubis.
The ilium is a large, curving flat-type bone that connects the sacrum to the pelvic girdle. It has a very broad area of muscle attachment and many palpable bony prominences, such as the anterior superior iliac spine (ASIS). The ischium attaches to the ilium at the acetabulum and makes up the bony floor of the pelvis. It also has many muscular and ligamentous attachments. It is the bone that one sits on when seated.
The pubis also connects to the ilium and ischium at the acetabulum and forms the superior anterior portion of the ring. The anterior midline bony prominence that can be palpated represents the pubic bones coming together in the front at the symphysis pubis.
The 3 bones are fused and contribute to the acetabulum, a cup-shaped fossa that is the socket of the ball-and-socket hip joint (see the image below). In addition to the spine, the hip bone is the most important source of bone marrow in adult life.
The femur (see the images below) is the longest and strongest of the human bones. Proximally, the femur is the ball of the ball-and-socket joint of the hip (a highly congruent joint). The femoral head is grossly spherical in nature, permitting a great deal of joint motion in all planes. It has a tenuous blood supply and is sensitive to avascular necrosis.
The femoral head is attached to the femur through the femoral neck. The femoral neck is angled approximately 135 degrees in the coronal plane and approximately 20-30 degrees in the sagittal plane relative to the femoral shaft, with allowances for lateral offset of the shaft. This orientation gives the muscles working around this joint much more power, because of their extended lever arm.
The femoral shaft is long and tubular, with a gentle bow in the anteroposterior direction. It terminates at the femoral condyles, which make up half of the knee joint. It takes an immense amount of force to break a femur in a healthy individual; fracture of this bone is a marker of severe trauma.
The patella (see the image below) is essentially a giant sesamoid bone. It lies within the tendon of the quadriceps femoris and moves the tendon away from the center of joint rotation to give the muscles a greater mechanical ability to move the joint in extension. The patella can be subjected to as much as 8 times a person's body weight when the knee is actively in use. It has the thickest articular cartilage of any bone and rides in a groove between the medial and lateral femoral condyles (known as the trochlea).
The tibia (see the images below), commonly referred to as the shin bone, starts proximally as a wide, nearly flat surface called the tibial plateau, with which the femoral condyles articulate to form the knee joint. Because the condyles are rounded and the plateau is minimally concave, this joint is inherently unstable and requires multiple soft tissue supporting structures for stability. The knee joint mostly flexes and extends but does allow some internal and external rotation.
The tibial shaft is triangular and strong and, like the femur, has a slight bow. It terminates at the ankle joint, where the tibia forms a flat weight-bearing portion of the ankle (the plafond) and the medial stabilizer of the joint (the medial malleolus).
The fibula is an interesting bone, in that it bears no weight but nonetheless has crucial functions in knee and ankle articulation. At the knee, the fibular head articulates (minimally) with the proximal tibia and is crucial for the attachment of soft tissues, including the lateral collateral ligament (LCL), for knee stability.
The midshaft of the fibula has muscular attachments but is not essential and is often harvested if vascularized bone autografts are needed for reconstructions. The distal end makes up the strong tibiofibular joint and the lateral aspect of the ankle joint. The fibula and tibia are tightly connected through a set of strong soft tissue ligaments called the syndesmotic complex.
The talus has 2 distinct regions: body and head. These are connected through the talar neck. The body has a large superior dome that fits inside the box made up of the fibula, the tibial plafond, and the medial malleolus. This joint is what is considered the ankle joint (see the images below); it allows dorsiflexion and plantar flexion of the foot.
On the underside of the talar body and head is a series of complex articulations with the calcaneus; these are known as the subtalar joints. The subtalar joints allow inversion and eversion of the hind foot. The talar head articulates with the navicular to form one of the hindfoot-midfoot connections.
The calcaneus (see the image below) is a large, uniquely shaped bone. It makes up the remainder of the articulations with the midfoot and subtalar joint.
The calcaneus is the location of the calcaneal (Achilles) tendon attachment and therefore is where the muscles act to achieve plantar flexion of the foot. It also is the only bony component of the heel and therefore is subject to fracture in falls or trauma when a person lands on his or her feet. The calcaneus is the proximal extent of the soft tissue "windlass" mechanism that makes up the arch of the foot and is a common site of pain in disorders such as plantar fasciitis.
Midfoot and forefoot
Like the bones of the wrist, the midfoot is made up of a series of uniquely shaped bones that are all intimately connected to each other (see the image below). As a group, these bones allow significant motion, but individually, they have little articular motion. The bones of the midfoot include the navicular, cuboid, medial cuneiform, middle cuneiform, and lateral cuneiform.
The forefoot consists of the 5 metatarsals, which are long tubular bones radiating out from the midfoot to the toes. Each toe has its own metatarsal. The metatarsal heads make up the primary weight-bearing surface of the forefoot. All 5 are strongly connected through a series of soft tissue connections, especially between the proximal first and second metatarsal. At the ends of the metatarsals are the toes, each consisting of 3 phalanges (except the first, which, like the thumb, has only 2).
Cortical bone is the dense, extremely strong bone that is found at the periphery of bones. [3, 1] It makes up 80% of the skeleton. [3, 4] Its primary function is mechanical, but it has a role in calcium homeostasis as well. Mature cortical bone is lamellar, meaning it has a distinct layered structure (see the image below).
The primary microscopic unit of the bone is known as an osteon. An osteon is a cylinder-shaped network of bone centered on and surrounding a vessel that travels longitudinally in a tunnel in the bone known as a haversian canal (see the images below). [1, 4] Longitudinal haversian canals are interconnected obliquely by Volkmann canals, creating a network or plexus of vessels. Nerves enter the alongside the blood vessels and travel in the haversian and Volkmann canals. 
Each osteon is separated from other osteons by a cement line that isolates the osteon and may serve to arrest cracks in the bone. Osteons are oriented specifically along the long axis of the load placed on the bone, thus imparting strength.  Between the osteons are areas of interstitial lamellae, which are remnants of old absorbed osteons. [1, 4] Dispersed throughout the interstitial bone and osteons are lacunae and canaliculi that house cells crucial to bone regulation. Lacunae are also thought to function as crack arrestors. 
Trabecular bone is found on the interior of cortical bone and is less dense.  It is formed of a network of plates and rods. [1, 4] Plates are usually broad and flat, whereas rods are more cylindrical (see the image below).
Trabecular bone gets its nutrients via diffusion from the medullary cavity; accordingly, the thickness of plates and rods is limited to 200 μm, which is twice the maximum thickness diffusion allows (diffusion can occur from both sides).  Osteoporosis is a pathologic thinning of the plates and struts, leading to a substantial (30-90%) decrease in bone porosity. 
Mature trabecular bone is also lamellar (as opposed to woven) meaning it is laid down in distinct layers. Each layer is separated by a cement line, which is a glycoprotein-rich layer thought to be important for osteoblastic adherence in bone formation. [1, 3]
Woven bone is disorganized bone (see the image below).  It is the primary bone that is formed by intramembranous bone formation, callus formation, and bone made by tumors.  It is created through random organization of collagen and minerals.
Once woven bone is formed, osteoclasts and osteoblasts go through a process of adding and subtracting the disorganized bone until an organized and purposeful bone or segment of bone is created. The woven bone is then converted to either cortical or trabecular bone, after which point it is no longer considered woven bone. Woven bone is advantageous because it can be formed quickly and, with its low mineral content, can easily be converted to lamellar or organized bone.
The periosteum is a tough layer of connective tissue that surrounds bones everywhere that there is not a joint or attachment point.  It is composed of an outer layer of fibrous connective tissue and an inner layer of bone progenitor cells, which is responsible for radial growth of the bone. [1, 4] In addition to bone growth, the periosteum also provides the vascular supply and nutrients for the outer segment of the cortex and is crucial in fracture repair.
The endosteum is a 1-cell-thick lining on the trabecular and inner cortical surfaces of the bone. [1, 4] It is composed of bone lining cells, which are mostly inactive but prevent unwarranted bone resorption by osteoclasts. Peelback of bone lining cells is crucial for proper bone resorption to occur.
Bone as a whole has a low cell content and is made primarily of noncellular matrices. There are 2 forms of extracellular matrix (ECM): osteoid and mineralized matrix. Osteoid is immature matrix excreted by osteoblasts. It is then converted to mature mineralized matrix over time. Bone matrix consists of mineral, proteins (collagens), glycoproteins, proteoglycans, and water. 
Osteoid is made by osteoblasts (see the image below) and is found in areas of new bone formation.  It occurs in low quantities because it is quickly mineralized (except in pathologic bone conditions). Mineralization occurs in a matter of days, which allows enough time for protein crosslinking and consequent increases in strength.  Mineralization is an energetically favorable process and therefore progresses on its own without the need for a catalyst.  Osteoid is mostly proteinaceous.
There are numerous collagens in the human body, many of which play some role in the form or function of bone; however, type I collagen is by far the most important.
Type I collagen forms a triple helical structure (comprising 2 alpha1 chains and 1 alpha2 chain) that is then condensed and elongated into fibrils. Because of the unique arrangement of chains and the importance of proline in the formation of chains, type I collagen forms one of the longest, thinnest, and most rigid protein structures.  Hole zones regularly found in the collagen fibrils allow attachment of mineral crystals.
Mature ECM is largely (60-70%) mineral.  The principal minerals involved are calcium and phosphate. The amounts of these ions circulating in the blood stream are highly regulated by total body homeostasis, and the bone plays a crucial part in this process. (see bone homeostasis for more information). The ions in the bone form salts, mainly hydroxyapatite.
The remainder of the ECM is protein (25%) and water.  The protein portion of the bone is overwhelmingly dominated by type I collagen (90%). In addition to collagen, the other components of ECM are osteocalcin (mineral maturation), fibronectin/vitronectin (adhesive proteins), bone sialoprotein (initiates mineral attachment), proteoglycans (traps signaling molecules and water into bone), bone morphogenic proteins (initiation of bone formation), TGF-beta (recruitment of osteoblasts), and other signaling proteins.
The ECM gives the bone its mechanical properties but is also important for regulation and formation of new bone.
There are 4 major cell types within bone tissue itself: osteoclasts, osteoblasts, osteocytes, and bone lining cells. Within the cavities of the bone, there is also bone marrow, which has numerous cell types, including the progenitor cells for the hematopoietic cell lineages. 
The osteoblast is the cell responsible for construction of new osteoid (which eventually becomes ECM). It is also the precursor to the osteocyte and the bone lining cell and is a major regulator of the osteoclast.
The osteoblast is derived from the mesenchymal marrow stromal cells. [1, 3] These cells are pluripotential stem cells  . Transforming growth factor (TGF)-beta, bone morphogenetic proteins (BMPs), parathyroid hormone (PTH), and vitamin D are all important in stimulating mesenchymal stem cells (MSCs) to become osteoblasts.  MSCs can be found in both the bone marrow and the inner layer of the periosteum. Mature osteoblasts are highly regulated and survive for approximately 100 days before going on to their final fate.
Osteoblasts are incorporated into the osteoid and become osteocytes, line the bone and become bone lining cells, or undergo apoptosis.  They are stimulated by PTH, 1,25-hydroxyvitamin-D, and insulinlike growth factor (IGF)-1.  The mature osteoblast is designed for protein synthesis: it has a large and efficient rough endoplasmic reticulum, Golgi apparatus, and secretory vesicles. 
Osteoblasts synthesize collagens (primarily type I) and the other proteins found in the osteoid when stimulated. They are polarized, with their synthetic functions at one end (near the cellular attachment areas) and their regulatory functions and nucleus at the other.  The osteoblast is also the key cell in regulating bony absorption and the function of the osteoclast. This is known as coupling.
Bone lining cells
Bone lining cells are old osteoblasts that no longer play a role in synthesis. They are flat thin cells with little activity.  They cover all nonmetabolically active areas of the bone and close off the osteoid and underlying ECM to other cells.  Bone lining cells play an important role in bone resorption: it is the peelback of the lining cells that stimulates and allows the attachment of osteoclasts to bone.
The osteocyte is an osteoblast that has been incorporated into the cortical bone. It survives in single cell-sized hole in the bone known as a lacuna (see the image below). Although its function as an osteoblast has ceased, it still plays a vital role in bone homeostasis. It is also the most abundant of the bone cells: 90% of all bone cells are osteocytes, and they can survive for decades. 
The osteocytes are interconnected to one another through long cellular projections in tunnels through the bone known as canaliculi (see the image below). The osteocytes can sense and communicate with each other through the projections in the canaliculi, much like nerve cells. [1, 3, 4] Additionally, these tunnels serve as the source of nutrients and disposal of waste for the osteocytes.  The osteocytes are thought to be responsible for mechanosensing, and they respond to bone strain. [1, 3, 4]
The osteoclast is derived from the hematopoietic macrophage lineage. The stem cells undergo multiple steps before becoming a mature osteoclast, each of which is highly regulated. The osteoclast is a multinucleated giant cell (see the image below) that is responsible for bone absorption. [1, 4] Once activated, an osteoclast does only 1 job — resorbing mineralized bone — and it does this job for approximately 3 weeks without much regulation before it undergoes apoptosis.
Osteoclasts work along bone that has been exposed when the lining cells have pulled away from the bone surface; they cannot attach to unmineralized osteoid.  The osteoclast has some unique features, such as its ruffled border and the attachment proteins that allow it to seal itself to the bone surface and pump carbonic acid into the space between itself and the bone. 
In addition to the acidic environment, the osteoclast synthesizes enzymes to degrade extracellular matrix proteins. Once the mineralized ECM is degraded, the osteoclast reabsorbs, packages, and secretes the released mineral and proteins. Its function is intimately tied to the osteoblast, and in fact, it is the osteoblast that activates the osteoclastic function. This paired activity of bone-building and bone-absorbing cells is known as coupling and is crucial to the regulation of bone and calcium in the body.
Regulation of calcium in the serum is principally controlled by parathyroid hormone (PTH), vitamin D, and calcitonin (see the image below).
PTH is the principal hormone for increasing serum concentrations of calcium. When calcium is low, it stimulates the chief cells of the parathyroid gland to increase production of PTH. PTH has multiple downstream effects, as follows: 
It increases the kidney's ability to convert vitamin D to its active form
It stimulates osteoblasts to release receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF), thus upregulating osteoclasts and bone resorption
Vitamin D is derived from both the skin and the gut. It undergoes modification in the liver (25-hydroxyvitamin-D) and then the kidney (1,25-hydroxyvitamin-D).  Only after both modification steps does vitamin D become its active form, 1,25-hydroxyvitamin-D. This active form both increases uptake of calcium from the gut and decreases renal output of calcium.
In situations where serum calcium is too high, PTH is downregulated and calcitonin is released from the thyroid gland. Calcitonin works through direct receptors in the osteoclast to downregulate its function. 
Coupling and remodeling
Bone remodeling, the interplay between bone absorption and bone formation, involves intricate interactions between multiple bone cell types (see the image below). When remodeling is functioning properly, it keeps bone strong and heals damage to the bones. When coupling and remodeling fail, however, many pathologic conditions of the bone can arise.
Remodeling is regulated by both local factors and systemic factors. [1, 5] Systemic factors include vitamin D, PTH, and calcitonin. Local factors include low-density lipoprotein receptor-related protein 5 (LRP5), bone morphogenetic protein (BMP), transforming growth factor (TGF)-beta, and mechanical strain. These factors are all being studied as targets for pharmacologic intervention to alter bone mass and metabolism.
Remodeling is defined as the local removal and subsequent replacement of bone.  Remodeling is structurally important for eliminating old bone and bone that has suffered accumulated microdamage. It also allows the body to change the shape or composition of bones to respond to different stresses on the bones. Woven bone is also remodeled through this process to become lamellar bone.
In a general sense, the process is initiated when bone lining cells retract, exposing the ECM underneath to osteoclasts. Osteoclasts then resorb bone in the resorption pits, also known as Howship lacunae. [1, 3] Once this step is completed, osteoblasts fill in along the resorption pit and replace the resorbed bone with osteoid. Osteoblasts then either are incorporated or become quiescent bone lining cells. The osteoid is later mineralized.
Markers of bone turnover can be measured in both the urine and the serum. Osteocalcin is a marker for the osteoblast but is also found in ECM and therefore is upregulated in both resorption and formation. Collagen breakdown products, hydroxyproline and N-telopeptide, are released with resorption and can be used to assay the amount of bone breakdown. Tartrate-resistant acid phosphatase and cathepsin K are both markers of osteoclast metabolism and therefore of bone breakdown. 
Initiation of bone breakdown begins with resorption of the bone. Bone lining cells are stimulated to pull back off the bone (through a mechanism that has not yet been fully clarified) and expose the ECM underneath. It is likely that PTH initiates the retraction of the bone lining cells and the absorption of the thin layer of osteoid underneath them.  A second mechanism may be osteocyte stimulation of bone lining cells in response to mechanosensing.
The signal for the stimulation of precursor cells to become osteoclasts is complex. PTH and other induction factors are not recognized by the osteoclast. Instead, they are recognized by the osteoblast. The osteoblast serves as an intermediary in this process, receiving systemic signals and then releasing M-CSF and RANKL (see the image below). 
These 2 factors stimulate the precursor cells to become osteoclasts. At the same time, the osteoblast can also release osteoprotegerin (OPG), which is a competitive inhibitor of RANKL, and thereby decrease osteoclastic activity. [1, 3, 5] It is therefore the osteoblast that regulates much of the process.
Absorption is always followed by formation, except in pathologic states. This coupling of the 2 processes is crucial to bone homeostasis. The signals that drive osteoblasts to release factors to activate osteoclasts do not cause them to start bone formation. Instead, factors released from the ECM itself, including TGF-beta (migration), insulinlike growth factors (IGFs), and BMPs, cause the osteoblast to form new osteoid. There may also be an osteoclastic cell surface protein that stimulates local osteoblasts to start producing osteoid. 
Normal uncoupling occurs in selected instances; bone growth in childhood is the most notable example. Absorption eventually equals formation and homeostasis is achieved; however, in adulthood and old age, absorption exceeds formation and the bones become osteoporotic. The need for tight regulation of serum calcium outweighs the importance of coupling, and the body will allow uncoupled absorption to release calcium if it is needed. Pathologic uncoupling occurs in osteoporosis, osteopetrosis, tumors, Paget disease, and other conditions.