# Lecture 2: Bone Structure and Classification ## Unit 1.3: Human Gross Anatomy I - Musculoskeletal System --- ## Learning Objectives By the end of this lecture, students will be able to: 1. Describe the functions of the skeletal system 2. Classify bones by shape (long, short, flat, irregular, sesamoid) 3. Describe the macroscopic structure of a typical long bone 4. Explain the microscopic organization of compact and spongy bone 5. Describe the process of bone formation (intramembranous and endochondral ossification) 6. Explain bone remodeling and the roles of osteoblasts, osteoclasts, and osteocytes --- ## Functions of the Skeletal System The skeletal system serves multiple essential functions that extend far beyond simply providing a structural framework. Understanding these functions illuminates why bone is a dynamic, metabolically active tissue rather than an inert scaffold. Support is the most obvious function of the skeleton. The bones provide a rigid framework that supports the soft tissues of the body and maintains body shape. Without this internal scaffolding, the body would collapse under its own weight. The vertebral column supports the head and trunk, while the pelvic girdle supports the abdominal organs. Protection is another critical function. The skeleton shields vital organs from injury. The skull encases the brain, the vertebral column surrounds the spinal cord, the thoracic cage protects the heart and lungs, and the pelvis shelters the bladder, reproductive organs, and portions of the digestive tract. Movement is enabled by the skeleton serving as a lever system. Bones provide attachment points for muscles, and when muscles contract, they pull on bones to produce movement at joints. The arrangement of bones determines the range and type of motion possible at each joint. Mineral storage makes bone the body's primary reservoir of calcium and phosphorus. Approximately 99% of body calcium and 85% of phosphorus are stored in bone. When blood calcium levels fall, bone releases calcium; when levels rise, bone takes up excess calcium. This mineral exchange is critical for maintaining the ionic concentrations that nerve and muscle function require. Hematopoiesis occurs within the red bone marrow found in spongy bone. Here, blood cell production generates red blood cells, white blood cells, and platelets throughout life. In adults, hematopoietic marrow is concentrated in the axial skeleton and proximal portions of the limb bones. Energy storage occurs as yellow bone marrow, which consists largely of adipose tissue and occupies the medullary cavities of long bones in adults. This fat represents a significant energy reserve that can be mobilized when needed. The adult human skeleton contains 206 bones, divided into the axial skeleton and appendicular skeleton. The axial skeleton comprises 80 bones including the skull, vertebral column, ribs, and sternum, forming the central axis of the body. The appendicular skeleton contains 126 bones of the upper and lower limbs and the shoulder and pelvic girdles that attach them to the axial skeleton. Panel A: Complete human skeleton in anterior view with axial skeleton (skull, vertebral column, ribs, sternum) shown in blue color. Panel B: Appendicular skeleton (upper limbs, lower limbs, shoulder girdles, pelvic girdle) shown in gold color with shoulder girdle and upper limb bones labeled. Panel C: Lower body bones labeled including pelvic bones, femur, patella, tibia, fibula, and foot bones. Panel D: Total bone counts displayed showing axial 80 bones, appendicular 126 bones with major bone groups identified. --- ## Bone Classification by Shape Bones are classified into five categories based on their shape, with each shape relating to specific functions and locations in the body. Long bones are characterized by having greater length than width. They consist of a shaft called the diaphysis with expanded ends called epiphyses. Long bones are designed for leverage and movement, serving as the main levers of the appendicular skeleton. Examples include the femur and humerus of the limbs, the radius and ulna of the forearm, the tibia and fibula of the leg, and the metacarpals, metatarsals, and phalanges of the hands and feet. Despite their small size, the phalanges are classified as long bones because they share the same structural organization. Short bones are approximately cube-shaped, with roughly equal dimensions in all directions. Their structure provides stability while still allowing some movement. The carpals of the wrist and tarsals of the ankle are the primary examples. Their compact arrangement and multiple articulations with neighboring bones allow the complex movements of the wrist and the weight-bearing flexibility of the ankle. Flat bones are thin, flattened, and often curved. They typically consist of two layers of compact bone with a layer of spongy bone called the diploë sandwiched between them. Flat bones provide protection for underlying organs and offer broad surfaces for muscle attachment. Examples include the cranial bones of the skull, the sternum, the ribs, and the scapulae. The flat bones of the skull are particularly effective at protecting the brain while also providing attachment for the muscles of facial expression and mastication. Irregular bones have complex shapes that do not fit into any other category. Their varied forms reflect their specialized functions. The vertebrae are irregular bones that protect the spinal cord while allowing flexibility of the spine. Facial bones such as the maxillae and mandible are irregular in shape to accommodate the teeth, sinuses, and attachment points for muscles of expression and chewing. The hip bones are large irregular bones that support body weight and protect pelvic organs. Sesamoid bones develop within tendons, typically at locations where tendons cross joints. They protect tendons from wear and often improve the mechanical advantage of the muscles that act through those tendons. The patella, or kneecap, is the largest sesamoid bone, developing within the tendon of the quadriceps femoris. It protects the knee joint anteriorly and increases the leverage of the quadriceps by holding the tendon away from the axis of the joint. Small sesamoid bones are also found in the tendons of the hands and feet. Panel A: Long bone (femur) in longitudinal section displaying diaphysis shaft and proximal/distal epiphyses with length greater than width. Panel B: Short bone showing three carpal bones from wrist as roughly cube-shaped with equal dimension indicators. Panel C: Flat bone (parietal) showing outer and inner compact bone layers with diploe spongy bone between in thin curved shape. Panel D: Irregular bone (lumbar vertebra) from superior view with complex shape, and sesamoid bone (patella) within quadriceps tendon at knee joint. --- ## Structure of a Long Bone The structure of a long bone exemplifies the organization that allows bones to be both strong and relatively lightweight. Understanding this structure is essential for interpreting fracture patterns and bone pathology. The diaphysis, or shaft, forms the elongated tubular portion of the bone between the two ends. The wall of the diaphysis consists of thick compact bone that provides the strength to resist bending and torsional forces. The hollow center of the diaphysis is the medullary cavity, which contains yellow bone marrow in adults. This marrow consists primarily of adipose tissue. The tubular design of the diaphysis is mechanically efficient, providing maximum strength with minimum weight. The epiphyses are the expanded portions at each end of the bone, designated as proximal (closer to the trunk) and distal (farther from the trunk). The outer surface of each epiphysis where it articulates with another bone is covered by articular cartilage, a thin layer of hyaline cartilage that provides a smooth, low-friction surface for joint movement. The interior of the epiphysis contains spongy bone, whose trabeculae are arranged along lines of stress. The spaces between trabeculae contain red bone marrow, which is hematopoietic. The metaphysis is the flared region between the diaphysis and each epiphysis. In growing bone, this region contains the epiphyseal plate, a layer of hyaline cartilage where growth in length occurs. When growth is complete, the cartilage is replaced by bone, leaving only the epiphyseal line as a remnant marking where the plate once existed. Two membranes cover and line the bone. The periosteum is a fibrous connective tissue membrane that covers the external surface of bone everywhere except at the articular surfaces. It consists of an outer fibrous layer of dense irregular connective tissue and an inner osteogenic layer containing osteoprogenitor cells and osteoblasts. The periosteum is anchored to the underlying bone by collagen fibers called Sharpey's fibers that penetrate into the bone matrix. It is richly supplied with blood vessels and nerves, which accounts for the pain associated with bone trauma. Tendons and ligaments attach to bone through the periosteum. The endosteum is a thin membrane that lines the medullary cavity and all internal bone surfaces including the trabeculae of spongy bone. It contains osteoprogenitor cells and osteoblasts and is important for bone remodeling. Panel A: Longitudinal section of femur showing diaphysis with thick compact bone cortex and medullary cavity containing yellow marrow. Panel B: Proximal and distal epiphyses with outer compact bone shell, interior spongy bone trabecular network, red marrow in spaces, articular cartilage covering joint surfaces. Panel C: Metaphysis between diaphysis and epiphysis showing epiphyseal plate in growing bone inset and epiphyseal line in mature bone. Panel D: Periosteum detail inset showing outer fibrous and inner osteogenic layers with Sharpey's fibers, endosteum lining internal surfaces, blood vessels entering through nutrient foramen. --- ## Bone Tissue Types Bone exists in two forms that differ in their density and organization: compact bone and spongy bone. Both contain the same cells and matrix components but arranged differently. Compact bone, also called cortical bone, has a dense, solid appearance when examined without magnification. It constitutes approximately 80% of the skeletal mass and is found in the diaphysis of long bones and as the outer shell of all bones. Its organization provides strength while still allowing the passage of blood vessels and nerves and the exchange of materials with bone cells. The structural unit of compact bone is the osteon, also called the Haversian system. Each osteon is a cylindrical unit oriented parallel to the long axis of the bone. At the center of each osteon is the central canal, or Haversian canal, a channel containing blood vessels and nerves that supply the bone tissue. Surrounding the central canal are concentric rings of calcified matrix called lamellae, like the rings of a tree trunk. Within the lamellae, at regular intervals, are small spaces called lacunae, each containing an osteocyte. Radiating from each lacuna are tiny channels called canaliculi that connect adjacent lacunae to each other and to the central canal. The canaliculi contain the cytoplasmic processes of osteocytes, allowing these cells to communicate and exchange materials through gap junctions. Volkmann's canals, or perforating canals, run perpendicular to the central canals and connect adjacent osteons to each other and to the periosteum and endosteum. This canal system allows blood vessels and nerves to reach all regions of compact bone. Between complete osteons are interstitial lamellae, fragments of older osteons that were partially resorbed during bone remodeling. Circumferential lamellae form complete rings just deep to the periosteum and surrounding the medullary cavity. Spongy bone, also called trabecular or cancellous bone, has a honeycomb-like appearance created by a network of thin plates and rods of bone called trabeculae. It constitutes approximately 20% of skeletal mass but has a much larger surface area than compact bone due to its porous structure. Spongy bone is found in the epiphyses of long bones, within vertebrae, and within flat bones between layers of compact bone. The trabeculae of spongy bone are not randomly arranged. They align along lines of mechanical stress, providing maximum strength with minimum material. This arrangement allows spongy bone to resist forces from many directions, which is particularly important at joint surfaces where forces are transmitted through the bone. The spaces between trabeculae are filled with bone marrow, either red (hematopoietic) or yellow (fatty) depending on the location and age. Spongy bone does not contain osteons. Instead, the trabeculae are thin enough that nutrients can diffuse to osteocytes directly from the surrounding marrow through canaliculi. Panel A: Compact bone gross cross-section of long bone diaphysis showing dense cortical bone with magnified view of multiple osteons and interstitial lamellae between them. Panel B: High magnification of single osteon showing central Haversian canal, concentric lamellae, lacunae containing osteocytes, canaliculi radiating from lacunae, Volkmann's canal connecting osteons. Panel C: Spongy bone gross section through epiphysis showing trabecular network with spaces containing red marrow and arrows indicating stress lines. Panel D: High magnification of trabeculae showing thin plates of bone with osteocytes in lacunae, canaliculi present, no osteons in trabecular bone. --- ## Bone Cells Four types of cells are found in bone tissue, each with distinct functions in bone formation, maintenance, and resorption. Osteoprogenitor cells, also called osteogenic cells, are stem cells that can divide and differentiate into osteoblasts. They derive from mesenchyme, the embryonic connective tissue that gives rise to most connective tissues. Osteoprogenitor cells are found in the inner layer of the periosteum and in the endosteum. They remain quiescent in mature bone but can be activated during bone growth, repair, and remodeling to provide new osteoblasts. Osteoblasts are the bone-forming cells responsible for synthesizing new bone matrix. They are cuboidal cells found at bone surfaces where new bone is being deposited. Osteoblasts synthesize and secrete the organic components of bone matrix, including type I collagen and ground substance proteins such as osteocalcin, osteopontin, and osteonectin. This unmineralized matrix is called osteoid. Osteoblasts also regulate the mineralization of osteoid by controlling calcium and phosphate deposition. They express alkaline phosphatase, an enzyme often used as a marker of osteoblast activity. As osteoblasts secrete matrix around themselves, they become enclosed within the bone and differentiate into osteocytes. Osteoblasts that remain on the bone surface may become quiescent lining cells. Osteocytes are mature bone cells derived from osteoblasts that have become trapped within the bone matrix. They reside in lacunae and extend cytoplasmic processes through canaliculi to contact neighboring osteocytes. Through gap junctions between these processes, osteocytes form a vast communication network throughout the bone. Osteocytes are the most abundant bone cells, and despite appearing quiescent, they are metabolically active. They maintain the bone matrix in their immediate vicinity, sensing and responding to mechanical forces through a process called mechanotransduction. When bone is stressed, osteocytes detect the strain and signal to osteoblasts and osteoclasts to initiate appropriate remodeling responses. Osteocytes also participate in mineral homeostasis, capable of both depositing and removing calcium from the surrounding matrix. Osteoclasts are large, multinucleated cells responsible for bone resorption. They derive not from osteoprogenitor cells but from the fusion of monocyte-macrophage precursors, making them part of the myeloid lineage. Osteoclasts are found at bone surfaces in small depressions called Howship's lacunae or resorption pits. They possess a distinctive ruffled border, a region of deeply infolded plasma membrane that increases the surface area for bone resorption. The ruffled border is sealed to the bone surface, creating a compartment into which the osteoclast secretes hydrochloric acid to dissolve bone minerals and lysosomal enzymes to digest the organic matrix. Osteoclast activity is regulated by the RANK-RANKL-OPG system: osteoblasts express RANKL, which binds to RANK receptors on osteoclast precursors to stimulate their differentiation and activation; osteoblasts also secrete osteoprotegerin (OPG), a decoy receptor that can block RANKL and inhibit osteoclast activity. Panel A: Bone surface during active formation showing osteoprogenitor cells in periosteum inner layer and cuboidal osteoblasts lining surface secreting osteoid. Panel B: Mature bone showing star-shaped osteocytes within lacunae with cytoplasmic processes extending through canaliculi and gap junctions connecting adjacent cells. Panel C: Large multinucleated osteoclast in Howship's lacuna resorption pit with ruffled border detail inset showing acid and enzyme secretion. Panel D: Differentiation pathway arrows showing osteoprogenitor to osteoblast to osteocyte, inset showing RANK-RANKL-OPG signaling between osteoblast and osteoclast precursor. --- ## Bone Matrix The bone matrix is a composite material consisting of both organic and inorganic components. This combination gives bone its unique mechanical properties, providing both flexibility and hardness. The organic components constitute approximately 35% of the dry weight of bone matrix. Type I collagen accounts for about 90% of the organic component, forming the fibrous framework of bone. Collagen fibers provide tensile strength and some flexibility, allowing bone to resist stretching and bending forces without being brittle. The remaining organic component consists of ground substance, including proteoglycans and glycoproteins. Important bone-specific proteins include osteocalcin, which binds calcium and may regulate mineralization; osteopontin, which helps anchor cells to the matrix; and osteonectin, which binds both collagen and calcium and may regulate crystal formation. The inorganic components constitute approximately 65% of the dry weight and consist primarily of calcium phosphate in the form of hydroxyapatite crystals with the formula Ca₁₀(PO₄)₆(OH)₂. These mineral crystals are deposited within and around the collagen fibers, providing hardness and rigidity. Bone also contains smaller amounts of calcium carbonate and various ions including magnesium, sodium, and fluoride. The crystalline mineral component makes bone hard and resistant to compression. The integration of organic and inorganic components creates a material stronger than either component alone. The collagen fibers provide a flexible scaffold that can absorb energy, while the mineral crystals resist compression. This can be demonstrated experimentally: if bone is demineralized by treatment with acid, leaving only the organic matrix, it becomes rubbery and can even be tied in a knot. If the organic components are removed by heating, leaving only the mineral, the bone becomes extremely brittle and shatters easily. Normal bone, with both components integrated, is strong yet somewhat flexible, able to absorb impacts without fracturing. Panel A: Structural organization showing collagen fibers as wavy gold bundles arranged in parallel with hydroxyapatite crystals deposited along and between fibers. Panel B: Pie charts showing composition with 35% organic (collagen 90%, ground substance 10%) and 65% inorganic (primarily hydroxyapatite). Panel C: Normal bone supporting weight demonstrating both flexibility and strength, demineralized bone shown as flexible and bendable. Panel D: Deproteinized bone shattering into fragments when stressed, chemical structure of hydroxyapatite Ca10(PO4)6(OH)2 displayed. --- ## Bone Formation (Ossification) Bone tissue forms through two different processes depending on the type of bone. Understanding these processes is important for comprehending bone development, growth, and repair. Intramembranous ossification involves the direct conversion of mesenchymal tissue to bone without a cartilage intermediate. This process forms the flat bones of the skull, parts of the clavicle, and the mandible. The process begins when mesenchymal cells in the developing skeleton cluster and differentiate into osteoblasts. These osteoblasts secrete osteoid, the unmineralized bone matrix, which then becomes calcified to form small spicules of bone. The spicules extend and connect with one another, creating a network of woven bone trabeculae. Blood vessels grow into the developing bone, and mesenchyme caught between trabeculae becomes red bone marrow. A periosteum forms around the bone, and osteoblasts beneath the periosteum deposit layers of bone to form compact bone on the surfaces. The woven bone is gradually remodeled and replaced by organized lamellar bone. Endochondral ossification involves the replacement of a hyaline cartilage model by bone. This process forms most of the bones of the body, including all long bones, vertebrae, ribs, and the bones of the pelvis. The process begins when mesenchymal cells differentiate into chondroblasts that produce a hyaline cartilage model shaped like the future bone. As the cartilage model grows, the perichondrium around the diaphysis transforms into periosteum, and osteoblasts beneath it form a collar of bone around the cartilage. Simultaneously, chondrocytes in the center of the cartilage model enlarge and cause the matrix to calcify. The calcified cartilage prevents diffusion of nutrients, and the chondrocytes die. Blood vessels from the periosteum invade the calcified cartilage, bringing osteoblasts that deposit bone on the scaffolding of calcified cartilage. This creates the primary ossification center in the diaphysis. As ossification proceeds, osteoclasts excavate the center of the bone to form the medullary cavity. Secondary ossification centers develop in the epiphyses, usually after birth, through a similar process. The epiphyseal plate, a layer of cartilage between the diaphysis and each epiphysis, remains and allows continued growth in length until skeletal maturity. Panel A: Intramembranous ossification stages 1-3 showing mesenchymal cell cluster differentiating to osteoblasts, osteoid secretion forming spicules, trabecular network forming with blood vessel invasion. Panel B: Intramembranous stages 4-5 showing periosteum development with compact bone at surfaces and mature flat bone with diploe. Panel C: Endochondral ossification stages 1-3 showing hyaline cartilage model, bone collar forming around diaphysis, primary ossification center with blood vessel invasion. Panel D: Endochondral stages 4-6 showing medullary cavity formation, secondary ossification centers in epiphyses, mature long bone with epiphyseal plates/lines. --- ## Bone Growth Bones grow in both length and diameter through different mechanisms. This growth continues from fetal development until skeletal maturity is reached, typically in the late teens or early twenties. Growth in length, also called interstitial growth, occurs at the epiphyseal plate through the continuous production of cartilage that is then replaced by bone. The epiphyseal plate can be divided into five zones, each representing a different stage in the process. The reserve zone, nearest the epiphysis, contains quiescent chondrocytes that anchor the plate to the epiphyseal bone. The proliferative zone contains chondrocytes that are dividing rapidly, forming columns of stacked cells oriented parallel to the bone's long axis. These divisions increase the length of the cartilage plate. In the hypertrophic zone, the chondrocytes stop dividing and enlarge significantly, sometimes to five times their original volume. This expansion pushes the epiphysis away from the diaphysis, increasing bone length. In the calcification zone, the matrix around the enlarged chondrocytes becomes calcified, and the chondrocytes die because nutrients can no longer diffuse through the calcified matrix. The ossification zone lies at the diaphyseal border, where osteoblasts invade from the medullary cavity and deposit bone on the calcified cartilage scaffolding, converting cartilage to bone. As long as the rate of cartilage production in the proliferative zone equals the rate of cartilage replacement by bone in the ossification zone, the plate maintains its thickness while the bone lengthens. At puberty, sex hormones cause the rate of ossification to exceed the rate of cartilage production, and the plate becomes progressively thinner. Eventually the plate is entirely replaced by bone, a process called epiphyseal closure or fusion. The resulting epiphyseal line marks where the plate once existed. Once the plate closes, no further growth in length can occur. Growth in diameter, also called appositional growth, occurs through the addition of new bone to the outer surface of existing bone by osteoblasts in the periosteum. Simultaneously, osteoclasts in the endosteum resorb bone from the inner surface of the cortex. The rate of bone addition at the periosteal surface exceeds the rate of resorption at the endosteal surface, resulting in a net increase in bone diameter while maintaining an appropriately sized medullary cavity. Panel A: Growth in length at epiphyseal plate with longitudinal section showing Reserve zone with scattered small chondrocytes and Proliferative zone with columns of stacked flat chondrocytes. Panel B: Hypertrophic zone showing enlarged chondrocytes in columns and Calcification zone with dark matrix and dead chondrocytes. Panel C: Ossification zone with bone spicules on calcified cartilage and osteoblasts, arrows indicating growth direction toward epiphysis and ossification toward diaphysis. Panel D: Appositional growth cross-sections showing earlier smaller diameter with osteoblasts adding bone and osteoclasts removing bone, later larger diameter with increased cortical thickness. --- ## Bone Remodeling Bone remodeling is the continuous process of bone resorption and formation that occurs throughout life. Unlike growth, which ceases at skeletal maturity, remodeling continues until death. Approximately 10% of the adult skeleton is replaced each year through this process. Remodeling serves multiple purposes. It maintains calcium homeostasis by releasing calcium from bone when blood levels fall and depositing calcium when levels rise. It repairs microdamage that accumulates from daily activities, preventing the accumulation of stress fractures. It adapts bone structure to changing mechanical demands, strengthening bone in regions of increased stress and reducing bone mass where stress decreases. The remodeling cycle occurs through the coordinated action of groups of cells called basic multicellular units (BMUs). Each cycle has five phases. The activation phase begins when chemical or mechanical signals recruit osteoclast precursors to a bone surface. These precursors fuse to form mature osteoclasts. During the resorption phase, lasting two to four weeks, osteoclasts create a resorption pit by secreting acid and enzymes that dissolve the mineral and digest the organic matrix. When resorption is complete, osteoclasts undergo apoptosis. The reversal phase is a transition period during which the resorption pit surface is prepared for bone formation, possibly by macrophage-like cells. The formation phase follows, lasting four to six months, as osteoblasts deposit osteoid that subsequently mineralizes, filling the resorption pit with new bone. Finally, the quiescence phase represents the resting state in which bone-lining cells cover the surface. Bone remodeling is regulated by both hormones and local factors. Parathyroid hormone stimulates bone resorption, increasing blood calcium levels. It acts indirectly by causing osteoblasts to express RANKL, which activates osteoclasts. Calcitonin, secreted by the thyroid gland, inhibits osteoclast activity and lowers blood calcium. Vitamin D promotes calcium absorption from the gut and is necessary for normal mineralization. Growth hormone stimulates overall bone growth. Sex hormones, including estrogen and testosterone, promote bone formation and are responsible for the growth spurt of puberty and for epiphyseal plate closure. The loss of estrogen at menopause explains the accelerated bone loss and osteoporosis risk in postmenopausal women. Glucocorticoids in excess inhibit bone formation and increase bone resorption, leading to osteoporosis in conditions of glucocorticoid excess. Wolff's Law describes how bone adapts to mechanical stress. Bone is deposited in regions subjected to increased stress and is resorbed from regions where stress decreases. This explains why the bones of athletes are denser and stronger than those of sedentary individuals, and why bones lose mass during prolonged immobility or in microgravity environments. Panel A: Activation phase showing bone surface with osteoclast precursors arriving and RANKL signaling, Resorption phase (2-4 weeks) with active osteoclast in pit secreting acid and enzymes. Panel B: Reversal phase with osteoclasts gone and pit surface prepared by mononuclear cells, Formation phase (4-6 months) with osteoblasts secreting osteoid. Panel C: Quiescence phase showing flat lining cells covering completed new bone, center diagram with regulatory factors PTH, RANKL, calcitonin, estrogen, and mechanical loading. Panel D: Wolff's Law inset showing bone cross-section with thicker cortex on stressed side and thinner on unstressed side with time scale indicated. --- ## Bone Repair (Fracture Healing) When bone is broken, a predictable sequence of events leads to repair. Understanding this sequence helps explain how fracture treatment promotes healing and why certain conditions may impair it. The first phase is hematoma formation, occurring within hours of the fracture. Damage to blood vessels in the bone and periosteum causes bleeding, and a blood clot, or hematoma, forms at the fracture site. The hematoma creates a framework for repair and releases cytokines and growth factors that initiate healing. Bone cells deprived of blood supply die, creating additional debris that must be removed. The second phase is formation of a fibrocartilaginous (soft) callus, occurring over several days to weeks. Inflammatory cells invade the hematoma to remove debris. Granulation tissue forms as blood vessels grow into the damaged area. Fibroblasts within the granulation tissue produce collagen fibers. In regions with adequate blood supply near the bone surfaces, osteoblasts begin depositing bone. In the central regions where blood supply is initially poor, chondroblasts form fibrocartilage. The combination of fibrous tissue, cartilage, and early bone constitutes the soft callus, which bridges the fracture gap and provides initial stabilization. The third phase is formation of a bony (hard) callus, occurring over weeks to months. Osteoblasts progressively replace the fibrocartilaginous callus with woven bone through a process similar to endochondral ossification. Cartilage calcifies and is replaced by bone, and osteoblasts deposit bone on the remaining collagen scaffold. The hard callus is initially larger than the original bone, creating a bulge at the fracture site, and consists of disorganized woven bone that is not as strong as normal bone. The fourth phase is remodeling, occurring over months to years. The woven bone of the hard callus is gradually replaced by organized lamellar bone through the normal remodeling process. Excess callus is resorbed by osteoclasts. Eventually the bone is restored to near-original shape and strength, though remodeling may continue for years after the fracture. Complete restoration depends on factors including the patient's age, nutrition, blood supply, and the degree of immobilization maintained during healing. Panel A: Hematoma formation (hours to days) showing fractured bone ends with blood clot filling fracture gap, dead bone at fragment edges, inflammatory cells arriving. Panel B: Fibrocartilaginous callus (days to weeks) with external callus bridging gap, internal callus filling medullary cavity, blood vessels growing from periosteum. Panel C: Bony callus (weeks to months) showing woven bone replacing soft callus, callus larger than original diameter, cartilage converting to bone via endochondral ossification. Panel D: Remodeling (months to years) with excess callus resorbed, lamellar bone replacing woven bone, near-normal contour restored, factors affecting healing listed. --- ## Clinical Correlations Several disorders affect bone structure and metabolism, each reflecting disruption of normal bone biology. Osteoporosis is characterized by decreased bone density and mass, resulting in bones that are fragile and prone to fracture. The disease occurs when bone resorption exceeds bone formation over time, often due to aging, estrogen deficiency after menopause, or prolonged immobility. Fractures commonly occur in the vertebrae (causing height loss and kyphosis), proximal femur (hip fractures), and distal radius (Colles' fractures). Prevention and treatment include weight-bearing exercise, adequate calcium and vitamin D intake, and medications that either inhibit bone resorption or stimulate bone formation. Osteomalacia and rickets result from inadequate mineralization of bone matrix, usually due to vitamin D deficiency. In children, the condition is called rickets and causes soft, deformable bones that bend under body weight, producing bowed legs and other skeletal deformities. In adults, it is called osteomalacia and causes bone pain, muscle weakness, and increased fracture risk. Treatment involves correction of the vitamin D deficiency. Paget's disease of bone is characterized by excessive and disorganized bone remodeling. Both resorption and formation are markedly increased, but the new bone is structurally abnormal, with woven bone and disorganized architecture. Affected bones become enlarged and deformed, and despite the increased bone mass, they are weaker than normal and prone to fracture. The skull, spine, pelvis, and femur are commonly involved. Osteogenesis imperfecta, often called brittle bone disease, is a group of genetic disorders affecting type I collagen, the main structural protein of bone matrix. Without adequate normal collagen, bones are extremely fragile and fracture with minimal trauma or even spontaneously. Patients may experience dozens of fractures throughout childhood. Many patients also have blue sclerae due to abnormal collagen in the sclera of the eye, allowing the underlying choroid to show through. --- ## Summary The skeletal system provides support, protection, movement, mineral storage, hematopoiesis, and energy storage. The 206 bones of the adult skeleton are divided into the axial skeleton of the central body axis and the appendicular skeleton of the limbs and girdles. Bones are classified by shape as long, short, flat, irregular, or sesamoid, with each shape suited to particular functions. Long bones consist of a diaphysis (shaft) with compact bone walls and medullary cavity, and epiphyses (ends) filled with spongy bone. The periosteum covers external surfaces while endosteum lines internal surfaces. Compact bone is organized into cylindrical osteons containing central canals, concentric lamellae, osteocytes in lacunae, and canaliculi for communication. Spongy bone consists of trabeculae oriented along stress lines with marrow-filled spaces between. Four bone cells perform distinct functions: osteoprogenitor cells serve as stem cells, osteoblasts form bone, osteocytes maintain bone, and osteoclasts resorb bone. Bone matrix combines organic components (collagen and ground substance) providing flexibility with inorganic mineral (hydroxyapatite) providing hardness. Intramembranous ossification forms flat bones directly from mesenchyme. Endochondral ossification forms most bones by replacing a cartilage model. Bones grow in length at epiphyseal plates through five zones and in diameter by appositional growth. Bone remodeling continuously replaces old bone with new bone, regulated by hormones and mechanical stress. --- ## Key Terms | Term | Definition | |------|------------| | Diaphysis | The shaft of a long bone, consisting of compact bone surrounding a medullary cavity | | Epiphysis | The expanded end of a long bone, containing spongy bone and covered by articular cartilage | | Osteon | The structural unit of compact bone, consisting of a central canal surrounded by concentric lamellae | | Osteoblast | Bone-forming cell that synthesizes and secretes bone matrix | | Osteoclast | Large multinucleated cell that resorbs bone | | Epiphyseal plate | Growth plate; layer of cartilage between diaphysis and epiphysis where bone lengthening occurs | --- *This content is subject to the [MIT License](https://opensource.org/licenses/MIT). © 2024–2026 Hibbert School of Medicine.*