6.6: Bone Tissue

Functions of Bone Tissue 

One of the primary functions of the bone tissue is to protect vital organs. Bones create a sturdy framework around delicate structures like the brain, spinal cord, heart, and lungs, shielding them from potential injuries. Bones act as the framework of the body, providing structural support. They serve as the scaffolding upon which muscles, tendons, and ligaments attach, allowing for movement and maintaining the body's shape. Within the cavities of certain bones, particularly the long bones and flat bones such as the pelvis, the bone marrow produces red blood cells, white blood cells, and platelets by a process known as hematopoiesis or hemopoiesis. Bones also serve as sites for fat storage, primarily in the form of yellow bone marrow. This stored fat can be a source of energy in times of need. Bones also store essential minerals such as calcium, phosphate, and carbonate. These minerals are not only critical for the structural integrity of bones but are also vital for various physiological processes throughout the body. They can release or absorb minerals, particularly calcium and phosphate, to ensure the proper functioning of multiple systems. Moreover, bone tissue contributes to the body's acid-base balance by absorbing alkaline salts, notably carbonate. This process helps regulate the pH of bodily fluids, ensuring that they remain within the appropriate range for optimal physiological function.⁴⁸

Types of Bone Tissue 

Bone tissue in the human body consists of two primary types: compact (cortical) and spongy (trabecular) bone (Figure 27).

Compact bone forms the dense outer layer of bones. It is typically found beneath the periosteum, the tough membrane that covers bones. Compact bone appears solid to the naked eye and is composed of tightly packed units called osteons or Haversian systems. Compact bone is organized into a series of concentric layers or lamellae surrounding a central canal known as the Haversian canal (Figure 28). The central canal contains blood vessels, lymphatics, and nerves, providing essential nutrients. 

Compact bone is highly resistant to bending and compression forces. The primary function of compact bone is to provide strength and support to the bone. It helps protect the internal structures of the bone and provides a rigid framework for attaching muscles, tendons, and ligaments.⁷

Spongy bone is found in the inner regions of bones, especially within the marrow space. Unlike compact bone, spongy bone has a porous, lattice-like appearance. It is characterized by a network of thin, bony trabeculae (plates or rods) that form an intricate three-dimensional meshwork (Figure 29). These trabeculae create open spaces within the bone, filled with bone marrow. This arrangement makes spongy bone considerably less dense than compact bone. Spongy bone has several important functions. Despite its lower density, it contributes significantly to bone strength, especially in resisting forces applied from various directions. Spongy bone also plays a vital role in metabolic processes involving bone tissue. For example, it has a metabolic rate that is approximately ten times higher than that of compact bone. This increased metabolic activity is partly due to its rich blood supply, making it a critical site for hematopoiesis in the bone marrow. Additionally, spongy bone is involved in exchanging nutrients and gases within the bone.⁶

Periosteum and Endosteum

The periosteum is a vital connective tissue sheath that envelops the outer surface of compact bone. It comprises two layers: an outer fibrous layer and an inner cellular layer (Figure 30). The outer fibrous layer is composed of dense irregular connective tissue, which provides durability and protection to the bone. It safeguards the bone from external forces and potential injuries. The inner layer is where the dynamic activity occurs. It contains a network of blood vessels, nerve fibers, osteoblasts, and osteoclasts. Osteoblasts build new bone to support growth and repair, whereas osteoclasts break down old or damaged tissue to remodel and maintain bone density, referred to as bone resorption. One of the primary functions of the periosteum is to protect the underlying bone tissue from mechanical trauma, stress, and potential damage. The network of blood vessels within the periosteum supplies oxygen and nutrients to the bone tissue, ensuring its metabolic needs are met. Osteoblasts within the periosteum play a crucial role in bone formation. They contribute to a type of growth called appositional growth, which involves depositing new bone tissue on the outer surface of existing bone, thereby increasing its diameter. Through appositional growth, the periosteum allows bones to increase in diameter over time. Osteoblasts in the periosteum lay down new bone tissue on the outer surface, contributing to thickening of the bone. During fracture repair, the periosteum plays a critical role in coordinating the formation of callus tissue and the subsequent remodeling of bone tissue at the site of injury. 

The endosteum is a thin, membranous structure that lines the inner surfaces of both compact and spongy bone, as well as the canals of blood vessels known as Volkmann's canals (Figure 30). The endosteum consists of a layer of connective tissue that contains osteoblasts, osteoclasts, and a modest blood supply. Osteoclasts within the endosteum are involved in bone resorption. This remodeling function helps maintain bone integrity and adjust bone structure to adapt to mechanical stresses. The endosteum lines the inner surfaces of Volkmann's canals, which are channels that allow blood vessels and nerves to penetrate deep into the bone, providing essential nourishment and communication throughout the bone tissue.

Bone Cells

Osteoblasts are specialized bone-forming cells derived from mesenchymal stem cells called osteoprogenitor cells in the bone marrow and periosteum. They are often referred to as young bone cells because their primary function is to synthesize and deposit new bone tissue. They produce and secrete organic components of the bone matrix, including collagen fibers and various noncollagenous proteins. These organic components provide the framework for bone tissue. Morphologically, osteoblasts are a diverse group. Their shape can range from flat and elongated to plump and cuboidal, reflecting their dynamic activities. These cells line up along the bone-forming surfaces, whether it be on the outer periosteal surface or within the bone itself (Figure 31). 

Osteoblasts actively produce and secrete osteoid, the unmineralized organic portion of the bone matrix. Mineralization, the process of adding calcium and phosphate ions to osteoid, is a critical aspect of bone formation. Osteoblasts orchestrate this by coordinating the deposition of these essential mineral salts onto the osteoid matrix and convert the once-flexible osteoid into the rigid, mineralized bone tissue for support and protection.

Osteoblasts are not mere builders; they are also regulators of bone homeostasis. These versatile cells influence bone remodeling, a lifelong process maintaining skeletal integrity. One of their chief responsibilities is interacting with osteoclasts, the bone-resorbing cells, ensuring a delicate balance between bone formation and resorption. Moreover, osteoblasts are equipped with specialized receptors for essential hormones, such as parathyroid hormone (PTH) and estrogen. These receptors allow them to respond to hormonal signals that help maintain bone metabolism. Physical activity and various external stimuli can influence osteoblast activity. Engaging in weight-bearing exercise, for instance, stimulates osteoblasts to enhance bone formation, contributing to bone density and strength.

Many osteoblasts eventually transition into a more mature, quiescent state and take on a new identity as osteocytes. They surround themselves with bone matrices and become trapped within small spaces called lacunae. Once transformed, they cease secreting osteoid and assume the role of maintaining bone tissue and sensing mechanical stresses. They have numerous cellular extensions extending into tiny channels called canaliculi, allowing them to communicate with neighboring osteocytes, obtain nutrients, and remove waste products. 

When forces are applied to bone tissue through activities such as weight-bearing exercise, the deformation of bone triggers responses within osteocytes. They signal osteoblasts to deposit bone tissue where needed, reinforcing the structure. Simultaneously, they communicate with osteoclasts and instruct them to resorb bone in regions where it is no longer required. This elegant coordination ensures that bone remains robust, adapting to the ever-changing demands.

Various factors, such as estrogen deficiency during menopause or prolonged treatment with glucocorticoid medications, can trigger osteocyte apoptosis or programmed cell death. This process can be detrimental to bone structure, as these cells are vital for orchestrating bone remodeling. The loss of osteocytes disrupts the bone renewal process, potentially leading to decreased bone density and increased risk of fracture. Estrogen therapy, often prescribed to mitigate the effects of menopause-related estrogen deficiency, can help prevent osteocyte apoptosis and sustain bone structure. Another key player in preserving osteocyte function is bisphosphonate therapy. Bisphosphonates are a class of medications that have demonstrated the ability to maintain osteocyte viability and function. By doing so, they contribute to the overall well-being of bone tissue.³

             

Unlike many of their bone cell counterparts, osteoclasts are multinucleated and are responsible for the resorption, or breakdown, of bone tissue. They are derived from precursor cells in the bone marrow and belong to the monocyte-macrophage family, representing a link between the immune system and the skeletal structures. Osteoclasts are vital for the remodeling and maintenance of bone tissue. They are equipped with specialized ion channels embedded in their cell membranes (Figure 31). These ion channels function as miniature proton pumps, expelling protons into the extracellular space that surrounds the bone. This expulsion of protons leads to a profound drop in pH within their immediate microenvironment. The localized decrease in pH is instrumental in the dissolution of bone mineral, which primarily consists of calcium phosphate. This acidification effectively "softens" the bone, rendering it more amenable to resorption. As osteoclasts carry out this acid-mediated dissolution of bone minerals, they expose the organic matrix of the bone, primarily composed of collagen. 

Bone Formation (Ossification)

Bone formation, also known as ossification, is the intricate process by which bone tissue develops and matures. It occurs through two primary processes: intramembranous ossification, which directly forms bone within mesenchyme, and endochondral ossification, which replaces a cartilaginous model with bone tissue and is responsible for the development of long bones such as the femur, humerus, and tibia.

During intramembranous ossification, mesenchymal cells within the embryonic or fetal mesenchyme differentiate into osteoblasts as the first step. Osteoblasts cluster together and start laying down bone matrices directly within the mesenchyme. The area where osteoblasts begin adding bone is called the ossification center. The matrix consists of collagen fibers and organic components. As the bone matrix is deposited, it becomes mineralized through the deposition of calcium salts (calcification), the second step in this process. As the matrix hardens and forms the bone tissue, blood vessels grow into the developing bone, providing oxygen and nutrients to the bone cells. Some osteoblasts become entrapped in lacunae within the newly formed bone matrix and differentiate into osteocytes. The formation of bone at this stage (step 3) is in the form of small, irregularly shaped plates called trabeculae. Eventually, the spongy bone develops into compact bone (step 4) (Figure 32). Intramembranous ossification is commonly seen in flat bones of the skull, including the mandible and maxilla, clavicles, and during the healing of bone fractures, bridging the gap and facilitating bone repair.⁵⁴

Endochondral ossification involves several steps. The first step is the differentiation of mesenchymal cells into chondrocytes, cells within the cartilage, which begins with the formation of a hyaline cartilage model of the future bone. As the cartilage grows, it is gradually replaced by bone tissue, where osteoblasts replace chondrocytes (step 2). Chondrocytes in the primary center of ossification begin to grow (hyperplasia) and stop secreting collagen and other proteoglycans. Instead, they start secreting alkaline phosphatase, essential for mineral deposition and calcification of the matrix. Apoptosis of the hypertrophic chondrocytes forms cavities within the bone. The hypertrophic chondrocytes secrete vascular endothelial cell growth factor, which causes sprouting of blood vessels from the perichondrium. They invade the cavity left by the chondrocytes and branch in opposite directions along the shaft length. The blood vessels carry hematopoietic cells, osteoprogenitor cells, and other cells inside the cavity. The hematopoietic cells will later form the bone marrow. Once vascularized, the perichondrium, the outer covering of the cartilage, differentiates into periosteum. Undifferentiated cells (osteoprogenitor cells) become osteoblasts and begin to secrete osteoid against the shaft of the cartilage model using the calcified matrix. In the midshaft of the cartilage model, a primary ossification center appears along with the periosteum (step 3). The bone matrix becomes mineralized, forming the diaphysis (shaft) of the bone, where the initial bone formation is called trabeculae, which ultimately becomes compact bone. Osteoclasts break down spongy bone to form the medullary cavity (bone marrow).

The cartilage continues to grow in the ends of the long bones (step 4). Soon, secondary ossification centers develop in the center of the epiphyses (step 5). These centers undergo a similar process of bone formation as in the primary ossification center. The hyaline cartilage between the diaphysis and epiphysis remains active in the building of cartilage, adding to the length of the bone, and is called the epiphyseal plate (Figure 33). This area allows for longitudinal bone growth during childhood and adolescence. The epiphyseal growth plate is critical for bone growth, and its closure (ossification) marks the end of longitudinal bone growth, typically occurring in late adolescence or early adulthood.⁵⁶

Bone Growth

Bone growth is a dynamic and highly regulated process that ensures the skeletal system's integrity and function throughout life. It involves two distinct mechanisms: longitudinal or interstitial growth and appositional growth. Interstitial growth contributes to bone length, primarily occurring at the epiphyseal plates (Figure 34), while appositional growth increases bone thickness by adding a new extracellular matrix to the cartilage surface. 

Longitudinal growth primarily drives the increase in bone length during development. This process hinges on continuous cell division within chondrocytes, which are found in the epiphyseal plates, the growth plates located near the ends of long bones. The epiphyseal plates are crucial for longitudinal bone growth and are typically active until the end of adolescence. As chondrocytes divide, they form stacks of cells within the epiphyseal plates. These stacks, known as chondrocyte columns, contribute to the longitudinal expansion of the bone. As new chondrocytes form, older ones transform calcified cartilage, a process that precedes the mineralization of the matrix. This mineralization marks the termination of the bone's lengthening process in that particular region. Once a bone reaches its final length, the epiphyseal plates close, converting the remaining cartilage into bone tissue. This process signifies the cessation of longitudinal bone growth in that specific bone.⁵⁸

While longitudinal growth primarily influences bone length, appositional growth governs bone thickness. This process involves the addition of more extracellular matrix to the cartilage surface. It is orchestrated by specialized cells called chondroblasts, which develop from the perichondrium, a fibrous connective tissue surrounding the cartilage. Simultaneously, within the interior cavity of the bone, osteoclasts continue to play a crucial role. They are responsible for the degradation of bone tissue. This internal degradation process persists until the bone reaches its ultimate thickness. The formation rate on the outer surface and degradation from the inner surface are carefully balanced to maintain constant thickness of the bone. This equilibrium ensures that the bone structure remains robust and adaptable to mechanical demands. These two processes are essential for the continuous development and maintenance of the skeletal system throughout life. 

Bone Modeling and Remodeling 

Bones, being dynamic structures, can adapt to the forces they encounter and the physiological influences they experience. This adaptability, known as bone modeling, ensures that the skeleton maintains its structural integrity while responding to various biomechanical demands. One fundamental aspect of bone modeling involves the gradual adjustment of bone shape in response to mechanical forces, which can include widening or changing the axis of bones. Such changes are achieved through the independent actions of two key players: osteoblasts and osteoclasts. Osteoblasts add bone to appropriate surfaces, while osteoclasts remove bone from surfaces as dictated by biomechanical forces. As individuals age, bones may also widen in response to the periosteal apposition of new bone and endosteal resorption of old bone. While bone modeling is a continuous process throughout life, it is less frequent in adults compared to bone remodeling.

Unlike bone modeling, which occurs in response to developmental or adaptational changes, bone remodeling is a constant process in adults. It involves the removal of old bone and the addition of new, mechanically stronger bone. This perpetual cycle serves multiple vital functions. First and foremost, bone remodeling is essential to maintain the structural integrity of the skeleton, ensuring the bones remain robust and capable of withstanding mechanical stresses. Additionally, it plays a pivotal role in metabolic functions, serving as a reservoir for vital minerals such as calcium and phosphorus.

The process of bone resorption, a central aspect of remodeling, relies on the action of osteoclasts. These specialized cells secrete hydrogen ions and the enzyme cathepsin K. The hydrogen ions acidify the resorption compartment beneath the osteoclasts, leading to the dissolution of the mineral component of the bone matrix. Simultaneously, cathepsin K digests the proteinaceous matrix, facilitating the removal of old and damaged bone. Osteoclasts bind to bone matrix peptides via integrin receptors in their membranes, initiating the process of bone digestion and leading to the formation of saucer-shaped lacunae on the bone surface. Upon completing the resorption process, osteoclasts undergo apoptosis. Following the cessation of osteoclast activity, recruitment of osteoblasts to the resorption site occurs. During the formation phase, osteoblasts synthesize new bone matrices, depositing collagen and minerals to form osteoid. This transition from the activation to the formation phase is crucial, allowing osteoblasts to replace osteoclasts and lay down a new osteoid matrix. The mineralization of the osteoid matrix follows, ultimately culminating in the formation of a bone structure unit, which represents a fundamental building block of bone tissue. The bone returns to a resting state or the quiescent phase, with osteoblast and osteoclast activity balanced (Figure 35). ⁶⁰

The Role of Bones as Mineral Reservoirs 

Bones serve as critical reservoirs for essential minerals in the body, with approximately 99% of body calcium, 85% of phosphorus, and 65% of total body magnesium stored within them. This storage plays a pivotal role in maintaining the delicate balance of these minerals in the bloodstream, ensuring their availability for various physiological processes. Calcium and phosphate metabolism is a tightly regulated process involving multiple hormones and interactions between different organ systems.

PTH, a hormone produced by the parathyroid glands, is a key player in maintaining calcium and phosphate homeostasis. It exerts its influence on multiple organ systems, ensuring the appropriate levels of these minerals are maintained. One of its primary actions is to increase calcium reabsorption while inhibiting phosphate reabsorption in the kidneys. This mechanism is crucial for maintaining the delicate balance of these minerals in the bloodstream, highlighting the significant role of PTH in the body. Calcitonin, produced by the thyroid gland, is an antagonist to bone resorption. It acts by inhibiting the activity of osteoclasts, the cells responsible for bone breakdown. This regulatory mechanism helps to prevent excessive bone resorption and maintain bone density.

Vitamin D plays a multifaceted role in calcium and phosphate metabolism. It enhances the absorption of calcium and phosphate in the intestinal tract. This action is pivotal for maintaining adequate mineral levels in the body. Vitamin D also contributes to the mineralization of osteoid. This process is essential for ensuring the structural integrity of bones. Vitamin D indirectly influences bone resorption by promoting the production of RANK ligand (RANKL) in osteoblasts. This RANKL then interacts with osteoclast precursors, leading to their maturation and activation, which, in turn, enhances bone resorption. This complex regulation helps maintain the balance between bone formation and resorption. Additionally, vitamin D regulates the expression of several bone proteins, including the promotion of the transcription of osteocalcin, a protein involved in bone mineralization. Vitamin D also plays a role in reducing the excretion of calcium and phosphate in the kidneys. This action further contributes to maintaining mineral balance in the body. 

Markers of Bone Formation

Markers of bone formation help evaluate the rate of new bone tissue generation. They provide critical information about bone health and identify conditions associated with increased bone formation. Alkaline phosphatase is an enzyme found in osteoblasts. It promotes the deposition of calcium and phosphate ions into the bone matrix, facilitates the activity of osteoblasts, and helps maintain the proper mineral balance in bone tissue. Alkaline phosphatase helps remove pyrophosphate, a mineralization inhibitor, from the bone matrix by converting pyrophosphate into inorganic phosphate. It prevents the inhibition of hydroxyapatite crystal formation, allowing proper mineralization. Elevated serum alkaline phosphatase levels may indicate increased bone turnover, as seen in conditions like Paget's disease, fractures, or bone metastases. 

Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein, is a sensitive and specific marker of osteoblast activity. It is a protein primarily produced by osteoblasts. It helps in the assembly and arrangement of collagen fibers, which are a major structural component of bone. Osteocalcin plays a role in bone mineralization, the process by which calcium and phosphate ions are deposited into the bone matrix to form hydroxyapatite crystals. It acts as an autocrine regulator, influencing the activity of osteoblasts. Osteocalcin promotes osteoblast differentiation and maturation, leading to increased bone formation. It also enhances the synthesis of type I collagen, the primary protein in bone. 

Osteocalcin can also influence the activity of osteoclasts. By interacting with osteoclasts, osteocalcin helps regulate the balance between bone formation and resorption, maintaining skeletal integrity. The regulation of osteocalcin is complex, and the mechanism of its action is unknown. Elevated osteocalcin levels are associated with increased bone formation, such as hyperparathyroidism, hyperthyroidism, and bone metastases. Conversely, decreased osteocalcin levels may reflect reduced rates of bone formation, as seen during glucocorticoid treatment.

During collagen synthesis, procollagen peptides are released from both the amino-terminal (N-terminal) and carboxy terminal (C-terminal) ends of the procollagen molecule. Elevated levels of these peptides are observed during periods of growth and in situations with increased bone formation, such as Paget's disease, and in response to growth hormone.⁶²