Bone is a specialized type of connective tissue. It has a unique histological appearance and serves many important functions, such as haematopoiesis (the formation of blood cells from haematopoietic stem cells found in the bone marrow), lipid and mineral storage (bone is a reservoir holding adipose tissue within the bone marrow and calcium within the hydroxyapatite crystals), providing support (by forming the framework and shape of the body) and acting as a protective barrier (especially the axial skeleton which surrounds the major organs of the body). In this article, we shall look at the ultrastructure of bone – its components, structure, and development. We shall also examine how disease can affect its structure.
Bone is comprised of three types of cells: osteoblasts, osteocytes, and osteoclasts. Osteoblasts synthesise uncalcified/unmineralised extracellular matrix called osteoid, which will later become calcified/mineralised to form bone. As the osteoid mineralises, the osteoblasts become entombed between lamellae in lacunae and mature into osteocytes. Osteocytes then monitor the minerals and proteins to regulate bone mass. Osteoclasts, derived from monocytes, resorb bone by releasing H+ ions and lysosomal enzymes. Osteoclasts are large, multinucleated cells.
The extracellular matrix (ECM) is comprised of the molecules that provide biochemical and structural support to the cells. The ECM of bone is highly specialised. In addition to collagen and the associated proteins usually found in connective tissue, bone is impregnated with mineral salts, in particular calcium hydroxyapatite crystals. These crystals associate with the collagen fibres, making bone hard and strong. This matrix is organised into numerous thin layers, known as lamellae.
Under the microscope, bone can be divided into two types: woven bone (primary bone) and lamellar bone (secondary bone). Woven bone appears in embryonic development and fracture repair, as it can be laid down rapidly. It consists of osteoid (unmineralised ECM) with the collagen fibres arranged randomly. It is a temporary structure, soon replaced by mature lamellar bone. Lamellar bone, the bone of the adult skeleton, consists of highly organised sheets of mineralised osteoid. This organised structure makes it much stronger than woven bone.
Lamellar bone can be divided into two types: compact bone and spongy bone. The external surface of the bone is covered by a layer of connective tissue, known as the periosteum. A similar layer, the endosteum, lines the cavities within bone (such as the medullary canal, Volkmann’s canal and spongy bone spaces).
Compact bone forms the outer ‘shell’ of bone. In this type of bone, the lamellae are organised into concentric circles, which surround a vertical Haversian canal (which transmits small neurovascular and lymphatic vessels). This entire structure is called an osteon and is the functional unit of bone.
The Haversian canals are connected by horizontal Volkmann’s canals – these contain small vessels that anastomose (join) with the arteries of the Haversian canals. The Volkmann’s canals also transmit blood vessels from the periosteum. Osteocytes are located between the lamellae, within small cavities (known as lacunae). The lacunae are interconnected by a series of interconnecting tunnels, called canaliculi.
Bone formation occurs through ossification and remodelling. Ossification is the process by which bone cells (osteoblasts) form bone matrix (osteoid). Remodelling is the breakdown and replacement of existing bone tissue. Woven bone is the type of bone seen shortly after formation. It has a disorganised structure and is composed of randomly orientated collagen fibres. Lamellar bone consists of several layers of concentric bone matrix, which makes it strong against unidirectional lines of force. It is seen in mature bone and is the predominant form of bone in the human body.
Compact bone is made up of several concentric layers of lamellae, surrounding a central space – Haversian canal. Volkmann’s canals extend out from this in a star-shaped fashion, and they permit the passage of blood vessels. Spongy bone makes up the interior of most bones and is located deep to the compact bone. It contains many large spaces – this gives it a honeycombed appearance.
In order to maintain the structural integrity of bone, the process of ossification and remodelling must occur. As bone undergoes breaks down and is replaced by newly formed bone, certain hormones and growth factors are released, which stimulate the osteoblasts to form new bone. This process is known as bone remodelling and is essential to the health of the skeleton.
The process of bone remodelling is highly regulated and is influenced by various factors, such as age, activity level, nutrition, hormone levels, and disease. There are two distinct processes in bone remodelling: activation and resorption. During activation, osteoblasts are recruited to the affected area and begin to form bone matrix. During resorption, osteoclasts break down bone tissue in order to clear space for the new bone to form.
The process of bone remodelling is important for maintaining the structural integrity of the skeleton. It is essential for the growth and repair of bone, for calcium and phosphate homeostasis, and for generating new bone following injury or disease. Due to its importance in maintaining the health of the skeleton, it is important to understand the process of bone remodelling and the factors that influence its progression.
Bone is a specialised form of connective tissue that has a unique histological appearance which enables it to carry out its numerous functions. These functions include haematopoiesis - the formation of blood cells from haematopoietic stem cells found in the bone marrow, lipid and mineral storage – bone is a reservoir that holds adipose tissue within the bone marrow and calcium within the hydroxyapatite crystals, support – bones form the framework and shape of the body, and protection – especially the axial skeleton which surrounds the major organs of the body. In this article, we shall look at the ultrastructure of bone - its components, structure and development - as well as how disease can affect its structure.
The bony matrix consists of a 3-D network of fine columns which crosslink to form irregular trabeculae. This creates a light, porous bone which is strong against multidirectional lines of force. The lightness of spongy bone is crucial in allowing the body to move, as if compact bone was the only type, it would be far too heavy to mobilise. The spaces between trabeculae are often filled with bone marrow, which has two different types. Yellow bone marrow contains adipocytes and red bone marrow consists of haematopoietic stem cells. Spongy bone does not contain any Volkmann’s or Haversian canals.
Ossification is the process of producing new bone. This occurs through one of two mechanisms - Endochondral ossification – where hyaline cartilage is replaced by osteoblasts secreting osteoid. An example of a bone that undergoes endochondral ossification is the femur. Intramembranous ossification – where mesenchymal (embryonic) tissue is condensed into bone. This type of ossification forms flat bones such as the temporal bone and the scapula. In both mechanisms, primary bone is initially produced, and it is later replaced by mature secondary bone.
Remodelling is the process whereby mature bone tissue is reabsorbed, and new bone tissue is formed by the cellular component of bone. Osteoclasts break down bone via a cutting cone to reabsorb the nutrients, and osteoblasts lay down new osteoid. Remodelling primarily occurs at sites of stress and damage, strengthening the affected areas.
Alterations to the histological structure of bone, secondary to disease, can give rise to several clinical conditions. Osteogenesis imperfecta is a condition in which there is abnormal synthesis of collagen from the osteoblasts. Clinical features include fragile bones, bone deformities and blue sclera, and it is a rare, genetic disorder with an autosomal dominant inheritance pattern. The fragility of the bones predisposes them to fracture, which is of important medicolegal significance when it is mistaken for deliberate injury in children. Osteoporosis refers to a decrease in bone density, reducing its structural integrity, and is caused by osteoclast activity (bone reabsorption) outweighing osteoblast activity (bone production). The bones are fragile and at an increased risk of fracture. There are three types of osteoporosis: Type 1 - Postmenopausal osteoporosis – Develops in women after the menopause, due to decreased oestrogen production. Oestrogen protects against osteoporosis by increasing osteoblast and decreasing osteoclast activity. Type 2 – Senile osteoporosis – Usually occurs above the age of 70, and Type 3 - Secondary osteoporosis – Where osteoporosis occurs due to co-existing disease (e.g. chronic renal failure). Risk factors include age, gender, diet (vitamin D and calcium), ethnicity, smoking and immobility. It is usually managed by bisphosphonates which are taken up by osteoclasts, causing them to become inactive and undergo apoptosis. This limits further degradation of bone.
Rickets is Vitamin D or calcium deficiency in children with growing bones. This means that the osteoid mineralises poorly and remains pliable. The epiphyseal growth plates can then become distorted under the weight of the body, potentially leading to skeletal deformities. Osteomalacia is a Vitamin D or calcium deficiency in adults with remodelling bones. Here the osteoid laid down by osteoblasts is poorly mineralised leading to increasingly weak bones, increasing their susceptibility to fracture.
Like any connective tissue, the anatomy of bone tissue can be divided into cellular components and the extracellular matrix.
Within bone, there are three types of cells:
The extracellular matrix (ECM) refers to the molecules that provide both biochemical and structural support to the cells in bone tissue. This matrix is highly specialised, with collagen and proteins usually found in connective tissue, as well as mineral salts, particularly calcium hydroxyapatite crystals. These crystals attach to the collagen fibres, making bone strong and hard. The matrix is organised into multiple thin layers, also known as lamellae.
Under the microscope, bone can be divided into two types:
In both types of bone, the external surface is covered by the periosteum – a layer of connective tissue. The inner cavities of bone, such as the medullary canal, Volkmann's canal and spongy bone spaces, are all lined by the endosteum.
Compact bone forms the outer 'shell' of bone, with the lamellae arranged into concentric circles surrounding a vertical Haversian Canal. This entire structure is called an osteon, which is the functional unit of bone. The Haversian canals are connected horizontally by the Volkmann’s canals, which transmit small vessels that join with the arteries of the Haversian canals, as well as transmitting blood vessels from the periosteum. Osteocytes are located between the lamellae, within lacunae – small cavities that are interconnected by a series of interconnecting tunnels, known as canaliculi.
Spongy bone is located deep to the compact bone and consists of many large spaces, resulting in a honeycombed appearance. The bony matrix consists of a 3D network of fine columns, called trabeculae, which form an irregular pattern and produce a light, porous bone that is resistant to multidirectional lines of force. The spaces between trabeculae are often filled with bone marrow, which can either be yellow (containing adipocytes) or red (containing haematopoietic stem cells). Spongy bone does not contain any Volkmann’s or Haversian canals.
Ossification is the process of producing new bone, which occurs via one of two mechanisms:
In both these mechanisms, primary bone is initially produced, later replaced by mature secondary bone.
Remodelling refers to the process whereby mature bone tissue is reabsorbed and new bone tissue is formed. The cellular component of bone is responsible for this, with osteoclasts breaking down bone via a cutting cone.
Bone is a living, dynamic tissue composed ultrastructurally of woven, lamellar, and compact bone. Woven bone is the primary type or instant bone formed rapidly without finishing the normal processes of ossification. Lamellar bone, in contrast, is composed of concentric circles called lamellae, while compact bone is made up of closely-packed Haversian systems, or osteons. On a macroscopic level, bones are composed of spongy and compact bone. Spongy bone, or trabecular bone, is found at the ends of long bones and is comprised of a lattice-like matrix that contains red and yellow marrow. The inner layer of bone, compact or cortical bone, provides strength and support.
Bone formation occurs through either endochondral ossification or intramembranous ossification. Endochondral ossification is the process by which cartilage is slowly replaced with bone, while intramembranous ossification is the formation of bone directly from pre-existing mesenchymal cells. As bone is dynamic, remodeling of bone is a continuous process regulated by cytokines and growth factors. This process is especially important as it helps to maintain proper structural integrity and is seen particularly at sites of stress and damage, aiding in the strengthening of the affected area. Nutrients are reabsorbed and new osteoid is laid down by osteoblasts as part of this process.
Alterations to the histological structure of bone, secondary to disease, can result in several clinical problems. These include osteogenesis imperfecta, osteoporosis, rickets, and osteomalacia.
Osteogenesis imperfecta is a rare genetic disorder characterized by abnormal synthesis of collagen from the osteoblasts. Clinical features include fragile bones, bone deformities, and blue sclera. This condition is inherited in an autosomal dominant manner. The fragility of the bones predisposes them to fracture, which can be mistaken by medical professionals for deliberate injury in children. This has huge implications in a medicolegal setting.
Osteoporosis is a decrease in bone density, resulting in reduction of its structural integrity. This is due to excessive osteoclastic activity, or bone reabsorption, and is greater than osteoblastic activity, or bone production. As a result, the bones become fragile and are at an increased risk of fracture. Risk factors for the development of osteoporosis include age, gender, diet (specifically lack of vitamin D and calcium), ethnicity, smoking, and immobility. There are three types of osteoporosis: postmenopausal osteoporosis, senile osteoporosis, and secondary osteoporosis. Postmenopausal osteoporosis develops in women after the menopause due to decreased oestrogen production. Oestrogen is important in protecting against osteoporosis as it stimulates osteoblast and reduces osteoclast activity. Senile osteoporosis typically occurs in people above the age of 70, and secondary osteoporosis, which is most commonly seen in those with chronic renal failure, develops as a result of a co-existing disease. Osteoporosis is usually managed by bisphosphonates which inhibit osteoclast activity, leading to apoptosis, and thus limiting further degradation of bone.
Rickets is a vitamin D or calcium deficiency seen in children with growing bones, resulting in inadequate mineralisation of the osteoid and pliable bones. This can lead to distortion of the epiphyseal growth plates, potentially causing skeletal deformities. Osteomalacia is a vitamin D or calcium deficiency seen in adults with remodeling bones. Poor mineralisation of the osteoid laid down by osteoblasts leads to increasingly weak bones and increased susceptibility to fracture. Vitamin D deficiency can be due to poor dietary intake, lack of exposure to sunlight, or a metabolic disorder.
