Premed · Premed · Anatomy Physiology 1
Lecture 6: Bone Tissue and Skeletal Physiology
Anatomy and Physiology I
Learning Objectives
By the end of this lecture, students will be able to:
- List the functions of the skeletal system
- Classify bones by shape and provide examples
- Describe the gross anatomy of a long bone
- Describe the histology of compact and spongy bone
- Compare intramembranous and endochondral ossification
- Describe the process of bone growth in length and width
- Explain bone remodeling and the roles of osteoblasts, osteocytes, and osteoclasts
- Describe calcium homeostasis and the roles of parathyroid hormone, calcitonin, and vitamin D
- Describe the types of bone fractures and the steps of fracture repair
Lecture Content
I. Functions of the Skeletal System
The skeletal system serves multiple essential functions. It provides support, forming the body's framework, supporting soft tissues, and offering attachment points for muscles. It affords protection to vital organs, with the skull shielding the brain, the rib cage guarding the heart and lungs, and the vertebral column encasing the spinal cord. Bones serve as levers for movement, with joints acting as fulcrums. The skeleton functions as a mineral reservoir, storing 99 percent of the body's calcium and much of its phosphorus. Red bone marrow is the site of blood cell formation (hematopoiesis), producing red blood cells, white blood cells, and platelets. Yellow bone marrow stores adipose tissue as an energy reserve (triglyceride storage). Bone also helps maintain acid-base balance by absorbing or releasing alkaline salts to buffer the blood.
II. Classification of Bones by Shape
Long bones are longer than they are wide, possessing a shaft with two expanded ends; examples include the femur, humerus, tibia, and phalanges. Short bones are roughly cube-shaped, such as the carpals and tarsals; sesamoid bones like the patella are special short bones that form within tendons. Flat bones are thin, flattened, and often curved, including the skull bones, sternum, scapulae, and ribs. Irregular bones have complex shapes that do not fit the other categories, such as the vertebrae, hip bones, and facial bones.
III. Gross Anatomy of a Long Bone
The diaphysis is the elongated, cylindrical shaft composed of compact bone surrounding a central medullary (marrow) cavity that contains yellow bone marrow in adults. The epiphyses are the expanded ends (proximal and distal), composed internally of spongy bone covered by a thin shell of compact bone. Their articular surfaces are capped with articular (hyaline) cartilage to reduce friction at joints, and the spongy bone spaces within contain red bone marrow. The metaphysis is the transitional region between diaphysis and epiphysis. In growing bone, it contains the epiphyseal plate (growth plate), a layer of hyaline cartilage responsible for bone elongation; in adults, this plate ossifies into the epiphyseal line and growth ceases.
The periosteum is a double-layered connective tissue membrane covering the outer bone surface everywhere except at articular surfaces. Its outer fibrous layer of dense irregular connective tissue is anchored by Sharpey's fibers, while the inner osteogenic layer contains osteoblasts and osteoclasts. The periosteum is richly supplied with nerve fibers and blood vessels and serves as the attachment point for tendons and ligaments. The endosteum is a thin connective tissue membrane lining the medullary cavity and internal bone surfaces, also containing osteoblasts and osteoclasts active in remodeling. A nutrient artery enters the bone through a nutrient foramen to supply bone tissue and marrow.
<image>A longitudinal section of a long bone (femur) showing all gross anatomical features. The diaphysis (shaft) is labeled in the center with thick compact bone walls and a central medullary cavity filled with yellow marrow. The proximal and distal epiphyses show internal spongy bone (with red marrow in the spaces) covered by a thin shell of compact bone. Articular cartilage (hyaline) covers the joint surfaces. The metaphysis is shown between the diaphysis and each epiphysis, with the epiphyseal line indicated. The periosteum covers the outer surface (except at articular cartilage), and the endosteum lines the medullary cavity. A nutrient artery enters through a nutrient foramen. An inset shows a magnified view of the periosteum with its fibrous and osteogenic layers.</image>
IV. Histology of Bone Tissue
Bone Cells
Osteogenic (osteoprogenitor) cells are stem cells residing in the periosteum and endosteum that differentiate into osteoblasts. Osteoblasts are bone-forming cells that secrete osteoid, the organic bone matrix composed of collagen and ground substance. They line bone surfaces and do not divide; when they become surrounded by the matrix they have secreted, they mature into osteocytes. Osteocytes are mature bone cells trapped in lacunae within the calcified matrix. They maintain the bone matrix, communicate with each other through cytoplasmic extensions that pass through tiny canals called canaliculi, and act as mechanosensors that detect strain and signal osteoblasts and osteoclasts to remodel bone accordingly. Osteoclasts are large, multinucleated cells derived from monocytes that reside in shallow pits called Howship's lacunae (resorption bays). They break down bone by secreting hydrochloric acid and lysosomal enzymes, and their ruffled border increases the surface area available for resorption.
Bone Matrix Composition
The organic components (approximately 35% of bone mass) consist primarily of type I collagen fibers along with ground substance containing proteoglycans and glycoproteins such as osteocalcin. These organic elements provide flexibility and tensile strength. The inorganic components (approximately 65%) are mainly mineral salts, predominantly hydroxyapatite, which provide hardness and resistance to compression. The combination of organic and inorganic elements gives bone its exceptional strength — neither component alone would be sufficient.
Compact (Cortical) Bone
Compact bone forms the dense, solid-appearing external layer. Its structural unit is the osteon (Haversian system). Each osteon is built around a central (Haversian) canal running longitudinally through its center, carrying blood vessels and nerves. Surrounding the canal are concentric rings of calcified matrix called lamellae. Between the lamellae sit lacunae, small spaces 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, forming an extensive communication and nutrient network. Perforating (Volkmann's) canals run perpendicular to the central canals, connecting adjacent osteons and linking the blood vessels of the periosteum, central canals, and medullary cavity. Between complete osteons lie interstitial lamellae, remnants of older osteons partially resorbed during remodeling. Circumferential lamellae encircle the entire bone just beneath the periosteum and endosteum.
Spongy (Cancellous/Trabecular) Bone
Spongy bone consists of a network of bony plates and rods called trabeculae. It does not contain osteons; instead, osteocytes in lacunae receive nutrients by diffusion through canaliculi from the trabecular surfaces. The spaces between trabeculae are filled with red or yellow bone marrow. Trabeculae are aligned along lines of stress, providing maximum strength with minimum weight. Spongy bone is found in the epiphyses of long bones and the interior of short, flat, and irregular bones.
<image>A magnified cross-section of compact bone showing several osteons. Each osteon consists of concentric lamellae (ring-like layers) surrounding a central (Haversian) canal containing blood vessels. Osteocytes sit in lacunae between lamellae, with canaliculi radiating outward like tiny spokes connecting adjacent lacunae and reaching the central canal. A perforating (Volkmann's) canal runs horizontally connecting two central canals. Interstitial lamellae fill the spaces between complete osteons. The periosteum with its blood vessels is visible at the outer edge. An adjacent panel shows spongy bone with irregular trabeculae surrounding marrow-filled spaces, with osteocytes visible in lacunae on the trabecular surfaces.</image>
V. Bone Formation (Ossification/Osteogenesis)
Intramembranous Ossification
In intramembranous ossification, bone develops directly from a fibrous membrane of mesenchyme, producing the flat bones of the skull, the mandible, and the clavicle. The process begins when mesenchymal cells cluster and differentiate into osteoblasts within the fibrous membrane. These osteoblasts secrete osteoid, which mineralizes to form trabeculae of woven bone, trapping some osteoblasts as osteocytes. The accumulating trabeculae form spongy bone as blood vessels are incorporated. A periosteum forms on the outer surface, and osteoblasts beneath it deposit compact bone plates, creating the outer and inner tables of flat skull bones with spongy bone (the diploe) between them. The initial woven bone is later remodeled into mature lamellar bone.
Endochondral Ossification
Endochondral ossification replaces a hyaline cartilage model with bone and is responsible for forming most bones of the skeleton. During fetal development, a hyaline cartilage model forms first. The perichondrium around the mid-shaft becomes vascularized and transforms into a periosteum, and osteoblasts form a bone collar of compact bone around the diaphysis. Chondrocytes in the center of the cartilage model enlarge, secrete alkaline phosphatase to calcify the surrounding matrix, and die, leaving behind cavities. A periosteal bud of blood vessels, osteoblasts, osteoclasts, and red marrow cells invades these cavities, establishing the primary ossification center in the diaphysis. Osteoclasts break down the calcified cartilage while osteoblasts deposit new bone on the remaining cartilage remnants, forming spongy bone. Osteoclasts then hollow out the center to create the medullary cavity. Secondary ossification centers appear in the epiphyses around the time of birth. Hyaline cartilage ultimately remains in only two locations: the articular cartilage covering joint surfaces and the epiphyseal plate between the epiphysis and diaphysis, which drives longitudinal bone growth.
VI. Bone Growth
Growth in Length — at the Epiphyseal Plate
The epiphyseal plate is organized into four zones progressing from the epiphysis toward the diaphysis. The zone of resting (reserve) cartilage contains small, scattered chondrocytes that anchor the plate to the epiphysis. In the zone of proliferation, chondrocytes undergo rapid mitosis, forming columns that resemble stacks of coins, adding cartilage on the epiphyseal side. In the zone of hypertrophy, chondrocytes enlarge dramatically while the matrix between the columns thins. In the zone of calcification, the matrix calcifies and the chondrocytes die, after which osteoclasts and osteoblasts invade from the diaphyseal side to replace calcified cartilage with bone.
The net effect is that cartilage is produced on the epiphyseal side and replaced by bone on the diaphyseal side, causing the bone to lengthen. Growth ceases when the rate of cartilage production equals the rate of replacement, and the plate ossifies into the epiphyseal line. Closure occurs at different ages for different bones but is generally complete between ages 18 and 25. Growth hormone, thyroid hormone, and sex hormones (estrogen and testosterone) regulate growth plate activity. The sex hormones stimulate growth at puberty but ultimately cause closure of the plate, which is why growth stops after puberty.
Growth in Width (Thickness) — Appositional Growth
Bone grows in width through appositional growth. Osteoblasts in the periosteum add new bone matrix to the external surface, while osteoclasts in the endosteum resorb bone from the internal surface. This coordinated process increases bone diameter while maintaining a proportional medullary cavity.
VII. Bone Remodeling
Bone remodeling is a continuous process in which osteoclasts resorb old bone and osteoblasts deposit new bone. Approximately 5 to 7 percent of bone mass is recycled each week, and the entire skeleton is remodeled roughly every 10 years. Remodeling serves to maintain calcium homeostasis, repair microdamage, and reshape bone in response to mechanical demands.
Wolff's law states that bone grows or remodels in response to the mechanical stresses placed on it. Bones subjected to heavy loads through weight-bearing exercise become thicker and stronger, while bones deprived of normal stress, as occurs with immobilization, prolonged bed rest, or space travel, lose mass and weaken. Trabeculae in spongy bone align themselves along lines of stress to provide the greatest strength where it is most needed.
VIII. Calcium Homeostasis
Normal blood calcium levels are maintained at approximately 9 to 11 mg/dL. Calcium is critical for nerve impulse transmission, muscle contraction, blood clotting, enzyme activity, and cell signaling, making its regulation vitally important.
Parathyroid Hormone (PTH)
PTH is secreted by the parathyroid glands when blood calcium falls below normal. Its effects all serve to raise blood calcium: it stimulates osteoclasts to resorb bone, releasing calcium and phosphate into the blood; it enhances calcium reabsorption in the kidney tubules; and it promotes activation of vitamin D in the kidneys, which in turn increases calcium absorption from the intestine. PTH is the most important hormone for minute-to-minute calcium regulation.
Calcitonin
Calcitonin is secreted by the parafollicular (C) cells of the thyroid gland when blood calcium rises above normal. It inhibits osteoclast activity, reducing bone resorption, and stimulates calcium deposition in bone, thereby lowering blood calcium. In adults, calcitonin plays a relatively minor role, but it is more significant during childhood when bones are growing rapidly.
Vitamin D (Calcitriol — active form)
Vitamin D3 (cholecalciferol) is synthesized in the skin upon UV exposure or obtained from the diet. It is converted to calcidiol in the liver and then to the active form, calcitriol (1,25-dihydroxyvitamin D), in the kidneys, a conversion stimulated by PTH. Calcitriol promotes the absorption of calcium and phosphate from the small intestine and works synergistically with PTH to maintain calcium levels.
<image>A flowchart depicting calcium homeostasis. On the left, blood calcium drops below the set point: parathyroid glands release PTH, which stimulates osteoclast activity (bone resorption releasing Ca2+), increases renal Ca2+ reabsorption, and activates vitamin D to enhance intestinal Ca2+ absorption — blood calcium rises back to normal. On the right, blood calcium rises above the set point: thyroid C cells release calcitonin, which inhibits osteoclasts and promotes calcium deposition in bone — blood calcium falls back to normal. A horizontal bar in the center represents the normal set point with arrows indicating the two opposing feedback loops.</image>
IX. Bone Fractures and Repair
Common Fracture Types
A simple (closed) fracture breaks the bone without penetrating the skin, whereas a compound (open) fracture involves bone ends protruding through the skin, carrying a risk of infection. A comminuted fracture shatters the bone into three or more pieces. A greenstick fracture is an incomplete break in which the bone bends and cracks on one side, common in children. Transverse fractures run perpendicular to the bone's long axis, oblique fractures run at an angle, and spiral fractures produce a ragged break caused by twisting forces. Compression fractures crush the bone and are common in vertebrae affected by osteoporosis. Pathological fractures occur at sites weakened by disease such as bone cancer. Stress (fatigue) fractures are thin cracks from repetitive stress, frequently seen in athletes.
Stages of Fracture Repair
Repair proceeds through four stages. During hematoma formation (hours), torn blood vessels in the bone and periosteum produce a blood clot called a fracture hematoma. Bone cells at the fracture site die, and swelling and inflammation develop as phagocytes and osteoclasts begin removing dead tissue.
In the stage of fibrocartilaginous (soft) callus formation (days to weeks), new capillaries grow into the hematoma as granulation tissue. Fibroblasts and chondroblasts from the periosteum and endosteum bridge the gap, producing collagen fibers and fibrocartilage that form an internal and external callus to splint the fracture.
During bony (hard) callus formation (weeks to months), osteoblasts replace the fibrocartilaginous callus with woven (immature) bone through endochondral ossification. New bony trabeculae join the broken ends, and a hard callus spans the fracture.
Finally, bone remodeling (months to years) reshapes the repair. Osteoclasts resorb excess callus bone, compact bone replaces woven bone, and spongy bone forms where appropriate. In well-set fractures, the healed area may become undetectable on X-ray.
Factors Affecting Fracture Healing
Healing is influenced by age (children heal faster), nutrition (adequate protein and vitamins C and D along with calcium), blood supply, fracture severity, the type of bone involved, proper alignment and immobilization, and the absence of infection.
