Opening the book…
Cartilage Templates
In the early stages of embryonic development, the embryo’s skeleton consists of fibrous membranes and hyaline cartilage. By the sixth or seventh week of embryonic life, the actual process of bone development, ossification (osteogenesis), begins. There are two osteogenic pathways—intramembranous ossification and endochondral ossification—but bone is the same regardless of the pathway that produces it.
The process of bone formation, known as ossification, often begins with a cartilage template, a critical precursor in the development of many bones, particularly long bones. This cartilage model is composed primarily of hyaline cartilage, which provides a flexible yet sturdy framework for the initial stages of bone development. During fetal development, a framework is laid down that determines where bones will form. This framework is a flexible, semi-solid matrix produced by chondroblasts and consists of hyaluronic acid, chondroitin sulfate, collagen fibers, and water. As the matrix surrounds and isolates chondroblasts, they are called chondrocytes. Unlike most connective tissues, cartilage is avascular, meaning that it has no blood vessels supplying nutrients and removing metabolic wastes. All of these functions are carried on by diffusion through the matrix. This is why damaged cartilage does not repair itself as readily as most tissues do.
By the time a fetus is born, most of the cartilage has been replaced with bone. Some additional cartilage will be replaced throughout childhood, and some cartilage remains in the adult skeleton.
Intramembranous Ossification
Intramembranous ossification begins in utero during fetal development and continues on into adolescence. At birth, the skull and clavicles are not fully ossified nor are the sutures of the skull closed. This allows the skull and shoulders to deform during passage through the birth canal. The last bones to ossify via intramembranous ossification are the flat bones of the face, which reach their adult size at the end of the adolescent growth spurt.
During intramembranous ossification, compact and spongy bone develops directly from sheets of mesenchymal (undifferentiated) connective tissue. The flat bones of the face, most of the cranial bones, and the clavicles (collarbones) are formed via intramembranous ossification.
This process begins when mesenchymal cells in the embryonic skeleton gather together and begin to differentiate into specialized cells (Figure \(\PageIndex{1}\)) and occurs in four main steps to enable the direct formation of bone tissue from mesenchymal cells, producing the flat bones characteristic of the skull, face, and clavicles.
- Development of Ossification Centers - Mesenchymal cells cluster together and differentiate into osteoblasts, forming ossification centers where bone formation begins.
- Secretion and Calcification of Osteoid - Osteoblasts secrete osteoid (unmineralized bone matrix). The osteoid then calcifies (hardens) as mineral salts are deposited, trapping osteoblasts which become osteocytes.
- Formation of Trabeculae (Spongy Bone) - The osteoid accumulates around blood vessels, forming a network of trabeculae (thin columns of bone) that creates spongy bone. Blood vessels become enclosed, and the surrounding mesenchyme condenses to form the periosteum (outer bone covering).
- Development of Compact Bone and Red Marrow - Compact bone forms on the surface as osteoblasts in the periosteum lay down bone layers over the spongy bone. The spaces inside the spongy bone are eventually filled with red bone marrow.
Figure \(\PageIndex{1}\): Intramembranous ossification follows four steps. (a) Mesenchymal cells group into clusters, and ossification centers form. (b) Secreted osteoid traps osteoblasts, which then become osteocytes. (c) Trabecular matrix and periosteum form. (d) Compact bone develops superficial to the trabecular bone, and crowded blood vessels condense into red marrow. (CC BY 4.0; via OpenStax). Alternate text description of Figure \(\PageIndex{1}\).
Endochondral Ossification
In endochondral ossification, bone develops by replacing hyaline cartilage. Cartilage does not become bone. Instead, cartilage serves as a template to be completely replaced by new bone. Endochondral ossification takes much longer than intramembranous ossification. Bones at the base of the skull and long bones form via endochondral ossification.
In a long bone, for example, at about 6 to 8 weeks after conception, some of the mesenchymal cells differentiate into chondrocytes (cartilage cells) that form the cartilaginous skeletal precursor of the bones (Figure \(\PageIndex{2a}\). Soon after, the perichondrium, a membrane that covers the cartilage, appears Figure \(\PageIndex{2b}\).
As more matrix is produced, the chondrocytes in the center of the cartilaginous model grow in size. As the matrix calcifies, nutrients can no longer reach the chondrocytes. This results in their death and the disintegration of the surrounding cartilage. Blood vessels invade the resulting spaces, not only enlarging the cavities but also carrying osteogenic cells with them, many of which will become osteoblasts. These enlarging spaces eventually combine to become the medullary cavity.
As the cartilage grows, capillaries penetrate it. This penetration initiates the transformation of the perichondrium into the bone-producing periosteum. Here, the osteoblasts form a periosteal collar of compact bone around the cartilage of the diaphysis. By the second or third month of fetal life, bone cell development and ossification ramps up and creates the primary ossification center, a region deep in the periosteal collar where ossification begins (Figure \(\PageIndex{2c}\)).
While these deep changes are occurring, chondrocytes and cartilage continue to grow at the ends of the bone (the future epiphyses), which increases the bone’s length at the same time bone is replacing cartilage in the diaphyses. By the time the fetal skeleton is fully formed, cartilage only remains at the joint surface as articular cartilage and between the diaphysis and epiphysis as the epiphyseal plate, the latter of which is responsible for the longitudinal growth of bones. After birth, this same sequence of events (matrix mineralization, death of chondrocytes, invasion of blood vessels from the periosteum, and seeding with osteogenic cells that become osteoblasts) occurs in the epiphyseal regions, and each of these centers of activity is referred to as a secondary ossification center (Figure \(\PageIndex{2e}\)).
| Step | Description |
|---|---|
| Cartilage model formation | Mesenchymal cells → chondroblasts → hyaline cartilage model |
| Cartilage growth and maturation | Chondrocytes proliferate and hypertrophy, matrix changes, cartilage enlarges |
| Calcification and chondrocyte death | Matrix calcifies, chondrocytes die, cavities form |
| Primary ossification center forms | Blood vessels invade, osteoblasts replace cartilage with bone in diaphysis |
| Secondary ossification centers form | After birth, epiphyses ossify, articular cartilage and epiphyseal plate remain |
How Bones Grow in Length
Bones grow in length through activity at the epiphyseal (growth) plate by a process similar to endochondral ossification. The epiphyseal plate is a layer of hyaline cartilage where ossification occurs in immature bones. On the epiphyseal side of the epiphyseal plate, cartilage is formed. On the diaphyseal side, cartilage is ossified, and the diaphysis grows in length. The longitudinal growth of bone is a result of cellular division in the proliferative zone and the maturation of cells in the zone of maturation and hypertrophy. The epiphyseal plate is composed of four zones of cells and activity (Figure \(\PageIndex{3}\)).The following is a description of activities in each zone.
- Resting (reserve) zone - Small, inactive chondrocytes closest to the epiphysis serve as a reserve and anchor the plate to the epiphysis.
- Proliferation zone - Chondrocytes divide rapidly, forming columns and producing new cartilage, which pushes the epiphysis away from the diaphysis and lengthens the bone.
- Hypertrophic zone - Chondrocytes enlarge (hypertrophy) and the lacunae (spaces) around them expand.
- Calcification zone - The matrix surrounding the hypertrophic chondrocytes calcifies, chondrocytes die, and the area is left with calcified cartilage. Capillaries and osteoblasts from the diaphysis penetrate this zone, and the osteoblasts secrete bone tissue on the remaining calcified cartilage. Thus, the zone of calcified matrix connects the epiphyseal plate to the diaphysis. A bone grows in length when osseous tissue is added to the diaphysis.
Figure \(\PageIndex{3}\): The epiphyseal plate is responsible for longitudinal bone growth. (CC BY 4.0; via OpenStax). Alternate text description of Figure \(\PageIndex{3}\).
Bones continue to grow in length until early adulthood. The rate of growth is controlled by hormones, which will be discussed later. When the chondrocytes in the epiphyseal plate cease their proliferation and bone replaces the cartilage, longitudinal growth stops. All that remains of the epiphyseal plate is the epiphyseal line (Figure \(\PageIndex{4}\)).
Figure \(\PageIndex{4}\): As a bone matures, the epiphyseal plate progresses to an epiphyseal line. (a) Epiphyseal plates are visible in a growing bone. (b) Epiphyseal lines are the remnants of epiphyseal plates in a mature bone. (CC BY 4.0; via OpenStax). Alternate text description of Figure \(\PageIndex{4}\).
How Bones Grow in Diameter
While bones are increasing in length, they are also increasing in diameter; growth in diameter can continue even after longitudinal growth ceases. Bones grow in diameter through a process called appositional growth, where new bone is added to the surface while old bone is removed from the inside. This involves osteoblasts in the outer layer building new bone, and osteoclasts on the inner surface breaking down old bone to create a larger medullary cavity. This balance increases the bone's overall thickness and width.
- Osteoblasts build new bone: Osteoblasts on the outer surface of the bone (under the periosteum) secrete new bone matrix, adding layers to the bone's exterior.
- Osteoclasts resorb old bone: Simultaneously, osteoclasts on the inner surface of the bone (lining the medullary cavity) break down and remove old bone tissue.
This dual process increases the diameter of the bone while also widening the internal marrow cavity, which helps keep the bone from becoming too heavy. This activity continues throughout life, allowing bones to remodel and thicken in response to mechanical stress.
Bone Remodeling
The process in which matrix is resorbed on one surface of a bone and deposited on another is known as bone modeling. Modeling primarily takes place during a bone’s growth. However, in adult life, bone undergoes remodeling, in which resorption of old or damaged bone takes place on the same surface where osteoblasts lay new bone to replace that which is resorbed. Injury, exercise, and other activities lead to remodeling. Those influences are discussed later in the chapter, but even without injury or exercise, about 5 to 10 percent of the skeleton is remodeled annually just by destroying old bone and renewing it with fresh bone.
Use It or Lose It: Principles of Wolff’s Law
Julius Wolff, a German surgeon and anatomist, articulated Wolff’s law, which describes how bone adapts to the loads it experiences. Bone is living tissue that continually remodels in response to mechanical stress: regular loading reinforces its structure, while lack of use leads to weakening. This principle explains how activity, rehabilitation, and mechanical loading shape skeletal health and recovery.
Wolff’s law refers to the reshaping of bone to meet functional demands. Mechanotransduction is the cellular process by which bone cells detect mechanical forces and convert them into biochemical signals that direct remodeling. It proceeds through four main stages:
- Mechanocoupling: Movement or exercise slightly deforms bone and drives fluid through its microscopic channels; bone cells sense these changes and are activated.
- Biochemical coupling: Mechanical cues trigger intracellular signaling pathways via specialized proteins.
- Signal transmission: Activated cells communicate with neighbors through gap junctions and by releasing factors such as IGF and prostaglandins.
- Effector response: Depending on the magnitude, rate, and frequency of loading, cells promote bone formation or limit resorption. Repeated, cyclic loading tends to strengthen bone.
In physiotherapy, this principle guides both rehabilitation and prevention. Appropriately dosed weight‑bearing and resistance exercises provide controlled mechanical stress that stimulates remodeling and increases bone strength. Clinicians apply progressive loading programs for patients recovering from fractures or at risk of osteoporosis, carefully balancing protection with sufficient mechanical stimulus to rebuild bone and reduce future injury risk.
Nutrition provides the substrates and cofactors for this remodeling
Adequate calcium and vitamin D are foundational for mineralization, while protein supports collagen matrix synthesis. Magnesium, phosphorus, vitamin K, and overall energy availability further influence bone quality and turnover. Insufficient intake—or chronic low energy availability—impairs formation and increases injury risk.
Hormones orchestrate these processes
Estrogen and testosterone favor bone formation and suppress resorption; their decline (e.g., menopause or hypothalamic amenorrhea) accelerates bone loss. Parathyroid hormone and active vitamin D regulate calcium balance; thyroid hormone, growth hormone/IGF-1, insulin, and cortisol also affect remodeling rates and bone mass. The interplay is life-stage dependent: growth demands high nutrient supply and activity to build peak bone mass, while aging requires strategies to preserve it.
Together, appropriate exercise, sound nutrition, and balanced endocrine function act synergistically to optimize bone strength and reduce risks such as stress fractures and osteoporosis.
Diseases of the...
Skeletal System
Osteogenesis imperfecta (OI) is a genetic disease in which bones do not form properly and therefore are fragile and break easily. It is also called brittle bone disease. The disease is present from birth and affects a person throughout life.
The genetic mutation that causes OI affects the body’s production of collagen, one of the critical components of bone matrix. The severity of the disease can range from mild to severe. Those with the most severe forms of the disease sustain many more fractures than those with a mild form. Frequent and multiple fractures typically lead to bone deformities and short stature. Bowing of the long bones and curvature of the spine are also common in people afflicted with OI. Curvature of the spine makes breathing difficult because the lungs are compressed.
Because collagen is such an important structural protein in many parts of the body, people with OI may also experience fragile skin, weak muscles, loose joints, easy bruising, frequent nosebleeds, brittle teeth, blue sclera, and hearing loss. There is no known cure for OI. Treatment focuses on helping the person retain as much independence as possible while minimizing fractures and maximizing mobility. Toward that end, safe exercises, like swimming, in which the body is less likely to experience collisions or compressive forces, are recommended. Braces to support legs, ankles, knees, and wrists are used as needed. Canes, walkers, or wheelchairs can also help compensate for weaknesses.
When bones do break, casts, splints, or wraps are used. In some cases, metal rods may be surgically implanted into the long bones of the arms and legs. Research is currently being conducted on using Bisphosphonates to treat OI. Smoking and being overweight are especially risky in people with OI, since smoking is known to weaken bones, and extra body weight puts additional stress on the bones.
6.4: Bone Formation and Development is shared under a CC BY 4.0 license and was authored, remixed, and/or curated by LibreTexts.
The book could not be loaded just now.