Bone Development

Stages of Bone Development

Although bone initially forms during fetal development, it undergoes secondary ossification after birth and is remodeled throughout life.

Learning Objectives

Describe the process and purpose of bone remodeling

Key Takeaways

Key Points

  • The formation of bone during the fetal stage of development occurs by two processes: intramembranous ossification and endochondral ossification.
  • Secondary ossification occurs after birth and forms the epiphyses of long bones and the extremities of irregular and flat bones.
  • After initial bone development, bones are remodeled throughout life to regulate calcium homeostasis and repair micro-damaged bones (from everyday stress ), as well as to shape the skeleton during growth.

Key Terms

  • diaphysis: The central shaft of any long bone.
  • epiphyses: The rounded ends of a long bone at its joint with adjacent bone(s).

Examples

When a tooth is lost and not replaced, bone remodeling will fill in much of the socket. Although the remodeling will be obvious within a few weeks (especially when smiling), the process will continue for some months.

Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support and protect the various organs of the body, produce red and white blood cells, and store minerals. Bone tissue is a type of dense connective tissue that appears static, but is actually constantly remodeled throughout the life of the vertebrate organism. This occurs with the synchronized action of osteoclasts and osteoblasts, cells that reabsorb and deposit bone, respectively. Bone remodeling also occurs in response to trauma, such as following an accidental fracture or placement of dental implants.

Initial Bone Formation

The formation of bone during the fetal stage of development occurs by two processes: intramembranous ossification and endochondral ossification.

Intramembranous Ossification

Intramembranous ossification mainly occurs during the formation of the flat bones of the skull, as well as the mandible, maxilla, and clavicles. The bone is formed from connective tissue such as mesenchyme tissue rather than from cartilage. The steps in intramembranous ossification are:

  • Development of ossification center
  • Calcification
  • Formation of trabeculae
  • Development of periosteum

Endochondral Ossification

Endochondral ossification begins with points in the cartilage called “primary ossification centers.” They mostly appear during fetal development, though a few short bones begin their primary ossification after birth. These cartilage poitns are responsible for the formation of the diaphyses of long bones, short bones, and certain parts of irregular bones.

Secondary ossification occurs after birth and forms the epiphyses of long bones and the extremities of irregular and flat bones. The diaphysis and both epiphyses of a long bone are separated by a growing zone of cartilage (the epiphyseal plate). When the child reaches skeletal maturity (18 to 25 years of age), all cartilage is replaced by bone, fusing the diaphysis and both epiphyses together (epiphyseal closure).

Remodeling

Remodeling or bone turnover is the process of resorption followed by replacement of bone with little change in shape, and occurs throughout a person’s life, long beyond the initial development of bone. Osteoblasts and osteoclasts, coupled together via paracrine cell signalling, are referred to as a bone remodeling unit. Approximately 10% of the skeletal mass of an adult is remodeled each year.

The bone remodeling period consists of the duration of the resorption, the osteoclastic reversal (the phase marked by shifting of resorption processes into formative processes), and the formation periods of bone growth and development. The bone remodeling period refers to the average total duration of a single cycle of bone remodeling at any point on a bone surface.

The purpose of remodeling is to regulate calcium homeostasis and repair micro-damage from everyday stress, as well as to shape the skeleton during growth. Repeated stress, such as weight-bearing exercise or bone healing, results in the bone thickening at the points of maximum stress (Wolff’s law).

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Osteoclasts and Osteoblasts: Bone tissue is removed by osteoclasts, and then new bone tissue is formed by osteoblasts. Both processes utilize cytokine (TGF-β, IGF) signalling.

Exercise and Bone Tissue

Bones adapt to the muscle force loads placed on them, becoming thicker and stronger under stress and use and weaker and thinner when unused.

Learning Objectives

Distinguish among the responses of bone to activity and hormones

Key Takeaways

Key Points

  • Bone mass is lost if unused because it is metabolically costly to maintain it.
  • Gender differences in sex hormones contribute to larger, stronger bones in men since testosterone stimulates muscle mass, which increases bone density.
  • As a result of declines in estrogen, aging women suffer from decreased responsiveness to exercise and therefore have difficulty maintaining skeletal strength.
  • To maintain skeletal strength, older women need to increase their exercise levels by walking more.

Key Terms

  • Wolff’s law: Bone in a healthy person or animal will adapt to the loads under which it is placed.
  • skeletal strength: Determined by the relationship of trabecular bone to cortical bone.
  • muscle forces: The result of increased muscle mass, producing increases in bone dimension and strength.

Examples

Although we often think of the elderly as feeble and weak, regular exercise can fight osteoporosis and maintain strength and flexibility. This is demonstrated by Johanna Quaas, an 86-year-old gymnast who can still perform an amazing routine on the parallel bars.

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NASA Shuttle Astronaut: Astronauts who spend a long time in space will often return to earth with weaker bones, since gravity hasn’t been exerting a load. Their bodies have reabsorbed much of the mineral that was previously in their bones.

According to Wolff’s law, bone in a healthy person or animal will adapt to the load under which it is placed. If loading on a particular bone increases, the bone will remodel itself to provide the strength needed for resistance. The internal architecture of the trabeculae undergoes adaptive changes, followed by secondary changes to the external cortical portion of the bone, perhaps becoming thicker as a result. The opposite is true as well. If the load on a bone decreases, the bone will become weaker due to turnover. It is less metabolically costly to maintain and there is no stimulus for continued remodeling required to maintain bone mass.

Muscle force is a strong determinant of bone structure, particularly during growth and development. The gender divergence in the bone-muscle relationship becomes strongly evident during adolescence. In females, growth is characterized by increased estrogen levels and increased mass and strength of bone relative to that of muscle. In men, increases in testosterone fuel large increases in muscle, resulting in muscle force that coincides with substantial growth in bone dimensions and strength.

In adulthood, significant age-related losses are observed for both bone and muscle tissues. A large decrease in estrogen levels in women appears to diminish the skeleton’s responsiveness to exercise more than in men. In contrast, the aging of the muscle-bone axis in men is a function of age-related declines in both hormones. In addition to the well-known age-related changes in the mechanical loading of bone by muscle, newer studies appear to provide evidence of age and gender-related variations in molecular signaling between bone and muscle that are independent of purely mechanical interactions. In summary, gender differences in acquisition and age-related loss in bone and muscle tissues may be important for developing gender-specific strategies for ways to reduce bone loss with exercise.

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Tim Henman performs a backhand volley at the Wimbledon tournament in 2004.: The racquet-holding arm bones of tennis players become much stronger than those of the other arm. Their bodies have strengthened the bones in their racquet-holding arm since they are routinely placed under higher than normal stress.

Simple aerobic exercises like walking, jogging, and running could provide an important role in maintaining and/or increasing bone density in women. Walking is an inexpensive, practical exercise associated with low injury rates and high acceptability among the elderly. For these reasons, walking could be an appropriate approach to prevent osteoporosis and maintain bone mass.

Bone Tissue and the Effects of Aging

As individuals age, bone resorption can outpace bone replacement, which can lead to osteoporosis and fractures.

Learning Objectives

Analyze osteoclastic activity

Key Takeaways

Key Points

  • Bone resorption is the process by which osteoclasts break down bone and release its minerals, resulting in a transfer of calcium from bone to blood.
  • Bone resorption is highly regulated. It can be stimulated or inhibited by signals from other parts of the body depending on the demand for calcium.
  • As people age, the rate of bone resorption far exceeds the rate of bone formation. Thus, bones can weaken, leading to conditions like osteoporosis.
  • Osteoporosis can be prevented with lifestyle changes such as proper nutrition and exercise.
  • The risks of osteoporosis can also be reduced through the prevention of falls. Fall-prevention advice includes exercise to tone deambulatory muscles, proprioception-improvement exercises, and equilibrium therapies.

Key Terms

  • osteon: Any of the central canals and surrounding bony layers found in compact bone.
  • periosteum: A membrane surrounding a bone.

Examples

Joints undergo substantial wear and tear. The longer one lives, the more a joint is used. Gardeners and flooring installers put a lot of stress on their knees. Use of knee pads can relieve some of that stress.

Bone resorption is the process by which osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone to blood.

The Role of Osteoclasts

The osteoclasts are multi-nucleated cells that contain numerous mitochondria and lysosomes. These cells are responsible for the resorption of bone and are generally present on the outer layer of bone, just beneath the periosteum. Attachment of the osteoclast to the osteon begins the process. The osteoclast then induces an infolding of its cell membrane and secretes collagenase and other enzymes important in the resorption process. High levels of calcium, magnesium, phosphate, and collagen products are released into the extracellular fluid as the osteoclasts tunnel into the mineralized bone. Osteoclasts are also prominent in the tissue destruction commonly found in psoriatic arthritis and other rheumatology-related disorders.

Regulation of Bone Tissue

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Osteoclast: Osteoclast, displaying many nuclei within its “foamy” cytoplasm above a bone’s surface.

Bone resorption is highly constructible, stimulated or inhibited by signals from other parts of the body depending on the demand for calcium.

Calcium-sensing membrane receptors in the parathyroid gland monitor calcium levels in the extracellular fluid. Low levels of calcium stimulate the release of parathyroid hormone (PTH) from chief cells of the parathyroid gland. In addition to its effects on the kidney and the intestine, PTH also increases the number and activity of osteoclasts to release calcium from bone, thus stimulating bone resorption. High levels of calcium in the blood, on the other hand, lead to decreased PTH release from the parathyroid gland. This decreases the number and activity of osteoclasts, resulting in less bone resorption.

Aging

As people get older, the rate of resorption tends to exceed the rate of replacement, leading to conditions like osteoporosis. Bone resorption can also be the result of disuse and the lack of stimulus for bone maintenance. For instance, astronauts undergo a certain amount of bone resorption due to the lack of gravity providing the proper stimulus for bone maintenance. In addition, certain medical conditions such as hormone imbalances can cause bone resorption to increase, leading to increased susceptibility to fractures.

Osteoporosis risks can be reduced with lifestyle changes and sometimes medication. Lifestyle change includes diet, exercise, and fall-prevention measures. Medication includes calcium, vitamin D, and bisphosphonates. Fall-prevention advice includes exercise to tone deambulatory muscles, proprioception-improvement exercises, and equilibrium therapies. With its anabolic effect, exercise may simultaneously stop or reverse osteoporosis, a component of frailty syndrome.