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Although bone initially forms during fetal development, it undergoes secondary ossification after birth and is remodeled throughout life.
![]() Stages of Bone Development
Aug 24, 2017 Is it true that astronauts in space lose on average 1% of their bone mass a month? This question was originally answered on Quora by Robert Frost.
Learning Objectives
Describe the process and purpose of bone remodeling
Key TakeawaysKey Points
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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:
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).
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 TakeawaysKey Points
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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.
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.
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.
Key TakeawaysKey Points
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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
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.
Microgravity weakens muscles in several ways, which were explored in a 2003 study by the University of Udine in Italy. After about 240 days in space, astronauts' total strength drops to about 70 percent of their starting strength.
Human muscles have two types of muscle fibers, which are affected slightly differently, though both weaken. The slow-twitch fibers weaken at about the same rate as total strength.
However, fast-twitch muscle fibers atrophy even more quickly, and after about six months have about 45 percent of their starting strength. This leaves astronauts' muscles greatly weakened. Curiously, muscle loss seems to happen most radically in the upper body, while bone loss tends to cause the most serious effects in the lower body. Microgravity causes osteopenia, the loss of bone density, a condition related to osteoporosis. In fact, accord to Dr. Jay Shapiro, the team leader for bone studies at the National Space Biomedical Research Institute, 'the magnitude of this (problem) has led NASA to consider bone loss an inherent risk of extended space flights.'
A major component in this problem stems from activity at the cellular level. Under normal conditions, a set of cells called osteoclasts break bone apart while another type of bone cell, osteoblasts create new bone at the same time. However, osteoblasts respond to stress, building up bone where the body pushes on it.
In space, bones feel very little stress, since gravity is not pulling on bones and weakened muscles put less stress on bones. This causes the process of tearing down old bone and building new bone to fall out of synch, resulting in weakened bones. But other factors appear to contribute to the issue as well.
For example, the body tends to produce malformed collagen fibers in microgravity, which contributes to declining bone health. At the clinical level, these changes to the bone and muscle cause many problems for astronauts. The bone loss is most pronounced in the lower half of the body, where a astronauts may lose 1 to 2 percent of their bone mass per month, though it seems to level off at around 20 percent bone loss in the longest spaceflights. The weakening of bone and muscle ultimately resemble the effects of prolonged periods of bed rest.
Astronauts need time to re-adapt their muscles to Earth's gravity. On top of this, calcium builds up in the blood as bones lose mass. This promotes kidney stones in astronauts. Countering Health Problems. NASA has several methods at its disposal to combat these conditions. First, exercise in space helps lessen bone loss and muscle weakness.
Adding 'explosive' type exercises with sudden movements may further increase the benefit of exercise in staving off the worst effects of microgravity. Similarly, exercising in a centrifuge can further reduce the long-term effects of microgravity and help strengthen the muscles of the heart. Additionally, changes to astronauts' diet has shown promise in decreasing the effects of microgravity on bone and muscle.
Lastly, NASA has begun to experiment with using medications to combat bone loss. Specifically, NASA has begun issuing astronauts bisphosphonate, a medication used to treat and prevent osteoporosis on Earth. Scientists hope that understanding microgravity bone loss may translate into better treatment for people on earth with bone disorders like osteoporosis.
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