Skeletal Development and its Influential Factors

A typical adult human skeleton consists of 206 bones. The skeleton gives support to the body and acts as a reservoir of various minerals. In spite of its solid appearance, the bone constitutes a very dynamic tissue that undergoes a continuous process of formation and resorption. The complex molecular mechanisms regulating bone remodeling are not fully understood, but we know that it involves a crosstalk between two types of cells: bone breakdown and resorption cells called osteoclasts and cells that form bone called osteoblasts. Osteoclasts degrade the mineral matrix in response to a variety of signals, while osteoblasts deposit new matrix at the resorption sites. This delicate balance varies during the body’s development stages: in children and adolescents, the rate of formation of bone mineral predominates over the rate of resorption, while in later life, the resorption predominates. A gradual loss of bone density accompanies the normal aging process and in certain cases, it gives rise to age-related bone diseases such as osteoporosis.

The Process of Building Bones

Many factors affect the rate and extent of bone remodeling, including mechanical stress and hormonal imbalances. Extracellular calcium is one of the main factors regulating this process. Calcium is involved in the recruitment and activation of osteoclasts and their subsequent detachment from bone. The systemic mechanism regulating calcium availability, storage and disposal is regulated by parathyroid hormone (PTH) and vitamin D. The bone remodeling process is also under the influence of other hormones (calcitonin, oestrogens and glucocorticoids), messenger proteins called cytokines and bone matrix-embedded factors.

Normally, the level of calcium in the blood is carefully controlled. By means of a feedback loop, concentrations of extracellular calcium are kept balanced. The parathyroid glands respond to low levels of calcium (hypocalcemia) by secretion of PTH. PTH, in turn, stimulates the liver conversion of vitamin D3 to its active form. PTH and vitamin D3 act on calcium homeostasis by stimulating its retention in the kidney and intestines. Both hormones also increase circulating calcium by promoting the formation of new osteoclast cells which release calcium from the bones. When the blood concentration of calcium reaches a certain level, the negative feedback interrupts the secretion of PTH and the production of active vitamin D3. When the calcium concentration rises too high (hypercalcemia), the process is reversed: calcium excretion is increased and the bone resorption from increased osteoclast activity is slowed down.

Bone development is a never-ending process, initiated during fetal growth and lasting throughout adulthood and old age. And despite the notion that milk is the best thing around for building healthy bones, the story is much more complex than that. In fact, a new study actually found that drinking milk in adolescent years has no impact on fracture rates in adulthood!1 So, if milk isn’t the answer for healthy bones, then what is?

Let’s take a look at the developmental process, the physiological importance of our skeletal system and the many factors that affect the health of our bones.

How Do Bones Grow?

The human body contains 206 adult bones and the development process is quite complex, as one could imagine. We are actually born with a very small amount of “bone” tissue and, instead, a great amount of soft cartilage. As we grow into adulthood, the body must transform this cartilage into bone through a highly regulated system called endochondral ossification.2

On a cellular level, three important cell types have been identified: osteocytes, osteoblasts and osteoclasts (see Key Terms). Now, all of these different cell types are always present and active in the body but, depending on the stage of growth and location of the bone, certain cells are more active than others. By examining their activity, we can divide the bone development process into the two distinct categories of modeling and remodeling.

Bone modeling is implemented during our infant, childhood and adolescent years and it involves elongation and physical increases in the size of our bones.3 This process requires a higher rate of osteoblastic activity at the site of growth plates, where endochondreal ossification actually takes place. Ultimately, modeling is highly regulated by hormones that stimulate the growth of many tissues such as sex hormones (estrogen and testosterone), growth hormone (GH), thyrotropin and insulin-like growth factor 1 (IGF-1).3

Once a bone is fully ossified and formed, it enters the constant state of readjustments called remodeling. Essentially, remodeling consists of a constant replacement of old bone cells with new osteocytes to keep them strong and healthy.3 In this scenario, osteoclastic activity and osteoblastic activity are balanced.

Generally speaking, we want predominantly osteoblastic activity or at least a balanced activity of osteoclasts and osteoblasts. In the cases of osteopenia and osteoporosis, osteoclastic activity predominates, thereby leading to a decreased bone mineral density (BMD) and higher risk of fractures.

What Do Bones Do For Us?

Our bones are involved in much more than simply forming our physical structure. Sure, they give us shape, but they are still an organ system. And any organ interacts with the rest of our body through multiple mechanisms. What follows are some of the skeletal system’s key functions.

Movement: Although our muscles allow us to move, they are only a part of the equation. Bones act as anchor points for muscle attachments. In turn, when muscles contract then they are pulling on bones, allowing for movement.

Mineral Balance: The calcium and phosphorus within our bones actually act as a reservoir for our body to maintain acid-base equilibrium. The ability to keep a balanced acidity level is so important that our bodies will sacrifice bone health to do so. In fact, up to 15% of skeletal calcium can be lost over a decade to buffer a mild metabolic acidosis due to acidic dietary practices!4

Organ Protection: Many people overlook the fact that our bones are designed as a shield and a form of armor for our vital organs such as our brain, lungs and heart. A stronger set of armor makes for a better defense against injury!

Blood Cell Manufacturing: Bone contains bone marrow, a manufacturing facility for red blood cells, white blood cells and platelets. This means that we need our bones to form our immune system and regulate the cells responsible for oxygen and nutrient delivery.5

Hormone Balance: Components of bone have been shown to exhibit a hormonal impact on multiple organ systems. For example, osteocalcin found in the bone tissue is now known to regulate energy expenditure through fat deposition and insulin secretion.3 What is perhaps even more impressive is that osteoblasts have been found to stimulate testosterone production by the testis in males.3

Why Do Our Bones Breakdown?

Poor Diet: First and foremost, building healthy bones involves much more than just getting enough calcium and vitamin D. This is evident by the aforementioned study on milk and fracture risk! Although these nutrients are crucial for bone mineral density, a wide variety of vitamins and minerals are needed to develop optimal bone structure and function.6,7 Bones are at a greater risk of breakdown when any of these are deficient, collectively or in some combination.

By reviewing the various mechanisms that different nutrients play in relation to the skeleton, it is easy to see that they all interact and work synergistically to create healthy bones. On the whole, the dietary emphasis needs to change from calcium sources to whole foods including green leafy vegetables, nuts, seeds, legumes (i.e. beans) and whole grains.6 This combination of foods will specifically provide the aforementioned minerals and vitamins important for your skeletal system. Even green tea, rich in bioflavonoids such as epigallocatechin gallate (ECGC), has shown a positive impact on BMD – so drink up!8

Hormonal Imbalances: Many hormones are involved in regulating bone mineral density, and estrogen is often cited as the prime example. It has long been known that the estrogen deficiency that accompanies menopause is a major contributing factor for osteoporosis. This should be of no surprise when we consider that estrogen receptors are actually found on the surface of osteoclasts, osteoblasts and osteocytes9, and so their activation (or lack of) will dictate how each set of cells behaves. In addition, estrogen deficiency has been shown to increase oxidative stress and have a pro-inflammatory effect in the body.9

Although estrogen is considered the most important sex hormone to influence bone health, the roles of progesterone and testosterone cannot be overlooked. In fact, a study in perimenopasual women suggests that higher progesterone levels might be associated with more bone formation and less bone resorption.10 Treatment with testosterone replacement in middle-aged men has been shown to reduce bone resorption markers and improve BMD in the lumbar spine.11 Clearly, the hormonal component of bone health cannot be undervalued and more work must be done to better understand how all of these sex hormones work together for proper skeletal protection.

Lastly, cortisol (a hormone released from our adrenal organs when under stress) plays a monumental role in bone development. Chronic stress and elevated cortisol leads to an increased rate of bone turnover, impaired absorption of calcium and inhibition of sex hormones!12 What is more concerning is that even if cortisol is within a normal range in women as young as age 19-35, a negative association between cortisol and BMD has been observed.12 Overall, this highlights the importance of regular stress management and stress coping techniques throughout life.

Inadequate Sleep: In our previous issue of Advances (Stress Part II), we detailed the importance of sleep and briefly mentioned its impact on healthy bones. Numerous studies have demonstrated that irregular sleep patterns may have detrimental impacts on bone health. One study in over 600 Chinese women found that shorter sleep duration was associated with decreased total BMD in those over the age of 45.13 Specifically, significant impairments in bone health were seen in those women sleeping less than six hours per night. The corresponding decreased BMD in those with less sleep is most likely due to the resultant elevations in cortisol during the daytime.13 In other words, stress can cause sleep deprivation and sleep deprivation can cause stress. This forms a vicious cycle of elevated cortisol that suppresses bone marrow cell production and triggers osteoclasts.13 Increased inflammation via activation of proinflammatory cells is a compounding problem that develops as a result of sleep deprivation.14 To prevent this destructive process, it’s imperative to get seven to eight hours of sleep per night on a consistent basis!

Lack of Exercise: exercise has long been known to contribute to strong bones by inducing a strain on the tissue. As the bone is stressed, mechanoreceptors and hormones are activated to induce osteoblastic activity (leading to modeling and remodeling). Quite simply, if we challenge our bones on an ongoing basis, they must adapt and grow in order to keep up with the ongoing demand!15 This is why lack of exercise, in adolescence and adulthood, is such a huge risk factor for osteoporosis: no challenge leads to no reward.

However, not all exercise types are equally efficacious for stimulating bone health. Research has found that exercise cannot be static and instead must be dynamic, meaning that the body must be constantly moving.15 In addition, exercise movements must be different than our “normal” patterns of daily living. The stimulation of bone growth has been found to be most substantial with “relatively abnormal changes produced during unusual loading situations”.15 All of this goes to say that exercises like volleyball and basketball are best for maintaining bone mineral density because of their abnormal movement patterns and high impact. Exercises like cycling and swimming are more ideal for cardiorespiratory exercise as opposed to bone health. Building lean muscle mass should be a priority for building strong bones, too. Peak rates of bone mineral density are closely timed with peak rates of muscle mass gain, just as losses in one area tend to correlate with losses in the other.15 High-intensity resistance training involves muscle contractions that pull on the bone surface. This creates another positive stressor and stimulation for growth.15 All in all, it’s important to keep moving and to safely challenge your body within your physical limits.

Key Terms

Osteocyte: a mature bone cell.
Osteoblast: a cell designed to form new bone
Osteoclast: a cell designed to destroy or eat away bone

What You Need to Know

Having healthy bones is essential in order to have good health. The skeletal system is responsible for providing a site for muscle attachment, protecting the organs, acting as a mineral reservoir and for influencing hormone balance. The skeletal development and breakdown process is affected by several lifestyle and nutritional factors. Bones require vitamins and minerals to remain healthy, and are also significantly affected by sleep, hormones and exercise patterns.


Having healthy bones is essential in order to have good health. The skeletal system is responsible for providing a site for muscle attachment, protecting the organs, acting as a mineral reservoir and for influencing hormone balance. The skeletal development and breakdown process is affected by several lifestyle and nutritional factors. Bones require vitamins and minerals to remain healthy, and are also significantly affected by sleep, hormones and exercise patterns.


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