Tuesday, November 24, 2009

This post is for my friend H—here’s to healthy bones and calcium levels!

I always thought of bones as dense and unchanging. As with many things I’ve been learning about in my Anatomy & Physiology course (and in Biochemistry), the human body is constantly changing and adapting…right down to specific tissues and types of cellular reactions, the body knows exactly what needs to be done in any given situation. As you’ll see in this post, hormones, calcium levels, diet, and other factors all come together to influence bone health.

What are bones made of? Bone has organic and inorganic components:
  • The organic portion decays after death and constitutes 1/3 of the bone weight, consisting mostly of protein fibers that provide flexibility
  • The inorganic portion is 2/3 of the bone weight, composed of mineral salts, called the bone matrix. This inorganic portion is 85% hydroxyapatite (the primary way that calcium and phosphorus are stored in bone). This is the part of the bone that remains after death, and it provides strength and storage of minerals while you’re alive.

The living cells of bone are osteogenic cells (osteo means “bone” and genic means “genesis,” which means to make or create). Perhaps now you can infer where the term “osteoporosis” comes from? Osteoblasts make bone matrix; osteoclasts break down bone matrix.

What function do bones have (besides the obvious)?
Bones provide attachment for muscles that produce movement, and provide protection for delicate structures (e.g., brain, lungs), but bones also do the following:

  • Act as storage repositories for mineral salts such as calcium and phosphorus
  • Produce all formed elements in blood by red bone marrow (hemopoiesis)
  • Assist in acid/base balance by controlling release of minerals from storage
  • Detoxify: If you have been exposed to environmental toxins, the bones are one place to look for their storage. For example, your bones could store heavy metals until they can be slowly excreted by the kidneys

Most importantly, your bones are a storage repository for minerals that are constantly being exchanged between bones, muscles, and blood, depending on the needs of your body. Calcium is stored in the bone until needed (constantly replaced and removed through the action of osteoblasts and osteoclasts). Calcium is needed for proper function of the following:

  • Blood clotting
  • Nervous system function
  • Cardiac function
  • Skeletal muscle function
  • Smooth muscle function (found in your digestive tract, reproductive system—smooth muscle can contract, such as during digestion or labor)
  • Cofactor for many enzymes (enzymes facilitate numerous biochemical reactions in your cells)
  • Second messenger in many hormone systems (e.g., epinephrine).
  • Proper tendon and ligament health

What types of stressors do bones respond to?
Some of the osteogenic cells can sense strain on bone, adding or subtracting bone matrix, thus changing bone density and remodeling bone.

  • Gravitational stress: Weight gain/loss, pregnancy, fluid gain/loss, eating more/less, all influence bone density. Weightlessness in outer space caused osteoporosis in the early astronauts
  • Functional stress: Use of muscles (not to an extreme) causes increase in osteoblast activity. Increases bone mass as muscle mass and strength increase. Overtraining reduces bone mass
  • Research shows that as little as 15 minutes of exercise changes calcium levels in the blood of the lower leg

What factors influence bone health? Diet affects bone health. Vitamins A, C, and D are essential for bone health. For instance, Vitamin A and D in milk and Vitamin C in fruit and fruit juices. Specifically, what does Vitamin D do?

  • Increases absorption of calcium, phosphorus, and magnesium from your small intestine into the bloodstream, controlling the availability of these for matrix formation
  • Controls whether calcium and phosphate are deposited in bone or released from bone
  • Causes less calcium to be lost from the body in the urine—so influences kidney function

Hormones Affect Bone Health. The following are a few of more than 20 hormones known to affect bone health.

Calcitonin Affects Bone Health. Calcitonin is made by the thyroid gland. Calcitonin is released into the blood from the thyroid gland if calcium is too high in the blood. This causes a decrease in blood calcium, by causing calcium to be stored into the bone matrix. (Remember, osteoblasts generate bone matrix, while osteoclasts break down bone matrix). Calcitonin increases osteoblast activity and decreases osteoclast activity. Calcitonin is important in growing children and also in adults, in response to specific physical and/or mental stressors. For example, during pregnancy and lactation.

Parathyroid Hormone (PTH) Affects Bone Health:

  • Made by the parathyroid glands, which are part of the thyroid gland
  • Released into the bloodstream if blood calcium is too low, causing blood calcium to increase (increases osteoclast activity, which breaks down matrix to release calcium into blood Decreases osteoblast activity, which prevents calcium from being removed from the blood in order to build matrix)
  • Inhibits calcium excretion in urine, to keep calcium in the body and not be lost in urine
  • Promotes phosphate excretion in urine, which inhibits matrix formation

Hypersecretion (overproduction) of PTH weakens bones, similar to osteoporosis caused by menopause. In addition, this can cause metastatic calcification (e.g., kidney stones).

Growth Hormone Affects Bone Health. Made by the anterior pituitary gland, growth hormone is not a steroid, but is often confused by the public with testosterone, which is a steroid. You may have heard of growth hormone used in cows—bovine growth hormone. Growth hormone levels usually fluctuate on a daily basis but can increase dramatically with physical or mental stress. At normal levels, with small daily fluctuations, growth hormone is important for the following:

  • Important during childhood for proper growth in height, proper development of the skeleton
  • Stimulates cartilage proliferation in the epiphyseal plates (growth plates in bone)
  • Increases absorption from small intestine of nutrients important for bone health and growth
  • Stimulates osteoblasts (matrix formation in bone)
  • Even in adults, growth hormone is still important to bone health and metabolism…not just for growth in height

People experiencing extraordinary physical and mental stressors may experience hypersecretion (overproduction) of growth hormone, also known as the General Adaptation Syndrome, or stress response. This has been seen among prisoners of war, such as Vietnam, or in the Nazi death camps of World War II. This stress response includes other hormonal changes, such as increased Cortisol, Epinephrine, Norepinephrine, and Aldosterone. The result is a form of osteoporosis and derangements in metabolism.

In general, hypersecretion of growth hormone in children or adults results in osteoporosis—brittle bones/fractures. This can be caused by stress (physical or mental), tumors, or other causes. (High levels of growth hormone have a paradoxical effect on the body—producing the opposite effect of what happens at normal levels of growth hormone).

Sex Hormones (Testosterone or Estrogen) Affect Bone Health. Sex hormones produce a growth spurt at puberty. At menopause, estrogen levels decrease for women….osteoblasts become less active, so less bone matrix is made, so in some women there is not enough estrogen to maintain bone health. Treatments include calcium supplements, less caffeine and less alcohol, and possibly estrogen supplements. Men typically do not experience a drop in testosterone, and therefore would not experience osteoporosis as the result of changes in their levels of sex hormones.

Cortisol Affects Bone Health. Cortisol is made by the adrenal cortex of the adrenal glands. It fluctuates throughout the day, but can become quite elevated under unusual physical and mental stressors. Normal cortisol levels are important to carbohydrate, lipid, and protein metabolism, and bone health (increases osteoblast activity and decreases osteoclast activity). For post-menopausal osteoporosis, mild exercise and a happy situation would increase cortisol levels slightly, contributing to bone health. At vastly increased levels, cortisol has a paradoxical effect, negatively affecting bone health, similar to growth hormone. Cortisol levels can increase with too much athletic training, trauma, or surgery.

Thyroid Hormones and Thyroid Stimulating Hormone Affect Bone Health. Thyroid hormones (triiodothyronine T3 and tetraiodothyronine, also called thyroxine T4) are made by the follicular cells of the thyroid gland, both of which contain iodine. (This is the main reason for iodized salt, to supply iodine to the thyroid gland to manufacture the hormones). Thyroid Stimulating Hormone (TSH) is made by the anterior pituitary gland. TSH travels to the thyroid gland, where it increases production of thyroid hormones. Without TSH, you can’t stimulate the thyroid to create thyroid hormones.

Hypersecretion of these hormones causes a form of osteoporosis…too much calcium lost from the body in urine. You need proper levels of TSH to get normal levels of T3 and T4 and need proper levels of all three for normal bone growth and maintenance.

Sunday, November 1, 2009

Finally, some justice for Rosalind Franklin?

In an earlier post, I criticized my Biochemistry textbook for its failure to mention Rosalind Franklin as a key player in the discovery of the DNA double helix. My A&P textbook is Anatomy & Physiology: The Unity of Form and Function, by Saladin, Fifth edition, Copyright 2010. Maybe it is a sign of the times. I am including their section on Franklin below, as it is the first time I’ve seen a science textbook give credit where credit is due:

Discovery of the Double Helix

Credit for determining the double-helical structure of DNA has gone mainly to James Watson and Francis Crick. The events surrounding their discovery form one of the most dramatic stories of modern science—the subject of many books and at least one movie. When Watson and Crick came to share a laboratory at Cambridge University in 1951, both had barely begun their careers. Watson, age 23, had just completed his Ph.D. in the United States, and Crick, 11 years older, was a doctoral candidate in England. Yet the two were about to become the most famous molecular biologists of the twentieth century, and the discovery that won them such acclaim came without a single laboratory experiment of their own.

Others were fervently at work on DNA, including Rosalind Franklin and Maurice Wilkins at King’s College in London. Using a technique called X-ray diffraction, Franklin had determined that DNA had a repetitious helical structure with sugar and phosphate on the outside of the helix. Without her permission, Wilkins showed one of Franklin’s best X-ray photographs to Watson. Watson said, “The instant I saw the picture my mouth fell open and my pulse began to race.” It provided a flash of insight that allowed the Watson and Crick team to beat Franklin to the goal. They were quickly able to piece together a scale model from cardboard and sheet metal that fully accounted for the known geometry of DNA. They rushed a paper into print in 1953 describing the double helix, barely mentioning the importance of Franklin’s 2 years of painstaking X-ray diffraction work in unlocking the mystery of life’s most important molecule. Franklin published her findings in a separate paper back to back with theirs.

For this discovery, Watson, Crick, and Wilkins shared the Nobel Prize for Physiology or Medicine in 1962. Nobel Prizes are awarded only to the living, and in the final irony of her career, Rosalind Franklin had died in 1958, at the age of 37, of a cancer possibly induced by the X-rays that were her window on DNA architecture.

Also included are pictures of Rosalind Franklin, one of her X-ray photographs, and Watson and Crick with their model of the double helix.