What Is A Bone
The tissue comprising bone has 2 components: a protein matrix or osteoid, which is produced by osteocytes, and the mineral elements that become lodged within it. The mineral elements are calcium and phosphate. There are smaller amounts of bicarbonate, citrate, potassium, sodium and magnesium. Each element is replaced periodically.
The minerals calcium and phosphate forma crystal-like structure, hydroxyapatite, with chemical formula Ca10 (PO4)6(OH)2. Both protein and mineral elements are necessary for bones to have their essential characteristics. We can understand the function of these elements by observing what happens when they are missing.
In osteomalacia, a disease in which bones do not have enough calcium, the bones are soft and bending, not supportive. When the protein elements are removed experimentally from normal bones, they crumble like chalk.
There are a number of subtle balances here, too. Even the metabolic process has a requisite speed. Protein’s life cycle has its own timing, like the tempering of steel. When the process is hurried, problems occur as in an unusual medical condition, osteitis fibrosa cystic, which results in fibrous bones.
Failure of a child’s bones to pick up adequate minerals from the available dietary sources or from the bloodstream results in rickets, bones that bend under the strains of daily life. Adults who are losing boney mineral have osteomalacia, too little calcium per volume of bone. But too much calcium, which results in the condition osteopetrosis is not good either. The marrow cavities where blood cells are make become narrow and are eventually obliterated, leading to anemia that may be fatal.
Too little protein and inadequate mineral content have effects similar to osteoporosis, the chances of fracture increase. But neither condition is the same as osteoporosis, where the proportions of protein and mineral in the bones are well-balanced.
Understanding The Bone Structure
Osteoid and minerals make up the basic substance of bone which consists of 2 distinct parts. The compact part, the cortex or cortical bone, forms a hard shell just below the surface. The spongy part, the cancellois or trabecular bone, lies deeper within.
The strength of each varies along with with proportions of its 2 main components, the protein spicules that make up the matrix and harden it. Both are composed of the same osteoid matrix and hydroxyapatite core, but they are different.
Cortical bone forms a hard outer ring and constitutes a large part of any bone’s strength. While there are variations in the mineral content of cortical bone, it is more or less the same thickness, and has essentially the same form in just about everyone.
Although there are certainly variations in the consistency and strength of cortical bone, by far the greater variations appear to be within the trabecular region, with its variably formed and differently angled inner struts and latticework. Bone density is responsible for only 60% of bone strength and consequent likelihood of fracture. The other 40% appears to be due to the formations of the trabecular bone.
The fracture risk inherent in bone is determined by 2 physical factors which is bone density and bone quality. Bone density is well understood and can be accurately measured. Bone quality is well understood and can be accurately measured. Bone quality is currently still under intense investigation.
Considerations such as mental status, activity level and environmental factors like stairs and rugs in the house, slippery surfaces and occupation are all relevant. However, at this moment, the most reliable test for the risk of fractures is still the DEXA scan for bone mineral density.
Until recently, the only way to assess overall bone quality was to take a biopsy. The high cost of a biopsy and its invasive nature discouraged its use in the general population. But a virtual bone biopsy, a non-invasive tool for bone quality assessment, is already being tested. Micro-MRI studies find striking differences between different individual’s bones, and these differences are almost sure to relate to the bones strength.
How Bones Grow
Bones begin to develop long before an infant leaves the womb, lengthening until approximately age 17, and strengthening until age 25 or 30. Although the length of bones does not change significantly after age 30, their strength declines as hormones change in midlife, that decline tapers off after age 65. While bone loss actually slows down after 65, this inexorable cumulative bone loss irresponsible for most osteoporosis cases.
All bones, be it long or short, round or flat, men’s or women’s are constantly subject to 2 processes: one builds up their mass and strength, and one eats their substance away. Like just about every tissue in the body, and the quiet imperishable quality of life itself, there is an incessant metabolism, a constant flux of the constituents of bone.
There are the osteoblasts which are themselves derived from cartilage-making cells, the chondrocytes. These cells secrete collagen, proteoglycans, and glycoproteins that form a woven organic fabric of proteins, which is the osteoid. The matrix then attracts calcium and phosphates to make up the molecule hydroxyapatite.
Some of the flat bones spring directly from osteoblasts secretions, other bones, the long bones of the arms and legs, first appear in small cartilaginous forms that subsequently ossify. The osteoblasts form a thin lining around the bones until they incorporate themselves into it.
At that point they become osteocytes. They change shape from rectangular to star-shaped, with long thin tendrils that connect to other osteocytes. Ultimately, the first ones in these lines of connected cells linked up to a blood vessel, one of the tiny capillaries for exchange of nutrients and the products of metabolism.
It is believed that a chain of as many as 15 osteocytes can effectively transport substances to and from the one that is farthest from the central canal containing the blood vessel and a nerve. The metamorphoses of osteoblasts, the cells they come from (chondrocytes), and the cells they may become (osteocytes) are all sensitive to a number of hormonal influences including progesterone, estrogen, testosterone, growth hormone, thyroid hormones and parathyroid hormone all play a role.
Osteoclasts are strange and gigantic cells, derived from bone marrow, that can often have more than 50 nuclei. They literally digest bone, sending the proteins and minerals they swallow back into the bloodstream. They are attracted to injured and old sections of bone and to places where the supporting osteocytes have died, leaving a region of bone unattended.
Many factors affect the behavior of osteoclasts. Some are relatively simple. Osteoclasts are inhibited by calcitonin, a hormone secrete by the thyroid gland. Parathryroid hormone, on the other hand, has contradictory effects. This hormone stimulates osteocytes, the osteoclasts competitor, activating them so that they produce more protein and secrete a molecule that arouses the osteoclasts.
7 Medications For Osteoporosis
This is the first modern drug to treat osteoporosis that really took hold of the American medical community. In fact, it is a bisphosphonate, a class of drugs that inhibit the osteoclasts, the cells that reabsorb calcium from bones. In osteopenia and osteoporosis, osteoclasts destroy bone faster than osteocytes lay it down.
There is a study done that indicates Fosamax slows down the destruction and reduced the incidence of hip, vertebral and wrist fractures by 53%, 45% and 31% respectively. A randomized placebo-controlled Canadian study shows that alendronate is as effective in men as it is in women, regardless of the men’s male (or female) hormone levels, or the magnitude of the patient’s bone resorption. In either gender, patients’ BMD usually gain 6% in the first year of use and 2% each year thereafter.
95% of the patients who have participated in clinical trials of this drug show a significant increase in BMD. The risk of any kind of fracture goes down about 50%. The usual dose is 5mg daily for osteopenia, 10mg per day for osteoporosis.
The most common side effects are gastrointestinal. Patients are advised to stay clear of food for at least an hour after taking the medication. Acid reflux, nausea, and irregular bowels, along with muscular, abdominal and bone pain are the main things to worry about and they are not uncommon.
Other side effects such as osteonecrosis (disintegration of the jawbone, auditory canal or other bones) and slower healing of fractures that do not occur have been discussed in the media over the past few years, but are estimated to be quite unusual, related to dental surgery, cancerous conditions and the duration of treatment. In addition, there is eveidence that bisphosphonates stay in the body for long periods of time, possibly throughout life and can cross the placenta.
- Actonel (Risedronate)
A second bisphosphonate, Actonel has many of the same negative side effects as Fosamax, but it is a coated capsule. This lowers the chance of esophageal irritation.
- Boniva (Ibandronate)
More recently, and possibly because of the low compliance seen with the other bisphosphonates, Boniva, a once-a-month oral or injectible drug, has been introduced.
Ibandronate works the same way the other 2 bisphosphonates do, slowing down the resorption of bone by osteoclasts, but is so powerful that patients are strongly advised not to take it. Unless they are also taking calcium and Vitamin D to supply the building blocks for healthy bone, have no kidney problems that would disturb their bodies relatively constant levels of serum calcium, and can remain vertical for at least an hour after taking the medicine to minimize gastrointestinal side effects. Major side effects include abdominal pain, hypertension, joint pain, nausea, upset stomach and diarrhea.
- Reclast (Zoledronic Acid)
Reclast, the ultimate bisphosphonate is given as an annual intravenous infusion. Only 5 mg have proven 50% more effective than Actonel in treating people with osteoporosis acquired through exposure to steroids and over 4 times more effective in building bone mass as a preventive measure. Atrial fibrillation is a major adverse effect.
Regardless of which bisphosphonate one chooses, it is always wise to use calcium and vitamin D supplements as well. These nutritional supplements are used by controls and intervention patients in most of the studies that support the efficacy of these medications.
This is an anti-body that prevents the activator molecule RANKL from stimulating cells to evolve into osteoclasts, therefore reducing bone resorption. Side effects reported were few, and the gastric upset that is commonly associated with oral bisphosphonate use was substantially reduced.
Increase in bone mass was greater with denosumab than with alendronate in a study of 412 patients and bone synthesis was in full swing after only 3 days. Early trials have begun to to find separate cortical and trabecular effects, and also indicate that the drug slows the development of rheumatoid arthritis. A recent radiological study using densitometry and examination of bone structure suggests that denosumab actually improves bone quality.
- Estrogen, Progesterone and Selective Estrogen Receptor Modulators (SERMs)
Hormone replacement therapy after menopause (HRT) is commonly used by women to tame the changes that come with menopause. Many conflicting studies associate HRT with an increased risk of uterine and breast cancer, heart disease and thrombosis, but also with an improvement in bone mineral density.
Birth control medications, premenopausal forms of HRT, keep their users’ bones quite youthful much of the time. A popular compromise solution is for menopausal women to take half the usual HRT dose, either orally or transcutaneously through a skin patch. The patch, enables the body to acquire the estrogen and/ or progesterone without the hormones passing through the liver. Progesterone alone increased the bone mineral density of first year users up to 10% with approximately 4% improvements each year thereafter.
Progesterone medications are frequently combined with estrogens such as estriol, estradiol and estone. Of these, 17 alpha-estriol appears to be the least toxic, actually reducing the progress of breast cancer, and the one of all of the estrogens that has a very low likelihood of re-intiating monthly menstruation.
- Forteo (Teriparatide)
Synthetic parathyroid hormone, teriparatide appears to increase bone mineral density and reduce vertebral and non-vertebral fractures without a substantial risk of raising calcium in the bloodstream to dangerous levels. It does this by tipping the balance in favor of bone build-up and slightly against bone breakdown. Both lower and higher doses of parathyroid hormone appear to favor build-up, but high doses (40mg) were actually found to promote resorption at the forearm.
One study found that injections of 40mg were only slightly more effective than 20mg, but had a greater likelihood of causing nausea and headache, the other chief side effects. Besides vitamin D, parathyroid hormone is the only other known naturally occurring substance that in and of itself will build bone.