Osteoporosis, the most common bone disease in the U.S., is becoming more prevalent as an increasing number of women are living into their eighties and beyond. Currently there are 44 million Americans with osteoporosis—80% of them are women. Fifty percent of women will be affected by this disease and are at greater risk for a variety of fractures. Over 1.3 million osteoporosis-related fractures occur in the U.S. each year—some are asymptomatic and contribute only to loss of height. Other fractures (of the spinal column) are painful and disfiguring (Dowager’s hump and kyphosis) causing some elderly women to appear stooped over. The distribution of osteoporosis-related fractures is as follows: half of them involve the spinal column (vertebral), a quarter of them involved the hip and the remaining quarter involve a bone in the arm called the radius (Colles’ fracture).
Wrist and hip fractures are both painful and debilitating. Hip fractures, in particular, can be life-threatening, resulting in surgery, hospitalization and prolonged periods of recovery and rehabilitation. Unfortunately, many otherwise healthy women, after sustaining osteoporosis-related hip fractures, succumb to other diseases during the prolonged period of disability that follows. Deep vein thrombosis, pulmonary emboli and pneumonias are often the sequelae that befall women who had previously enjoyed excellent health. Those women who complete their recovery often suffer a loss of mobility and function once complete healing has occurred.
The incidence of fractures increases with age–the risk for white women at age 50 is about 16% (versus 5% for men). Osteoporosis and its precursor, osteopenia, are silent diseases that generally manifest themselves for the first time when someone has sustained a fracture that involved minimal trauma. Fortunately we are able to identify the early forms of osteoporosis on screening tests. Because these bone-thinning diseases can diminish the quantity and quality of life it’s important for every woman to know about this silent disease, how to detect, prevent and treat it.
Osteoporosis and osteopenia can be detected with specialized scans and treated thereby preventing many of painful and debilitating sequelae to this disease.
NORMAL BONE ANATOMY
Bones provide the structural support for muscles and also protect vital organs—heart, lungs, kidneys, spinal cord and pelvic organs. We often think of bones as inanimate or dead tissue because we know that archeologists have unearthed intact skeletons that are hundreds and even thousands of years old. But the truth is that bones are living, constantly changing structures made up of connective tissue (collagen) that provides a soft internal framework and calcium phosphate which provides bones with structural and weight-bearing strength.
There are 2 types of bone tissue: an outer shell called cortical bone and an inner “spongy” core called trabecular bone. These bones are constantly being injured—the result of day to day stresses that cause “micro-fractures”—and repaired. The process of injury and repair is called remodeling. In a normal adult 10-30% of the skeleton is remodeled every year.
The bone “breakdown” is caused by cells called osteoclasts which are formed from certain blood cells and are responsible for the breakdown or resorption of the skeleton. These cells dig holes in the bone and release the small amounts of calcium into the blood stream that are necessary for vital body functions. Other cells known as osteoblasts are produced by specialized bone cells and are the “bone builders”. Their job is to lay down crystals of calcium and phosphates contributing the bone’s strength and supportive structure. The balance of osteoclasts and osteoblasts is controlled by a complex mix of hormones and other chemical factors. Remodeling, which is the result of interplay between these two types of cells, requires calcium, vitamin D, estrogen, testosterone as well as other hormones. The repair process, in addition to requiring calcium and vitamin D, can be also be enhanced by exercise and diet. In young children and adults the rate of building is greater than the rate of resorption—the result is a net increase in bone mass. This process continues until women are in their early 30s and 40s at which point peak bone mass is achieved.
HOW AND WHEN DOES OSTEOPOROSIS START?
Before you reach age 40, bone tissue breaks down and rebuilds in perfect unison. However, as we age this balance becomes out of sync, causing osteoclast cells to breakdown bone at a greater rate than the osteoblast cells can rebuild it. The breakdown of bone overtakes the buildup leading to a decrease in bone mass. Whether due to the onset of age (doctors aren’t particularly sure why this occurs with aging) or the presence of certain conditions this system of remodeling (breakdown and buildup) becomes unbalanced. For some people this process is gradual and for others it’s very quick–nevertheless the breakdown of bone eventually overtakes the buildup. Post-menopausal women see a greater rate of bone loss with a decrease in estrogen which helps the osteoblasts to keep working and form new bone. In some women the bone loss is mild and osteopenia results. In other women the loss of bone mass is so great that they develop osteoporosis. Left untreated bones become so weak that a sudden strain, bump, or fall causes fracture which wouldn’t have happened to a person with “normal” bones.
In both osteopenia and osteoporosis outer cortical bone and inner trabecular bone is lost. The result is a thinner cortex and trabecular bone that contains larger “holes.”
UNDERSTANDING WHAT IT MEANS TO BE “NORMAL” OR “AVERAGE”
Before we can understand osteopenia and osteoporosis we need some basic knowledge of statistics. We first must understand that many human activities and features can be plotted and “averaged”. For instances, we know that the “average” American man is 5’9″ tall, that the average woman in this country is 5’4″ and that Mr. “Average 40-year old white guy” weighs 183 pounds, while his “average” female counterpart weighs about 40 pounds less. We know that the life expectancy of the “average” male born in the year 2000 is about 74 years and is 79 years for the “average” woman. That said, we all know men and women who are very tall or short, very thin or massively obese as well as those that die young and live well into their nineties and beyond.
Even when we go to our doctor’s office and have a simple blood test such as a “blood count” or a serum cholesterol we seek reassurance that we are “normal” and get very concerned about anything that falls outside the “normal range”. We know, intuitively that being on one side of the “normal range”—taller than normal, stronger than normal, wealthier than normal or having a cholesterol lower than normal is (in most cases) good. We also know that having a blood pressure much higher than normal is likely to be harmful.
Many years of scientific work are often required to determine what “normal” means. It’s easy to determine what “normal height” is for men and women and much more complicated to determine what a “normal” cholesterol value is. In fact, laboratories have drastically changed their definitions of “normal” over the past 30 years with respect to serum cholesterol. In the 1950s serum cholesterol under 300 mg/dL was considered “normal”. Now we know that our doctor would like to see it below 200 mg/dL and lower still in men and women with hypertension or smoking. The new “normal” is based on what is harmful to your health and your life expectancy.
Because of the development of safe and inexpensive tests to determine bone density we have a means to measure the density of various bones that tend to break in the elderly –those in the wrist, hip and spinal column. By studying groups of men and women over time we also know that those men and women who are a certain percentile below normal have an increased risk of fractures.
HOW DO WE DEFINE OSTEOPENIA AND OSTEOPOROSIS?
Simply put we can measure a woman’s bone density and then compare it to women of the same ethnic group who are young and healthy. If her bone density is better than average her T-score is on the positive side and there are no problems to worry about as far as bone thinning is concerned.
Since most women being tested are over the age of 50 and they’re being compared to younger women (I know it doesn’t sound fair!) they can expect to have bones that are less dense than “average” and therefore their T-scores will be on the negative side. Having a slightly negative T- score (-0.1 to – 1.0) is of little or not consequence. But having a T-score that is substantially below the average (-1.0 or less) requires a discussion with your health care provider on what your specific health risks are. Having a low T-score doesn’t mean you will require medication but it does mean that it needs to be looked at as part of your overall health to determine what, if any effect it may have on the quality and quantity of your life.
WHAT ARE THE RISK FACTORS THAT I NEED TO KNOW ABOUT?
Despite the prevalence of osteoporosis, not all women are at risk for the disease. In fact, you can gauge your own individual risk by taking a look at yourself, your lifestyle and your family history.
In general, the older you get the greater your risk becomes to developing osteoporosis. Body Composition: Women with slender builds and low body weight are at greater risk because their bone mass is low to begin with and thus deterioration is faster.
You’re at greatest risk of osteoporosis if you’re white (especially those with blonde hair and fair skin) or of Southeast Asian descent. African American and Hispanic women have a lower but still significant risk.
Estrogen exposure also plays a role in protecting you from bone loss. The length of time between your first period (menarche) and last period (menopause) influences your likelihood to osteoporosis. The later you began menstruating or the earlier your menopause occurs the more likely you are to develop thinning of your bone mass. You can also understand why women who undergo early surgical removal of their ovaries (oophorectomy) are at increased risk for osteoporosis. Hysterectomy itself—which is the surgical removal of the uterus—does not predispose to osteoporosis. One of the reasons that physicians often prescribe hormone replacement therapy (HRT) to women who’ve undergo oophorectomies is to prevent osteoporosis.
Osteoporosis runs in families. For that reason, having a parent or sibling with osteoporosis puts you at greater risk, especially if you also have a family history of fractures.
Living a sedentary lifestyle increases your risk of low bone density. Weight bearing activities and general exercise are beneficial to bone density. It’s important to know that bone density can increase at any age. Tobacco and excessive drinking also diminish your bones ability to absorb calcium.
Anorexia and bulimia—left untreated–are often associated with the development of osteopenia/osteoporosis.
Although a wonderful method of contraception, Depo-Provera used over a period of many years also predisposes some women to develop osteoporosis.
Postmenopausal women who have had breast cancer are at increased risk of osteoporosis, especially if they were treated with a group of drugs known as aromatase inhibitors such as anastrozole, letrozole and exemestane, which suppress estrogen. This doesn’t appear to be true of women treated with tamoxifen. Also women who’ve been exposed to long course of methotrexate (used for various cancers as well as rheumatoid arthritis) are at increased risk for osteoporosis.
There are many medications that adversely affect bone health. Some of there are:
Corticosteroids:(prednisone, cortisone, prednisolone, dexamethasone). Many of these medications are used to treat asthma, psoriasis, and rheumatoid arthritis.
Coumadin: often used to treat thrombophlebitis or prevent pulmonary emboli
Heparin another “blood thinner” whose long-term use may cause loss of bone structure
Cyclosporine: an anti-rejection drug used after organ transplants
Vitamin A: high level of this vitamin have been associated with osteoporosis
Thiazide Diuretics Furosemide: (Lasix), hydrochlorthiazide are some of the commonly used ones
Methotrexate: sometimes used to treat osteosarcoma or acute lymphoblastic leukemia
Antiepilectic: medications such as phenobarbital, phentoin and carbamazepine interfere with vitamin D activity and are associated with bone loss.
Crohn’s Disease and Ulcerative Colitis
WHEN SHOULD A WOMAN BE SCREENED FOR OSTEOPOROSIS?
Expert groups now recommend bone density screening for the following people:
- All women over age 65.
- Any postmenopausal women under 65 years with one or more risk factors for osteoporosis (e.g., being thin, being a smoker, having a family history of fractures, using corticosteroids for longer than three months, or any serious high-risk condition, such as hyperthyroidism or malabsorption).
- Any older woman who suffers a fracture. Unfortunately, studies suggest that only a minority of these patients are evaluated and treated for osteoporosis.
WHAT IS A DEXA SCAN?
DEXA stands for Dual energy X-ray absorptiometry. This procedure is quick, simple and gives accurate results in two to four minute It measures the density of bones or BMD (bone mass density) in your spine, hip and wrist — the areas most likely to be affected by osteoporosis — and it’s used to accurately follow changes in these bones over time. DEXA measures bone density by detecting the extent to which bones absorb photons that are generated by very low-level X-rays. (Photons are atomic particles with no charge.) Lower density bones at are greater risk for developing fractures. This, along with a patient’s medical history, is a useful aid in evaluating the probability of a fracture and whether any preventative treatment is needed.
WHAT ARE THE RISKS OF A LOW T-SCORE RESULT ON DEXA SCAN?
- A T-score of 0 to -1.0 indicates normal BMD. (This carries a lifetime chance for a hip fracture of up to about 20%, depending on age and other risk factors.)
- A T-score of -1.0 to -2.5 defines osteopenia, which is low bone density. This carries between a 20% and 50% lifetime risk for fracture.
- A T-score less than 2.5 (osteoporosis) carries a 60% chance for hip fracture. Additional risk factors increase the risk. They include low weight, smoking, and an increased risk for falling and history of previous fractures. For example, in women 65 years old with low bone density but no adverse factors, the risk for fracture is 4.3% in one year and 28.6% over five years. In similar women with a previous fracture, the probability of fracture at one year is 11% and at five years is 71.8%.
SHOULD EVERYONE WITH OSTEOPENIA OR OSTEOPOROSIS BE TREATED?
It’s not necessary for everyone to be treated. If you are a healthy post menopausal women with a T-score below the norm (osteopenia) this doesn’t mean that you should automatically take medications to prevent osteoporosis. In fact, your chance of breaking your hip in the next five years would be 1%, and 20% in your lifetime–perhaps not worth the risk of certain side effects of the drugs. Calcium and exercise are always a good measure but unless a fracture is looming or already occurring such as seen in women in their 60’s, medication may not be necessary in younger women.
WHAT ARE THE TREATMENTS FOR OSTEOPOROSIS?
Hormone replacement treatment (HRT)
There are many good reasons for hormone replacement therapy. The subject has been confused by poor scientific studies, hysterical journalists, television reporters who sensationalize the news and even Suzanne Sommers. The issue of whether or not you should take HRT is an individual one that you should carefully discussion with your health care provider. But among several clear benefits of HRT is the alleviation of hot flashes unmatched by any other herb or medication and improvement in bone growth. More importantly the improvement of bone growth is directly related to the prevention of hip fractures.
In the Women’s Health Initiative (WHI) Study, the combined use of estrogen-progestin replacement therapy was associated with a significant reduction in the number of hip fractures as depicted in the chart below.
Every woman should take a minimum of 1200 mg per day of Calcium beginning at age 35. Calcium alone will not prevent bone loss but it is an essential part of the ingredients for bone health. There’s even some evidence that calcium intake helps to decrease the risk of heart disease.
Vitamin D should be taken along with calcium in a dose of 800 Units per day beginning at age 35.Women who have a malabsorption syndrome or take certain anti-seizure medication may need higher doses of vitamin D.
The importance of exercise cannot be overstated. A prospective study in JAMA (November 2002) by Feskanich and Colditz that included 61,000 postmenopausal women found that those that walked 4 hours or more a week had a 41% lower risk of hip fracture than those who walked less than an hour a week.
Smoking one pack per day throughout adult life decreases bone density by 5-10%!
There are many encouraging developments along the lines of medications that can prevent and treat osteoporosis and its precursor, osteopenia.
The available medications can be divided into two groups: (1) anabolic agents that stimulate bone formation (increasing the activity of the osteoblast) and, (2) anti-resorptive agents or those that decrease bone resorption (decreasing the activity of the osteoclast).
The vast majority of today’s pharmaceuticals focus on the latter—decreasing bone resorption.
The medications that work by this mechanism of action are called anti-resorptive. They include:
- SERMS (selective estrogen receptor modulators)
The other class of medication is one that increases bone formation by increasing osteoblast activity. The only pharmaceutical in this class is
parathyroid hormone (PTH).
BISPHOSPHONATES (these drugs prevent bone resorption by osteoclasts). Although most women who take these medications take an oral form of the drug these agents are poorly absorbed orally and need to be taken on an empty stomach. In some women the combination of estrogen and a bisphosphate is appropriate.
- Fosamax (alendronate) — 5 mg every day for prophylaxis; 10 mg per day for treatment of osteoporosis or 70 mg once a week
- Actonel (risedronate) — 5 mg once a day for treatment or prophylaxis or 35 mg once a week
- Boniva (ibandronate) — 150 mg once a month
Boniva (ibandronate) –3 mg every three months, appears to improve BMD to a similar or greater degree than the oral equivalent daily oral ibandronate (2.5 mg/day) and provides an alternative option for patients who cannot tolerate oral bisphosphates.
Despite manageable side-effects, most women stop taking their medication after a year because the symptoms of osteoporosis are unnoticeable and therefore the benefits are not clearly recognized. However, many of these medications work over a period of time and do what they’re meant to—prevent bone loss and fractures. No one should discontinue treatment if their medication is preserving bone density and there are no severe side effects. It should be noted that some women taking these agents actually lose bone density during the first year. Of interest in this regard was a 2000 study reporting that the women who lost the most bone during the first year of treatment experienced the greatest gains during subsequent years. Researchers recommend continuing treatment after the first year, even if a bone mass density (BMD) test is unpromising.
Side effects of oral agents
Bisphosphonates are poorly absorbed orally (less than one percent of the dose), and must be taken on an empty stomach for maximal absorption. About 5-10% of women do experience heartburn or some other gastric disturbance. Other less common side effects include muscular pain, joint pain, blurring of vision and a rare condition called ONJ (osteonecrosis of the jaw). Most ONJ complications have been in women undergoing cancer therapies. There is concern, however, in women undergoing invasive dental procedures such as extractions or implants. Many physicians and dentists suggest stopping bisphosphonates for 1-2 months before and after the procedure. One can also expect women treated with bisphosphates to have a slight drop in serum calcium levels. This, however, does not appear to be significant.
In order to maximize absorption and minimize the esophageal and gastric side effects
- don’t take this medication if you have an upper GI disease such as esophageal reflux, peptic ulcer or esophagitis.
- Stop the medication if you develop heartburn and consult your provider.
- Take the medication on an empty stomach, first thing in the morning with at least 8 ounces of water while sitting or standing. After taking
Monitoring the response
You will be asked to obtain serial bone mineral density scans (DEXA) to be certain that the medication is having the desired effect.
Estrogen itself prevents bone resorption and therefore favors bone growth. The appropriateness of estrogen alone or in combination with another agent such as a bisphosphonates is a discussion you should have based on your individual needs and comfort level.
Calcitonin is a small protein composed of 32 amino acids that binds to the osteoclasts and prevents bone resorption. In general, most studies suggest that calcitonin is less effective than the bisphosphonates for preventing fractures.
SERMS (SELECTIVE ESTROGEN RECEPTOR MODULATORS)
There are many women that cannot and should not take estrogen. However, there is a group of medications that has estrogenic effects on bone without estrogen’s effect on the breast, uterus and blood vessels and other estrogen sensitive organs. These are selective estrogen compounds. In particular, these compounds are designed to have estrogen-like activity on the bone without the other undesirable estrogenic activity—including estrogen’s possible adverse effect on cholesterol.
The commonly used medication in this class is Evista (Raloxifene). Raloxifene works by inhibiting bone resorption (similar to estrogen’s effect on bone). Interestingly it’s in a class similar to Tamoxifen (used to treat breast cancer). Like Tamoxifen, Raloxifene appears to protect against breast cancer.
The second group of medications are anabolic agents—ones that increase the activity of the bone- building (osteoblast) cells.
PTH (PARATHYROID HORMONE)
This medication actually causes bone formation and stimulates the osteoblast precursor cell (pre-osteoblast) to mature. It is this cell that is responsible for new bone formation. If you require this medication we will refer you to an appropriate specialist.
SUMMARY AND CONCLUSIONS
Osteoporosis is a significant disease in women—particularly women of small stature, light skin with a history of smoking and certain medication use. It is a silent disease often manifesting itself for the first time with a fracture brought on by a relatively minor event. Women should undergo routine screening at age 65 though some women, particularly those with small, thin frames, a family history of osteoporosis and other risk factors should be screened earlier. There are many forms of prevention and treatment that women need to be aware of. Clearly this is a disease that requires more than taking supplemental calcium and is best managed by prevention