Remember that commercial where the graceful but aging woman is talking about how she got shorter? And that if you had the same problem you should 'talk to your doctor'? What she wants you to tell your doctor is that you want a prescription for Fosamax, the bisphosphonate medication for osteoporosis. Now we've got Sally Fields yacking at us about Boniva, another med in the category. Thank God for Tivo so we can fast forward past these over medicated talking heads.
But what about my bone mineral density (BMD) test, you protest? What if I have hidden osteoporosis and my leg snaps off while I am pirouhetting across the skating rink? Well have no fear, my dears, your limbs won't snap off as soon as you think. You see the most disabling of fractures occurs in the elderly, in the hipbone, specifically the femoral neck, which is associated with considerable loss of mobility. More commonly, fractures occur in the vertebral body (bones in your spine), which usually are not associated with pain; they may cause a bowing of the back, and shortness. Bone density, or how thick your bones are, is currently tested using a bone mineral density test (BMD). Normal values for these tests are based on how far off the patient's results are from those of the average healthy young woman, using something called t scores. I believe the logic of this measure is deeply flawed -- to judge older women by applying standards for young women doesn't make any sense. That's like having a 70 year old run a 100 yard dash against a 20 year old, and then if he loses, saying that the older man has a disease. Bone density normally declines with age, and therefore there is no reason to think that this is necessarily a cause for concern.
For example, if you are a woman who gets BMD testing and follows the WHO criteria, there is a 50% chance you will be diagnosed with osteoporosis at the age of 72 (t score less than -2.5), and a good chance your doctor will recommend medication treatment. Your risk of having osteopenia (t score less than -1.0), for which your doctor may recommend medication to "prevent" osteoporosis, is 50% by age 52. In other words, according to the guidelines, half of postmenopausal women should be taking medication for osteoporosis. However, recommendations for so many women to take bone medications don't make any sense.
Osteoporosis is commonly treated with bisphosphonates like Fosamax, Boniva, Actonel and Zometa. Bone turnover is regulated by cells called osteoblasts and osteoclasts. While the osteoblasts are building up bone in one area, the osteoclasts are breaking down bone in another. This leads to a balance in normal bone. What the bisphosphonates drugs do is turn off the osteoclasts, so that bone isn't broken down, thereby slowing the loss of bone density with aging.
Bisphosphonates increase BMD and reduce the risk of vertebral fracture in women with osteoporosis (t score of less than -2.5). But what is the significance of a vertebral fracture? Vertebral fracture is merely defined as a reduction of the height of the vertebra by 20% on radiological tests like MRI. To have a vertebral fracture defined in this way, you don't have to have pain, change in posture, or anything at all that would make you aware of any problem. In fact, much of the time the only person who knows you have a vertebral fracture is your radiologist.
What about fractures that matter? Most of the studies, including the the Alendronate Phase III Osteoporosis Treatment Study, the Fracture Intervention Trial (FIT), The FOSamax International Trial (FOSIT), and the Vertebral Efficacy with Risedronate Therapy (VERT) study collectively performed in thousands of women with osteoporosis based on BMD, did not show a reduction in hip fractures, the kind of fracture most clearly associated with lasting disability. In terms of fractures in other parts of the body, referred to collectively as nonvertebral fractures (in places like the clavicle or the wrist) the findings are more mixed, with differing findings depending on whether there is a prior history of fractures and other factors. In general, the studies have not shown impressive results for women with osteoporosis but no history of fracture, while the results are more positive for women with a history of fracture.
The Hip Intervention Program (HIP) Study assessed the effects of three years of risedronate or placebo in 9331 women over age 70 with dramatic losses of bone mineral density (t score less than -4), with -2.5 being regular osteoporosis) or t score less than -3 with a risk factor for hip fracture, like propensity to fall. Overall 2.8% of women on risedronate suffered hip fracture versus 3.9% on placebo, a difference of 1.1% that although statistically significant was not very impressive. In the only study of men to date, bisphosphonates did not prevent painful vertebral fractures or nonvertebral fractures, including fractures of the hip.
And what about treatment beyond three years? The implication of the educational campaigns about osteoporosis is that this is a disease for which you need to be treated for the rest of your life. But is there evidence of added benefit of long-term treatment, or perhaps harm? The studies I reviewed above showed that after five years there is little evidence of benefit. In other words after five years they seem to stop working. How could this be?
Again, bisphosphonates act by inhibiting osteoclasts, the cells that act to break down bone. So although they increase BMD for a few years, in the long run they decrease bone turnover. Animals treated with bisphosphonates have a decrease in bone turnover. Women on alendronate were found to take up to two years to heal after a fracture, and had markedly suppressed bone formation on biopsy. In the long run bisphosphonates may decrease the ability of bones to resist fracture, making bones more brittle. They also are not metabolized, meaning that they bisphosphonates you are taking now will be in your bones for life, resulting in a long term reduction in bone turnover.
This decrease in bone turnover underlies the scariest potential side effect of bisphosphonates: osteonecrosis. Osteonecrosis is a degeneration of the bone in the jaw that may require surgery. Osteonecrosis was seen in "Fossy Jaw" or "Phossy Jaw", which developed in workers in 19th Century match making factories exposed to phosphorus. The phosphorus would get into the bone of the jaw, much like the bisphosphonates do, and stop bone turnover, leading to death of the bone tissue. The outcome was so painful and disfiguring that it sometimes led people to kill themselves.
Although most of the cases of osteonecrosis of the jaw have been reported in patients with bone metastases or myeloma treated with intravenous bisphosphonates, there are now emerging cases in patients who took the medication only for the prevention of osteoporosis. More commonly women complain of bone pain with these drugs. They can also cause arrhythmias, erosive esophagitis, and ulcers.
Maybe the "Fossy Jaw" should refer to Fosamax, and not Phosphorus!
Are there alternatives to prescription medications for the prevention of osteoporosis? Yes, there are. Physical activity and exercise play a dramatic role in prevention of fractures. Studies have shown that the simple act of aging is ten times more important in terms of fracture risk than bone mineral density. People who get hip fractures are those who become frail and inactive, through lack of physical exercise, and are more likely to fall. In fact, osteoporotic fractures of the hip are inversely related to exercise. Furthermore, although bone thinning contributes to the risk of fracture, it is primarily related to a loss of balance and falling, which is also maintained by exercise in old age. In fact, there is no difference in bone density between those with and without fractures.
The best exercise for increasing bone-mass is strength training. Numerous studies demonstrate that engaging in regular resistance exercises increase bone mass, most especially spinal bone mass. A research study by Ontario's McMaster University found that a yearlong strength-training program increased the spinal bone mass of postmenopausal women by nine percent. And it found that women who do not participate in strength training lose bone density.
Weight lifting, even with as little as 2, 5, or 10 pound weights to start, dancing, stair-climbing, walking on an incline (uphill), and brisk walking are all weight-bearing exercises, which promote mechanical stress in the skeletal system, can contribute to the placement of calcium in bones.
How does this work? When you are doing weight bearing exercise, you are exerting force on parts of your bones. The body reacts to this by stimulating osteoblasts, those cells that are responsible for laying down calcium in the bone and building up the bones. The body is in effect responding to the message that more bone strength is needed, much as it does when it increases muscle mass and tone with exercise. And the good news is that it builds up bone strength in a better way than bisphosphonates. Rather than randomly laying down calcium in parts of the bone that may not greatly enhance the strength of the bone, like bisphosphonates do, exercise results in a laying down of calcium in parts of the bone that matter. And what is more, the effects don't wear off after five years.
Doug Bremner MD is author of Before You Take That Pill: Why the Drug Industry May Be Bad For Your Health
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