Stephen Paget, MD: What is osteoporosis?
Robert Lindsay, MD: Osteoporosis is a disease in which there is insufficient bone in the skeleton to withstand the stresses that you might put on it every day. As a result, bones are likely to break or fracture. The most common are vertebral fractures in the back (which can cause serious pain and a hump-backed appearance), and hip fractures (which can cause serious disability).
Stephen Paget, MD: Is there anyone not at risk for osteoporosis?
Robert Lindsay, MD: Eventually, we would all get osteoporosis -- if we lived long enough. But two groups of people are most at risk in younger years: women after the menopause, particularly Caucasian or Asian women; and people who take glucocorticoids or steroid therapy, such as prednisone.
Stephen Paget, MD: What is the best way to measure whether someone has -- or is at risk for -- osteoporosis?
Robert Lindsay, MD: Bone densitometry allows us to measure the skeleton with high degree of accuracy and precision. There are many different types available. The work-horse is a dual energy x-ray absorptiometry (DEXA), which measures bone primarily in the spine and in the hip. These are the two most important sites in terms of osteoporosis-related fractures. But many other bone densitometry tests can measure the risks of any fracture.
Stephen Paget, MD: Does having a fracture -- particularly a "fragility" fracture (that occurs with minimal trauma) mean you are at greater risk of problems?
We have learned about this in clinical trials in which some people get a bone-strengthening drug and others get a placebo -- an inactive pill. In the placebo-treated groups people who have new fractures are at high risk of future fractures, especially during the year following the fracture. For example, we found that about 20% of the people who have a vertebral fracture are likely to fracture again in the next year. We also know from the same clinical trials that when you give people a bone-strengthening drug, you get a treatment benefit in all groups. However, because of the increased risk that is associated with a prior fracture, even when there is a treatment benefit, you can't reduce the risks back to baseline. Thus, the critical issue for both physicians and patients is to establish who is at risk for this disease. If you and your doctor believe you are at risk, get a measurement of bone density to determine the real risks of fracture. If the bone densitometry identifies a problem, then treatment is important to try to prevent fractures.
Stephen Paget, MD: Are there effective therapies today to prevent osteoporosis?
Robert Lindsay, MD: Yes. Our ability to diagnose, measure, and treat osteoporosis has really progressed in the last 10 years. There are now a variety of different medicines that help the skeleton. They can be broadly divided into two groups: First are the agents that have multiple effects in the body -- hormone replacement therapy (HRT) and tissue selective estrogens (also known as selective estrogen receptor modulators or SERMs). Second are agents that specifically affect the skeleton -- bisphosphonates and calcitonin. So we have a variety of effective choices.
Stephen Paget, MD: How do the patient and the physician select the best agent for the individual?
Robert Lindsay, MD: The nice thing is that they all work. That is a good starting point. Hormone replacement therapy is most commonly given to women with menopausal symptoms; it is clearly the treatment of choice for such women because they also get the added benefit of osteoporosis prevention. In the older individual who has osteoporosis, the physician is more likely to recommend an agent that specifically affects the skeleton, and the bisphosphonates become particularly important. There is an "in the middle group" of postmenopausal women between the ages of 55 and 65 who don't have symptoms and who have family members or peers who have developed breast cancer. They are more likely to seek out agents such as the SERMs because they seem to reduce the clinical appearance of breast cancer as well as prevent bone loss.
Stephen Paget, MD: How do you choose between the bisphosphonates?
Robert Lindsay, MD: The differences between the bisphosphonates are relatively modest compared to their effectiveness. Both of the bisphosphonates now available -- alendronate (brand named Fosamax) and risedronate (Actonel ) - are clearly very effective. Bisphosphonates are the most important drug for people who have significant osteoporosis. The choice perhaps depends on the patent's medical profile. For people with a history of upper gastrointestinal disease, you might be more likely to choose risedronate. But with bisphosphonates, you have to conform to a somewhat awkward regimen: arising early in the morning, taking the pill on an empty stomach, then staying in an upright position and waiting a half hour until breakfast. For people who would have difficulty conforming to that regimen, you might chose a drug you only need to take given once a week, such as alendronate. So there are clear choices between the bisphosphonates based on the person's medical history and lifestyle.
Stephen Paget, MD: Do you ever use combinations of these agents?
Robert Lindsay, MD: Rarely, because there is no evidence showing that combinations give a greater effect on decreasing fractures than each individual agent by itself. However, I sometimes get pushed into combination therapy when a patient gets a fracture while on the initial therapy. Why does that happen? Probably because, while these agents reduce the risk of fracture, they do not eliminate fracture completely. But to patients, if a fracture occurs while they are on treatment, then they think that drug has failed. Thus, often they say, "I had a fracture so the treatment is not working. What are you going to do?" In those situations, I sometimes will say that we can either change the therapy or add a second treatment to see if we get a better effect.
Stephen Paget, MD: Are there new and even more effective therapies on the horizon?
Robert Lindsay, MD: Yes. Current drugs simply help slow or stop bone loss. The exciting thing for the future is that we are beginning to see the development of agents that actually build new bone. We have been involved for a number of years in research on parathyroid hormone for osteoporosis treatment. Parathyroid hormone stimulates bone formation. Parathyroid hormone may not be the ideal drug for osteoporosis because it currently has to be given by daily injection. But parathyroid hormone tells us is that here is an agent that will: build new bone, change bone mass to a greater degree than any other agent that we have; and correct underlying architectural problems seen in osteoporosis. That may point a way in the future for a cure.
Stephen Paget, MD: As always in medicine, the benefit depends upon a good relationship and partnership between patient and physician, doesn't it?
Robert Lindsay, MD: Absolutely. It's particularly difficult for people to take these medicines long-term when they don't have any symptoms -- because we are trying to prevent the crisis of fractures. It's the same as for other chronic diseases that don't have any obvious symptoms until there's a crisis, such as hypertension and high cholesterol levels. That's why patients need a good understanding of what the disease is and the importance of sticking with the treatment. So it's the responsibility of the physician to educate patients and listen to their concerns. Once that relationship is established, then we have medicines that can significantly affect not only individual patients but also the growing major public health problem of osteoporosis.
From an interview with Dr. Robert Lindsay by Dr. Stephen A. Paget