There are several aspects of Ankylosing Spondylitis that are only now becoming more widely appreciated in the medical community that have major implications for its treatment. As is so often the case, this has arisen following the application of a new technology, in this case Magnetic Resonance Imaging (MRI). This has enabled us to better understand the conundrum as to why patients with AS have a more fragile skeleton despite the overgrowth of bone that is so typical of this disease. This, in turn, has led to the introduction of additional therapeutic approaches for this disease. Why do patients with AS have a more fragile skeleton? It is of some considerable interest that this was first noted almost a century ago when post-mortem analysis of spines was the only available approach to conducting research in this disease. Several pathologists remarked on the fact that cutting through the bones of patients with AS was like cutting through putty -- the knife met no resistance whatsoever. These observations were largely forgotten and/or ignored until the modern era of advanced radiological imaging techniques and molecular immunology. The introduction of MRI showed several interesting findings that readily helped to show just how different AS was from rheumatoid arthritis (RA). Although AS patients understand that, like RA, this is an inflammatory disease of joints, what is not well appreciated is that the major site of inflammation is in the bone next to the joint. We call this an osteitis, which means inflammation in bone. Very often, MRIs from AS patients show minimal inflammation in the joint but striking inflammation in the bone next to the joint. This is different from RA where inflammation within the joint is the major feature of disease. In addition, what is essentially unique for AS is that this inflammation in bone is also typically seen where ligaments and tendons attach to the bone. A classic example would be the Achilles tendon attachment to the heel bone. In our institution we have seen examples where the entire heel bone is inflamed. These patients often receive cortisone injections around the Achilles tendon with little benefit. This is not surprising since the major source of pain and inflammation is actually within the heel bone. Another example is the shoulder. This is a problem that is not well recognized by medical practitioners and often dismissed as "bursitis" or "tendonitis." These patients also have inflammation within the bone where the shoulder tendons attach to the point of the shoulder. Cortisone injections around the tendon are unlikely to be of benefit for many patients because the major site of inflammation is within the bone. These same features are observed on MRIs in the spines of patients with AS. The major site of inflammation is within the bone of the vertebrae. If this local inflammation in the vertebrae is not checked, it will ultimately cause severe loss of bone mineral, resulting in fragile bones. But there is also a second way in which patients with AS can get fragile bones. We now know that severe inflammation -- wherever it exists -- causes the release of certain chemicals into the blood that activate cells in bone that can literally dissolve bone mineral. These cells are called osteoclasts. They are normally present in bone but are only activated periodically when bone undergoes re-modelling in response to the stresses of various activities, e.g., sports. These cells secrete acid, which dissolves bone very efficiently. It is therefore understandable that the body keeps these cells under tight control -- most effectively by secreting sex hormones, which typically shut these cells down. This is why the menopause is a precarious period for the bones of women. The rapid decrease in sex hormone production results in the activation of osteoclasts -- as if they are emerging from a period of hibernation. Women then become at high risk for osteoporosis. Long-standing inflammation also causes persistent activation of osteoclasts. How does this occur? Inflammation, whether it occurs in the joints, the intestine, the lungs, causes the release of a whole variety of molecules into the blood. Some of these cause an elevation of body temperature. Others cause fatigue. Yet others cause persistent activation of osteoclasts. This is why RA is a major risk factor for osteoporosis and fractures of the spine, even though the inflammation of RA does not occur within the spine other than the neck. Similarly, chronic inflammation of the bowel -- colitis ?? also results in osteoporosis and an increased risk for fractures of the spine and hips. AS patients also release these same molecules into the blood that cause activation of the osteoclasts. So AS patients suffer from a double-whammy when it comes to the development of fragile bones. They have inflammation locally within the bones of the spine but also release molecules into the blood that cause activation of osteoclasts. This is one of the reasons why patients with AS are at much higher risk of developing fractures of the spine. To make matters worse, the AS spine is not that flexible and so is more likely to fracture if subjected to any significant impact. We don't usually advise patients to play football! Is there anything that can be done about this? The answer is -- a great deal. First, patients must make sure that they stay active, not only to preserve strength and flexibility but also to preserve bone mineral. The cells that make bone mineral -- osteoblasts -- love weight-bearing exercise. But they can only make bone effectively if they are supplied with the proper nutrients. This means plenty of calcium, about 1500mg per day. A good rule of thumb is that a good helping of a diary product, e.g., yoghurt, cheese, tall glass of skimmed milk, amounts to 300mg of elemental calcium a day. So does one tablet of extra-strength Tums. Beware of expensive calcium preparations that often fail to deliver on the required amount of elemental calcium. Read the label and make sure you know how much elemental calcium is in the product because this is what really counts and not the total grams of each tablet (which is what is often on the front label). Good nutrition also means 800 units of vitamin D per day. It is surprising how many patients with AS are vitamin D deficient -- about 20% in my practice. North Americans are not great milk drinkers, and if you are amongst them, then over-the-counter supplementation is important. Is there a way of testing whether you are already at increased risk of having a spinal fracture? This is normally done by having a bone density test -- often confused with a bone scan. Bone density testing is widely available in North America, and, in my view, everyone who has had AS for at least 10 years should have this done. If a fracture has already occurred, a bone density test should be done regardless of how long the AS has been present. This is the same approach to the assessment of osteoporosis for women of post-menopausal age. Is such screening currently being done for patients with AS? A recent survey of British rheumatologists showed that only a minority of AS patients had received bone density tests, and it is likely that the figures in North America would not be very different. Osteoporosis in AS patients is clearly not a well-recognized problem and requires more vigorous intervention. Are there any effective pharmaceuticals for this problem? Several agents have now been shown to be effective for the treatment of osteoporosis. These include agents such as fosamax and actonel, which belong to a general class of drugs called bisphosphonates. These are amongst the safest drugs ever developed in the history of pharmacology. They have been shown to be effective in most forms of osteoporosis and to be equally beneficial in men as well as women. Although they have not yet been specifically tested in AS, there is no reason to expect that they would not be equally effective in this condition also. Our group at the University of Alberta has studied another bisphosphonate, pamidronate, in patients with AS. A surprising finding was that some patients also experienced relief of their back pain and stiffness. A remarkable property of these drugs is that they "home-in" to bone, particularly where inflammation is very active, but they are very rapidly eliminated from the body otherwise through excretion in the urine. This means that they can reach high concentrations exactly where this is desirable -- at the site of bone inflammation. At these high concentrations they not only kill the bone-dissolving cells, the osteoclasts, but also inflammatory cells. This might explain why they not only prevent the loss of bone mineral but also relieve symptoms of inflammation. The drawback to pamidronate is that it is given as an intravenous, although we have developed a protocol that requires only a limited pulse of treatment, with many patients experiencing benefit for substantial periods. Occasional patients may experience bodily aches and pains after the first intravenous, particularly if they are vitamin D deficient, that is usually not observed at subsequent treatments. The newer anti-inflammatory therapies for AS, enbrel and remicade, may also prevent loss of bone mineral by shutting down inflammation and putting the osteoclast back into hibernation mode. It is not known if the simple anti-inflammatories, such as celebrex and vioxx, are sufficiently effective to do this.
AS patients have a major opportunity to practice effective health care prevention. Osteoporosis is a readily preventable complication of AS. Most primary care practitioners are unfamiliar with this complication of AS. Sounds like more work for the SAA!
Think I'll just print this out for ALL my doctors to read. So tired of knowing more about my disease than the doctors do.
AS has my body, but NOT me!