WHAT'S NEW AT THE IOF WORLD CONGRESS ON OSTEOPOROSIS?
NEW RESEARCH PROVIDES DATA ON THE BURDEN OF THE DISEASE, MALE OSTEOPOROSIS, LIFE STYLE FACTORS, WHY DOCTORS DON'T DIAGNOSE, MONITORING TREATMENT WITH A BLOOD TEST, AND NUMEROUS NEW TREATMENTS.
What new advances in our understanding of osteoporosis will be presented at the IOF World Congress of Osteoporosis in May 2002?
This summary of news that will emerge from Lisbon has been prepared by Professor Ego Seeman, a member of IOF's board, editor of Progress in Osteoporosis and contributing editor to Osteoporosis Action.
For the complete Lisbon program please see the Congress website: www.osteofound.org/wco/2002
The complete book of abstracts will be available on arrival as part of the registration package.
Oral presentations are identified as O, posters as P.
The Silent Epidemic
Osteoporosis is a disease in which the bone structure has been eroded so that the mass of bone is reduced and the architecture is disrupted, predisposing to fragility or a susceptibility to fracture with minimal trauma, particularly of the spine, hip, wrist, pelvis and upper arm. Osteoporosis and associated fractures are an important cause of mortality and morbidity.
In many affected people, bone loss, which occurs in women and men of all races, is gradual and without symptoms or warning signs until the disease is advanced. Osteoporosis is a global problem which is increasing in significance as the population of the world both grows and ages. For these reasons, osteoporosis is often referred to as the "silent epidemic".
Basic bone biology: bone loss and structural degradation of the skeleton
The loss of bone occurs throughout life and becomes more severe after menopause in women when lack of estrogen, the female hormone, results in an increase in bone remodeling or renewal on the inner surface. We do not understand why bone remodeling occurs so intensely after estrogen withdrawal after menopause but when this is prevented from occurring fine structural arrangement of bone and its mass are maintained.
After menopause, osteoclasts erode the honeycomb structure of trabecular bone. As a result the spine loses its flexibility, its ability to act as a shock absorber or spring moving in its elastic range. With the erosion of the trabecular network, loading, even daily walking, can result in the loss of flexibility in the vertebrae of the spine and may produce microfractures. In the long bones, which are weight-bearing pillars, the cortical shell is placed around the perimeter with a marrow cavity between to confer bending rigidity so necessary in ambulant persons. As we age the cortical shell becomes porous and liable to fracture as the mass of bone is compromised. The result: these structures can no longer support the loads and may crack.
The bone thinning process during ageing can be likened to a block of ice that disappears particularly rapidly in the last stages of melting. Bones become more fragile, more quickly during old age. One in every two women, and one in every four men will sustain an osteoporotic fracture in their lifetime. Spine fractures result in increased risk of death, physical deformity, dependence and severe pain. One fracture occurs every seven minutes and the burden of fractures is increasing because more and more persons are living into old age.
Fractures kill, cause pain, disability, loss of independence, loss of self-esteem and drain the health care budget
Virtually all aspects of the problem of fractures and bone fragility are to be discussed at the Congress. The importance of vertebral fractures is underestimated. Vertebral fractures cost €329 million annually in direct costs alone; this is just 25% less than hip fractures which are much more frequently reported. Patients with vertebral fractures have a lower quality of life than patients with hip fractures (P222, P290). Many spine fractures result in severe pain that produces long-term disability, curvature of the spine, and respiratory problems because of the collapse of the vertebral column.
Hip fractures have a profound impact on quality of life. Twenty percent of patients with hip fractures die within the first six months of fracture, and are likely to be unable to live at home, and require nursing homes or assistance from family members of health professionals (P232), and many require assistance in daily activities. It costs twice as much to treat a hip fracture patient (€6000 per patient) than it does to treat obstructive lung disease or myocardial infarction, and a hip fracture is three times more costly to treat than alcoholic liver disease.
Doctors, patients, governments don't know
Despite the devastating impact on quality of life and costs to health care systems throughout the world, doctors, patients and governments do not recognize how serious osteoporosis is (P295). To put this lack of knowledge in context, it would be totally unacceptable if a doctor failed to treat high blood pressure and the patient then had a stroke. Similarly, if a doctor failed to lower cholesterol in a patient who later suffered a myocardial infarction, this would be regarded as negligence. Yet doctors are not diagnosing patients at risk of osteoporosis, nor are they treating patients who have already fractured a bone, despite the fact that easy diagnostic techniques exist and any fracture is a predictor of future fractures (P213, P257).
The reasons doctors do not diagnose osteoporosis partly relate to the mistaken belief that brittle bones reflect a 'natural' ageing process and that nothing can be done.
We now have safe and effective ways of measuring bone density using densitometry, ultrasound and quantitative computed tomography, techniques that identify women and men at greatest risk for fracture due to low bone density. The loss of bone during ageing can be prevented. The thinning of trabeculae, which form the naturally spongy honeycomb network of bone, can be stopped, the porosity of the cortical shell of the long bones can be reduced. Most important, bone density can be increased and now newer agents are becoming available that can rebuild the decayed structure of bone. Drug therapy is cost effective (O35, P264), yet doctors are not investigating or treating women or men with fractures (O16, O22, P104, P259, P271, P272, P290, P293, P294, P295, P306, P309). This situation is unacceptable and efforts are being made to increase the awareness that this disease is preventable and treatable.
Men suffer from osteoporosis as well as women and estrogen deficiency is an important cause of bone thinning in men
Fractures are a serious problem in men as well as women (O6, O8, O26, P136, P291, P306, P341, P334, P358, P411, P466, P469). One third of hip fractures occur in men. By the year 2025 the numbers of hip fractures in men will be equal to that seen in women now, and the burden on health care systems will be compounded by the increasing numbers of hip fractures in women. The numbers of hip fractures is increasing because more and more women and men are living into old age. In addition, it appears that the age-specific risk of hip fractures is increasing as well. In other words, more elderly men and women suffer hip fractures today than the same number a generation ago. The reason for this is uncertain. Perhaps young people today produce a weaker skeleton than their elders because of changes in diet, environment and life styles. Perhaps elderly people lose more bone as they age.
Although spine and hip fractures are less common in men, men suffer greater disability, morbidity and mortality than women for reasons that are incompletely understood. One possible explanation: men have more illnesses than women in general because men are more reluctant than women to seek medical care. (P233, P254). The prevalence of spine fractures is similar in men and women (P210) about 15-25% after the age of 50.
Tobacco use, excess alcohol and male hormone (testosterone) deficiency contribute to the risk of osteoporosis in men but new data suggests that estrogen deficiency is important in men as well as women, and may be more important than testosterone deficiency as a cause of bone loss. Should we treat men with estrogen? The answer to this is not known but new estrogen drugs with specific benefits for the skeleton without feminizing effects may be an option in men. Testosterone regulates bone size in males and may be important in making the bone wider in men (O1, O8). Smoking interferes with production of estrogen and increases the degradation of estrogens and produces bone fragility in men as well as women (O6).
Osteoporosis begins before birth and develops during growth as well as during ageing
Bone fragility in old age has its origins in youth, if not during intrauterine growth (O2, O4, O5, O7). We know that the basic plan of the skeleton is hidden in the genetic code and passed down from generation to generation. Abnormalities in structure or variation in size and density probably originate in the genes but are modifiable through environmental factors acting throughout life. Maternal leptin levels may affect bone mass in the fetus, while vitamin D deficiency, protein malnutrition, and sex hormone deficiency in growth influence peak skeletal size and density. Exercise is probably most important during the early years of growth at which time the skeleton is extremely responsive to loading and will grow larger and denser as a result. It is possible that children's current passive life styles, with hours spent in front of computers and TV, causes lower peak skeletal development, which then sets up the situation for bone fragility in old age.
Similarly, adults face numerous life style factors that contribute to low bone density lack of exercise, little calcium (because of the fear that dairy products contain cholesterol and fat), insufficient protein, tobacco use in younger adults, and avoidance of sunlight in a skin cancer-fearing world. (O18, O34, P71, P229, P236, P239, P241, P269, P296, P308, P319, P326, P345, P332, P400, P439, P442). As well, geography plays a role (O14).
Monitoring progress and the effects of treatment can be done with a simple blood test
Just as we need ways of identifying persons at risk for osteoporosis and fractures we need tools that are easy to use and that can monitor who may be at risk for fracture, who may be taking treatment properly, and whether the patient is responding to treatment. New evidence suggests that measurement of circulating biochemical markers of remodeling predicts bone loss, fracture risk and response to drug therapy (P73, P95, P122, P140, P160, P165, P180, P185, P187, P221). A blood sample or urine sample in the doctor's office can be used to help the doctor determine whether the patient is at risk for osteoporosis, whether the patient is complying with treatment and whether the patient is responding to treatment. These tests, not yet in common use, are important in monitoring treatment and may encourage patients to comply with treatment.
The cure is not too far away
Perhaps the most exciting data to be presented at this meeting concerns a wealth of evidence supporting the efficacy and safety of new therapies for prevention of bone loss, and restoration of bone mass, structure and strength using bone building agents such as intermittent subcutaneous injection of parathyroid hormone (PTH) and oral strontium ranelate (O39, P62, P66, P67, P70, P72, P370).
PTH is a hormone which in large doses causes bone thinning but in low intermittent doses is 'anabolic' or bone building. For reasons that are still not understood, low dose administration stimulates the bone forming cells to make new bone so that the bone mass increases. The drug rebuilds the skeleton by increasing cortical and trabecular thickness and perhaps even trabecular connectivity the connectedness of the honeycomb structure needed for the spine bones, the vertebra, to act as sponges or springs to be shock absorbers. Strontium ranelate, a new orally active drug, has been reported to increase bone formation and reduces bone resorption. The effects on fractures will be reported at this meeting but the data remain confidential at this time.
The new antiresorptive drug ibandronate reduces spine and non-spine fractures (O36, O37, P42). Residronate maintains trabecular architecture (P49), reduces spine and non-spine fractures within 12 months (P46), and halves intertrochanteric hip fracture risk in people over 80 years old (not just in 70-79 year old women as believed) (P41, P44, P45, P54, P69, P97, P114, P137) . Alendronate reduces spine fracture risk in women with osteopenia as well as osteoporosis, and increases bone density in women and men with primary and secondary osteoporosis (P50, P60, P64, P75, P83, P84, P92, P96, P103, P108, P123, P130). Raloxifene is likely to have benefits outside the skeleton such as reducing the risk of breast cancer and ischemic cardiac events and may protect the skeleton in men as well as women (P48, P63, P67). Newer drugs such as minodronate (P111), a bisphosphonate, and bazedoxifene acetate (P113), a third generation selective estrogen receptor modulator, expand the therapeutic alternatives in the field.
The ease, safety and efficacy of new regimens like once weekly alendronate and residronate, three monthly ibandronate, neridronate or pamidronate (O40, P91), and once yearly zolendronate reduce the inconvenience, adverse events and improve compliance compared to current treatments. (O37, O38, O40). There are many other advances, including confirmatory work regarding antifracture efficacy of vitamin D and calcium (P68, P120 P134, P142, P175), alendronate in women and men with primary and secondary osteoporosis, the combination of monofluorophosphate and raloxifene ( P127, P48, P166), and reanalyses of the calcitonin PROOF study (P138).
The epidemic proportions of osteoporotic fractures will continue as people live longer, particularly in densely populated Asian countries. Will osteoporosis become a major 21st century epidemic? The osteoporosis epidemic parallels that seen in the 19th century with infections and in the 20th century with ischemic heart disease, diabetes, tobacco use and other diseases. The concerted efforts of scientists and governments throughout the world are needed to reduce the burden of fractures that ruin the lives of millions of people and will drain health care resources.