European Commission carries out research towards preventing the occurrence of osteoporosis
Osteoporosis, which means porous bones, is a disease that thins and weakens bones, making them fragile and more likely to break. The vast majority of individuals affected by osteoporosis are women. Although the disease can strike at any age, the greatest risk for fractures from osteoporosis occurs after menopause. This is because women’s bodies produce less oestrogen after menopause, and oestrogen plays an important role in helping to prevent bone loss. As the EU population continues to age, the occurrence of osteoporosis becomes an increasing source of worry. But the good news is that osteoporosis can be prevented and treated. The European Commission is involved in research studying the impact of diet and gene-nutrient interactions on calcium and bone metabolism, and a novel isotopic tracer method is also being evaluated to study and quantify these processes. This new method will be compared to already-established methods (bone mineral density, biochemical markers) in an effort to protect and improve the quality of life of Europe’s ageing population. Further research on the biomechanical aspects of bone structure and strength, and on the reliability and safety of prosthetic implants is also being carried out at the European Commission’s Joint Research Centre (JRC) to address the area of post-fracture treatment strategies. These projects are funded by the European Commission’s Directorates General for Research, Health and Consumer Protection, and the JRC.
Commissioner Philippe Busquin expresses his own concern: “Fractures are the most frequent and serious complication of osteoporosis. Any bone can be affected, but of special concern are fractures of the hip and spine. A hip fracture almost always requires hospitalisation and major surgery. It can impair a persons ability to walk unassisted and may cause prolonged or permanent disability and reduce the quality of life. Hospital costs for hip fractures alone amounted to over 3,500 million Euro in the EU in 1999. And the problem will only increase, as it has been quoted that the proportion of the EU population aged over 80 will triple over the next 50 years. EU action is therefore essential to tackle this problem.”
Menopause is the single greatest risk for osteoporosis; others include gender, age, family history, hormone deficiencies, low calcium, excessive alcohol and caffeine consumption, and cigarette smoking. In many cases, bones weaken when levels of calcium, phosphorous and other minerals in bones are low. As the prevalence of osteoporosis increases it must be considered as a serious public health concern.
Therefore, new alternative techniques to assess the impact of diet on bone loss are needed to establish recommendations for the prevention of osteoporosis, as well as improving existing methods of treatment after fractures have occurred.
This is why an EU-funded project called OSTEODIET has been established to explore the capabilities of a new isotopic tracer method technique. The European Commission’s Joint Research Centre (Institute for Reference Materials and Measurements) is working with the project partners* to evaluate a novel isotopic tracer method for assessing the impact of diet on bone loss. IRMM has certified a series of 41Ca enriched isotopic reference materials (RMs) to be used, and this new method will be compared to already established methods (bone mineral density, biochemical markers) to evaluate its effectiveness.
Isotopic Tracer Research:
To date, 24 post-menopausal women in the Zurich area have received an oral dose of 41Ca. (A woman is considered postmenopausal when she has not had a menstrual period for more than 12 consecutive months). The 1-year labelling period for the first subjects involved will be completed in August 2002. Urine samples are currently analysed for 41Ca to establish the urinary excretion pattern and to confirm that steady state conditions are reached. When confirmed, the women will participate in a randomised crossover calcium supplementation trial to assess the potential of the technique. Biomarkers and compartmental analysis using stable isotope techniques will be used in parallel for validation purposes, and will allow the evaluation of the power of 41Ca as a novel tool in bone research for establishing recommendations for osteoporosis prevention.
Smart approaches for women of all ages towards this potential health risk include taking preventive steps and understanding and reviewing the risk factors involved in developing osteoporosis. However, the impact of factors such as caffeine consumption and high protein intake, as well as the beneficial effect of taking calcium supplements is still being debated – despite decades of research. This can be attributed, at least partly, to the limitations of the methodologies available to bone researchers. Bone mineral density measurements are still considered the “gold standard” in bone research, as changes in bone health can be measured directly. However, it takes several years to identify small changes induced by dietary or life style factors. Biochemical markers, or ‘biomarkers’ of bone metabolism are more sensitive and small changes in bone accretion and bone resorption can be identified in a couple of months, when based on the concentration of the respective biomarkers in urine or plasma. However, their usefulness is limited, as they are indirect measures of bone metabolism and, as independent measures, they do not allow the assessment of bone balance. This is why alternative techniques such as the isotopic tracer method are needed.
In osteoporosis research, 41Ca, a long-lived radionuclide with a half-life of 105,000 years – virtually non-existent in nature – is a very promising novel approach. Because 41Ca can be detected at highest sensitivity and only minute amounts are required to label bone calcium isotopically, any potential health risks are negligible. After being administered orally, 41Ca that is not incorporated into bone is excreted in urine within one year. Later, 41Ca in urine is released directly from bone. First human experiments suggest that a change in bone Ca turnover can be identified in less than 2 months via changes in urinary 41Ca excretion. This makes it the most powerful technique to monitor changes in bone metabolism to date.
In order to establish urinary 41Ca excretion patterns, ratios of 41Ca relative to natural Ca have to be measured in urine over 8 orders of magnitude down to 10-11 – which compares to the detection of a single grain of salt in 5 tons of sugar. Three of the most powerful mass spectrometric techniques available to date, i. e. Thermal Ionisation Mass Spectrometry (TIMS), Resonance Ionisation Mass Spectrometry (RIMS) and Accelerator Mass Spectrometry (AMS) have to be used in combination for these challenging measurements. The set of reference materials covering 41Ca/40Ca isotope ratios over 9 orders of magnitude, will allow calibration of the techniques against each other and provides the basis for future data comparison. The emergence of new techniques such as the isotopic tracer method will held determine detailed recommendations for the prevention of osteoporosis to protect the health and safety of EU citizens.
Further research at the JRC’s Institute for Health and Consumer Protection involves studies of the biomechanics of bone and bone-implant interfaces at both macroscopic and microscopic scales. This includes studies of the curing of bone cements using advanced optical metrology techniques, and measurements of the actual mechanical properties of basic bone material using the nanoindentation technique. The reliability and safety of prosthetic implants is also being investigated – in particular, clinically relevant testing methods for prosthetic devices (mainly orthopaedic hip implants) are being developed and assessed.
Millions of people in the European Union suffer to some degree from osteoporosis, which may not become evident until a fracture actually occurs. At that point there is no cure, only treatments or diets that may help to reduce further bone loss and prevent further fractures. Therefore, a low-cost, easy-to-use method for osteoporosis diagnosis and bone-quality monitoring would allow high-risk patients to be identified, and appropriate action to be taken to reduce bone fracture probability. The JRC’s multi-faceted research into osteoporosis aims to help achieve such a method.
* ETH Zurich (Switzerland), University of Mainz (Germany), University College Cork (Ireland) and The Danish Veterinary and Food Administration (Denmark)
For further information, please contact:
IRMM, JRC Geel
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