Pierre D Delmas
International Osteoporosis Foundation
Osteoporosis was first officially recognised as a disease by the World Health Organization (WHO) in 1994, and has since attracted increasing public and professional concern. Aside from its personal and human cost, osteoporosis is a major public health problem with enormous social and economic impact. Worldwide it is estimated that one in three women and one in five men over the age of 50 years will sustain an osteoporotic fracture. In the EU, someone has a fracture as a result of osteoporosis every 30 seconds, and with an ageing population, the yearly incidence of hip fracture alone in the EU is expected to more than double from approximately 500,000 to 1,000,000 over the next 50 years.(1) Of the estimated nine million osteoporotic fractures that occurred worldwide in the year 2000, 1.6 million were hip fractures, 1.7 million were forearm fractures, and 1.4 million were clinical vertebral fractures; the greatest number of osteoporotic fractures occurred in Europe (34.8% of the total).(2)
Although osteoporosis can be easily diagnosed and treated, studies have shown that it remains seriously underdiagnosed and undertreated. It is estimated that only one out of three vertebral fractures comes to clinical attention.(3) Despite this, it is known that having one spine fracture increases the risk for sustaining additional spine fractures fivefold within the next year, a phenomenon commonly known as the fracture cascade.(4) In Europe, osteoporotic fractures are responsible for a higher disease burden, in terms of disability and excess mortality, than common cancers with the exception of lung cancer.(2)
Advances in diagnosis
The most common diagnostic method is a bone mineral density (BMD) test of the hip or spine using dual energy X-ray absorptiometry (DXA). DXA employs a very low radiation X-ray, which is capable of detecting quite low percentages of bone loss with high precision, and is a fast, painless and non-invasive scan. According to WHO guidelines, a BMD score in a postmenopausal Caucasian woman that is more than 2.5 standard deviations below the average for the young healthy female population implies a diagnosis of osteoporosis. For every standard deviation below the reference BMD, fracture risk increases by 50% to 100%.
Despite DXA being the gold standard for osteoporosis diagnosis, DXA provision within many European countries is patchy. In addition, in the absence of population-screening programmes, DXA-based diagnosis relies on case-finding strategies which results in many high-risk individuals remaining undetected. A new diagnostic paradigm for osteoporosis is currently in development under the auspices of the WHO, supported by the International Osteoporosis Foundation (IOF) and the US’s National Osteoporosis Foundation (NOF), and publication of the associated Technical Report is anticipated in late 2006 or 2007. The new approach employs an algorithm based on clinical risk factors, can be used either alone or in conjunction with DXA, and represents a more accurate way of identifying those at risk of osteoporotic fractures.(5)
The clinical risk factors included in the WHO model have been validated in an analysis of 12 international cohorts (approximately 60,000 men and women) and include age, gender, femoral neck BMD, prior fragility fracture after age 50 years, body mass index, use of glucocorticoids, secondary osteoporosis (eg, associated with rheumatoid arthritis), parental history of hip fracture, current cigarette smoking and alcohol intake of more than two units per day. The algorithm will yield a score that will be an estimate of 10-year absolute fracture risk for an individual.
Current and potential treatments
The management of osteoporosis necessitates appropriate drug treatment, particularly since this chronic disease may affect up to a third of a patient’s life. Several new treatments for osteoporosis have been introduced in the past decade and many more are in the pipeline. The majority of currently available treatments are antiresorptive agents (those that inhibit bone resorption and attenuate bone loss), namely bisphosphonates, selective oestrogen receptor modulators (SERMs), and calcitonin. Bisphosphonates are the most commonly prescribed, and have been demonstrated to reduce fracture risk by up to 50%. Daily and weekly (alendronate and risedronate) and monthly (ibandronate) oral formulations are currently used, and intravenous formulations with reduced dosing frequency are available (ibandronate) or are in late-phase development (zoledronate). Currently the only marketed SERM is raloxifene, which is indicated for the prevention of vertebral fractures in postmenopausal women, although other SERMs are currently in late-stage clinical development (lasofoxifene, bazedoxifene and arzoxifene).
The only available anabolic (bone forming) treatment for osteoporosis is recombinant human parathyroid hormone (PTH). PTH reduces the risk of both vertebral and nonvertebral fractures, and is indicated for the treatment of severe osteoporosis (low bone density plus prevalent fractures). Another newly available treatment in some European countries is strontium ranelate, whose mechanism of action is not fully understood, but appears to involve a dual effect of reduced bone resorption and a maintenance or modest increase of bone formation. One drug in the pipeline, denosumab, has a potentially novel mechanism of action and is a human monoclonal antibody to the receptor activator of nuclear factor kß ligand (RANKL), the primary mediator of osteoclastic differentiation, activation and survival. Given as a subcutaneous injection every three or six months, denosumab decreased bone resorption and increased bone density, and is currently in phase III trials to evaluate fracture efficacy.
Founded in 1998, the IOF is a global, nonprofit, nongovernmental organisation dedicated to the worldwide fight against osteoporosis. The structure of the IOF is somewhat unique, comprising three committees:
- A committee of scientific advisors (currently 76 members).
- A committee of national societies (currently 172 members in 85 countries, patient, medical and research societies).
- A committee of corporate advisors (currently 35 members from different sectors including pharmaceuticals, diagnostics, banking, advertising, food and packaging).
The mission of the IOF is threefold: to support national osteoporosis societies in order to maximise their effectiveness; to increase the awareness and understanding of osteoporosis; and to motivate people to take action to prevent, diagnose and treat osteoporosis.
The IOF supports an ambitious science programme including publication of two scientific journals, Osteoporosis International and Progress in Osteoporosis, organisation of scientific meetings around the world including the biannual IOF World Congress on Osteoporosis, and running training courses for physicians and other healthcare professionals. The IOF also provides direct support to its global members, through a wide range of activities including events such as World Osteoporosis Day (held every 20 October) and a biannual World Wide Conference of Osteoporosis Patient Societies, plus the provision of numerous grants and targeted support. Within its policy and advocacy programme, IOF supports national, European and international policy initiatives to increase access to diagnosis and treatment, publishes the newsletter Osteoporosis Action, and carries out workshops and media events. The IOF membership grows at approximately 20% annually, and it is anticipated that this will continue as the organisation provides a focal point for a disease that has increasingly important public health implications.
- Blanchard F. EC Report CE-09-97-915-EN-C. Building strong bones and preventing fractures – action for prevention. Brussels: European Communities; 1998.
- Johnell O, Kanis J. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006; in press.
- Cooper C, Atkinson EJ, O’Fallon WM, et al. Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985-1989. J Bone Miner Res 1992;7:221-7.
- Lindsay R, Silverman SL, Cooper C, et al. Risk of new vertebral fracture in the year following a fracture. JAMA 2001;285:320-3.
- Kanis JA, Borgstrom F, De Laet C, et al. Assessment of fracture risk. Osteoporos Int 2005;16:581-9.