Osteoporosis: an emerging epidemic

Pierre D Delmas
MD PhD
President
International Osteoporosis Foundation
W: www.iofbonehealth.org

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.(1) 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.(2) 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).(3)

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.(4) 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.(5) 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 low percentages of bone loss with high precision, and is a fast, painless and noninvasive 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 50–100%.

Despite DXA being the gold standard for osteoporosis diagnosis, DXA provision is patchy within many European countries. 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 being developed under the auspices of WHO, supported by the International Osteoporosis Foundation (IOF) and the US National Osteoporosis Foundation (NOF), and publication of the associated Technical Report is anticipated in 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.(6)

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 the age of 50 years, low 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 one-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, 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). Less frequent dosing may be promising in terms of adherence and persistence to treatment.(7) Currently the only marketed SERM is raloxifene, which is indicated for the prevention of vertebral fractures in postmenopausal women. Raloxifene has been shown to significantly decrease the risk of invasive breast cancer in postmenopausal women.(8) However, other SERMs are ­currently in late-stage clinical development (lasofoxifene, bazedoxifene and arzoxifene) and are expected to demonstrate antifracture efficacy at the hip level, whilst retaining the extraskeletal benefits (such as in the breast) that are obtained with raloxifene.

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 mineral density plus prevalent fractures).(9) 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. This drug has beneficial effects both on vertebral and nonvertebral fractures.(10,11) 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 κB 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.(12)

International Osteoporosis Foundation
Founded in 1998, the IOF is a global, not-for-profit, nongovernmental organisation dedicated to the worldwide fight against osteoporosis. The structure of IOF is somewhat unique, comprising three committees:

• A committee of scientific advisors (currently 78 members).
• A committee of national societies (currently 175 members in 86 countries, patient, medical and ­research societies).
• A committee of corporate advisors (currently 36 members from different sectors, including pharmaceuticals, diagnostics, banking, advertising, food and packaging).

The IOF’s mission 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 such as the biannual IOF World Congress on Osteoporosis, and running training courses for ­physicians and other healthcare professionals. In addition, IOF has developed educational resources ­specifically tailored to the needs of radiologists and orthopaedic surgeons, as they are often the first health professionals to diagnose or treat a fragility fracture. 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 new IOF website, www.iofbonehealth.org, has recently been launched and is a user-friendly tool providing information on the latest developments on osteoporosis and policy actions at national and international levels. IOF membership grows at approximately 20% annually, and it is anticipated that this growth will continue as the organisation provides a focal point for a disease that has increasingly important public health implications.

References

1. World Health Organisation. Assessment of fracture risk and its implication to screening for postmenopausal osteoporosis. Technical report series 843. Geneva: WHO,1994.
2. Blanchard F. EC Report CE-09-97-915-EN-C. Building strong bones and preventing fractures – action for prevention. Brussels: European ­Communities; 1998.
3. Johnell O, et al. Osteoporos Int 2006;17:1726-33.
4. Cooper C, et al. J Bone Miner Res 1992;7:221-7.
5. Lindsay R, et al. JAMA 2001;285:320-3.
6. Kanis JA, et al. Osteoporos Int 2005;16:581-9.
7. Reginster JY, et al. Bone 2006;38:S2-6.
8. Barrett-Connor E, et al. N Engl J Med 2006;355:125-37
9. Neer RM, et al. N Engl J Med 2001;344:1434-41.
10. Meunier PJ, et al. N Engl J Med 2004;350:459-68.
11. Reginster JY, et al. J Clin Endocrinol Metab 2005;90:2816-22.
12. McClung MR, et al. N Engl J Med 2006;354-821-31.