John A. Goldman, MD, FACP, FACR, CCD
Bone mineral density (BMD) is used to diagnose osteoporosis and estimate fracture risk, but there are a number of clinical factors that provide information for fracture risk above that given by BMD alone. The World Health Organization (WHO) is analyzing a number of factors that contribute to clinical risk of fracture that are independent of BMD, including:
- prior fragility fracture
- current cigarette smoking
- parental history of hip fracture
- rheumatoid arthritis
- past or current use of glucocorticoids.
A WHO project lead by Professor John A. Kanis, is developing an approach to evaluate the independent contribution of these risk factors and the ability to integrate them to calculate a fracture risk probability with and without the use of BMD. Such a calculation might then be used to develop a threshold for pharmacological intervention. There is a distinction between diagnosis of osteoporosis and assessment of fracture risk — thus a distinction between diagnostic and therapeutic thresholds.
Although these clinical risk factors are known, there is a need to establish the interrelationship of these factors and then validate them internationally before application in clinical practice. An approach to integrating all osteoporotic fractures is to weight the incidence of osteoporotic fractures at different age groups. When BMD testing is not available, perhaps clinical risk factors alone may be used to establish the need for pharmacological intervention.
To develop “intervention thresholds” the WHO has been analyzing data from large prospective observational studies in collaboration with other stakeholder medical organizations. The concept is to combine BMD testing with clinical risk factors when BMD testing is accessible and affordable as in the USA. In regions of the world where BMD testing is not available, then the WHO may be proposing that clinical risk factors alone can be used to select patients to be treated. The problem with the latter is that no studies have validated that treating patients based on clinical risk factors alone can reduce the risk of fractures. The final WHO recommendations will not be known until the Technical Report is published, probably sometime in 2006.
Some of our ISCD colleagues, Drs. Mike Lewiecki, Mike McClung, and Paul Miller, have contributed to the dialogue of this committee as the work continues.
I have discussed the issue of assessment with Dr. Lewiecki recently who pointed out…
Current treatment guidelines are in general agreement that postmenopausal women with T-scores of -2.5 or less are likely to benefit from pharmacological therapy to prevent fractures, and that those with T-scores of -1.5 or greater are not likely to benefit. There is lack of agreement on whom to treat when the T-score is between -1.5 and -2.5. In addition, there is variability on which clinical risk factors for fracture should be considered in combination with T-score, and no validated method for quantifying fracture risk when T-score and clinical risk factors are combined. For these reasons, the WHO, under the direction of Prof. John Kanis, has been involved in an ambitious project to develop a methodology to estimate fracture probability, validated in men and women of different ethnicities in different world regions. They are doing this by performing a “mega-analysis” of data obtained from 12 cohorts involving a total of over 60,000 subjects. Clinical risk factors for fracture that are independent of BMD can be combined with BMD to estimate the 10-year fracture probability of fracture. By then applying cost-utility analysis, using country- or region-specific socio-economic assumptions, cost-effective intervention thresholds can be calculated.
The ISCD Fracture Risk Reporting Task Force, chaired by Dr. Paul Miller, has worked in collaboration with the WHO and other stakeholder organizations (NOF, IOF, ASBMR) on this important project. The long-anticipated results will soon be published in the form of a WHO Technical Report — the same venue used in 1994 to announce to the medical world the BMD classification of normal, osteopenia, and osteoporosis. The underlying assumption is that patients at the greatest risk of fracture are the ones who are most likely to benefit from therapy, and that combining BMD with clinical risk factors can better identify those at risk than BMD alone. The ISCD is a strong supporter of fracture risk reporting, and will be working with other organizations to use this methodology to develop clinically useful treatment guidelines.
The future and impact on evaluation of fracture risk assessment by the WHO project led by Professor Kanis will have a long lasting impact. As clinicians and technologists who are ardently involved in helping our patients, this is a step forward that will greatly benefit our ability to assess and treat them.
See additional article in this edition of OsteoFlash® by Andrew Laster, MD with VFA updates from the ISCD Position Development Conference this summer in Vancover, BC and the correspondence from ISCD this September 2005 to BC/BS. This data is included to help those who need it for correspondence with third party payers. This effort was a joint undertaking with the AACE, ACR and ASBMR. This information is available for use of our members to locally continue these efforts.
Last modified: December 17, 2012