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FRAX Bone Treatment Algorithm: A Revised Clinician's Guide to the Prevention and Treatment of Osteoporosis- commentary
  The Journal of Clinical Endocrinology & Metabolism July 2008 Vol. 93, No. 7 2463-2465
Bess Dawson-Hughes on behalf of the National Osteoporosis Foundation Guide Committee
Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111 INTRODUCTION
Osteoporosis is an important health problem now, and the incidence of fractures and their associated costs are rising rapidly as our population ages (1). The National Osteoporosis Foundation (NOF) has estimated that by 2010, 12 million men and women in the United States will have osteoporosis and over 40 million more will have low bone mass (2). There is little controversy about whether individuals who present with osteoporosis should be considered for pharmacotherapy. Among patients with low bone mass, however, we need better discrimination of those at high risk for fracture, to maximize the benefit while limiting the risks and costs that accompany treatment. In this spirit, the NOF has collaborated with the World Health Organization (WHO) to adapt its newly developed fracture prediction algorithm (FRAX) to the U.S. population (3), performed an economic analysis to identify levels of fracture risk above which it is cost-effective to consider pharmacotherapy in this country (4), and revised the NOF Clinician's Guide for the Prevention and Treatment of Osteoporosis ( This Commentary provides a brief overview of this process, a summary of the key recommendations of the Guide, and a consideration of work that remains.
Guide Development
In 2003, the WHO embarked on a project to integrate information on risk factors and bone mineral density (BMD) to better predict fracture risk in men and women worldwide. The result was the release in February 2008 of a WHO Technical Report and an algorithm for assessing the 10-yr risk of a major osteoporosis-related fracture, including hip, spine, forearm, and humerus fractures (5). The clinical risk factors in the algorithm (age, body massindex, prior fragility fracture, use of oral glucocorticoids, parental history of fracture, current smoking, excess alcohol intake, secondary osteoporosis, and rheumatoid arthritis) have been validated in 60,000 men and women from 12 prospective,population-based cohorts and confirmed in other studies, including the Study of Osteoporotic Fractures and the Women's Health Initiative.
Concurrently, a NOF committee collaborated with the WHO to calibrate the FRAX algorithm for use in the United States by incorporatingU.S. hip fracture and mortality rates. The U.S.-adapted FRAX algorithm is available on the NOF website ( and The Committee also performed a cost-effectiveness analysis to estimate the levels of fracture risk above which it is reasonable to consider treatment (4). The practical implications of this analysis are described in a companion paper (3). The new NOF Clinician's Guide (available on the NOF website at indicates 10-yr fracture risk thresholds above which it is reasonable to consider pharmacological treatment. Work is now underway to evaluate the potential impact of the Guide by estimating the number of men and women who are expected to meet the new treatment criteria.
Guide Summary
The new Clinician's Guide pertains to women and men of all races/ethnicities, age 50 yr and older, who are not currently on a pharmacological agent for the prevention or treatment of osteoporosis. The recommendations in the Guide are meant to serve as a reference point for decision making but are not intended to represent rigid standards. Based on clinical judgment, estimated prospective risk, patient preferences, and other factors, clinicianswill need to tailor their recommendations to individual patients. The main recommendations of the NOF Guide are summarized in Table 1.


Guide Implementation
Facilitating appropriate implementation of FRAX in the United States remains an important task. The FRAX algorithm uses femoral neck T-scores (total hip is an option) based on the National Health and Nutrition Examination Survey III young Caucasian female reference values. In the United States and in many otherlocations, however, dual-energy x-ray absorptiometry (DXA) scans report T-scores based on same-sex reference values, and there is variation in the reference standard used for non-Caucasians. DXA T-scores on Caucasian females can be entered directly into FRAX, but corresponding T-scores for all men and for non-Caucasian women must first undergo an adjustment to the young Caucasian female reference standard before they can be used appropriately in FRAX. An effort is currently underway by the NOF and the International Osteoporosis Foundation to facilitate the needed T-score conversions. In the meantime, guidance for making these conversions is available at Ideally, the U.S.-adapted FRAX 10-yr fracture risk scores will eventually be available on DXA reports.
Analyses by the WHO have revealed that the impact of many secondary causes on fracture risk is mediated primarily through their effects on BMD (5). It is for this reason that checking the "secondary causes" box in FRAX does not alter the risk scores once BMD is entered into the algorithm. In contrast, the other clinical risk factors, including glucocorticoid use and rheumatoid arthritis, increase 10-yr fracture risk scores by mechanisms that are to a significant degree independent of their effects on BMD, and so their presence increases the risk scores in the presence of BMD.
The current assessment tool does not account for all important clinical information. For example, glucocorticoid use in FRAX is defined as "ever/never" use for 3 months, whereas the amount and duration of glucocorticoid use is known to affect risk and varies widely among patients. Additionally, the NOF economic analysis identified treatment thresholds based on an overall drug efficacy of 35% and takes no account of the fact that some drugs are more effective at specific skeletal sites, such as the spine, than at others or that available treatments differ in tolerability or patient adherence. Finally, potential added benefits of selected therapies (e.g. breast cancer risk reduction associated with use of raloxifene) have not been formally evaluated. The value of clinical judgment and patient preference for the management of a complex disease such as osteoporosis can never be replaced by an algorithm or a cost-effectiveness analysis. But information about the level of fracture risk available through use of FRAX can be helpful in informing treatment decisions made together by healthcare providers and their patients when considered relative to recommended treatment thresholds.
The Future
The WHO has provided a solid global platform that lends itself to expansion as additional evidence emerges. In the future, we can anticipate the incorporation of spinal BMD T-scores into the algorithm. Eventually, other bone measurements, biochemical tests, and risk factors may also be added. Meanwhile, the WHO Center is currently collaborating with organizations in many countries to adapt FRAX by incorporating their respective fracture and mortality rates into the algorithm, as done already for the United States. This will allow the use of FRAX to expand around the globe and enable those who are interested to develop region-specific treatment thresholds. The ultimate test of thevalidity of FRAX will come when its ability to predict fracture and to select patients for therapy is evaluated prospectively in large clinical trials.
The Guide Committee members are Sanford Baim, Murray J. Favus, Sundeep Khosla, Robert L. Lindsay, L. Joseph Melton III, Anna N. A. Tosteson, and Bess Dawson-Hughes.
This work was supported by a grant from the National Osteoporosis Foundation.
This article does not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.
Disclosure Summary: The author has received research support from Unilever and consultation fees from Amgen, Cytochroma, Danone, Eli Lilly, Merck, Procter & Gamble, Servier, and Wyeth.
First Published Online June 10, 2008
Abbreviations: BMD, Bone mineral density; DXA, dual-energy x-ray absorptiometry; FRAX, fracture prediction algorithm.
Received April 29, 2008.
Accepted May 29, 2008.
1. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A 2007 Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res 22:465-475
2. National Osteoporosis Foundation 2002 America's bone health: the state of osteoporosis and low bone mass in our nation. Washington, DC: National Osteoporosis Foundation; 1-55
3. Dawson-Hughes B, Tosteson AN, Melton 3rd LJ, Baim S, Favus MJ, Khosla S, Lindsay RL 2008 Implications of absolute fracture risk assessment for osteoporosis practice guidelines in the USA. Osteoporos Int 19:449-458
4. Tosteson AN, Melton 3rd LJ, Dawson-Hughes B, Baim S, Favus MJ, Khosla S, Lindsay RL 2008 Cost-effective osteoporosis treatment thresholds: the United States perspective. Osteoporos Int 19:437-447
5. Kanis JA, on behalf of the World Health Organization Scientific Group 2008 Assessment of osteoporosis at the primary health-care level. Technical Report. WHO Collaborating Center, University of Sheffield, UK
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