FRAX, GARVAN Seen as Best for Predicting Fracture Risk

Janis C. Kelly

October 21, 2015

A new systematic review and meta-analysis of 13 tools for predicting osteoporotic fracture risk found that most were feasible in clinical practice; the World Health Organization Fracture Risk Assessment Tool (FRAX) was the most validated instrument, whereas the QFracture score (designed to be used with electronic medical records) was the most accurate.

"QFracture and updated QFracture (2012) include a larger number and wider variety of clinical risk factors than FRAX and GARVAN," the authors write. "It is likely that algorithms with the longest lists of risk factors will have feasibility and adherence problems, but also greater accuracy. On the other hand, shorter lists may decrease the accuracy of the prediction."

Andréa Marques, from the Rheumatology Department, Centro Hospitalar e Universitário de Coimbra, and the Health Sciences Research Unit: Nursing, Coimbra, Portugal, and colleagues, published their findings online August 6 and in the November issue of the Annals of the Rheumatic Diseases.

The authors expressed hope that wider use of these online tools might help get many more patients into treatment before a first osteoporotic fracture, or at least prevent a second one.

"The occurrence of fragility fractures can be predicted with high accuracy by relatively simple algorithms incorporating easily accessible clinical risk factors, with or without bone mineral density," senior author José António P. Da Silva, MD, PhD, head of the Rheumatology Department of Rheumatology at the Centro Hospitalar e Universitário de Coimbra, told Medscape Medical News.

"These algorithms, namely FRAX and GARVAN [the Garvan Institute's Fracture Risk Calculator] (which requires bone mineral density, BMD), are easily accessible through the web at no cost. These tools provide the practicing clinician with an invaluable aid to make [an] informed decision on whether to treat, which should clearly be based on risk of fracture rather than merely the densitometric diagnosis of osteoporosis."

FRAX score should be the first choice in daily practice for patients with no history of recurrent falls, and GARVAN might be more appropriate for patients who have already had falls, Willem F. Lems, MD, associate professor of rheumatology, VU University Medical Centre, Amsterdam, The Netherlands writes in an accompanying editorial.

The researchers systematically searched the PubMed MEDLINE, Embase, and Cochrane databases to 2014 for studies of fracture risk prediction tools, scores, algorithms, or other instruments. The primary outcome measure was the area under the curve of the fracture risk prediction. The analysis included cohort studies (prospective or retrospective) and case-control studies.

Dr da Silva said this study differed from previous meta-analyses because it focused only on tools for predicting fracture risk, rather than tools for predicting osteoporosis or low BMD. "We also include both genders in our analysis," he said. The systematic review identified 45 studies that met inclusion criteria. Only three tools (FRAX, GARVAN, and QFracture) had been tested more than once in population-based studies. The tools require from 4 to 31 factors for calculation, and most calculate 5- or 10-year fracture risk. The researchers selected 20 studies for the meta-analysis.

The researchers concluded that FRAX, GARVAN, and QFracture can differentially predict risk in men and women for hip and major osteoporotic fractures, but they point out that each tool defines "major osteoporotic" differently, making direct comparisons impossible.

"The use of the FRAX-score as the first choice in patients in whom a BMD is available can be advocated, since it is certainly a robust score, has been tested in many studies and has country-specific data," Dr Lems writes. "However, FRAX also has some limitations; for example, fall risk is not incorporated, while the number of fall events is one of the five risk factors in the Garvan scoring method. Thus, it can be preferred for routine performance of the FRAX-score, while in frequent fallers the Garvan-score should (also) be performed three or four times per year or even more."

Treat Patients After First Low-Trauma Fracture

Clinicians are likely to have more effect on osteoporotic fracture rates if they focus first on getting patients who have suffered one mild traumatic fracture into treatment, however, John Eisman AO, MB BS, PhD, director of clinical translation and advanced education at the Garvan Institute of Medical Research, Darlinghurst Sydney, Australia, told Medscape Medical News.

Dr Eisman helped develop the GARVAN nomogram but was not involved in the meta-analysis. "One thing that we know is that treatment after a first low-trauma fracture reduces both the risk of future fracture and mortality," Dr Eisman said.

Looking ahead, Dr Eisman noted that effective anti-osteoporotic treatment after a first low-trauma fracture is delivered to only about 25% of women and 5% to 10% of men who are candidates for these drugs. He suggested that using a fracture liaison service to identify and "capture" people after the first low-trauma fracture and get them treated would have a bigger and more immediate payoff than focusing initially on trying to predict which lower-risk patients are likely to benefit from anti-osteoporotic treatment. The number needed to treat to produce a significant benefit is much lower in the first patient group than in the second, he said.

A program of more intensive intervention after the first low-trauma fracture would likely benefit from the use of a compelling narrative with the patient, such as, "You've had a fracture? Let's get you onto a treatment that can be as much as 95% effective at preventing a second fracture," Dr Eisman said.

International Osteoporosis Foundation President John A. Kanis, MD, told Medscape Medical News that he agreed with Dr Eisman regarding fracture liaison services.

Dr Kanis, who is emeritus professor in human metabolism and director, World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, United Kingdom, led the team that developed the FRAX system for fracture risk assessment. He was not involved in the meta-analysis of fracture prediction tools.

"In all countries there is a significant treatment gap between individuals at high risk and those receiving treatment. This is also true for the most serious osteoporotic fracture; namely, hip fracture, where treatment uptakes as low as 20% have been recorded in the US and elsewhere," Dr Kanis said.

"The development of fracture liaison services such as those promoted by the International Osteoporosis Foundation ("Capture the Fracture") is likely to help in this regard. To put a proper perspective on this, I am uncertain whether the treatment gap in osteoporosis is greater than that seen for hypertension, obesity, or type II diabetes."

Dr da Silva was involved in validating the FRAX algorithm for the Portuguese population. The other authors have disclosed no relevant financial relationships. Dr Lems reports speaker's fees from Amgen, Eli Lilly, Merck, Will Pharma, Servier, and Novartis. Dr Eisman was part of the team that developed the GARVAN nomograph.

Ann Rheum Dis. 2015;74:1958-1967. Article full text, Editorial full text

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