Personalized fracture risk assessment: where are we at?

ABSTRACT

Introduction: Osteoporotic fracture imposes a significant health care burden globally. Personalized assessment of fracture risk can potentially guide treatment decisions. Over the past decade, a number of risk prediction models, including the Garvan Fracture Risk Calculator (Garvan) and FRAX®, have been developed and implemented in clinical practice. Areas covered: This article reviews recent development and validation results concerning the prognostic performance of the two tools. The main areas of review are the need for personalized fracture risk prediction, purposes of risk prediction, predictive performance in terms of discrimination and calibration, concordance between the Garvan and FRAX tools, genetic profiling for improving predictive performance, and treatment thresholds. In some validation studies, FRAX tended to underestimate fracture by as high as 50%. Studies have shown that the predicted risk from the Garvan tool is highly concordant with clinical decision. Expert opinion: Although there are some discrepancy in fracture risk prediction between Garvan and FRAX, both tools are valid and can aid patients and doctors communicate about risk and make informed decision. The ideal of personalized risk assessment for osteoporosis patients will be realized through the incorporation of genetic profiling into existing fracture risk assessment tools.

KEYWORDS:

• Osteoporosis
• fragility fracture
• fracture risk assessment
• Garvan
• Frax
• Qfracture
• skeletal age

Article highlights

• Fragility fracture, especially hip fracture, is associated with increased risk of mortality. Among those who survived a fracture, they suffer an increased risk of refracture.

• Although bone mineral density is the primary indicator of fracture risk, low bone mineral density (e.g. osteoporosis) accounts for 50% or less cases of fracture. Non-BMD factors such as a personal history of fracture and fall contribute to elevated fracture risk.

• Assessment of absolute risk of fracture based on an individual’s risk profile is a critical step in the current approach to treatment and prevention. Over the past 10 years, at least 3 models of risk assessment (Garvan, FRAX, and Qfracture) have been developed to estimate an individual’s risk of fracture.

• These fracture risk assessment models have acceptable-to-good discriminatory values but modest accuracy. Inclusion of new risk factors such as trabecular bone score and genetic profiling (e.g. polygenic risk score) modestly improved discrimination.

• Future fracture risk assessment models should predict the risk of incident refracture and mortality, and extend to predicting lifetime risk for age-specific groups and ethnicity-specific groups.

Declaration of interest

The author is the developer of the Garvan Fracture Risk Calculator which is freely available to doctors and the public. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported, in part, by a grant from the Amgen Competitive Grant Program (2019) and NHMRC grant APP1195305.