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Guideline

Risk factors, fracture risk assessment and case-finding

Assessment of absolute fracture risk

Assessment of absolute fracture risk

 

Recommendation 5

Grade

Assessment of absolute fracture risk, using the Fracture Risk Assessment Tool (FRAX®; https://fraxplus.org) may be useful in assessing the need for treatment in individuals who do not clearly fit established criteria.

B

Recommendation 6

Grade

Patients with a very high and/or imminent fracture risk should be promptly referred to a specialist for consideration of osteoanabolic therapy as first-line treatment.

C

In addition to BMD, there are other clinical factors associated with minimal trauma fracture risk. Two individuals with similar BMD measurements but different clinical risk factors will have different fracture risk. Increasing age, prior minimal trauma fracture, and propensity to fall are the clinical risk factors most strongly associated with increased fracture risk.1 Fracture risk may be expressed as either relative or absolute risk.

Absolute risk is the numerical risk of an event for an individual over a specified period. This is commonly expressed as an individual’s percentage chance of suffering a minimal trauma fracture over a given period, generally five or 10 years. Relative risk compares an individual’s risk of an event (such as a fracture) to the risk of that event in a reference population, or to the baseline risk at a given time point. An individual’s relative risk will depend on the comparison group used. Assessing only relative risk can lead to erroneous conclusions. For example, if the background absolute risk of a fracture at a given time is low (e.g., 0.2% five-year risk), then even with a doubling of risk (relative risk increases to 2), absolute risk remains low (0.4% five-year risk).

Imminent fracture risk

The identification of patients at imminent or very high/high fracture risk is emerging as an important part of osteoporosis care. Imminent fracture risk could either be interpreted as the short-term (1–2 year) absolute fracture risk or the markedly high fracture risk period following the incident fracture (e.g., patients with a fracture within the past 24 months).

Very high and high fracture risk

In addition to a BMD T-score ≤–3.0, the following risk factors may further increase fracture risk: concurrent glucocorticoid therapy; low BMI; and recent acute weight loss and recurrent falls. ‘Very high fracture risk’ is an evolving concept with variability in definition. For example, the US Endocrine Society defines ‘very high risk’ as an individual with multiple spine fractures and a T-score of ≤−2.5.2 The Scottish Intercollegiate Guidelines Network uses a similar approach, defining severe osteoporosis as the presence of one severe or two or more moderate vertebral fractures with a T-score of ≤−1.5, or a lumbar spine T-score of ≤–4.0, regardless of fracture.3

Recent UK guidelines suggest that ‘very high fracture risk’, incorporating the concept of imminent fracture risk in the shorter term, may be captured by the presence of a recent fracture and a 10-year FRAX® major osteoporotic fracture risk of ≥30%.4 The American Association of Clinical Endocrinologists also defines ‘very high fracture risk’ as including a recent fracture (within 12 months), a T-score of <–3.0, multiple fractures while on therapy, the use of drugs causing skeletal harm, and a 10-year FRAX® major osteoporotic fracture risk of ≥30% or hip fracture risk of >4.5%.5 Not all criteria need to be present in the one patient, and instead, they are meant to represent different patient groups at very high fracture risk.5 Across guidelines, the most common criteria were a recent fracture (within 12 or 24 months), multiple fractures, fractures while on therapy, and a 10-year FRAX® major osteoporotic fracture risk of ≥30% or a hip fracture risk of >4.5%.3–5 Although more data are required to cement an internationally accepted definition, these various definitions highlight the types of patient who should be identified for prompt specialist referral, especially if the fracture has occurred within two years with multiple clinical risk factors (e.g., glucocorticoid use, falls, rheumatoid arthritis, and age ≥70 years).6,7

Although advanced age is associated with a greater risk of osteoporotic fracture, younger patients may also be at very high fracture risk, and early identification and specialist referral of these patients is warranted. Exclusion of secondary causes of osteoporosis and consideration of osteoanabolic therapies (i.e., drugs that form new bone; refer to Sections 3.3 and 3.5) should be undertaken. In the absence of access to specialist care, early initiation of parenteral antiresorptive therapy should be considered with regular review.

Several absolute fracture risk calculators are available. These aim to better estimate an individual’s fracture risk by considering age and clinical risk factors, as well as BMD, and may allow more effective targeting of therapy for osteoporosis. The Garvan Fracture Risk Calculator (https://www.garvan.org.au/promotions/bone-fracture-risk/calculator/) was developed in Australia using data from the Dubbo Osteoporosis Epidemiology Study.8 FRAX® (https://fraxplus.org) uses data from nine epidemiological studies, including the Dubbo Osteoporosis Epidemiology Study, as well as results from the placebo arms of clinical trials to estimate absolute fracture risk.9

DXA scanners that incorporate specialised software can provide a FRAX® estimate of absolute fracture risk. The three international studies of a population-based fracture screening program have used FRAX®.10–12 FRAX® models are currently available in 73 countries covering around 80% of the world population, and the tool is used in over 100 guidelines worldwide.13–15

While aiming to achieve the same outputs, FRAX® and the Garvan Fracture Risk Calculator use different algorithms and inputs to estimate absolute fracture risk (refer to Table 3). Both have similar predictive discriminative ability (area under the curve range 0.67–0.70 for hip fracture, 0.62–0.64 for osteoporotic fracture and 0.60–0.63 for any fracture).16 The input factors for FRAX® are listed in Table 3. FN BMD is an optional input.

Table 3: FRAX® and Garvan Fracture Risk Calculator input factors

 

FRAX®

Garvan Fracture Risk Calculator

Age

Graded

Graded

Sex

Binary, (ie yes/no)

Binary

Ethnicity/nationality

Graded

Not Included

BMI

Graded

Not Included

BMD

Graded

Graded

Prior fracture

Binary

Graded

Falls

Not Included

Graded

Glucocorticoid use

Binary

Not Included

Family history of fracture

Binary

Not Included

Rheumatoid arthritis

Binary

Not Included

Smoking

Binary

Not Included

Alcohol use

Binary

Not Included

Secondary osteoporosis

Binary

Not Included

 

The limitations of FRAX® have been extensively discussed.17,18 In particular, secondary causes of osteoporosis are assigned an identical risk using binary (yes/no) responses only, falls are not considered, and the calculation algorithm is not publicly available.19

However, most international guidelines suggest its use3–5,13 due to the wide validation of FRAX® in multiple large international populations, ease of access as part of DXA machine software, and ongoing refinement with responsiveness to user feedback.20 A unique feature of FRAX® is its consideration of the competing hazard of death, meaning that fracture risk is reduced in those with low life expectancy (e.g., older, frailer people). For these reasons, FRAX® appears the most robust fracture risk calculator, especially as ongoing refinements to it are being implemented. Clearly, clinical judgement is still required to interpret FRAX® outputs of 10-year fracture risk.

However, the Garvan Fracture Risk Calculator still has a role. Its simplicity, requiring only five input factors, makes it very convenient. Exclusion of falls as a risk factor by FRAX® leads to a marked divergence in risk estimates between it and the Garvan Fracture Risk Calculator for patients with frequent falls.21 Hence, using the Garvan Fracture Risk Calculator in patients with falls may be more appropriate.

  1. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet 2002;359(9319):1761–67.
  2. Shoback D, Rosen CJ, Black DM, Cheung AM, Murad MH, Eastell R. Pharmacological management of osteoporosis in postmenopausal women: An Endocrine Society guideline update. J Clin Endocrinol Metab 2020;105(3):dgaa048.
  3. Scottish Intercollegiate Guidelines Network (SIGN). Management of osteoporosis and the prevention of fragility fractures. SIGN, 2021 [Accessed 30 October 2023]
  4. Gregson CL, Armstrong DJ, Bowden J, et al. UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 2022;17(1):58.
  5. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis – 2020 update. Endocr Pract 2020;26(Suppl 1):1–46.
  6. Curtis EM, Reginster JY, Al-Daghri N, et al. Management of patients at very high risk of osteoporotic fractures through sequential treatments. Aging Clin Exp Res 2022;34(4):695–714.
  7. Söreskog E, Ström O, Spångéus A, et al. Risk of major osteoporotic fracture after first, second and third fracture in Swedish women aged 50 years and older. Bone 2020;134:115286.
  8. Nguyen ND, Frost SA, Center JR, Eisman JA, Nguyen TV. Development of prognostic nomograms for individualizing 5-year and 10-year fracture risks. Osteoporos Int 2008;19(10):1431–44.
  9. Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 2008;19(4):385–97.
  10. Shepstone L, Lenaghan E, Cooper C, et al. Screening in the community to reduce fractures in older women (SCOOP): A randomised controlled trial. Lancet 2018;391(10122):741–47.
  11. Rubin KH, Rothmann MJ, Holmberg T, et al. Effectiveness of a two-step population-based osteoporosis screening program using FRAX: The randomized Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study. Osteoporos Int 2018;29(3):567–78.
  12. Merlijn T, Swart KM, van Schoor NM, et al. The effect of a screening and treatment program for the prevention of fractures in older women: A randomized pragmatic trial. J Bone Miner Res 2019;34(11):1993–2000.
  13. Kanis JA, Harvey NC, Cooper C, Johansson H, Odén A, McCloskey EV, et al. A systematic review of intervention thresholds based on FRAX: A report prepared for the National Osteoporosis Guideline Group and the International Osteoporosis Foundation. Arch Osteoporos 2016;11(1):25.
  14. Kanis JA, Cooper C, Rizzoli R, Reginster JY; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2019;30(1):3–44.
  15. Kanis JA, Harvey NC, Johansson H, et al. A decade of FRAX: How has it changed the management of osteoporosis? Aging Clin Exp Res 2020;32(2):187–96.
  16. Bolland MJ, Siu AT, Mason BH, et al. Evaluation of the FRAX and Garvan fracture risk calculators in older women. J Bone Miner Res 2011;26(2):420–27.
  17. Nguyen TV. Personalised assessment of fracture risk: Which tool to use? Aust J Gen Pract 2022;51(3):189–90.
  18. McCloskey EV, Harvey NC, Johansson H, et al. Fracture risk assessment by the FRAX model. Climacteric 2022;25(1):22–28.
  19. Allbritton-King JD, Elrod JK, Rosenberg PS, Bhattacharyya T. Reverse engineering the FRAX algorithm: Clinical insights and systematic analysis of fracture risk. Bone 2022;159:116376.
  20. Vandenput L, Johansson H, McCloskey EV, et al. Update of the fracture risk prediction tool FRAX: A systematic review of potential cohorts and analysis plan. Osteoporos Int 2022;33(10):2103–36.
  21. Baim S, Blank R. Approaches to fracture risk assessment and prevention. Curr Osteoporos Rep 2021;19(2):158–65.
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