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

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 use^3–5,13 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.