Osteoporosis prevention, diagnosis and management in postmenopausal women and men over 50 years of age


Assessment of absolute fracture risk

The two major factors limiting widespread uptake of absolute fracture-risk calculators by clinicians are a general lack of awareness about how and when to use fracture risk calculators, and the requirement for significant general practitioner and specialist education. The PBS does not recognise absolute fracture risk as an indication for access to subsidised therapies to treat osteoporosis.

The main goal of treatment for osteoporosis is fracture prevention. Quantitative assessment of an individual’s fracture risk has the potential to better guide decisions on pharmaceutical treatment.17–20 This could, for example, lead to high-risk osteopenic patients without fracture receiving effective therapy. Conversely, in situations of low absolute fracture risk where treatment can be safely delayed, the fracture-risk calculators may potentially limit unnecessary therapy, as well as the associated costs and side effects. The absolute fracture-risk estimates also provide medical practitioners with a tool to educate patients, potentially allowing them to better understand their own fracture risk. This would lead to more informed decisions on whether or not treatment is warranted.

Table 4.

Table 4.

Clinical risk factors used in GFRC and FRAX

Grade: D

Recommendation 6
Assessment of absolute fracture risk, using either the Garvan Fracture Risk Calculator or the Fracture Risk Assessment Tool (www.shef.ac.uk/FRAX) may be useful in assessing the need for treatment in individuals who do not clearly fit established criteria.

In addition to bone mineral density (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 risk of fracture. 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 risk or absolute risk.

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

  • Absolute fracture risk is not a qualifier for access to Pharmaceutical Benefits Scheme (PBS)-subsidised therapies.
  • Estimation of absolute fracture risk using a fracture risk calculator does not take into account lumbar spine BMD, and such estimates should not disqualify therapeutic decisions made on the basis of a low lumbar spine T-score.
  • Calculator-based estimations of fracture risk are estimates only, and should always be interpreted in the clinical, racial and cultural context of the patient.
  • Absolute fracture risk is currently in use internationally as a basis for treatment decisions. Cost-effectiveness evaluation studies are underway.

A number of absolute fracture risk calculators are now available. These aim to better estimate an individual’s fracture risk by taking into account age and clinical risk factors as well as BMD, and have the potential to allow more effective targeting of therapy for osteoporosis. In Australia, the most common absolute fracture risk calculators in use are the following:

  • Garvan Fracture Risk Calculator (GFRC). The GFRC was developed in Australia using data from the Dubbo

Osteoporosis Epidemiology Study.2,3

  • Fracture Risk Assessment Tool (FRAX). FRAX uses data from nine epidemiological studies as well as the results of the placebo arms of clinical trials to estimate absolute fracture risk.4,5 Dual energy X-ray absorptiometry (DXA) scanners that incorporate specialised software have the ability to provide a FRAX estimate of absolute fracture risk.

While aiming to achieve the same outputs, FRAX and GFRC use different algorithms to estimate absolute fracture risk. The FRAX algorithm uses 13 risk factors, while GFRC uses five (Table 4). More variables however do not necessarily improve prediction, and fracture-risk calculators with five or fewer variables have been shown to perform as well as those with more variables.6 Both FRAX and GRFC can be used to calculate absolute fracture risk when BMD measurement is not available, because BMD is largely determined by age and weight. The different algorithms do result in different estimates of absolute fracture risk. FRAX was developed using multinational epidemiological data, and as such provides a country-specific fracture risk that takes into to account different baseline fracture and mortality rates. If a particular country is not available, FRAX recommends the use of the country most similar to the patient’s background.

There are a number of other differences between FRAX and GFRC:

  • FRAX predicts ‘major osteoporotic fractures’, categorised as clinical spine, hip, forearm or shoulder fracture. GFRC predicts any osteoporotic fracture.
  • FRAX determines an individual’s fracture risk over a 10-year period, while GFRC provides both five- and 10-year fracture predictions.
  • FRAX links to a website that can adjust fracture risk estimate based on the patient’s trabecular bone score.
  • Both FRAX and GFRC are available online. FRAX is also available as part of the latest DXA software from all DXA scanner manufacturers and is therefore more readily accessible at the present time.

The FRAX and GFRC calculators both have limitations:

  • Falls as a risk factor for fracture is not included in the FRAX calculator. Falls risk is, however, recognised as an independent risk factor for fracture. Falls and number of falls are included in the GFRC.
  • The FRAX questionnaire provides a number of risk factors as binary variables (yes/no) and does not allow graduations in exposure to risk factors, including prior fractures, smoking, alcohol use and glucocorticoid use.
  • FRAX calculates a 10-year fracture risk for hip fracture and the combined group of ‘major osteoporotic’ fractures. Many other fractures, including rib, other femur, tibia and fibular fractures, are excluded.
  • GFRC uses fewer risk factors and does not include known variables which increase fracture risk (ie family history of fracture).
  • GFRC was determined from a broad based Australian population of mixed ethnicity, predominantly Caucasian. Its applicability to other racial groups and to immigrants who have spent a significant period of their lives overseas is uncertain. GFRC has, however, been validated in a number of international populations, including Canada, the Netherlands and Poland.7,8

A number of studies have compared FRAX to GFRC in estimating fracture risk. The majority of these studies suggest that FRAX may underestimate fracture risk in men and women. GFRC possibly performs better than FRAX in men and at least as well in postmenopausal women,9 but overestimates fracture risk in patients in the highest quintile of risk. The impact of this overestimate on clinical practice is likely to be small, as osteoporosis treatment would generally be recommended in this group.10 Interestingly, some studies suggest that neither FRAX nor GFRC provide a better estimate of fracture risk than using age and BMD alone.11,12

A potential important clinical application for fracture-risk calculators is to improve selection of individuals in whom to recommend treatment. Individuals who have not fractured but are in the osteoporotic BMD range, or middle-aged to elderly individuals with prior minimal trauma fracture, generally have high calculated absolute fracture risk, supporting a recommendation for treatment. Individuals with BMD values within the osteopenic range but without a prior history of fracture are more likely to benefit from fracture-risk algorithms. In this group, a high fracture risk estimate may change management and lead to therapy recommendation. Health economic modelling in the UK13,14 and USA15 has demonstrated that treatment is cost-effective when FRAX is used to identify at-risk patients. Based on a drug cost of $US600 per year for five years (with 35% fracture reduction) and an average cost per quality-adjusted life year (QALY) designated at $US60,000 or less, the US National Osteoporosis Foundation guidelines recommend treatment when the 10-year risk of hip fracture estimated by FRAX is 3% or higher, or the 10-year risk of major osteoporotic fracture is 20% or higher.16 Prospective studies to validate the clinical benefit and cost-effectiveness of this recommendation are not yet available.

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