Individual patient details comprise age (50 to 90 years), sex, weight (in kg) and height (in cm). BMI is automatically computed from height and weight. Dichotomised risk variables are then entered:

A prior fragility fracture (yes/no)

Parental history of hip fracture (yes/no)

Current tobacco smoking (yes/no)

Ever long-term use of oral glucocorticoids (yes/no)

Rheumatoid arthritis (yes/no)

Other causes of secondary osteoporosis (yes/no)

Daily alcohol consumption of three or more units daily (yes/no)

A distinction is made between rheumatoid arthritis and other secondary causes of osteoporosis. Rheumatoid arthritis carries a fracture risk over and above that provided by BMD [11 (link)]. Whereas this may hold true for other secondary causes of osteoporosis, the evidence base is weak. Of the many secondary causes of osteoporosis, the following have been consistently documented to be associated with a significant increase in fracture risk:

Untreated hypogonadism in men and women, e.g., bilateral oophorectomy or orchidectomy, anorexia nervosa, chemotherapy for breast cancer, hypopituitarism [33 (link)–40 (link)]

Inflammatory bowel disease, e.g., Crohn’s disease and ulcerative colitis [41 (link)–43 (link)]. It should be noted that the risk is in part dependent on the use of glucocorticoids, but an independent risk remains after adjustment for glucocorticoid exposure [44 (link)].

Prolonged immobility, e.g., spinal cord injury, Parkinson’s disease, stroke, muscular dystrophy, ankylosing spondylitis [45 (link)–50 (link)]

Organ transplantation [51 –54 (link)]

Type I diabetes [55 (link)–58 (link)]

Thyroid disorders, e.g., untreated hyperthyroidism, over-treated hypothyroidism [59 (link)–63 (link)]

Whereas there is strong evidence for the association of these disorders and fracture risk, the independence of these risk factors from BMD is uncertain. It was conservatively assumed, therefore, that the fracture risk was mediated via low BMD, but with a risk ratio similar to that noted in rheumatoid arthritis. From an operational view, where the field for rheumatoid arthritis is entered as ‘yes’, a risk is computed with and without BMD. If the field for other secondary osteoporosis is also filled as ‘yes’ this does not contribute to the calculation of fracture probability. Conversely, where the field for rheumatoid arthritis entered as ‘no’, and the field for secondary osteoporosis is ‘yes’, the same β coefficients as used for rheumatoid arthritis contribute to the computation of probability where BMD is not entered. In the presence of BMD, however, no additional risk is assumed in the presence of secondary osteoporosis, since its independence of BMD is uncertain.
If any of the fields for dichotomous variables is not completed, a negative response is assumed. Fractures probability can then be calculated. The output (without BMD) comprises the 10-year probability of hip, clinical spine, shoulder or wrist fracture and the 10-year probability of hip fracture (Fig. 1).

Input and output for the FRAX™ model

Femoral neck BMD can additionally be entered either as a Z-score or a T-score. The transformation of Z- to T-score and vice versa is derived for the NHANES III database for female Caucasians aged 20–29 years [64 (link)]. When entered, calculations give the 10-year probabilities as defined above with or without the inclusion of BMD.