Fracture Risk Prediction With FRAX®

Further background and the FRAX® tool are available at: http://www.shef.ac.uk/FRAX

Introduction
The diagnosis of osteoporosis is usually made by the measurement of bone mineral density (BMD).  The established diagnostic threshold of a BMD T-score of -2.5 is a relatively sensitive diagnostic criterion (most patients with osteoporosis are at high fracture risk) but is not a very specific one (most patients who have fractures related to osteoporosis, including spine and hip fractures, do not have osteoporosis by BMD criteria). Thus, identifying those patients who do not have osteoporosis but who are appropriate to treat with an osteoporosis drug is an important clinical objective. BMD alone cannot do this. Within the BMD category of low bone mass or “osteopenia” are patients at high fracture risk (e.g., a 75 year-old woman with a prior wrist fracture and a T-score of -2.3), as well as many patients at very low risk (e.g., a 58 year-old woman without other risk factors and T-score -1.3). While BMD is an important predictor of fracture risk in postmenopausal women and older men, other risk factors also contribute to risk. By combining these risk factors, patients can be stratified into categories of fracture risk.

FRAX® is a tool to estimate the probability (% chance) of an individual patient experiencing a fracture related to osteoporosis. The risk calculator is based on a compilation of multiple observational studies evaluating risk factors for fracture in men and women in several parts of the world. The studies included almost 250,000 patient years of follow-up during which about 3500 fractures related to osteoporosis occurred. By combining BMD and other important clinical risk factors, fracture risk is accurately estimated. The outputs of FRAX® are the 10-year probability of the patient developing a major osteoporotic fracture (spine, hip, forearm and proximal humerus) or a hip fracture. 

Risk factors included in FRAX®

1. Age, gender, height and weight

2. Ethnicity
   Age-specific fracture risk and mortality differ among Caucasian, Asian, Black and Hispanic Americans, and ethnic-specific FRAX® databases are available for use in the United States. We use the patient’s self-expressed description of ethnicity in FRAX calculations

3. The correct method to enter the BMD information into FRAX® is to choose the brand of DXA machine and then to enter the femoral neck BMD value in g/cm².

Caveats:
Because gender and ethnicity are included in the FRAX® calculator,  T-scores calculated with male or non-Caucasian databases are not appropriate to use in FRAX®.  However, entering the BMD as described about will result in the correct FRAX® estimates of risk. In men and non-Caucasian women, you will note that the T-score calculated by FRAX® will not be the same as the patient’s DXA T-score.  

T-scores or BMD values from other skeletal sites (e.g., lumbar spine, total hip, radius, calcaneus) cannot be used in FRAX® since the relationships between T-scores at different skeletal sites and fracture risk are not the same.

4. Prior fracture history
   Fractures at different skeletal sites have different implications about osteoporosis and future fracture risk. In our calculation of FRAX®, we include fractures that have occurred since menopause in women and since age 50 in men. Fractures of the face, hand, foot and ankle and those that occurred with significant trauma, (auto accident, fall from a height, etc.) are not included.

Caveat:
Fracture risk is likely underestimated in patients with spine fracture, with multiple fractures or with recent

5. Parental history of hip fracture
   Included if either parent has experienced a hip fracture.

Caveat:
It is possible FRAX® overestimates fracture risk in patients whose parent was very elderly when their hip fracture occurred.

6. Glucocorticoid use
   Fracture risk increases within 3 months of beginning glucocorticoid therapy and then decreases toward baseline values within 6 months of stopping treatment. Because of this, we include glucocorticoid use as a risk factor in FRAX® when the patient has received glucocorticoid therapy, at a dose of 5 mg or greater, for at least 3 months, and that course of therapy occurred within the previous 6 months.

Caveat:
FRAX® likely underestimates fracture risk in patients on prednisone doses of 20 mg/day or greater and overestimates fracture risk in those receiving low doses (≤ 5 mg/day).

7. Smoking
   Current smoking is a risk factor for fracture, so this is included as a component of FRAX® only in those patients who are currently smoking.

Caveat:
FRAX® may underestimate fracture risk is very heavy smokers.

8. High intake of alcohol
   Alcohol intake of 3 or more drinks a day is associated with increased fracture risk. Input is based on the patient’s history.

   
   

9. Rheumatoid arthritis
   A clear history of rheumatoid arthritis is a risk factor for fracture independent of BMD. We include rheumatoid arthritis if the patient clearly states that they have been diagnosed with this disorder.

   
   

10. Secondary causes of osteoporosis
    Other than rheumatoid arthritis and glucocorticoid therapy, the effects of medical and metabolic problems and drugs on fracture risk are not known. As a result, FRAX® assumes that the skeletal risks associated with secondary causes of osteoporosis are reflected in the BMD measurement. Since we include BMD in all calculations of FRAX®, having a secondary reason for osteoporosis does not influence the FRAX® calculation. We will report FRAX® in patients with secondary forms of osteoporosis or on drugs that adversely effect the skeleton, but the accuracy of that estimate has not been evaluated.

Other Thoughts About FRAX®

1. FRAX® is not calibrated for use in premenopausal women or younger men.

2. While BMD is an important tool for diagnosing osteoporosis, predicting fracture risk and identifying patients to treat, the change in BMD in response to therapy correlates only weakly with the fracture protection efficacy of our osteoporosis treatments. Consequently, FRAX® cannot be used to monitor response to treatment.

3. Additionally, the non-BMD effects of estrogen or osteoporosis treatments are not included in the FRAX® model, and fracture risk is underestimated by FRAX® in patients on osteoporosis treatment. We will report FRAX® in patients on osteoporosis treatment, but that estimate is of fracture risk if the patient were not on treatment.

 

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