Benefits and limitations of FRAX
To use FRAX, one needs to understand its benefits and limitations.
Benefits. FRAX can be used to estimate fracture risk in untreated women and men from age 40 to 90,22 although the National Osteoporosis Foundation guidelines recommend that it be used to make treatment decisions only in untreated postmenopausal women and men age 50 and older with osteopenia who do not otherwise qualify for treatment.9
Expressing fracture risk as a 10-year probability is more clinically useful than expressing it as a relative risk. For example, if the relative risk of fracture is five times that of a comparator population in which the risk is close to zero, then the patient’s risk is low, although a physician might feel compelled to treat upon learning that the relative risk is 5. A 50-year-old woman and an 80-year-old woman with identical T-scores of −2.5 have the same relative risk of fracture,36 even though the 10-year probability of fracture is far greater for the older woman.37
Limitations. FRAX has not been validated in treated patients, in women and men outside the specified age range, or in children. In the United States, the use of FRAX is limited to four ethnic groups—white, black, Hispanic, and Asian. FRAX has not been validated in patients of mixed ethnicity or of other ethnic groups in the United States.
The seven clinical risk factors in FRAX are entered as yes-or-no responses, whereas the actual risk in an individual patient may depend on the dose or severity of the risk factor. For example, a patient who was treated with the glucocorticoid prednisone 5 mg per day for 4 months many years ago has a much lower risk than a similar patient who has been taking prednisone 10 mg per day for the past 10 years, even though the FRAX input (“yes” for glucocorticoid therapy) is the same and the FRAX estimation of fracture risk is the same.
Only the bone mineral density in the femoral neck is used in FRAX, although in some patients, the density at another skeletal site may be better correlated with fracture risk (eg, low lumbar spine density may be associated with high fracture risk even when femoral neck density is not low).
Other important risk factors, such as falling, rate of bone loss, and high bone turnover are not part of the FRAX algorithm.
These limitations of FRAX may lead to overestimation or underestimation of actual fracture risk when used in some clinical circumstances, with an uncertain range of error for the calculated 10-year fracture probability.
Using FRAX appropriately
Clinicians must recognize when FRAX is likely to overestimate or underestimate fracture risk (see above).
FRAX also requires appropriate patient selection and a thorough understanding of its role in patient care decisions. Although it can be used to estimate fracture risk for a postmenopausal woman with osteoporosis, this use is not necessary and may be confusing; the National Osteoporosis Foundation guidelines recommend treatment for such a patient regardless of what FRAX says, while the FRAX calculation might result in a value that is below the treatment threshold.
Since the main clinical utility of FRAX is to help in making treatment decisions, strategies for using FRAX in the United States are discussed in association with the National Osteoporosis Foundation treatment guidelines in the section that follows.
NATIONAL OSTEOPOROSIS FOUNDATION GUIDELINES FOR TREATMENT
Many medical organizations have issued clinical practice guidelines for treating osteoporosis, with some recommendations that differ and therefore confuse more than enlighten.38
In an effort to unify these disparate recommendations, the National Osteoporosis Foundation, with the support and endorsement of numerous professional societies, developed the Clinician’s Guide to Prevention and Treatment of Osteoporosis.9 This document addresses postmenopausal women and men age 50 and older of all ethnic groups in the United States and is intended for use by clinicians in making decisions in the care of individual patients. The recommendations should not be taken as rigid standards of practice but rather as a framework for making clinical decisions with consideration of the needs of each individual patient.
Recommendations for all patients
- A daily intake of elemental calcium of at least 1,200 mg with diet plus supplements, if needed (with no more than 500–600 mg of calcium supplementation in a single dose due to limited absorption of higher doses)
- Vitamin D3 800–1,000 IU per day, with more needed in some patients to bring the serum 25-hydroxyvitamin D to a desirable level of 30 ng/mL (75 nmol/L) or higher
- Regular weight-bearing exercise
- Fall prevention
- Avoidance of tobacco use and excessive alcohol intake.
Who should be tested?
The National Osteoporosis Foundation recommends bone density testing in patients at risk of osteoporosis according to indications that are almost identical to those of the International Society for Clinical Densitometry, ie:
- Women age 65 and older
- Postmenopausal women under age 65 with risk factors for fracture
- Women during the menopausal transition with clinical risk factors for fracture, such as low body weight, prior fracture, or use of high-risk drugs such as glucocorticoids
- Men age 70 and older
- Men under age 70 with clinical risk factors for fracture
- Adults with a fragility fracture
- Adults with a disease or condition associated with low bone mass or bone loss
- Adults taking drugs associated with low bone mass or bone loss
- Anyone being considered for pharmacologic therapy
- Anyone being treated, to monitor treatment effect
- Anyone not receiving therapy in whom evidence of bone loss would lead to treatment.
Women discontinuing estrogen should be considered for bone density testing according to the indications listed above.
All patients with osteoporosis should have a skeletal-related history and physical examination, with appropriate laboratory testing to evaluate for contributing factors.
Who should be treated?
The National Osteoporosis Foundation recommends considering starting drug therapy in postmenopausal women and men age 50 and older who have any of the following:
- A hip or vertebral (clinical or morphometric) fracture
- A T-score of −2.5 or less at the femoral neck or spine after appropriate evaluation to exclude secondary causes
- Low bone mass (a T-score between −1.0 and −2.5 at the femoral neck or spine) and a 10-year probability of a hip fracture of 3% or more or a 10-year probability of a major osteoporosis-related fracture of 20% or more, based on the US version of FRAX (patient preferences may indicate treatment for people with 10-year fracture probabilities above or below these levels).