Question 1: a total of 45 studies addressed risk factor assessment. Seventeen studies (n=61,996) assessed factors predicting hip fracture, 8 studies (n=28,214) assessed factors predicting low bone density, 4 studies (n=4,016) assessed factors predicting bone loss, and 17 studies assessed the use of risk assessment tools.
Questions 2 and 3: 9 studies assessed bone measurement tests for the prediction of fracture, and 26 studies assessed agreement between different bone measurement tests.
Question 4: a total of 45 studies assessed biochemical markers of bone turnover. Five studies (n=1,427) assessed the diagnostic accuracy of biochemical markers in comparison with bone density, 6 studies (n=1,994) assessed the ability of markers to predict fracture in untreated individuals, 12 studies (n=1,522) assessed the ability of markers to predict bone loss in untreated individuals, and 18 studies examined the use of markers to monitor or predict response to therapy (n>2,974).
Question 5: no studies were found.
Question 1.
Factors consistently associated with increased risk of low bone density and fracture were increasing age, white race, low weight or weight loss, non-use of oestrogen replacement, history or family history of fracture, history of falls, and low scores on measures of physical activity or function. Other risk factors, which were statistically significant in some studies, were smoking, alcohol use, caffeine use, low calcium and vitamin D intake, and some drugs. Predictors of low bone density were similar to those for fracture. Some risk factors were as powerful as bone density in predicting hip fracture. People with multiple risk factors and low bone density have a particularly high risk of hip fracture.
There were few studies evaluating the use of risk factors to identify women at risk for fracture, and the accuracy of methods designed to assess the risk factors was generally poor.
No studies were identified that compared treatment decisions based on clinical risk factors with those based on bone measurement tests or a combination of the two.
Questions 2 and 3.
Bone density measured at the femoral neck by dual energy X-ray absorptiometry was the best predictor of hip fracture. It was comparable to forearm measurements for predicting other fractures. More recent studies of quantitative ultrasound measured at the heel showed comparable results. Individuals with high scores on one test and low scores on the other had intermediate probability of fracture.
Correlations between different bone measurement methods were generally low.
The likelihood of a diagnosis of osteoporosis varied with type of bone measurement test, brand of densitometer, relevance of reference range to local population, and number and location of sites tested. The results were often inaccurately reported to the patients.
One RCT suggested that women undergoing densitometry were more likely to start hormone replacement. One trial and one case series found that women who had undergone densitometry and who had been told that they had osteoporosis were more likely to start or continue hormone replacement. In one trial physicians found densitometry reports confusing and were not confident of their interpretations.
Evidence did not support repetition of bone density tests within the first year of treatment. There was insufficient evidence to determine the usefulness of repeating after two years of treatment. No studies assessing the effect of monitoring response to therapy, or choice of test on therapy outcome, were identified.
Question 4.
No single marker or combination of markers was accurate in predicting the results of bone densitometry. No marker could accurately predict increased fracture risk. One study suggested that using markers in combination with densitometry resulted in a more accurate prediction of fracture. Marker results did not correlate with bone loss. Some studies found better accuracy where markers were used in combination with other markers or risk factors to predict bone loss.
The accuracy of markers was too low to be useful in selecting patients for treatment. There was a small correlation between response to therapy (measured by densitometry) and marker results, but no marker was sufficiently accurate to identify individuals who will fail to respond to treatment.
Question 5.
There was no evidence on which to base the formulation of a strategy to determine secondary causes of osteoporosis.