Based in part on medical record documentation for these subjects that extended back 36 years prior to the initial assessment, baseline characteristics of the subjects are outlined in . Within the components of the FRAX algorithm, women and men were similar except for prior history of a fragility fracture (32% versus 24%; P
= 0.039) and lower FN BMD levels (0.700
< 0.001), as well as more “other secondary osteoporosis” (P
< 0.001), among the women. The latter discrepancy was accounted for by premature (<45 years) menopause; excluding that, the prevalence of the other causes of secondary osteoporosis, excluding rheumatoid arthritis, was similar in women and men (6% versus 7%). With regard to potential extensions of FRAX, women were more likely to have one or more risk factors for falling (85% versus 60%; P
< 0.001), but the difference in reported falls in the previous year was not significant. They also had lower LS BMD (0.971 versus 1.129
< 0.001) and lower bone formation as assessed by serum OC levels (5.80
ng/mL versus 6.52
= 0.003), despite comparable bone resorption as assessed by serum NTx levels (12.5 nMBCE versus 12.6 nMBCE; P
= 0.830). None of the men, compared to 19% of the women (P
< 0.001), were on an osteoporosis treatment at baseline.
Fracture risk factors at baseline among 250 women and 249 men ≥40 years of age randomly sampled from the Rochester, MN population.
Subjects were then followed and censored at death or loss to followup (if before 10 years) or after 10 years of followup among survivors (4455 person-years). Altogether, 74% were followed for at least 10 years, and death accounted for almost all of the shorter followup intervals (median followup of those who died was 7 years). Even so, observed survival at 10 years was 77% when 70% was expected (P < 0.001).
During this same 10-year followup interval, 218 subjects experienced 380 different fractures, including 165 asymptomatic, nonpathological vertebral fractures that were discovered incidentally; 4 pathologic fractures (including 2 vertebral fractures) were excluded from most analyses. Most fractures were due to no more than moderate trauma (). The primary analysis focused, however, on the major osteoporotic fractures (i.e., hip, symptomatic (clinical) spine, distal forearm, and proximal humerus). Forty-four women had at least one major osteoporotic fracture, including 11 with an incident hip fracture, as did 18 men, including 5 who had an incident hip fracture. In addition, 61 women and 33 men experienced at least one fracture at another skeletal site.
Fracture outcomes over 10 years among Rochester, MN women and men ≥40 years of age at baseline, by precipitating trauma.
The median FRAX probability for any major osteoporotic fracture was 7% (range, 0–45%), being 10% in women (range, 0–45%) and 5% in men (range, 0–30%). The predicted risk was greater among women than men and increased in accordance with the major osteoporotic fractures actually observed (). More fractures were observed than expected in most quartiles (overall SIR = 1.6, 95% CI 1.1–2.1 in women and SIR = 1.4, 95% CI 0.8–2.2 in men). Just 5 fractures were observed in the lowest FRAX quartile (2 women due to severe trauma and 3 men due to moderate trauma), whereas 28 occurred in the highest risk quartile. Only 16 hip fractures were observed during followup so statistical power was limited, but the risk estimates for hip fractures in women (SIR = 1.5, 95% CI 0.8–2.7) and men (SIR = 1.7, 95% CI 0.6–4.0) resembled those for all major osteoporotic fractures combined.
First major osteoporotic fractures observed among Rochester, MN women and men compared to numbers predicted by revised US FRAX (FN BMD), by age at baseline and quartile of full 10-year fracture probability (%).
To explore the apparent underestimation of 10-year fracture risk, we compared site-specific fracture counts with the numbers expected from the incidence rates used in revised US FRAX. For combined men and women age ≥50 years old (the age group reported for those rates), there were somewhat fewer observed first fractures of the hip (16 versus 24, P = 0.111), greater numbers of distal forearm (19 versus 15, P = 0.285) and symptomatic vertebral fractures (20 versus 15, P = 0.166), and similar numbers of proximal humerus fractures (8 versus 7, P = 0.834) compared to expected. Overall agreement between observed and expected fractures was better among the men ≥50 years of age (16 versus 14, P = 0.642) than the women (41 versus 32, P = 0.099), but none of these differences was statistically significant.
However, FRAX predicted fractures at other sites about as well as it did major osteoporotic fracture risk (). Thus, a relative 10% increase in FRAX 10-year fracture probability was associated with a 1.9-fold increase in major osteoporotic fractures, and a 1.4-fold increase in all other fractures, in the women. Among the men, a 10% increase in the FRAX probability was associated with a 2.1-fold increase in major osteoporotic fractures and with a 1.7-fold increase in other fractures. FRAX predicted asymptomatic vertebral fractures as well as symptomatic ones, as it did fractures generally.
First nonpathologic fracture of each type observed and hazard ratio (HR) per 10% increase in the full 10-year US FRAX (FN BMD) probability among Rochester, MN women and men ≥40 years of age, by type of fracture outcome.
After forcing the full FRAX probability for each subject into a model, the potential contribution of additional risk factors was evaluated (). Although statistical power was limited, there was no additional contribution from a history of falling; the presence of risk factors for falling was associated with an increased risk that was not statistically significant, but adding them did not improve the C-statistic over that for FRAX alone (C-statistic, 0.75 in women and 0.65 in men). Results were not changed by counting the number of falls or fall risk factors (data not shown). Likewise, the presence of additional causes of secondary osteoporosis or the use of estrogen had little effect on the results. There was also no significant contribution to fracture prediction, once the FRAX probability was known, from the addition of LS BMD T-scores, the discrepancy between FN and LS T-scores or measures of bone resorption (NTx) or formation (OC). However, the ratio of resorption to formation (NTx ÷ OC) did predict fractures independently of FRAX in both women (HR = 1.4, 95% CI 1.1–1.6) and men (HR = 1.2, 95% CI 1.04–1.4), although the C-statistic was little changed by this addition. Generally, all of the models predicted fractures better among women than men.
Effect of additional risk factors to predict first major osteoporotic fracture (Fx) over 10 years among Rochester, MN women and men ≥40 years of age, after adjusting for the full US FRAX (FN BMD) probability.