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Misdiagnosis of osteoporosis based on a single bone mineral density measurement
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Abstracts / Bone 44 (2009) S99–S120
vs. baseline in lumbar spine BMD. Trabecular bone turnover was assessed via transilial biopsies obtained from all consenting participants at 24 months. Results: There were progressive dose-related increases in BMD vs. baseline. Lumbar spine and total hip BMD increased 5.5% and 3.2%, respectively with the highest dose, but were essentially unchanged with placebo (−0.2% and −0.9%). Urinary N-telopeptides (NTx/Cr) and bone-specific alkaline phosphatase (BSAP) decreased 52% and 13%, respectively, with the 50-mg dose, whereas uNTx/Cr decreased 5% and BSAP increased 3% with placebo. Preliminary transilial biopsies (N = 27) indicate no significant effect on bone remodeling at the 24-year biopsy time point (Table 1). Conclusions: Two years of odanacatib treatment in postmenopausal women with low BMD increased lumbar spine and total hip BMD with no evidence of skeletal toxicity.
Variable
Bone formation rate (surface) × 100 Activation frequency Osteoclast surface/bone surface Mineralizing/ osteoid surface Mineralization lag time
Units
μm3/ μm2/d
Placebo
Odanacatib
N=6
3 mg N=7
3.7 ± 1.1
4.9 ± 1.0
/yr
0.50 ± 0.16 0.66 ± 0.15
%
0.62 ± 0.10
%
63 ± 18
days
27 ± 8
10 mg N=5 1.7 ± 0.5
178 ± 3
2.7 ± 0.6
50 mg N=4 3.3 ± 1.4⁎
0.24 ± 0.07 0.34 ± 0.07 0.42 ± 0.17⁎
0.58 ± 0.15 0.43 ± 0.16
82 ± 22
25 mg N=6
women (RSR 0.98; 95% CI 0.94–1.04). In comparison to forearm fracture, a hip fracture reduced the relative survival by 15% (men) and 19% (women), whereas a vertebral fracture reduced the relative survival by 23% (men) and 4% (women). In summary, these data indicate that the post-fracture risk of death in men was greater than in women, and that most of the excess of mortality was associated with hip and vertebral fractures. These results also indicate that the first 12 months after a fracture is an “ideal” time of intervention for reducing mortality.
0.59 ± 0.10
0.61 ± 0.20
54 ± 11
63 ± 11
43 ± 25
19 ± 5
15 ± 2
32 ± 12
All values are mean ± standard error; ⁎N = 3 for these endpoints in this group.
doi:10.1016/j.bone.2009.01.227
312 Excess of post-fracture mortality among men and women: A relative survival analysis S.A. Frost, N.D. Nguyen, J.R. Center, J.A. Eisman, T.V. Nguyen Bone and Mineral Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia The post-fracture mortality is assumed to be due to fracture and non-fracture causes. Deaths due to “other causes” are reflected by the background mortality rate. The aims of this study were therefore to estimate the “relative survival” among men and women following a fragility fracture, and to estimate the excess of mortality associated with a specific fracture. The Dubbo Osteoporosis Epidemiological Study was designed as a prospective epidemiologic investigation in which men and women aged 60+ as of 1989 had been followed for 19 years (between 1989 and 2007). During the follow-up period, the incidence of atraumatic fractures ascertained by X-ray reports, and mortality was ascertained by personal report and confirmed by the New South Wales Birth, Death and Marriage Registry. Relative survival ratio (RSR) was estimated by taking into account the age-and-sex specific expected survival in the general Australian population from 1900 to 2007. During the follow-up period 585 women and 230 men had sustained an incident fracture; among whom, 198 (34%) women and 108 (47%) men died after the fracture. The one-year relative survival after a fracture was reduced by 7% (RSR 0.93; 95% CI 0.88–0.98) in men and 1% (95% CI 0.97–1.01) in women. After 5 years, the relative survival was reduced by 17% (RSR 0.83; 95% CI 0.71–0.96) and 2% in
Fig. 1. Relative survival plots by fracture group, women (panel A) and men (panel B).
doi:10.1016/j.bone.2009.01.228
313 Misdiagnosis of osteoporosis based on a single bone mineral density measurement S.A. Frost, N.D. Nguyen, J.A. Eisman, T.V. Nguyen Bone and Mineral Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia A bone mineral density (BMD) T-score at or below −2.5 is considered to be osteoporotic However, the uncertainty of BMD measurement can result in a false positive or a false negative diagnosis. In this study, a Bayesian approach was developed to estimate the probability of having osteoporosis for an individual woman or man based on the individual's BMD measurement.
Abstracts / Bone 44 (2009) S99–S120
An individual's long-term (or “true”) BMD measurement is the weighted average of the individual's observed measurement and the population measurement from which the individual is sampled from, with the weight being measurement error and the variance of population BMD. In this study, the measurement error of BMD was determined by a reliability study in which BMD 25 individuals whose BMD was measured twice. The population variance of BMD was obtained from the Dubbo Osteoporosis Study (DOES). Sexspecific nomograms for the prognosis of osteoporosis as a function of age and observed BMD measurement were developed. For a single BMD T-score, the probability of osteoporosis increased with advancing age (see Fig. 1). A remarkable result of
this analysis is that an individual with an observed T-score of −2.5 has only 50% chance of being truly osteoporotic. Even a 60year old woman with a femoral neck BMD T-score being −2.7, her probability of having osteoporosis is only 61% (i.e. ∼ 1 in 3 women may be misclassified as having osteoporosis). In women and men with a single femoral neck BMD T-scores of −3.0, the probability of misdiagnosis of osteoporotic is below 5%. This analysis has shown that due mainly to random measurement error, the diagnosis of osteoporosis based on a single BMD measurement can result in a significant misclassification. The nomogram developed here can help reduce the chance of misdiagnosis.
Fig. 1. Relative survival plots by fracture group, women (panel A) and men (panel B).
doi:10.1016/j.bone.2009.01.229
S105
Abstracts / Bone 44 (2009) S99–S120
vs. baseline in lumbar spine BMD. Trabecular bone turnover was assessed via transilial biopsies obtained from all consenting participants at 24 months. Results: There were progressive dose-related increases in BMD vs. baseline. Lumbar spine and total hip BMD increased 5.5% and 3.2%, respectively with the highest dose, but were essentially unchanged with placebo (−0.2% and −0.9%). Urinary N-telopeptides (NTx/Cr) and bone-specific alkaline phosphatase (BSAP) decreased 52% and 13%, respectively, with the 50-mg dose, whereas uNTx/Cr decreased 5% and BSAP increased 3% with placebo. Preliminary transilial biopsies (N = 27) indicate no significant effect on bone remodeling at the 24-year biopsy time point (Table 1). Conclusions: Two years of odanacatib treatment in postmenopausal women with low BMD increased lumbar spine and total hip BMD with no evidence of skeletal toxicity.
Variable
Bone formation rate (surface) × 100 Activation frequency Osteoclast surface/bone surface Mineralizing/ osteoid surface Mineralization lag time
Units
μm3/ μm2/d
Placebo
Odanacatib
N=6
3 mg N=7
3.7 ± 1.1
4.9 ± 1.0
/yr
0.50 ± 0.16 0.66 ± 0.15
%
0.62 ± 0.10
%
63 ± 18
days
27 ± 8
10 mg N=5 1.7 ± 0.5
178 ± 3
2.7 ± 0.6
50 mg N=4 3.3 ± 1.4⁎
0.24 ± 0.07 0.34 ± 0.07 0.42 ± 0.17⁎
0.58 ± 0.15 0.43 ± 0.16
82 ± 22
25 mg N=6
women (RSR 0.98; 95% CI 0.94–1.04). In comparison to forearm fracture, a hip fracture reduced the relative survival by 15% (men) and 19% (women), whereas a vertebral fracture reduced the relative survival by 23% (men) and 4% (women). In summary, these data indicate that the post-fracture risk of death in men was greater than in women, and that most of the excess of mortality was associated with hip and vertebral fractures. These results also indicate that the first 12 months after a fracture is an “ideal” time of intervention for reducing mortality.
0.59 ± 0.10
0.61 ± 0.20
54 ± 11
63 ± 11
43 ± 25
19 ± 5
15 ± 2
32 ± 12
All values are mean ± standard error; ⁎N = 3 for these endpoints in this group.
doi:10.1016/j.bone.2009.01.227
312 Excess of post-fracture mortality among men and women: A relative survival analysis S.A. Frost, N.D. Nguyen, J.R. Center, J.A. Eisman, T.V. Nguyen Bone and Mineral Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia The post-fracture mortality is assumed to be due to fracture and non-fracture causes. Deaths due to “other causes” are reflected by the background mortality rate. The aims of this study were therefore to estimate the “relative survival” among men and women following a fragility fracture, and to estimate the excess of mortality associated with a specific fracture. The Dubbo Osteoporosis Epidemiological Study was designed as a prospective epidemiologic investigation in which men and women aged 60+ as of 1989 had been followed for 19 years (between 1989 and 2007). During the follow-up period, the incidence of atraumatic fractures ascertained by X-ray reports, and mortality was ascertained by personal report and confirmed by the New South Wales Birth, Death and Marriage Registry. Relative survival ratio (RSR) was estimated by taking into account the age-and-sex specific expected survival in the general Australian population from 1900 to 2007. During the follow-up period 585 women and 230 men had sustained an incident fracture; among whom, 198 (34%) women and 108 (47%) men died after the fracture. The one-year relative survival after a fracture was reduced by 7% (RSR 0.93; 95% CI 0.88–0.98) in men and 1% (95% CI 0.97–1.01) in women. After 5 years, the relative survival was reduced by 17% (RSR 0.83; 95% CI 0.71–0.96) and 2% in
Fig. 1. Relative survival plots by fracture group, women (panel A) and men (panel B).
doi:10.1016/j.bone.2009.01.228
313 Misdiagnosis of osteoporosis based on a single bone mineral density measurement S.A. Frost, N.D. Nguyen, J.A. Eisman, T.V. Nguyen Bone and Mineral Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, Australia A bone mineral density (BMD) T-score at or below −2.5 is considered to be osteoporotic However, the uncertainty of BMD measurement can result in a false positive or a false negative diagnosis. In this study, a Bayesian approach was developed to estimate the probability of having osteoporosis for an individual woman or man based on the individual's BMD measurement.
Abstracts / Bone 44 (2009) S99–S120
An individual's long-term (or “true”) BMD measurement is the weighted average of the individual's observed measurement and the population measurement from which the individual is sampled from, with the weight being measurement error and the variance of population BMD. In this study, the measurement error of BMD was determined by a reliability study in which BMD 25 individuals whose BMD was measured twice. The population variance of BMD was obtained from the Dubbo Osteoporosis Study (DOES). Sexspecific nomograms for the prognosis of osteoporosis as a function of age and observed BMD measurement were developed. For a single BMD T-score, the probability of osteoporosis increased with advancing age (see Fig. 1). A remarkable result of
this analysis is that an individual with an observed T-score of −2.5 has only 50% chance of being truly osteoporotic. Even a 60year old woman with a femoral neck BMD T-score being −2.7, her probability of having osteoporosis is only 61% (i.e. ∼ 1 in 3 women may be misclassified as having osteoporosis). In women and men with a single femoral neck BMD T-scores of −3.0, the probability of misdiagnosis of osteoporotic is below 5%. This analysis has shown that due mainly to random measurement error, the diagnosis of osteoporosis based on a single BMD measurement can result in a significant misclassification. The nomogram developed here can help reduce the chance of misdiagnosis.
Fig. 1. Relative survival plots by fracture group, women (panel A) and men (panel B).
doi:10.1016/j.bone.2009.01.229
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