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ABSTRACT: Osteoporosis is a skeletal disorder in which reductions in bone strength predispose to an increased risk for fractures. Currently, the diagnosis is officially made based exclusively on bone mineral density T-scores that are ≤-2.5 at the spine or hip. Limiting the clinical diagnosis of osteoporosis solely to a T-score-based criterion, which is the official convention in the USA, creates uncertainty about the use of the term osteoporosis to diagnose older women and men who have T-scores >-2.5, but either have already sustained low-trauma fractures or are recognized as having high fracture risk based on absolute fracture risk calculations from FRAX or other algorithms. A failure to diagnose such patients as having osteoporosis may be one component of the well-documented underdiagnosis and undertreatment of this disease which limits our ability to reduce the burden of fractures worldwide. There is a need to expand the criteria for making a clinical diagnosis and to codify these changes in order to help patients, physicians, policy makers, and payers better understand who has this disease and the elevated risk for fracture that it represents.
Osteoporosis International 04/2012; 23(8):2093-7. · 4.58 Impact Factor
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G Ioannidis,
J Flahive,
L Pickard,
A Papaioannou,
R D Chapurlat,
K G Saag,
S Silverman,
F A Anderson,
S H Gehlbach,
F H Hooven, [......],
A Z Lacroix,
R Lindsay,
J C Netelenbos,
J Pfeilschifter,
M Rossini,
C Roux,
P N Sambrook, E S Siris,
N B Watts,
J D Adachi
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ABSTRACT: We evaluated healthcare utilization associated with treating fracture types in >51,000 women aged ≥55 years. Over the course of 1 year, there were five times more non-hip, non-spine fractures than hip or spine fractures, resulting in twice as many days of hospitalization and rehabilitation/nursing home care for non-hip, non-spine fractures. INTRODUCTION: The purpose of this study is to evaluate medical healthcare utilization associated with treating several types of fractures in women ≥55 years from various geographic regions. METHODS: Information from the Global Longitudinal Study of Osteoporosis in Women (GLOW) was collected via self-administered patient questionnaires at baseline and year 1 (n = 51,491). Self-reported clinically recognized low-trauma fractures at year 1 were classified as incident spine, hip, wrist/hand, arm/shoulder, pelvis, rib, leg, and other fractures. Healthcare utilization data were self-reported and included whether the fracture was treated at a doctor's office/clinic or at a hospital. Patients were asked if they had undergone surgery or been treated at a rehabilitation center or nursing home. RESULTS: During 1-year follow-up, there were 195 spine, 134 hip, and 1,654 non-hip, non-spine fractures. Clinical vertebral fractures resulted in 617 days of hospitalization and 512 days of rehabilitation/nursing home care; hip fractures accounted for 1,306 days of hospitalization and 1,650 days of rehabilitation/nursing home care. Non-hip, non-spine fractures resulted in 3,805 days in hospital and 5,186 days of rehabilitation/nursing home care. CONCLUSIONS: While hip and vertebral fractures are well recognized for their associated increase in health resource utilization, non-hip, non-spine fractures, by virtue of their 5-fold greater number, require significantly more healthcare resources.
Osteoporosis International 04/2012; · 4.58 Impact Factor
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C Roux,
A Wyman,
F H Hooven,
S H Gehlbach,
J D Adachi,
R D Chapurlat,
J E Compston,
C Cooper,
A Díez-Pérez,
S L Greenspan,
A Z Lacroix,
J C Netelenbos,
J Pfeilschifter,
M Rossini,
K G Saag,
P N Sambrook,
S Silverman, E S Siris,
N B Watts,
S Boonen
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ABSTRACT: Among 50,461 postmenopausal women, 1,822 fractures occurred (57% minor non-hip, non-vertebral [NHNV], 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine fractures had the greatest detrimental effect on EQ-5D, followed by major NHNV and hip fractures. Decreases in physical function and health status were greatest for spine or hip fractures. INTRODUCTION: There is growing evidence that NHNV fractures result in substantial morbidity and healthcare costs. The aim of this prospective study was to assess the effect of these NHNV fractures on quality of life. METHODS: We analyzed the 1-year incidences of hip, spine, major NHNV (pelvis/leg, shoulder/arm) and minor NHNV (wrist/hand, ankle/foot, rib/clavicle) fractures among women from the Global Longitudinal study of Osteoporosis in Women (GLOW). Health-related quality of life (HRQL) was analyzed using the EuroQol EQ-5D tool and the SF-36 health survey. RESULTS: Among 50,461 women analyzed, there were 1,822 fractures (57% minor NHNV, 26% major NHNV, 10% spine, 7% hip) over 1 year. Spine fractures had the greatest detrimental effect on EQ-5D summary scores, followed by major NHNV and hip fractures. The number of women with mobility problems increased most for those with major NHNV and spine fractures (both +8%); spine fractures were associated with the largest increases in problems with self care (+11%), activities (+14%), and pain/discomfort (+12%). Decreases in physical function and health status were greatest for those with spine or hip fractures. Multivariable modeling found that EQ-5D reduction was greatest for spine fractures, followed by hip and major/minor NHNV. Statistically significant reductions in SF-36 physical function were found for spine fractures, and were borderline significant for major NHNV fractures. CONCLUSION: This prospective study shows that NHNV fractures have a detrimental effect on HRQL. Efforts to optimize the care of osteoporosis patients should include the prevention of NHNV fractures.
Osteoporosis International 03/2012; · 4.58 Impact Factor
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J Pfeilschifter,
C Cooper,
N B Watts,
J Flahive,
K G Saag,
J D Adachi,
S Boonen,
R Chapurlat,
J E Compston,
A Díez-Pérez,
A Z LaCroix,
J C Netelenbos,
M Rossini,
C Roux,
P N Sambrook,
S Silverman, E S Siris
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ABSTRACT: We examined variations in proportions of hip fractures and major fractures among postmenopausal women using the Global Longitudinal Study of Osteoporosis in Women (GLOW). The proportion of major fractures that were hip fractures varied with age and region, whereas variations in the proportion of fractures that were major fractures appeared modest.
In many countries, the World Health Organization fracture risk assessment tool calculates the probability of major fractures by assuming a uniform age-associated proportion of major fractures that are hip fractures in different countries. We further explored this assumption, using data from the GLOW.
GLOW is an observational population-based study of 60,393 non-institutionalized women aged ≥55 years who had visited practices within the previous 2 years. Main outcome measures were self-reported prevalent fractures after the age of 45 years and incident fractures during the 2 years of follow-up.
The adjusted proportion of prevalent and incident major fractures after the age of 45 years that were hip fractures was higher in North America (16%, 17%) than in northern (13%, 12%) and southern Europe (10%, 10%), respectively. The proportion of incident major fractures that were hip fractures increased more than five-fold with age, from 6.6% among 55-59-year-olds to 34% among those aged ≥85 years. Regional and age-associated variations in the proportion of all incident fractures that were major fractures were less marked, not exceeding 16% and 28%, respectively.
The data suggest that there may be regional differences in the proportion of major fractures that are hip fractures in postmenopausal women. In contrast, the regional and age-related variations in the proportion of fractures that are major fractures appear to be modest. However, because of the limited number of fractures in our sample, further studies are necessary to confirm these findings.
Osteoporosis International 11/2011; 23(8):2179-88. · 4.58 Impact Factor
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S Silverman,
H N Viswanathan,
Y-C Yang,
A Wang,
S Boonen,
S Ragi-Eis,
P Fardellone,
N Gilchrist,
P Lips,
M Nevitt,
S Palacios Gil-Antuñano,
K Pavelka,
D Revicki,
J Simon,
D Macarios, E S Siris
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ABSTRACT: In the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) study, women with incident clinical fractures reported significant declines in health-related quality of life (HRQoL). The largest declines were observed when the assessment was <3 months post fracture. The largest impact of incident clinical fractures was on physical function, and that of incident clinical vertebral fractures was on back pain.
In the FREEDOM trial, denosumab significantly reduced the risk of new vertebral, hip, and nonvertebral fractures. We evaluated the effect of denosumab on HRQoL and the association between incident clinical fractures and HRQoL.
The FREEDOM trial enrolled 7,868 women aged 60-90 years with a total hip and/or lumbar spine BMD T-score <-2.5 and not <-4.0 at either site. Women were randomized to receive denosumab 60 mg or placebo every 6 months, in addition to daily calcium and vitamin D. HRQoL was assessed with the Osteoporosis Assessment Questionnaire-Short Version (OPAQ-SV) at baseline and every 6 months for 36 months. The OPAQ-SV assesses physical function, emotional status, and back pain. Higher scores indicate better health status.
No statistically significant differences in mean change in HRQoL from baseline to end of study were found when comparing treatment groups. Compared with women without any incident fractures during the study, women with incident clinical fractures reported significant declines in physical function (-4.0 vs. -0.5) and emotional status (-5.0 vs. -0.8) at month 36 (P < 0.001 for both). Importantly, time-dependent covariate analyses demonstrated that the largest declines were observed when the assessment was <3 months post fracture. The largest impact of incident clinical fractures was on physical function, and that of incident clinical vertebral fractures was on back pain.
These findings not only demonstrate that incident clinical fractures impact HRQoL but also contribute new information regarding the impact of these fracture events on HRQoL over time.
Osteoporosis International 07/2011; 23(4):1361-9. · 4.58 Impact Factor
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E S Siris,
S Gehlbach,
J D Adachi,
S Boonen,
R D Chapurlat,
J E Compston,
C Cooper,
P Delmas,
A Díez-Pérez,
F H Hooven, [......],
J C Netelenbos,
J Pfeilschifter,
M Rossini,
C Roux,
K G Saag,
P Sambrook,
S Silverman,
N B Watts,
A Wyman,
S L Greenspan
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ABSTRACT: We compared self-perception of fracture risk with actual risk among 60,393 postmenopausal women aged ≥55 years, using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW). Most postmenopausal women with risk factors failed to appreciate their actual risk for fracture. Improved education about osteoporosis risk factors is needed.
This study seeks to compare self-perception of fracture risk with actual risk among postmenopausal women using data from GLOW.
GLOW is an international, observational, cohort study involving 723 physician practices in 17 sites in ten countries in Europe, North America, and Australia. Participants included 60,393 women ≥55 years attended by their physician during the previous 24 months. The sample was enriched so that two thirds were ≥65 years. Baseline surveys were mailed October 2006 to February 2008. Main outcome measures were self-perception of fracture risk in women with elevated risk vs women of the same age and frequency of risk factors for fragility fracture.
In the overall study population, 19% (10,951/58,434) of women rated their risk of fracture as a little/much higher than that of women of the same age; 46% (27,138/58,434) said it was similar; 35% (20,345/58,434) believed it to be a little/much lower. Among women whose actual risk was increased based on the presence of any one of seven risk factors for fracture, the proportion who recognized their increased risk ranged from 19% for smokers to 39% for current users of glucocorticoid medication. Only 33% (4,185/12,612) of those with ≥2 risk factors perceived themselves as being at higher risk. Among women reporting a diagnosis of osteopenia or osteoporosis, only 25% and 43%, respectively, thought their risk was increased.
In this international, observational study, most postmenopausal women with risk factors failed to appreciate their actual risk for fracture.
Osteoporosis International 04/2010; 22(1):27-35. · 4.58 Impact Factor
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ABSTRACT: The short-term association between wrist-fracture history and future fracture has not been simultaneously compared between younger and older postmenopausal women. This 3-year follow-up study of 158,940 women showed a similar future fracture risk in younger and older women with wrist-fracture history.
We examined the association between prior wrist fracture and future osteoporosis-related fractures within 3 years in younger and older postmenopausal women.
In the National Osteoporosis Risk Assessment (NORA) study, 158,940 postmenopausal women, aged 50-98 (median 63) years, provided information on fracture history since age 45, and responded to follow-up surveys 1 or 3 years later when new fractures were queried. Cox regression models were used to obtain relative risk (RR) and 95% confidence interval (CI) estimates.
Of the 158,940 participants, 8,665 reported a history of wrist fracture at baseline; 4,316 women reported at least one new fracture within three years. The RR for any subsequent clinical fracture, adjusted for covariates and baseline BMD T-score, was 2.4 (2.0, 2.9) for younger and 2.1 (1.9, 2.3) for older women. A prior wrist fracture increased the risk of a future wrist fracture about 3-fold and doubled the risk of any osteoporotic fracture.
Prior wrist fracture strongly predicts three-year risk of any future osteoporotic fracture for older and younger postmenopausal women, independent of baseline BMD and common osteoporosis risk factors. More consideration should be given to evaluating and managing osteoporosis in younger and older women with a history of wrist fracture, independent of their BMD.
Osteoporosis International 06/2008; 19(5):607-13. · 4.58 Impact Factor
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ABSTRACT: This posthoc analysis of four trials studied the efficacy of risedronate to reduce fragility fractures in postmenopausal women with osteopenia (i.e., T-scores between -1 and -2.5). Risedronate reduced the fracture risk by 73% (p = 0.023) in this population of women with low femoral neck bone mass and no prevalent vertebral fractures.
Low bone mass represents an increasing health risk and burden. Half of fragility fractures occur in osteopenic women underscoring the need for treatments reducing fracture risk. This analysis reports the effect of risedronate to reduce fragility fracture risk in osteopenic women without prevalent vertebral fractures.
Postmenopausal women with osteopenia, defined as femoral neck T-score between -1 and -2.5 by DXA and no prevalent vertebral fractures, were identified from four controlled randomized trials (BMD Multinational, BMD North America, VERT Multinational and VERT North America). The risk reduction for fragility fractures in patients receiving 5 mg risedronate daily for 1.5 to 3 years compared to placebo was assessed. An additional sensitivity analysis excluded patients who were osteopenic at the femoral neck but had a BMD lower than -2.5 SD at the lumbar spine.
Six hundred and twenty postmenopausal women with osteopenia were included, receiving either placebo (n = 309) or risedronate 5 mg (n = 311). Risedronate reduced the risk of fragility fractures by 73% over 3 years versus placebo (p = 0.023); cumulative fragility fracture incidence was 6.9% in placebo-treated versus 2.2% in risedronate-treated patients. The magnitude of the effect was similar in the sensitivity analysis subset.
Risedronate significantly reduced the risk of fragility fractures in postmenopausal women with osteopenia (femoral neck T-score between -1 and -2.5 SD) and no prevalent vertebral fractures.
Osteoporosis International 06/2008; 19(5):681-6. · 4.58 Impact Factor
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ABSTRACT: The impact of calcium and vitamin D intake on bone density and one-year fracture risk was assessed in 76,507 postmenopausal Caucasian women. Adequate calcium with or without vitamin D significantly reduced the odds of osteoporosis but not the risk of fracture in these Caucasian women.
Calcium and vitamin D intake may be important for bone health; however, studies have produced mixed results.
The impact of calcium and vitamin D intake on bone mineral density (BMD) and one-year fracture incidence was assessed in 76,507 postmenopausal Caucasian women who completed a dietary questionnaire that included childhood, adult, and current consumption of dairy products. Current vitamin D intake was calculated from milk, fish, supplements and sunlight exposure. BMD was measured at the forearm, finger or heel. Approximately 3 years later, 36,209 participants returned a questionnaire about new fractures. The impact of calcium and vitamin D on risk of osteoporosis and fracture was evaluated by logistic regression adjusted for multiple covariates.
Higher lifetime calcium intake was associated with reduced odds of osteoporosis (peripheral BMD T-score < or =-2.5; OR = 0.80; 95% CI 0.72, 0.88), as was a higher current calcium (OR = 0.75; (0.68, 0.82)) or vitamin D intake (OR = 0.73; 95% CI 0.0.66, 0.81). Women reported 2,205 new osteoporosis-related fractures. The 3-year risk of any fracture combined or separately was not associated with intake of calcium or vitamin D.
Thus, higher calcium and vitamin D intakes significantly reduced the odds of osteoporosis but not the 3-year risk of fracture in these Caucasian women.
Osteoporosis International 05/2008; 19(5):673-9. · 4.58 Impact Factor
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ABSTRACT: This study investigated osteoporosis management trends from 1998 to 2006 among 808 primary care physicians involved in the US-based NORA (National Osteoporosis Risk Assessment) study. These results suggest some significant improvements in osteoporosis management over the past eight years.
The purpose of this study was to investigate osteoporosis management trends among a large cohort of primary care physicians (PCPs) involved in the US-based NORA (National Osteoporosis Risk Assessment) study.
In 2006, we undertook a resurvey of the 2,836 NORA PCPs who completed a baseline survey in 1998. Of the 2,199 PCPs for whom we had current contact information and who were still practicing, we collected usable surveys from 808 (37% response rate).
From 1998 to 2006, more than double the percentage of NORA PCPs reported using BMDs "often" (35% vs. 87%). There was a doubling of the percentage of NORA PCPs who reported that a T-score of < or = -2.5 was the threshold indicating the presence of osteoporosis (34% vs. 67%). The percentage of NORA PCPs who reported using bone turnover markers to screen, diagnosis, or monitor osteoporosis almost tripled (19% vs. 55%). The percentage of patients prescribed or recommended hormone therapy dropped sixfold (67% to 11%), and the percentage of patients prescribed bisphosphonates increased fourfold from 15% to 59%.
These results suggest some significant improvements in osteoporosis management over the past eight years.
Osteoporosis International 12/2007; 18(11):1473-80. · 4.58 Impact Factor
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ABSTRACT: Using data from NORA, we used 18 potential risk factors in a classification and regression tree analysis to build two algorithms. These algorithms correctly identified postmenopausal women between the ages of 50 and 64 years who were at the highest risk of osteoporotic fracture within 36 months.
The objective was to develop algorithms that best predict short-term fracture risk (3 years) in postmenopausal women 50-64 years old.
Data were from 91,652 women who responded to follow-up surveys as part of National Osteoporosis Risk Assessment (NORA) study. Peripheral bone mineral density (BMD) and risk factors obtained at baseline; incident osteoporotic fractures obtained from follow-up surveys. Eighteen risk factors were entered into a classification and regression tree analysis to build two algorithms, one with and one without BMD.
Two thousand and seven (2.2%) women reported new osteoporotic fractures. Prior fracture, a peripheral BMD T-score <or= -1.1, and self-reported fair/poor health status were the most important determinants for short-term fracture and were associated, respectively, with 7.2%, 3.1%, and 2.4% fracture risk within 3 years. This algorithm with three risk factors correctly classified 65% of the women who experienced an incident fracture and 59% of the women who did not experience an incident fracture. Without BMD T-score, the most important determinants for fracture prediction were previous fracture, self-reported fair/poor health status, and no current use of postmenopausal hormone therapy.
NORA-based algorithms may be useful for health care providers to guide further assessment and management decisions to prevent fractures in younger postmenopausal women.
Osteoporosis International 09/2007; 18(9):1287-96. · 4.58 Impact Factor
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ABSTRACT: Prevalent vertebral fractures are associated with increased fracture risk, but the magnitude of this effect across a range of BMD T-scores has not been quantified. In this analysis, for any given BMD T-score, incident fracture risk varied up to twelve fold when information regarding prevalent radiographic vertebral fracture status was considered.
Clinical fracture risk evaluation of older women usually includes assessment of bone mineral density (BMD) but often not vertebral fracture status. In this analysis, we quantified the impact of vertebral fracture burden on two year fracture risk across a range of BMD T-scores.
Data were from 2,651 postmenopausal women who were assigned to the placebo groups of the Fracture Prevention Trial (median observation 21 months) and the Multiple Outcomes of Raloxifene Evaluation Trial (MORE; observation 2 years). Using the Genant visual semiquantitative criteria, we defined prevalent vertebral fracture status as: a) presence or absence of fracture; b) fracture number; c) maximum semi-quantitative (SQ) score (normal=0, mild fracture=1, moderate fracture=2, severe fracture=3); and d) spinal deformity index (SDI) score (sum of SQ scores of T4 to L4 vertebrae). Incident fractures over two years were identified via lateral spine radiographs and outside the spine by questioning of patients and review of radiographs or radiographic reports.
Femoral neck BMD T-score provided significant information regarding fracture risk. Across the range of T-scores, vertebral fracture status provided additional prognostic information. The risk increased with increasing number and severity of prevalent vertebral fractures and SDI, a summary measure of spine fracture burden. Across a range of BMD values, prevalent spine fracture burden as assessed by SDI increased the risk of incident vertebral fractures by up to 12-fold, nonvertebral fractures by about twofold, and any fractures by up to sevenfold.
These findings indicate that at any given BMD T-score, the risk of incident vertebral, non-vertebral, and any fracture depended heavily on prevalent radiographic vertebral fracture status. Assessment of vertebral fracture status, in addition to BMD, provides practical and relevant clinical information to aid in predicting fracture risk in postmenopausal women.
Osteoporosis International 07/2007; 18(6):761-70. · 4.58 Impact Factor
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ABSTRACT: This study evaluates the effect of age and bone mineral density (BMD) on the absolute, excess, and relative risk for osteoporotic fractures at the hip, wrist, forearm, spine, and rib within 3 years of peripheral BMD testing in postmenopausal women over a wide range of postmenopausal ages.
Data were obtained from 170,083 women, aged 50-99 years, enrolled in the National Osteoporosis Risk Assessment (NORA) following recruitment from their primary care physicians' offices across the United States. Risk factors for fracture and peripheral BMD T-scores at the heel, forearm, or finger were obtained at baseline. Self-reported new fractures at the hip, spine, rib, wrist, and forearm were obtained from questionnaires at 1- and 3-year follow-ups. Absolute, excess (attributable to low BMD), and unadjusted and adjusted relative risks of fracture were calculated.
At follow-up, 5312 women reported 5676 fractures (868 hip, 2420 wrist/forearm, 1531 rib, and 857 spine). Absolute risk of fracture increased with age for all fracture sites. This age-effect was most evident for hip fracture--both the incidence and the excess risk of hip fracture for women with low BMD increased at least twofold for each decade increase in age. The relative risk for any fracture per 1 SD decrease in BMD was similar across age groups (p>0.07). Women with low BMD (T-score <-1.0) had a similar relative risk for fracture regardless of age.
At any given BMD, not only the absolute fracture risk but also the excess fracture risk increased with advancing age. Relative risk of fracture for low bone mass was consistent across all age groups from 50 to 99 years.
Osteoporosis International 01/2006; 17(4):565-74. · 4.58 Impact Factor
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ABSTRACT: Although osteoporosis and fragility fracture are common amongst postmenopausal women, the extent of risk varies, and measurement of bone mineral density (BMD) is the standard tool used to diagnose and assess fracture risk. Rates of diagnosis remain relatively low, and several groups have developed instruments to help identify individuals who would most benefit from BMD testing. In this paper, we review and compare the performance of these instruments to identify those most useful in the primary care setting.
Review of screening instruments comprised osteoporosis clinical risk factors and comparison of the sensitivity and specificity of these algorithms.
Validated instruments have varying complexity, but similar sensitivity and specificity for identifying individuals who are likely to have low BMD. The area under the receiver operating characteristic curve ranges from 0.75 (SOFSURF) to 0.81 (SCORE). The simplest of the instruments (OST) uses only age and weight and has an AUC of 0.79.
The Osteoporosis Self-assessment Tool, the simplest of the instruments, performs as well as more complex tools and, because of its simplicity, may be the most useful means for the busy clinician to identify postmenopausal women who would most benefit from BMD testing.
Journal of Internal Medicine 12/2004; 256(5):375-80. · 5.48 Impact Factor
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ABSTRACT: Large segments of the population at risk for osteoporosis and fracture have not been evaluated, and the usefulness of peripheral measurements for short-term prediction of fracture risk is uncertain.
To describe the occurrence of low bone mineral density (BMD) in postmenopausal women, its risk factors, and fracture incidence during short-term follow-up.
The National Osteoporosis Risk Assessment, a longitudinal observational study initiated September 1997 to March 1999, with approximately 12 months of subsequent follow-up.
A total of 200 160 ambulatory postmenopausal women aged 50 years or older with no previous osteoporosis diagnosis, derived from 4236 primary care practices in 34 states.
Baseline BMD T scores, obtained from peripheral bone densitometry performed at the heel, finger, or forearm; risk factors for low BMD, derived from questionnaire responses; and clinical fracture rates at 12-month follow-up.
Using World Health Organization criteria, 39.6% had osteopenia (T score of -1 to -2.49) and 7.2% had osteoporosis (T score </=-2.5). Age, personal or family history of fracture, Asian or Hispanic heritage, smoking, and cortisone use were associated with significantly increased likelihood of osteoporosis; higher body mass index, African American heritage, estrogen or diuretic use, exercise, and alcohol consumption significantly decreased the likelihood. Among the 163 979 participants with follow-up information, osteoporosis was associated with a fracture rate approximately 4 times that of normal BMD (rate ratio, 4.03; 95% confidence interval [CI], 3.59-4.53) and osteopenia was associated with a 1.8-fold higher rate (95% CI, 1.49-2.18).
Almost half of this population had previously undetected low BMD, including 7% with osteoporosis. Peripheral BMD results were highly predictive of fracture risk. Given the economic and social costs of osteoporotic fractures, strategies to identify and manage osteoporosis in the primary care setting need to be established and implemented.
JAMA The Journal of the American Medical Association 12/2001; 286(22):2815-22. · 30.03 Impact Factor
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Journal of Bone and Mineral Research 09/2001; 16(8):1379-87. · 6.37 Impact Factor
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E S Siris
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ABSTRACT: The goals of treatment of Paget's disease must be readdressed in the context of the availability of potent bisphosphonate compounds, including pamidronate and, more recently, alendronate and risedronate. These agents differ from the traditional mainstays of therapy, salmon calcitonin and etidronate, in several respects. First, they achieve a reduction in the elevated indices of pagetic bone turnover of about 80%, in contrast with the 50% reduction seen with the older agents. Second, a majority of patients (in the range of 50-75%, depending on the series) achieve biochemical remission, and the duration of remission may exceed 1 year or more after a single course of therapy. Third, with the newer bisphosphonates the quality of newly forming bone after successful treatment is lamellar in appearance (as was the case with etidronate) but there is no clinically significant mineralization abnormality associated with these more recent agents. With prior therapies, the primary goal of treatment was to relieve symptoms. In the absence of complete suppression of abnormal turnover, disease progression was not completely halted in many patients, increasing the risk of long-term complications. The characteristics of the newer agents, however, suggest that in those patients who achieve remission there is a possibility, albeit not yet proven, of arresting progression and reducing the risk of later complications. Many patients have no symptoms at presentation but have active disease at locations where progression could cause bone enlargement and deformity over time. These patients may be considered to be at increased risk of future complications if untreated. Thus, it is recommended that such individuals receive therapy with a potent bisphosphonate with the goal of attaining normal (or near normal) biochemical indices after initial treatment and/or retreatment. Patients should be followed with measurement of serum alkaline phosphatase every 4-6 months after a course of therapy, and retreatment is suggested when indices rise above the upper limit of normal or by 25% above the previous nadir. The uncommon possibility of secondary resistance to a given agent after more than one treatment course should be assessed in all patients.
Journal of Bone and Mineral Research 11/1999; 14 Suppl 2:49-52. · 6.37 Impact Factor
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E S Siris
Bone 06/1999; 24(5 Suppl):55S-56S. · 4.02 Impact Factor
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ABSTRACT: To compare the efficacy and tolerability of oral risedronate and etidronate for treatment of Paget's disease of bone.
Patients from 12 centers in North America received risedronate 30 mg daily for 2 months (62 patients) or etidronate 400 mg daily for 6 months (61 patients) in a prospective, randomized, double-blind study. Serum alkaline phosphatase (the primary variable), serum bone-specific alkaline phosphatase, and urinary deoxypyridinoline concentrations were monitored for 12 to 18 months.
Serum alkaline phosphatase concentration normalized by month 12 in 73% of risedronate-treated patients, compared with 15% of those receiving etidronate (P <0.001). Median time to normalization was 91 days for risedronate-treated patients and >360 days for etidronate-treated patients (P <0.001); relapse rates were 3% in the risedronate group and 15% in the etidronate group (P <0.05). At month 18, 53% of the risedronate group and 14% of the etidronate group remained in biochemical remission. Urinary deoxypyridinoline normalized in 87% of patients on risedronate and 57% of patients receiving etidronate (P <0.01); serum bone-specific alkaline phosphatase normalized in 73% of patients on risedronate and 18% of patients on etidronate (P <0.001). Patients who had received etidronate previously had a blunted response to etidronate, but not to risedronate. Reductions in pain were statistically significant in the risedronate group, but not in the etidronate group. Both drugs were well tolerated.
Although etidronate is effective, risedronate offers a shorter duration of therapy, better and longer-lasting remission, significant reductions in pain, and provides additional remission in subjects who exhibited an incomplete response to previous etidronate treatment.
The American Journal of Medicine 05/1999; 106(5):513-20. · 5.43 Impact Factor
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E S Siris
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ABSTRACT: Paget's disease of bone is a localized disorder of bone remodeling. Increased numbers of larger than normal osteoclasts initiate the process at affected skeletal sites, and the increase in bone resorption is followed by an increase in new bone formation, altering bone architecture. The signs and symptoms of Paget's disease are varied, depending in part on the location of the involved sites and the degree of increased bone turnover. Recent progress in Paget's disease research includes new data regarding the etiology of this disorder and the ongoing development of more effective therapies. Although the cause of Paget's disease remains unproven, the creation of pagetic osteoclasts seems ever more likely to result from both genetic and environmental factors. Many studies indicate that in patients with Paget's disease, both osteoclasts and their precursors harbor evidence of a paramyxovirus infection, although not all studies confirm this finding. Very recent genetic investigations have identified one candidate gene on chromosome 18q, although genetic heterogeneity is almost certainly present. Advances in treatment have resulted from the availability of several potent bisphosphonate compounds (e.g., pamidronate, alendronate, and risedronate) that, unlike earlier treatments, produce normal or near normal bone turnover indices in a majority of patients. New bone formation after such treatment has a more normal, lamellar pattern, and mineralization abnormalities are rare to absent with the newer compounds. The availability of such agents has prompted a more aggressive management philosophy in which both symptomatic disease and also asymptomatic disease at sites with a risk of progression and future complications are viewed as clear indications for pharmacologic intervention.
Journal of Bone and Mineral Research 08/1998; 13(7):1061-5. · 6.37 Impact Factor