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1.  Utilization of DXA Bone Mineral Densitometry in Ontario 
Executive Summary
Systematic reviews and analyses of administrative data were performed to determine the appropriate use of bone mineral density (BMD) assessments using dual energy x-ray absorptiometry (DXA), and the associated trends in wrist and hip fractures in Ontario.
Dual Energy X-ray Absorptiometry Bone Mineral Density Assessment
Dual energy x-ray absorptiometry bone densitometers measure bone density based on differential absorption of 2 x-ray beams by bone and soft tissues. It is the gold standard for detecting and diagnosing osteoporosis, a systemic disease characterized by low bone density and altered bone structure, resulting in low bone strength and increased risk of fractures. The test is fast (approximately 10 minutes) and accurate (exceeds 90% at the hip), with low radiation (1/3 to 1/5 of that from a chest x-ray). DXA densitometers are licensed as Class 3 medical devices in Canada. The World Health Organization has established criteria for osteoporosis and osteopenia based on DXA BMD measurements: osteoporosis is defined as a BMD that is >2.5 standard deviations below the mean BMD for normal young adults (i.e. T-score <–2.5), while osteopenia is defined as BMD that is more than 1 standard deviation but less than 2.5 standard deviation below the mean for normal young adults (i.e. T-score< –1 & ≥–2.5). DXA densitometry is presently an insured health service in Ontario.
Clinical Need
Burden of Disease
The Canadian Multicenter Osteoporosis Study (CaMos) found that 16% of Canadian women and 6.6% of Canadian men have osteoporosis based on the WHO criteria, with prevalence increasing with age. Osteopenia was found in 49.6% of Canadian women and 39% of Canadian men. In Ontario, it is estimated that nearly 530,000 Ontarians have some degrees of osteoporosis. Osteoporosis-related fragility fractures occur most often in the wrist, femur and pelvis. These fractures, particularly those in the hip, are associated with increased mortality, and decreased functional capacity and quality of life. A Canadian study showed that at 1 year after a hip fracture, the mortality rate was 20%. Another 20% required institutional care, 40% were unable to walk independently, and there was lower health-related quality of life due to attributes such as pain, decreased mobility and decreased ability to self-care. The cost of osteoporosis and osteoporotic fractures in Canada was estimated to be $1.3 billion in 1993.
Guidelines for Bone Mineral Density Testing
With 2 exceptions, almost all guidelines address only women. None of the guidelines recommend blanket population-based BMD testing. Instead, all guidelines recommend BMD testing in people at risk of osteoporosis, predominantly women aged 65 years or older. For women under 65 years of age, BMD testing is recommended only if one major or two minor risk factors for osteoporosis exist. Osteoporosis Canada did not restrict its recommendations to women, and thus their guidelines apply to both sexes. Major risk factors are age greater than or equal to 65 years, a history of previous fractures, family history (especially parental history) of fracture, and medication or disease conditions that affect bone metabolism (such as long-term glucocorticoid therapy). Minor risk factors include low body mass index, low calcium intake, alcohol consumption, and smoking.
Current Funding for Bone Mineral Density Testing
The Ontario Health Insurance Program (OHIP) Schedule presently reimburses DXA BMD at the hip and spine. Measurements at both sites are required if feasible. Patients at low risk of accelerated bone loss are limited to one BMD test within any 24-month period, but there are no restrictions on people at high risk. The total fee including the professional and technical components for a test involving 2 or more sites is $106.00 (Cdn).
Method of Review
This review consisted of 2 parts. The first part was an analysis of Ontario administrative data relating to DXA BMD, wrist and hip fractures, and use of antiresorptive drugs in people aged 65 years and older. The Institute for Clinical Evaluative Sciences extracted data from the OHIP claims database, the Canadian Institute for Health Information hospital discharge abstract database, the National Ambulatory Care Reporting System, and the Ontario Drug Benefit database using OHIP and ICD-10 codes. The data was analyzed to examine the trends in DXA BMD use from 1992 to 2005, and to identify areas requiring improvement.
The second part included systematic reviews and analyses of evidence relating to issues identified in the analyses of utilization data. Altogether, 8 reviews and qualitative syntheses were performed, consisting of 28 published systematic reviews and/or meta-analyses, 34 randomized controlled trials, and 63 observational studies.
Findings of Utilization Analysis
Analysis of administrative data showed a 10-fold increase in the number of BMD tests in Ontario between 1993 and 2005.
OHIP claims for BMD tests are presently increasing at a rate of 6 to 7% per year. Approximately 500,000 tests were performed in 2005/06 with an age-adjusted rate of 8,600 tests per 100,000 population.
Women accounted for 90 % of all BMD tests performed in the province.
In 2005/06, there was a 2-fold variation in the rate of DXA BMD tests across local integrated health networks, but a 10-fold variation between the county with the highest rate (Toronto) and that with the lowest rate (Kenora). The analysis also showed that:
With the increased use of BMD, there was a concomitant increase in the use of antiresorptive drugs (as shown in people 65 years and older) and a decrease in the rate of hip fractures in people age 50 years and older.
Repeat BMD made up approximately 41% of all tests. Most of the people (>90%) who had annual BMD tests in a 2-year or 3-year period were coded as being at high risk for osteoporosis.
18% (20,865) of the people who had a repeat BMD within a 24-month period and 34% (98,058) of the people who had one BMD test in a 3-year period were under 65 years, had no fracture in the year, and coded as low-risk.
Only 19% of people age greater than 65 years underwent BMD testing and 41% received osteoporosis treatment during the year following a fracture.
Men accounted for 24% of all hip fractures and 21 % of all wrist fractures, but only 10% of BMD tests. The rates of BMD tests and treatment in men after a fracture were only half of those in women.
In both men and women, the rate of hip and wrist fractures mainly increased after age 65 with the sharpest increase occurring after age 80 years.
Findings of Systematic Review and Analysis
Serial Bone Mineral Density Testing for People Not Receiving Osteoporosis Treatment
A systematic review showed that the mean rate of bone loss in people not receiving osteoporosis treatment (including postmenopausal women) is generally less than 1% per year. Higher rates of bone loss were reported for people with disease conditions or on medications that affect bone metabolism. In order to be considered a genuine biological change, the change in BMD between serial measurements must exceed the least significant change (variability) of the testing, ranging from 2.77% to 8% for precisions ranging from 1% to 3% respectively. Progression in BMD was analyzed, using different rates of baseline BMD values, rates of bone loss, precision, and BMD value for initiating treatment. The analyses showed that serial BMD measurements every 24 months (as per OHIP policy for low-risk individuals) is not necessary for people with no major risk factors for osteoporosis, provided that the baseline BMD is normal (T-score ≥ –1), and the rate of bone loss is less than or equal to 1% per year. The analyses showed that for someone with a normal baseline BMD and a rate of bone loss of less than 1% per year, the change in BMD is not likely to exceed least significant change (even for a 1% precision) in less than 3 years after the baseline test, and is not likely to drop to a BMD level that requires initiation of treatment in less than 16 years after the baseline test.
Serial Bone Mineral Density Testing in People Receiving Osteoporosis Therapy
Seven published meta-analysis of randomized controlled trials (RCTs) and 2 recent RCTs on BMD monitoring during osteoporosis therapy showed that although higher increases in BMD were generally associated with reduced risk of fracture, the change in BMD only explained a small percentage of the fracture risk reduction.
Studies showed that some people with small or no increase in BMD during treatment experienced significant fracture risk reduction, indicating that other factors such as improved bone microarchitecture might have contributed to fracture risk reduction.
There is conflicting evidence relating to the role of BMD testing in improving patient compliance with osteoporosis therapy.
Even though BMD may not be a perfect surrogate for reduction in fracture risk when monitoring responses to osteoporosis therapy, experts advised that it is still the only reliable test available for this purpose.
A systematic review conducted by the Medical Advisory Secretariat showed that the magnitude of increases in BMD during osteoporosis drug therapy varied among medications. Although most of the studies yielded mean percentage increases in BMD from baseline that did not exceed the least significant change for a 2% precision after 1 year of treatment, there were some exceptions.
Bone Mineral Density Testing and Treatment After a Fragility Fracture
A review of 3 published pooled analyses of observational studies and 12 prospective population-based observational studies showed that the presence of any prevalent fracture increases the relative risk for future fractures by approximately 2-fold or more. A review of 10 systematic reviews of RCTs and 3 additional RCTs showed that therapy with antiresorptive drugs significantly reduced the risk of vertebral fractures by 40 to 50% in postmenopausal osteoporotic women and osteoporotic men, and 2 antiresorptive drugs also reduced the risk of nonvertebral fractures by 30 to 50%. Evidence from observational studies in Canada and other jurisdictions suggests that patients who had undergone BMD measurements, particularly if a diagnosis of osteoporosis is made, were more likely to be given pharmacologic bone-sparing therapy. Despite these findings, the rate of BMD investigation and osteoporosis treatment after a fracture remained low (<20%) in Ontario as well as in other jurisdictions.
Bone Mineral Density Testing in Men
There are presently no specific Canadian guidelines for BMD screening in men. A review of the literature suggests that risk factors for fracture and the rate of vertebral deformity are similar for men and women, but the mortality rate after a hip fracture is higher in men compared with women. Two bisphosphonates had been shown to reduce the risk of vertebral and hip fractures in men. However, BMD testing and osteoporosis treatment were proportionately low in Ontario men in general, and particularly after a fracture, even though men accounted for 25% of the hip and wrist fractures. The Ontario data also showed that the rates of wrist fracture and hip fracture in men rose sharply in the 75- to 80-year age group.
Ontario-Based Economic Analysis
The economic analysis focused on analyzing the economic impact of decreasing future hip fractures by increasing the rate of BMD testing in men and women age greater than or equal to 65 years following a hip or wrist fracture. A decision analysis showed the above strategy, especially when enhanced by improved reporting of BMD tests, to be cost-effective, resulting in a cost-effectiveness ratio ranging from $2,285 (Cdn) per fracture avoided (worst-case scenario) to $1,981 (Cdn) per fracture avoided (best-case scenario). A budget impact analysis estimated that shifting utilization of BMD testing from the low risk population to high risk populations within Ontario would result in a saving of $0.85 million to $1.5 million (Cdn) to the health system. The potential net saving was estimated at $1.2 million to $5 million (Cdn) when the downstream cost-avoidance due to prevention of future hip fractures was factored into the analysis.
Other Factors for Consideration
There is a lack of standardization for BMD testing in Ontario. Two different standards are presently being used and experts suggest that variability in results from different facilities may lead to unnecessary testing. There is also no requirement for standardized equipment, procedure or reporting format. The current reimbursement policy for BMD testing encourages serial testing in people at low risk of accelerated bone loss. This review showed that biannual testing is not necessary for all cases. The lack of a database to collect clinical data on BMD testing makes it difficult to evaluate the clinical profiles of patients tested and outcomes of the BMD tests. There are ministry initiatives in progress under the Osteoporosis Program to address the development of a mandatory standardized requisition form for BMD tests to facilitate data collection and clinical decision-making. Work is also underway for developing guidelines for BMD testing in men and in perimenopausal women.
Increased use of BMD in Ontario since 1996 appears to be associated with increased use of antiresorptive medication and a decrease in hip and wrist fractures.
Data suggest that as many as 20% (98,000) of the DXA BMD tests in Ontario in 2005/06 were performed in people aged less than 65 years, with no fracture in the current year, and coded as being at low risk for accelerated bone loss; this is not consistent with current guidelines. Even though some of these people might have been incorrectly coded as low-risk, the number of tests in people truly at low risk could still be substantial.
Approximately 4% (21,000) of the DXA BMD tests in 2005/06 were repeat BMDs in low-risk individuals within a 24-month period. Even though this is in compliance with current OHIP reimbursement policies, evidence showed that biannual serial BMD testing is not necessary in individuals without major risk factors for fractures, provided that the baseline BMD is normal (T-score < –1). In this population, BMD measurements may be repeated in 3 to 5 years after the baseline test to establish the rate of bone loss, and further serial BMD tests may not be necessary for another 7 to 10 years if the rate of bone loss is no more than 1% per year. Precision of the test needs to be considered when interpreting serial BMD results.
Although changes in BMD may not be the perfect surrogate for reduction in fracture risk as a measure of response to osteoporosis treatment, experts advised that it is presently the only reliable test for monitoring response to treatment and to help motivate patients to continue treatment. Patients should not discontinue treatment if there is no increase in BMD after the first year of treatment. Lack of response or bone loss during treatment should prompt the physician to examine whether the patient is taking the medication appropriately.
Men and women who have had a fragility fracture at the hip, spine, wrist or shoulder are at increased risk of having a future fracture, but this population is presently under investigated and under treated. Additional efforts have to be made to communicate to physicians (particularly orthopaedic surgeons and family physicians) and the public about the need for a BMD test after fracture, and for initiating treatment if low BMD is found.
Men had a disproportionately low rate of BMD tests and osteoporosis treatment, especially after a fracture. Evidence and fracture data showed that the risk of hip and wrist fractures in men rises sharply at age 70 years.
Some counties had BMD utilization rates that were only 10% of that of the county with the highest utilization. The reasons for low utilization need to be explored and addressed.
Initiatives such as aligning reimbursement policy with current guidelines, developing specific guidelines for BMD testing in men and perimenopausal women, improving BMD reports to assist in clinical decision making, developing a registry to track BMD tests, improving access to BMD tests in remote/rural counties, establishing mechanisms to alert family physicians of fractures, and educating physicians and the public, will improve the appropriate utilization of BMD tests, and further decrease the rate of fractures in Ontario. Some of these initiatives such as developing guidelines for perimenopausal women and men, and developing a standardized requisition form for BMD testing, are currently in progress under the Ontario Osteoporosis Strategy.
PMCID: PMC3379167  PMID: 23074491
2.  Osteoporosis in ankylosing spondylitis - prevalence, risk factors and methods of assessment 
Arthritis Research & Therapy  2012;14(3):R108.
Osteoporosis can be a complication of ankylosing spondylitis (AS), but diagnosing spinal osteoporosis can be difficult since pathologic new bone formation interferes with the assessment of the bone mineral density (BMD). The aims of the current study were to investigate prevalence and risk factors for reduced BMD in a Swedish cohort of AS patients, and to examine how progressive ankylosis influences BMD with the use of dual-energy x-ray absorptiometry (DXA) of the lumbar spine in different projections.
Methods of assessment were questionnaires, back mobility tests, blood samples, lateral spine radiographs for syndesmophyte grading (mSASSS), DXA of the hip, radius and lumbar spine in anteroposterior (AP) and lateral projections with estimation of volumetric BMD (vBMD).
AS patients (modified New York criteria), 87 women and 117 men, mean age 50 ± 13 years and disease duration 15 ± 11 years were included. According to World Health Organization (WHO) criteria 21% osteoporosis and 44% osteopenia was diagnosed in patients > = 50 years. Under age 50 BMD below expected range for age was found in 5%. Interestingly lateral lumbar DXA showed significantly lower BMD and revealed significantly more cases with osteoporosis as compared with AP DXA. Lumbar vBMD was not different between sexes, but women had significantly more lumbar osteoporosis measured with AP DXA (P < 0.001). Men had significantly higher mSASSS (P < 0.001). Low BMD was associated with high age, disease duration, mSASSS, Bath Ankylosing Spondylitis Metrology Index (BASMI), inflammatory parameters and low body mass index (BMI). Increasing mSASSS correlated significantly with decreasing lateral and volumetric lumbar BMD, while AP lumbar BMD showed tendency to increase.
Osteoporosis and osteopenia is common in AS and associated with high disease burden. Lateral and volumetric lumbar DXA are more sensitive than AP DXA in detecting osteoporosis and are less affected by syndesmophyte formation.
PMCID: PMC3446485  PMID: 22569245
3.  Prevalence and correlates of osteoporosis in chronic obstructive pulmonary disease patients in India 
Chronic obstructive pulmonary disease (COPD) is a syndrome of progressive airflow limitation caused by the abnormal inflammatory reaction of the airway and lung parenchyma. Osteoporosis is one of the major extrapulmonary manifestations of COPD. The, prevalence of osteoporosis in COPD patients in Indian population is unknown.
To study the prevalence of osteoporosis in COPD and to define various risk factors associated with reduced bone mineral density (BMD) in COPD.
Materials and Methods:
The study was done in the department of Pulmonary Medicine of a tertiary care hospital. All the diagnosed cases of COPD according to the Global Initiative for Obstructive Lung Disease (GOLD) guidelines were included in this study. The present study was a prospective study in for a period of 1 year. A brief history of the patients was taken, especially regarding duration of illness, number of exacerbations in the past 3 years, smoking in pack years, and history of steroid use (both systemic and inhaled steroids) after which cumulative dose of steroids was calculated. Spirometry was done in all these patients to stage the severity of COPD according to GOLD criteria. DEXA scan of the lumbar spine was done using bone densitometer to determine osteoporosis. A world Health Organization (WHO) criterion for definition of osteoporosis was applied and patients with T-score of > –2.5 standard deviation (SD) were diagnosed to have osteoporosis, –1 SD to –2.5 SD were diagnosed to have osteopenia and < –1 SD as normal. Statistical analysis for association of COPD with osteoporosis was done using chi-square test. Risk factors for osteoporosis were identified by univariate and multivariate logistic regression analysis.
A total of 102 COPD patients were included in the study. Among these, 68 patients (66.6%) had osteoporosis and 20 patients (19.6%) had osteopenia. Majority (64.7%) of the patients who had osteoporosis had stage III and stage IV COPD disease. It was observed that as the severity grade of COPD increased, the risk of osteoporosis also increased. The bone mineral density (BMD) showed a significant difference among different stages of COPD. As the severity of the stage of COPD increased, BMD decreased. It was also observed that patients with lower body mass index (BMI) had higher prevalence of osteoporosis (37.3%) as compared to overweight patients. On univariate analysis, it was observed that risk factors for osteoporosis were female sex, higher number of exacerbations, BMI, and severity of COPD. After using multivariate logistic regression analysis, stage IV COPD (odds ratio (OR): 34.48, 95% confidence interval (CI): 1.59–1,000, P < 0.02), number of acute exacerbations >3 (OR: 30.3, 95% CI: 4.74–200, P < 0.01), and steroid cumulative dose >1,000 mg (OR: 7.35, 95% CI: 0.92–58.5, P < 0.04) were observed to be significant risk factors for osteoporosis in COPD patients.
In the present study, the prevalence of osteoporosis was 66.6% and another 19.6% had osteopenia. As the severity of COPD increased, the risk of osteoporosis increased. GOLD stage III and stage IV patient had significantly lower BMD as compared to stage I and stage II of COPD disease. Stage IV COPD disease, use of oral or parenteral glucocorticoids, and repeated number of exacerbations were found to be independent risk factors for osteoporosis in COPD patients. Thus, high clinical suspicion and early diagnosis and treatment is required in the evaluation of osteoporosis in COPD patients so that the quality of life can be improved in these patients.
PMCID: PMC4129592  PMID: 25125807
COPD; correlates; DEXA scan; osteoporosis; repeated exacerbations; risk factors
4.  Assessment of Osteoporosis in Family Medicine Obtained by Ultrasound Densitometry 
Acta Informatica Medica  2013;21(4):274-276.
Osteoporosis is a disease characterized by a decrease in bone mineral density, making bones become less rigid, and therefore susceptible to fractures, either spontaneously or with force, which is lower than otherwise needed for healthy bones fractured. Nearly 10% of the world population and 30% of women after menopause, suffer from osteoporosis. Clinical assessment of osteoporosis in family medicine is key to prevention, early detection and treatment of osteoporosis.
To investigate the possibility of early detection and diagnosis of osteoporosis by analyzing the risk factors for osteoporosis and to compare the results with the parameters obtained by ultrasound densitometry of calcaneus, and determine the relationship of calcaneus densitometry with DXA findings, as the gold standard for the diagnosis of osteoporosis.
Patients and methods:
The study included all patients of Family Medicine Kalesija Team 1, aged 50 years and over, a total of 711 patients, of whom 425 were women and 286 men. In all patients we assessed the existence of the following risk factors for osteoporosis: Constitutional: gender, age, weight, constitution, menarche and menopause, loss of height and stooped posture; Living habits: smoking, alcohol consumption, coffee, physical activity, and medications: long-term use corticosteroids, anticonvulsants, antacids, thyroid hormones. Comorbidity: history of fractures, hyperthyroidism, COPD, Chussing’s disease, diabetes. In the group of high-risk patients determined by the clinical assessment, quantitative ultrasound densitometry screening was carried out. Monitoring parameters derived with densitometry: the value of T-score, BUA (Broadband Ultrasound Attenuation), SOS (Speed of Sound), QUI (Quantitative Ultrasound Index). To confirm the diagnosis of osteoporosis, in all patients with positive findings using ultrasound densitometry (T score lower than 2.5), another densitometry was performed by standard DXA method.
The incidence of osteoporosis was 96% in women and 4% in men. Differences in prevalence between men and women are statistically significant. People with and without osteoporosis significantly differ in gender, age, weight, constitution (BMI-Body Mass Index). The parameters that distinguish those with and without osteoporosis: age, weight, height, BMI, gender. Out of the total of 711 patients, in 11% of patients the clinical evaluation showed the existence of high risk of osteoporosis. In 9.8% patients, the values were determined by ultrasound densitometry, where T score was lower than 2.5 what induces a high risk of fractures, and for 8.8% patients the DXA confirmed the diagnosis of osteoporosis.
Clinical assessment of osteoporosis in the family medicine clinic performed in timely and focused history of risk factors for osteoporosis, with additional findings from quantitative densitometry of calcaneus, was sufficient for the early detection and screening of patients with high risk for osteoporosis. With good clinical assessment of osteoporosis it will be necessary to send all patients who enter the high-risk group to undergo ultrasound densitometry of calcaneus, to make it possible to determine the risk of bone fractures and osteoporosis in time, and then refer patients for further processing and DXA measurements according to the guidelines by the WHO.
PMCID: PMC3916165  PMID: 24554805
bone density; early detection; risk factors; quantitative ultrasound densitometry; osteoporosis.
5.  Opportunistic Screening for Osteoporosis Using Abdominal Computed Tomography Scans Obtained for Other Indications 
Annals of internal medicine  2013;158(8):588-595.
Osteoporosis is a prevalent but underdiagnosed condition.
To evaluate computed tomography (CT)-derived bone mineral density (BMD) assessment compared with dual-energy x-ray absorptiometry (DXA) measures for identifying osteoporosis by using CT scans performed for other clinical indications.
Cross-sectional study.
Single academic health center.
1867 adults undergoing CT and DXA (n = 2067 pairs) within a 6-month period over 10 years.
CT-attenuation values (in Hounsfield units [HU]) of trabecular bone between the T12 and L5 vertebral levels, with an emphasis on L1 measures (study test); DXA BMD measures (reference standard). Sagittal CT images assessed for moderate-to-severe vertebral fractures.
CT-attenuation values were significantly lower at all vertebral levels for patients with DXA-defined osteoporosis (P < 0.001). An L1 CT-attenuation threshold of 160 HU or less was 90% sensitive and a threshold of 110 HU was more than 90% specific for distinguishing osteoporosis from osteopenia and normal BMD. Positive predictive values for osteoporosis were 68% or greater at L1 CT-attenuation thresholds less than 100 HU; negative predictive values were 99% at thresholds greater than 200 HU. Among 119 patients with at least 1 moderate-to-severe vertebral fracture, 62 (52.1%) had nonosteoporotic T-scores (DXA false-negative results), and most (97%) had L1 or mean T12 to L5 vertebral attenuation of 145 HU or less. Similar performance was seen at all vertebral levels. Intravenous contrast did not affect CT performance.
The potential benefits and costs of using the various CT-attenuation thresholds identified were not formally assessed.
Abdominal CT images obtained for other reasons that include the lumbar spine can be used to identify patients with osteoporosis or normal BMD without additional radiation exposure or cost.
Primary Funding Source
National Institutes of Health.
PMCID: PMC3736840  PMID: 23588747
6.  Comparison of QCT and DXA: Osteoporosis Detection Rates in Postmenopausal Women 
Objective. To compare the osteoporosis detection rates in postmenopausal women when measuring bone mineral density (BMD) with quantitative computed tomography (QCT) in the spine versus dual X-ray absorptiometry (DXA) in the spine and hip and to investigate the reasons for the discrepancy between the two techniques. Methods. Spinal volumetric BMD was measured with QCT, and areal spinal and hip BMDs were measured with DXA in 140 postmenopausal women. We calculated the osteoporosis detection rate for the two methods. Lumbar CT images of patients who had a discrepancy between QCT and DXA findings were reviewed to evaluate vertebral fractures, spinal degeneration, and abdominal aortic calcification. Results. For the entire 140 patients, the detection rate was 17.1% for DXA and 46.4% for QCT, a significant difference (P < 0.01). Of the 41 patients with conflicting diagnoses, 7 whose diagnosis by QCT was osteoporosis had vertebral fractures even though their DXA findings did not indicate osteoporosis. Varying degrees of spinal degeneration were seen in all of the 41 patients. Conclusion. QCT may avoid the overestimation of BMD by DXA associated with spinal degeneration, abdominal aortic calcification, and other sclerotic lesions. It may be more sensitive than DXA for detecting osteoporosis in postmenopausal women.
PMCID: PMC3623474  PMID: 23606843
7.  Simultaneous screening for osteoporosis at CT colonography 
Journal of Bone and Mineral Research  2011;26(9):2194-2203.
To evaluate the utility of lumbar spine attenuation measurement for bone mineral density (BMD) assessment at screening CT colonography (CTC), using central dual-energy x-ray absorptiometry (DXA) as the reference standard.
Material and Methods
252 adults (240 women, 12 men; mean age, 58.9 years) underwent CTC screening and central DXA BMD measurement within 2 months (mean interval, 25.0 days). The lowest DXA T-score between the spine and hip served as the reference standard, with low BMD defined per WHO as osteoporosis (DXA T-score ≤-2.5) or osteopenia (DXA T-score between −1.0 and −2.4). Both phantomless QCT and simple non-angled ROI MDCT attenuation measurements were applied to T12-L5 levels. Ability to predict osteoporosis and low BMD (osteoporosis or osteopenia) by DXA was assessed.
A BMD cut-off of 90 mg/cc at phantomless QCT yielded 100% sensitivity for osteoporosis (29/29) and specificity of 63.8% (143/224); 87.2% (96/110) below this threshold had low BMD and 49.6% (69/139) above this threshold had normal BMD at DXA. At L1, a trabecular ROI attenuation cut-off of 160 HU was 100% sensitive for osteoporosis (29/29), with a specificity of 46.4% (104/224); 83.9% (125/149) below this threshold had low BMD and 57.5% (59/103) above had normal BMD at DXA. ROI performance was similar at all individual T12-L5 levels. At ROC analysis, AUC for osteoporosis was 0.888 for phantomless QCT (95% CI: 0.780–0.946) and ranged from 0.825–0.853 using trabecular ROIs at single lumbar levels (0.864 [0.752–0.930] at multivariate analysis). Supine-prone reproducibility was better with simple ROI method compared with QCT.
Both phantomless QCT and simple ROI attenuation measurements of the lumbar spine are effective for BMD screening at CTC, with high sensitivity for osteoporosis as defined by the DXA T-score.
PMCID: PMC3304444  PMID: 21590738
Osteoporosis; Screening; Bone mineral density; Computed tomography; CT colonography
8.  Tibial cortical thickness: A dependable tool for assessing osteoporosis in the absence of dual energy X-ray absorptiopmetry 
Background and Objective:
Bone mineral density measurements with absorptiometry dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing low bone mass and risk for fragility fractures. DXA is not available at every center, and physicians require an alternative method of diagnosis before referring patients. We conducted this study to assess and compare total cortical thickness (TCT) and its relation to the T score by DXA and its correlation-ship in the diagnosis of osteoporosis.
Patients and Methods:
Total cortical thickness was carried out in 50 Saudi Arabian females ≥ 45 years with DXA scans and 25 patients with age of ≤ 35 years whose radiographs of the upper tibia were available for analysis. Postero-medial cortical thickness of the tibia was measured 13 cm from the joint line and an average was calculated. The average T score of the spine and the hip was taken. A comparison was made between age, T score, and the TCT. Inter cortical distance (ICD) was measured and compared in both groups. Data were analyzed for predictive value for diagnosis of osteopenia and osteoporosis.
There was a significant association between the T score and the TCT and age. As the age advanced the T score and TCT was very low (<0.05, 95% confidence interval [CI] <0.2). Forty patients were osteopenic and 10 osteoporotic. The T score in the former was − 1.33 ± 0.71 and the later was − 3.22 ± 0.56 (P < 0.0001 95% CI: <−1.67) and the TCT was 0.655 ± 0.06 versus 0.51 ± 0.05 (P < 0.0001 95% CI: <−0.17). In women ≤35 years the average TCT was 0.804 ± 0.155 cm and IMD was 3.34 ± 0.45 cm.
We conclude that if TCT is less than the threshold value of ≤ 0.5 cm, patients should be referred for further investigations with DXA. We believe that further studies are needed to confirm our findings and in areas where DXA is not available, based on the TCT measurement anti-osteoporotic therapy could be initiated when other risk factors for osteoporosis is present.
PMCID: PMC4318096  PMID: 25664263
Dual-energy X-ray absorptiometry diagnosis; osteoporosis; tibial cortical thickness
9.  The Clinical Utility of Spine Bone Density in Elderly Women 
It is common clinical practice to obtain bone mass measurement at both the hip and spine to evaluate for osteoporosis. With aging, degenerative changes in the lumbar spine may elevate the bone mineral density (BMD) results giving false assurances that the fracture risk at the spine is low. We examined the association of spine osteoarthritis and bone mineral density in 1082 community-dwelling ambulatory older women aged 50–96 years who participated in a 1992–1996 osteoporosis research clinic visit. Bone mineral density (BMD) was measured at the hip, PA and lateral lumbar spine using dual energy x-ray absorptiometry (DXA). Spine osteoarthritis was identified on the PA lumbar spine DXA images by a musculoskeletal radiologist. Forty percent of women had evidence of spine osteoarthritis (OA). Women with spine OA had mean age of 77.4 years (95% CI, 76.5–78.2), were significantly older than women without (mean age 66.8; 95% CI, 65.9–67.7), and were more likely to have prevalent radiographic fractures (14.2% vs. 9.5%, p< 0.05). Age-adjusted BMD at the femoral neck, total hip, PA spine, and lateral spine was significantly higher in women with spine OA. Women with spine OA were more likely to have osteoporosis by WHO classification at the femoral neck and total hip than those without spine OA, but less likely based on the PA spine site (14.4% vs 24.5%). Despite higher BMD levels, women with OA of the lumbar spine had higher prevalence of osteoporosis at the hip and radiographic vertebral fractures. In elderly women 65 years and older who are likely to have spine OA, DXA measurement of the spine may be not useful in assessing fracture risk and DXA of the hip is recommended for identification of osteoporosis.
PMCID: PMC2642644  PMID: 16931341
Spine osteoarthritis; bone mineral density; osteoporosis; elderly
10.  Vertebral Fractures and Trabecular Microstructure in Men with Prostate Cancer on Androgen Deprivation Therapy 
Androgen deprivation therapy (ADT), a treatment for prostate cancer, is associated with bone loss and fractures. Dual energy x-ray absorptiometry (DXA) measured bone mineral density does not assess vertebral fractures (VF). High resolution microMRI (HR-MRI) assesses bone microarchitecture and provides structural information.
To determine if VF identification increased the diagnosis of osteoporosis beyond DXA and if HR-MRI demonstrated skeletal deterioration in men with VF, we cross-sectionally studied 137 men ≥ 60 years with nonmetastatic prostate cancer on ADT for ≥6 months. Vertebral fracture assessment (VFA) by DXA was confirmed with x-rays. HR-MRI of the wrist included bone volume to total volume (BV/TV), surface density (trabecular plates), surface/curve ratio (plates/rods) and erosion index (higher depicts deterioration).
VF were found in 37% of men; the majority were unknown. 7% of participants were classified as osteoporotic by hip or spine DXA. 37% of men without osteoporosis by DXA had VF identified, suggesting that 90% of patients with clinical osteoporosis would have been misclassified by DXA alone. By ANOVA comparison across VF grades, the BV/TV, surface density and spine, hip and wrist DXA were lower, and erosion index was higher in men with moderate-severe VF compared to lesser grades (all p<0.05). By unadjusted ROC analysis, the addition of HR-MRI to DXA at the spine, hip and femoral neck, added substantially (AUC increased 0.831 to 0.902, p<0.05) to prediction of moderate-severe vertebral fracture. HR-MRI indices were associated with spine, hip and wrist DXA measures (p< 0.01). Longer duration of ADT was associated with lower BV/TV, surface density and surface/curve ratio (p<0.05).
ADT for men with prostate cancer is associated with silent VF. DXA alone leads to misclassifications of osteoporosis which can be avoided by VF assessment. HR-MRI provides a novel technique to assess deterioration of structural integrity in men with VF and adds microstructural information.
PMCID: PMC3889112  PMID: 22991066
prostate cancer; osteoporosis; bone densitometry; radiology
11.  Prevalence of osteopenia and osteoporosis and factors associated with decreased bone mineral density in elderly inpatients with psychiatric disorders in Huzhou, China 
Shanghai Archives of Psychiatry  2012;24(5):262-270.
Little is known about the risks of bone fractures in elderly patients with mental disorders in China.
Assess the bone mineral density (BMD) of elderly patients with mental disorders in China and identify factors that are associated with low BMD, osteopenia and osteoporosis.
One hundred and two psychiatric inpatients 60 years of age or older (including patients with schizophrenia, depression, bipolar disorder and dementia) were randomly selected from patients in the geriatric wards of the Third People's Hospital of Huzhou. Detailed demographic, clinical and biometric data were obtained and the BMD of the lumbar spine was assessed using standard dual energy X-ray absorptiometry (DXA) procedures. Based on WHO criteria, individuals with BMD 1 to 2.5 standard deviations below the mean value for healthy young adults were diagnosed as osteopenia and those with BMD values 2.5 or more standard deviations below the mean value were diagnosed as osteoporosis.
The prevalence of osteopenia was 33.3% (95% CI, 24.4%-43.2%) and the prevalence of osteoporosis was 35.3% (26.0%-45.2%) but none of these patients – even the five patients who had had non-traumatic fractures – had ever been treated for these conditions. The prevalence of osteoporosis in females was 10-fold that in males (53% versus 5%). BMD decreased with age and increased with increasing body mass index (a reflection of nutritional status). The prevalence of osteoporosis was much higher in patients with a diagnosis of depression (58%) than in those with schizophrenia (33%), Alzheimer's disease (30%) or bipolar disorder (13%). Regression analyses found that low BMD and the combined category of osteopenia and osteoporosis were both independently associated with female gender, increasing age, decreasing body mass index, and a diagnosis of depression. BMD and osteoporosis were not significantly associated with regular use of antipsychotic medication.
Osteopenia and osteoporosis are common conditions in elderly patients with mental disorders that can seriously affect their quality of life but they often go undiagnosed and untreated. Long-term prospective studies are needed to clarify the relative importance of nutritional status, activity level, medication usage, and other factors in the causal pathways that connect mental illnesses to BMD.
PMCID: PMC4198874  PMID: 25328349
12.  Bone mineral density among elderly patients with chronic obstructive pulmonary disease patients in India 
Osteoporosis is one of the major extra-pulmonary manifestations of chronic obstructive pulmonary disease (COPD), which limits the physical activity. The present study was undertaken to study the bone mineral density (BMD) and osteoporosis in the elderly COPD patients.
Materials and Methods:
This was a cross-sectional study carried out among elderly COPD patients. After a detailed clinical history spirometry was done to stage the severity of COPD. DEXA scan of the lumbar spine was performed using bone densitometer to determine osteoporosis. Statistical analysis was based on Chi-square test. Risk factors were identified by univariate and multivariate logistic regression analysis.
A total of 70 elderly COPD patients were included. Fourty-six patients (65.7%) had osteoporosis and 13 (18.6%) had osteopenia. Majority of the osteoporosis patients had stage III or stage IV COPD disease (77.2%). As the severity grade of COPD increased, the risk of osteoporosis also increased. Also, with the increasing severity of COPD, BMD decreased. Patients with lower body mass index (BMI) had higher prevalence of osteoporosis (45.7%). Using multivariate regression analysis, stage IV COPD, number of acute exacerbations >3 and steroid cumulative dose >1000 mg were independent risk factors for osteoporosis in elderly COPD patients.
The prevalence of osteoporosis was 65.7%, and 18.6% had osteopenia. Stage III and IV patients had significantly lower BMI in elderly COPD patients. High clinical suspicion and early diagnosis and treatment are required in the evaluation of osteoporosis in elderly COPD patients.
PMCID: PMC3883226  PMID: 24403704
Bone mineral density; osteoporosis; risk factors
13.  Early decrements in bone density after completion of neoadjuvant chemotherapy in pediatric bone sarcoma patients 
Bone mineral density (BMD) accrual during childhood and adolescence is important for attaining peak bone mass. BMD decrements have been reported in survivors of childhood bone sarcomas. However, little is known about the onset and development of bone loss during cancer treatment. The objective of this cross-sectional study was to evaluate BMD in newly diagnosed Ewing's and osteosarcoma patients by means of dual-energy x-ray absorptiometry (DXA) after completion of neoadjuvant chemotherapy.
DXA measurements of the lumbar spine (L2-4), both femora and calcanei were performed perioperatively in 46 children and adolescents (mean age: 14.3 years, range: 8.6-21.5 years). Mean Z-scores, areal BMD (g/cm2), calculated volumetric BMD (g/cm3) and bone mineral content (BMC, g) were determined.
Lumbar spine mean Z-score was -0.14 (95% CI: -0.46 to 0.18), areal BMD was 1.016 g/cm2 (95% CI: 0.950 to 1.082) and volumetric BMD was 0.330 g/cm3 (95% CI: 0.314 to 0.347) which is comparable to healthy peers. For patients with a lower extremity tumor (n = 36), the difference between the affected and non-affected femoral neck was 12.1% (95% CI: -16.3 to -7.9) in areal BMD. The reduction of BMD was more pronounced in the calcaneus with a difference between the affected and contralateral side of 21.7% (95% CI: -29.3 to -14.0) for areal BMD. Furthermore, significant correlations for femoral and calcaneal DXA measurements were found with Spearman-rho coefficients ranging from ρ = 0.55 to ρ = 0.80.
The tumor disease located in the lower extremity in combination with offloading recommendations induced diminished BMD values, indicating local osteopenia conditions. However, the results revealed no significant decrements of lumbar spine BMD in pediatric sarcoma patients after completion of neoadjuvant chemotherapy. Nevertheless, it has to be taken into account that bone tumor patients may experience BMD decrements or secondary osteoporosis in later life. Furthermore, the peripheral assessment of BMD in the calcaneus via DXA is a feasible approach to quantify bone loss in the lower extremity in bone sarcoma patients and may serve as an alternative procedure, when the established assessment of femoral BMD is not practicable due to endoprosthetic replacements.
PMCID: PMC3022904  PMID: 21190557
14.  Vertebral Fractures and the Misclassification of Osteoporosis in Men with Prostate Cancer 
Androgen deprivation therapy (ADT) has become the cornerstone of treatment for both advanced and non-metastatic prostate cancer. The presence of a non-traumatic vertebral fracture (VF) identifies a patient who has clinical osteoporosis. Vertebral Fracture Analysis (VFA), a dual-energy X-ray absorptiometry (DXA)-based technology identifies VFs in conjunction with a standard bone mineral densitometry (BMD) exam. The objective of this study is to determine if VFA will increase the diagnosis of osteoporosis in men with prostate cancer on ADT.
Materials and Methods
116 men ≥ 60 years of age with non-metastatic prostate cancer receiving androgen-deprivation therapy (ADT) for ≥ 6 months underwent DXA of the spine, hip, and one-third distal radius, VFA), and conventional vertebral x-rays.
Approximately 40% of the men had clinically defined osteoporosis. The use of conventional DXA criteria (spine and hip) alone resulted in the misdiagnosis of approximately 75% of patients. VFA and addition of the one-third distal radius site performed by DXA both increased the rate of diagnosis and reduces the misclassification of osteoporosis in men with prostate cancer, compared to conventional DXA criteria alone. Analysis indicated that VFA assessment of mild, moderate, and severe fractures from all readable vertebrae (T5-L4) had a kappa, sensitivity, and specificity of 0.92, 100% and 95%, respectively, with semi-quantitative radiography.
Men with prostate cancer on ADT should be screened for osteoporosis at the initiation of therapy, and evaluation should include DXA of the one-third distal radius in addition to the spine and hip, as well as evaluation for VFs.
PMCID: PMC3150288  PMID: 21723763
androgen deprivation therapy; vertebral fractures; vertebral fracture assessment; osteoporosis; bone mineral density
15.  New Reference Data on Bone Mineral Density and the Prevalence of Osteoporosis in Korean Adults Aged 50 Years or Older: The Korea National Health and Nutrition Examination Survey 2008-2010 
Journal of Korean Medical Science  2014;29(11):1514-1522.
This cross-sectional study was performed to investigate the reference values for bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) and the prevalence of osteoporosis in the Korean population by applying domestic reference data. In total, 25,043 Korean adults ≥20 yr of age (11,792 men and 13,251 women) participated in the study. The BMDs of the total hip, femoral neck, and lumbar spine were measured by DXA (Discovery-W, Hologic Inc.), and subjects with a BMD - 2.5 standard deviations or lower than the mean BMD for young adults (20-29 yr old) were considered to have osteoporosis. When applying the new reference values determined in this study from Korean subjects, the overall prevalence of osteoporosis increased in men aged ≥50 yr compared with that provided by the DXA manufacturer from Japanese subjects (12.2% vs. 7.8%, P<0.001) and decreased in postmenopausal women aged ≥50 yr (32.9% vs. 38.7%, P<0.001). According to the findings of this study, use of the reference values provided by the DXA manufacturer has resulted in the underdiagnosis of osteoporosis in Korean men and the overdiagnosis of osteoporosis in Korean women. Our data will serve as valuable reference standards for the diagnosis and management for osteoporosis in the Korean population.
Graphical Abstract
PMCID: PMC4234919  PMID: 25408583
Bone Density; Reference Values; Osteoporosis; Absorptiometry, Photon; Korean
16.  Bone mineral density status in urolithiasis patients with vitamin D inadequacy followed at a tertiary stone centre 
We assessed abnormalities in bone mineral density (BMD) and the risk of hip and major osteoporotic fractures in urolithiasis patients with vitamin D inadequacy (VDI) followed at a tertiary stone centre.
Stone-free patients with VDI were invited to undergo dual-energy x-ray absorptiometry (DXA) scans to assess for BMD abnormalities at the femoral neck and lumbar spine. The World Health Organization’s validated Fracture Risk Assessment Tool (FRAX) was used to calculate the risk of hip and major osteoporotic fractures within 10 years. Patients with primary hyperparathyroidism or hypercalcemia were excluded.
In total, 50 consecutive patients were included between June 2011 and August 2012, including 26 (52%) males. The median age was 51 years and the median 25-hydroxyl vitamin D (25[OH] D) was 18.8 ng/mL. Thirty patients (60%) had abnormal T-scores on DXA studies. This decreased to 22 (44%) when age-matched Z-scores were used; 36% had osteopenia and 8% had osteoporosis. Femoral neck and lumbar spines were affected in 24% and 32% of patients, respectively. Recurrent stone-formers had significantly lower BMD when compared with first-time stone formers. Median serum 25(OH)D was comparable between patients with normal and abnormal DXA scans (18.6 vs. 18.8 ng/mL; p = 0.91). Five patients (10%) were at high risk (≥3%) of hip fractures within 10 years.
A high prevalence of abnormal DXA scans was found in urolithiasis patients with VDI, including 5 patients (10%) at high risk of hip fractures. Future studies need to assess the economic impact of obtaining DXA scans on urolithiasis patients with VDI, especially in recurrent stone-formers.
PMCID: PMC4216288  PMID: 25408797
17.  Prevalence of Low Bone Mineral Density in a Low-Income Inner-City Population 
Bone mineral density (BMD) is an important factor linked to bone health. Little is known of the prevalence of low BMD and its associated risk factors in an urban underserved population. Between 2001 and 2004, we recruited 338 subjects who completed drug use and medical history questionnaires, underwent hormonal measurements, and underwent whole-body dual-energy X-ray absorptiometry (DXA) for evaluation of BMD and body composition. Of these, 132 subjects had site-specific DXA (lumbar spine and hip) performed. Osteoporosis was defined as a T-score of –2.5 or less for men 50 years of age and older and postmenopausal women and a Z-score of –2.0 or less in men younger than 50 years of age and premenopausal women at either the lumbar spine, total hip, or femoral neck, according to National Osteoporosis Foundation (NOF) guidelines. The cohort consisted of mostly African-American, middle-aged people with a high prevalence of illicit drug use, 50% HIV+, and 39% hepatitis C+. Osteoporosis was identified in 22% of subjects (24 men, 5 women), with the majority of cases (90%) attributable to osteoporosis at the lumbar spine. Osteoporosis was more common in men than in women. Lower whole-body BMD among women was associated with multiple risk factors, but only with lower lean mass among men. Osteoporosis was highly prevalent in men, mainly at the spine. The risk factors for bone loss in this population need to be further clarified. Screening men for osteoporosis starting at age 50 might be warranted in this population given the multiple risk factors and the unexpectedly high prevalence of low BMD. © 2011 American Society for Bone and Mineral Research.
PMCID: PMC3179342  PMID: 20721937
18.  Relationship between body mass index and bone mineral density in HIV-infected patients referred for DXA 
Journal of the International AIDS Society  2014;17(4Suppl 3):19569.
Reduced bone mass density (BMD) is a frequent observation in HIV-infected persons. Relationship between body mass index (BMI), weight, height and BMD was reported for many populations. In particular, BMI has been found to be inversely related to the risk of osteoporosis.
This is a cross-sectional, monocentric study where all HIV-infected patients referred to first DXA scan in clinical routine during 2010–2013 were included. Osteopenia and osteoporosis were defined by T- score <−1 and <−2.5, respectively. Patients were categorized according to WHO BMI classification: underweight <18.5 kg/m2; normal weight 18.5–24.9 kg/m2; over weight 25–29.9 kg/m2; obese >30 kg/m2. Statistical analysis was carried using logistic regression.
A total of 918 patients were included: median age 49 years (IQR, 44–55); 59.4% male; 93% Caucasian. Median anthrometric characteristics were: 68 kg (IQR, 59–78); 1.7 m (IQR, 1.6–1.75); 23.5 kg/m2 (IQR, 21.4–26.2). Underweight was found in 5%, normal weight in 61%, overweight in 26% and obesity in 8% of patients. According to T-scores, 110 (11.2%) patients were osteoporotic and 502 (54.7%) had osteopenia. In the femoral neck area, the prevalence of osteoporosis was slightly lower (5.7%) than lumbar spine site (9.2%). Agreements between sites of T-scores for the diagnosis of osteoporosis were 26 and 172 and 346 for osteopenia and normal BMD values, respectively. T-scores at femoral neck or lumbar spine positively correlated with BMI (p<0.001) (Figure 1). Among predictors of osteopenia/osteoporosis, univariable analysis showed: older age (p<0.0001); lower weight (p<0.0001); increasing height (p<0.002). Patients underweight had a higher risk of osteopenia (p=0.02) as well as of osteoporosis (p=0.003). Patients with BMI above normal had a reduced risk of low BMD (osteopenia p<0.0001; osteoporosis p<0.03). Controlling for calendar year, gender, ethnicity, and age, BMI was confirmed as risk factor if below normal (AdjOR of osteopenia 2.42 [95% CI 1.16–5.07] p=0.02; AdjOR of osteoporosis 3.22 [95% CI 1.60–6.49] p=0.001).
Our findings indicate that almost 66% of HIV-infected patients have subnormal bone mass. Further, as in other patient populations, in the HIV infection also low BMI is an important risk factor for osteopenia/osteoporosis. This finding highlights the compelling need for standardized screening actions, particularly in patients weighting below normal.
PMCID: PMC4224848  PMID: 25394076
19.  A new technique for precisely and accurately measuring lumbar spine bone mineral density in mice using clinical dual energy X-ray absorptiometry (DXA) 
Toxicology Mechanisms and Methods  2009;19(3):225-231.
Dual Energy X-ray Absorptiometry (DXA) is effective in measuring bone mineral density (BMD) in mice for early detection of osteoporosis. However, scanners designed for use with small animals (i.e. PIXImus) are very expensive. Used human DXA machines are cheaper to obtain, but analysis of scans from these instruments is operator-dependent. Obtaining reliable data depends on having a single operator analyze the scans in a blinded fashion. Scan quality is improved by excising the bone prior to scanning, which does not allow serial measurements. This study describes a novel method of analyzing lumbar spine BMD in mice using whole body DXA. This non-invasive technique has a high degree of precision and reproducibility, with good correlation between multiple observers. Inter-observer variability (0.063 ± 0.00317 g/cm2 [mean ± SD], 5.05 [% coefficient of variation (CV)], repeat scan variability (0.063 ± 0.00364 g/cm2 [mean ± SD], 5.94 [%CV]) were very low compared to variability between different animals (0.063 ± 0.00588 g/cm2 [mean ± SD], 9.64 [%CV]) and variability seen in same animal over time (0.011 ± 0.00885 g/cm2 [mean ± SD], 80.68 [%CV]). The measurement error is thus smaller than the biological variation. Accuracy was determined by comparing average peak BMD from two scans per mouse in-vivo (0.066 g/cm2) versus excised spine (0.065 g/cm2). Furthermore, correlation between bone ash weights and whole body lumbar spine BMD measurements (p < 0.0001) was highly significant. This technique thus shows a high degree of precision and accuracy, even with multiple observers, for measuring BMD in mice using a DXA machine designed for clinical use.
PMCID: PMC2739646  PMID: 19750018
Accuracy; Bone mineral density (BMD); DXA; Mice; Precision
20.  Assessment of volumetric bone mineral density of the femoral neck in postmenopausal women with and without vertebral fractures using quantitative multi-slice CT 
Objective: To demonstrate the validity and reliability of volumetric quantitative computed tomography (vQCT) with multi-slice computed tomography (MSCT) and dual energy X-ray absorptiometry (DXA) for hip bone mineral density (BMD) measurements, and to compare the differences between the two techniques in discriminating postmenopausal women with osteoporosis-related vertebral fractures from those without. Methods: Ninety subjects were enrolled and divided into three groups based on the BMD values of the lumbar spine and/or the femoral neck by DXA. Groups 1 and 2 consisted of postmenopausal women with BMD changes <−2SD, with and without radiographically confirmed vertebral fracture (n=11 and 33, respectively). Group 3 comprised normal controls with BMD changes ≥−1SD (n=46). Post-MSCT (GE, LightSpeed16) scan reconstructed images of the abdominal-pelvic region, 1.25 mm thick per slice, were processed by OsteoCAD software to calculate the following parameters: volumetric BMD values of trabecular bone (TRAB), cortical bone (CORT), and integral bone (INTGL) of the left femoral neck, femoral neck axis length (NAL), and minimum cross-section area (mCSA). DXA BMD measurements of the lumbar spine (AP-SPINE) and the left femoral neck (NECK) also were performed for each subject. Results: The values of all seven parameters were significantly lower in subjects of Groups 1 and 2 than in normal postmenopausal women (P<0.05, respectively). Comparing Groups 1 and 2, 3D-TRAB and 3D-INTGL were significantly lower in postmenopausal women with vertebral fracture(s) [(109.8±9.61) and (243.3±33.0) mg/cm3, respectively] than in those without [(148.9±7.47) and (285.4±17.8) mg/cm3, respectively] (P<0.05, respectively), but no significant differences were evident in AP-SPINE or NECK BMD. Conclusion: the femoral neck-derived volumetric BMD parameters using vQCT appeared better than the DXA-derived ones in discriminating osteoporotic postmenopausal women with vertebral fractures from those without. vQCT might be useful to evaluate the effect of osteoporotic vertebral fracture status on changes in bone mass in the femoral neck.
PMCID: PMC2704967  PMID: 19585667
Osteoporosis; Bone mineral density (BMD); Volumetric QCT; Hip fracture; Postmenopausal women
21.  Reference Ranges for Bone Mineral Density and Prevalence of Osteoporosis in Vietnamese Men and Women 
The aim of this study was to examine the effect of different reference ranges in bone mineral density on the diagnosis of osteoporosis.
This cross-sectional study involved 357 men and 870 women aged between 18 and 89 years, who were randomly sampled from various districts within Ho Chi Minh City, Vietnam. BMD at the femoral neck, lumbar spine and whole body was measured by DXA (Hologic QDR4500). Polynomial regression models and bootstraps method were used to determine peak BMD and standard deviation (SD). Based on the two parameters, we computed T-scores (denoted by TVN) for each individual in the study. A similar diagnosis was also done based on T-scores provided by the densitometer (TDXA), which is based on the US White population (NHANES III). We then compared the concordance between TVN and TDXA in the classification of osteoporosis. Osteoporosis was defined according to the World Health Organization criteria.
In post-menopausal women, the prevalence of osteoporosis based on femoral neck TVN was 29%, but when the diagnosis was based on TDXA, the prevalence was 44%. In men aged 50+ years, the TVN-based prevalence of osteoporosis was 10%, which was lower than TDXA-based prevalence (30%). Among 177 women who were diagnosed with osteoporosis by TDXA, 35% were actually osteopenia by TVN. The kappa-statistic was 0.54 for women and 0.41 for men.
These data suggest that the T-scores provided by the Hologic QDR4500 over-diagnosed osteoporosis in Vietnamese men and women. This over-diagnosis could lead to over-treatment and influence the decision of recruitment of participants in clinical trials.
PMCID: PMC3163638  PMID: 21831301
reference range; bone mineral density; osteoporosis; women; men
22.  Concordane of OSTA and lumbar spine BMD by DXA in identifying risk of osteoporosis 
To investigate the accuracy of Osteoporosis Self-assessment Tool for Asians (OSTA) in identifying the risk of osteoporosis in postmenopausal women. To validate use of OSTA risk index by comparing it with the bone mineral density (BMD) of lumbar spine measured by dual energy X-ray absorptiometry (DXA).
The data of lumbar spine BMD (LS BMD) measurements by DXA of 218 postmenopausal women of Han nationality in Sichuan province were compared with OSTA risk index. The concordance of OSTA and LS BMD were calculated and analyzed by fourfold table and receiver operating characteristic (ROC) curve.
The prevalence of osteoporosis in these women was 40.4% and 61.5%, with the LS BMD T score cutoffs -2.5 and -2.0, respectively. The sensitivity, specificity, and accuracy of OSTA risk index compared with T score cutoff -2.5 of LS BMD were 59.1%, 56.9% and 57.8%, respectively, while they were 57.5%, 63.1%, 59.6% by T score cutoff -2.0.
For identifying risk of osteoporosis, the concurrence was lower than those reported studies when comparing LS BMD measurements to OSTA risk index in Chinese Han nationality postmenopausal women of Sichuan province. Physicians should identify women who need BMD measurement according to more factors rather than age and body weight.
PMCID: PMC1693545  PMID: 17150121
23.  CTXA Hip—An Extension of Classical DXA Measurements Using Quantitative CT 
PLoS ONE  2014;9(3):e91904.
Bone mineral density (BMD) estimates for the proximal femur using Dual Energy X-ray Absorptiometry (DXA) are currently considered the standard for making a diagnosis of osteoporosis in an individual patient using BMD alone. We have compared BMD results from a commercial Quantitative CT (QCT) BMD analysis system, “CTXA Hip”, which provides clinical data for the proximal femur, to results from DXA. We have also used CTXA Hip to determine cortical and trabecular contributions to total BMD. Sixty-nine patients were scanned using 3D QCT and DXA. CTXA Hip BMD measurements for Total Hip and Femoral Neck were compared to DXA results. Twenty-two women were scanned at 0,1,2 years and CTXA Hip and DXA results analyzed for long-term reproducibility. Long-term reproducibility calculated as root-mean-square averages of SDs in vivo was 0.012 g/cm2 (CV = 1.8%) for CTXA Total Hip and 0.011 g/cm2 (CV = 2.0%) for CTXA Femoral Neck compared to 0.014 g/cm2 (CV = 2.0%) and 0.016 g/cm2 (CV = 2.7%), respectively, for DXA. The correlation of Total Hip BMD CTXA vs. DXA was R = 0.97 and for Femoral Neck was R = 0.95 (SEE 0.044 g/cm2 in both cases). Cortical bone comprised 62±5% (mean ± SD) of total hipbone mass in osteoporotic women. CTXA Hip provides substantially the same clinical information as conventional DXA and in addition provides estimates of BMD in separate cortical and trabecular bone compartments, which may be useful in evaluation of bone strength.
PMCID: PMC3956816  PMID: 24637515
24.  Validation of a CT-Derived Method for Osteoporosis Screening in IBD Patients Undergoing Contrast-Enhanced CT Enterography 
Osteoporosis and bone fractures are of particular concern in patients with inflammatory bowel disease (IBD). Biomechanical computed tomography (BCT) is an image-analysis technique that can measure bone strength and dual-energy X-ray absorptiometry (DXA)-equivalent bone mineral density (BMD) from noncontrast CT images. This study seeks to determine whether this advanced technology can be applied to patients with IBD undergoing CT enterography (CTE) with IV contrast.
Patients with IBD who underwent a CTE and DXA scan between 2007 and 2011 were retrospectively identified. Femoral neck BMD (g/cm2) and T-scores were measured and compared between DXA and BCT analysis of the CTE images. Femoral strength (Newtons) was also determined from BCT analysis.
DXA- and CTE-generated BMD T-score values were highly correlated (R2 = 0.84, P <0.0001) in this patient cohort (n = 136). CTE identified patients with both osteoporosis (sensitivity, 85.7%; 95% confidence interval (CI), 48.7–97.4 and specificity, 98.5%; 95% CI, 94.5–99.6) and osteopenia (sensitivity, 85.1%; 95% CI, 72.3–92.6 and specificity, 85.4%; 95% CI, 76.6 –91.3). Of the 16 patients who had “fragile” bone strength by BCT (placing them at the equivalent high risk of fracture as for osteoporosis), 6 had osteoporosis and 10 had osteopenia by DXA.
CTE scans can provide hip BMD, T-scores, and clinical classifications that are comparable to those obtained from DXA; when combined with BCT analysis, CTE can identify a subset of patients with osteopenia who have clinically relevant fragile bone strength. This technique could markedly increase bone health assessments in IBD patients already undergoing CTE to evaluate small bowel disease.
PMCID: PMC4033296  PMID: 24445572
25.  Bone Metabolism Disorders in Patients with Spinal Cord Injuries 
In Italy, 60–70 thousand people are affected by spinal cord lesions, which have an incidence of 20/25 new cases per million per year and a male:female ratio of 4:1. The age group most affected is 10–40 years. In 65% of cases the origin of the lesion is traumatic. According to the ASIA (American Spinal Injury Association) Impairment Scale (AIS), the lesion is defined complete or incomplete, depending on whether or not partial conservation of sensory and/or motor functions is found below the level of the lesion in the first 24 hours following the trauma. Patients with spinal injuries show alterations of phosphocalcic metabolism, with osteoporosis, neurogenic para-osteo-arthropathy and renal calculi. Even though post-lesion osteoporosis is traditionally considered secondary to reduced loading, it has characteristics different from those of primary osteoporosis and osteoporosis caused by endocrine disorders or by simple disuse. Indeed, there is usually no significant demineralisation of the bone segments above the level of the neurological lesion and the site and entity of the bone resorption are influenced by factors such as age, sex, muscle spasticity, but above all by lesion site, lesion severity, and post-lesion period.
Osteocytes (the mechanosensors in bone tissue), via extracellular and intracellular signal transmitters, transmit mechanical load signals to the osteoblasts, stimulating bone formation and inhibiting bone resorption by the osteoclasts.
A spinal injury results in prolonged limitation of both the loading and the movement of the lower limbs; this leads to marked muscle atrophy, inhibition of the osteoblasts and activation of the osteoclasts, and an inevitable loss of bone tissue. The increase in bone resorption following a spinal injury is reflected in increased urinary excretion of hydroxyproline, pyridinoline, deoxypyridinoline and type I collagen C-telopeptide. Significantly increased expression of RANKL mRNA and protein in cultures of osteoblast-like cells from spinal injured rats has also been observed, while OPG expression is significantly reduced and osteoclastogenesis increased. Spinal lesions are also associated with supplementary production, in the bone marrow, of cytokines like IL-6, potential mediators of bone mass loss.
Recent studies suggest that bone remodelling is also influenced by nervous signals: after denervation, due to a spinal lesion, there is a marked reduction in innervation density and in neuropeptides, such as VIP, PACAP, NPY, SP, CGRP, noradrenaline, glutamate and serotonin, mainly in bone segments below the level of the lesion; this upsets the balance between bone resorption and formation. In addition to its direct role in bone metabolism, denervation can induce alterations of vascular regulation: indeed, a complete spinal injury causes alterations of the sympathetic innervation with possible opening of intraosseous venous shunts that, leading to venous and capillary stasis with increase in local pressure, could favour the formation of osteoclasts, accelerating the process of bone resorption; osteopenia is indeed predominant in the meta-epiphyseal areas of long bones, which are highly vascularised.
In the first months following the injury, the demineralisation generally affects mainly the distal femur and proximal tibia, segments rich in trabecular bone, while the femoral and tibial diaphyses, which are rich in cortical bone, are relatively spared.
Paradoxically, in the lumbar spine, in which the trabecular component is prevalent, DXA scans do not reveal significant reductions in bone mineral density, independently of the lesion level or duration. This may be because the spinal column exerts an ongoing bodyweight-supporting action during wheelchair use. Nevertheless, on DXA studies, BMD at lumbar level can sometimes erroneously appear increased on account of the presence of osteophytes due to neuropathic spondylopathy. To overcome the limits of this approach, the most recent studies have used densitometric methods such as QCT (quantitative computerised tomography) to assess the density of trabecular and cortical bone in the distal radius and tibia.
Up to a third of spinal cord injured patients are liable to sustain fragility fractures. Although they are asymptomatic, these fractures can cause complications, such as abnormal bone callus formation, bedsores and increased spasticity, all factors that can further deteriorate the patient’s already precarious state of health.
Reduction of fracture risk through an appropriate treatment of osteoporosis after spinal cord injury is particularly important for the prognosis and quality of life of these patients. In this context, the application of diagnostic protocols, both haematological and instrumental, for the monitoring and therapeutic control of bone demineralisation over time could be an effective help.
PMCID: PMC3213781

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