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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.  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
3.  Aged-Related Changes in Body Composition and Association between Body Composition with Bone Mass Density by Body Mass Index in Chinese Han Men over 50-year-old 
PLoS ONE  2015;10(6):e0130400.
Aging, body composition, and body mass index (BMI) are important factors in bone mineral density (BMD). Although several studies have investigated the various parameters and factors that differentially influence BMD, the results have been inconsistent. Thus, the primary goal of the present study was to further characterize the relationships of aging, body composition parameters, and BMI with BMD in Chinese Han males older than 50 years.
The present study was a retrospective analysis of the body composition, BMI, and BMD of 358 Chinese male outpatients between 50 and 89 years of age that were recruited from our hospital between 2009 and 2011. Qualified subjects were stratified according to age and BMI as follows: 50–59 (n = 35), 60–69 (n = 123), 70–79 (n = 93), and 80–89 (n = 107) years of age and low weight (BMI: < 20 kg/m2; n = 21), medium weight (20 ≤ BMI < 24 kg/m2; n = 118), overweight (24 ≤ BMI < 28 kg/m2; n = 178), and obese (BMI ≥ 28 kg/m2; n = 41). Dual-energy X-ray absorptiometry (DEXA) was used to assess bone mineral content (BMC), lean mass (LM), fat mass (FM), fat-free mass (FFM), lumbar spine (L1-L4) BMD, femoral neck BMD, and total hip BMD. Additionally, the FM index (FMI; FM/height2), LM index (LMI; LM/height2), FFM index (FFMI; [BMC+LM]/height2), percentage of BMC (%BMC; BMC/[BMC+FM+LM] × 100%), percentage of FM (%FM; FM/[BMC+FM+LM] × 100%), and percentage of LM (%LM; LM/(BMC+FM+LM) × 100%) were calculated. Osteopenia or osteoporosis was identified using the criteria and T-score of the World Health Organization.
Although there were no significant differences in BMI among the age groups, there was a significant decline in height and weight according to age (p < 0.0001 and p = 0.0002, respectively). The LMI and FFMI also declined with age (both p < 0.0001) whereas the FMI exhibited a significant increase that peaked in the 80-89-years group (p = 0.0145). Although the absolute values of BMC and LM declined with age (p = 0.0031 and p < 0.0001, respectively), there was no significant difference in FM. In terms of body composition, there were no significant differences in %BMC but there was an increase in %FM (p < 0.0001) and a decrease in %LM (p < 0.0001) with age. The femoral neck and total hip BMD significantly declined with age (p < 0.0001 and p = 0.0027, respectively) but there were no differences in L1-L4. BMD increased at all sites (all p < 0.01) as BMI increased but there were declines in the detection rates of osteoporosis and osteopenia (both p < 0.001). A logistic regression revealed that when the medium weight group was given a BMI value of 1, a decline in BMI was an independent risk factor of osteoporosis or osteopenia, while an increase in BMI was a protective factor for BMD. At the same time, BMD in L1-L4 exhibited a significant positive association with FMI (p = 0.0003) and the femoral neck and total hip BMDs had significant positive associations with FFMI and LMI, respectively (both p < 0.0001).
These data indicate that LMI and FFMI exhibited significant negative associations with aging in Chinese Han males older than 50 years, whereas FMI had a positive association. BMD in the femoral neck and total hip declined with age but an increased BMI was protective for BMD. LMI and FFMI were protective for BMD in the femoral neck and total hip.
PMCID: PMC4475062  PMID: 26090818
4.  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
5.  The Effect of Long-term Corticosteroid Use on Bone Mineral Density in Children: A Prospective Longitudinal Assessment in the Childhood Asthma Management Program (CAMP) Study 
Pediatrics  2008;122(1):e53-e61.
Systemic corticosteroids are known to induce osteoporosis and increase the risk of fractures in adults and children. Inhaled corticosteroids have been shown to increase the risk of osteoporosis and fractures in adults at risk. However, long-term prospective studies in children to assess risks of multiple short courses of oral corticosteroids and chronic inhaled corticosteroids have not been done. Thus, we assessed the effects of multiple short courses of oral corticosteroids and long-term inhaled corticosteroids on bone mineral accretion over a period of years.
Patients and Methods
This was a cohort followup study for a median of 7 years of children with mild to moderate asthma initially randomized into the Childhood Asthma Management Program (CAMP) trial. Serial dual-energy x-ray absorptiometry (DEXA) scans of the lumbar spine for bone mineral density (BMD) were performed in all patients. Annual bone mineral accretion was calculated in 531 boys and 346 girls with asthma aged 5–12 years at baseline (84% of the initial cohort).
Oral corticosteroid bursts produced a dose-dependent reduction in bone mineral accretion (0.052, 0.049, and 0.046 gm/cm2/year, p=0.0002) and an increase in risk of osteopenia (10%, 14% and 21%, p=0.02) for 0, 1–4, and 5+ courses, respectively, in males but not females. Cumulative inhaled corticosteroid use was associated with a small decrease in bone mineral accretion in males (p=0.05) but not females, but no increased risk of osteopenia.
Multiple oral corticosteroid bursts over a period of years can produce a dose-dependent reduction in bone mineral accretion and increased risk of osteopenia in children with asthma. Inhaled corticosteroid use has the potential for reducing bone mineral accretion in male children progressing through puberty but this risk is likely to be outweighed by the ability to reduce the amount of oral corticosteroids used in these children.
PMCID: PMC2928657  PMID: 18595975
Cohort study; bone mineral density; corticosteroids; asthma; children; osteopenia
6.  Influence of Obesity on Bone Mineral Density in Postmenopausal Asthma Patients Undergoing Treatment with Inhaled Corticosteroids 
Clinics (Sao Paulo, Brazil)  2009;64(4):313-318.
The etiology of osteoporosis in asthma is complex as various factors contribute to its pathogenesis. The purpose of our study was to investigate the effects of obesity and inhaled steroids, as well as the severity and duration of asthma, on osteoporosis in postmenopausal asthma patients as compared to healthy controls.
A total of 46 patients with asthma and 60 healthy female controls, all postmenopausal, were enrolled in our study. Bone mineral density was assessed at the lumbar spine and hip using a Lunar DPX-L densitometer.
Bone mineral density (BMD) scores were comparable between the asthmatic and control groups, with average scores of 0.95 ± 0.29 and 0.88 ± 0.14 g/cm2, respectively. Likewise, osteoporosis was diagnosed in a similar percentage of patients in the asthmatic (39.1%) and control (43.3%) groups. Bone fracture was identified in four patients with asthma (8.6%) and in six patients from the control group (10%). We could not detect any relationship between BMD and duration of asthma, asthma severity, inhaled steroids or body mass index (BMI). There was no difference between the two groups with respect to age or years since menopause. Although asthma patients were more likely to be overweight and presented higher BMD scores on average than the control subjects, these differences were not statistically significant.
There is a slight positive protective effect of high BMI against osteoporosis in asthma patients, but this effect is overcome by time and menopause status. Therefore, the protective effect of obesity against osteoporosis in asthma patients seems to not be significant.
PMCID: PMC2694454  PMID: 19488588
Asthma; Obesity; Osteoporosis; Bone mineral densitometry; Inhaled steroids
7.  Bone Mineral Density Changes in Patients with Recent-Onset Rheumatoid Arthritis 
Osteoporosis and related fragility fractures are one of the most common complications seen in patients with rheumatoid arthritis (RA) and dramatically affect quality of life.
To evaluate changes in bone mineral density in patients with recent onset rheumatoid arthritis (<1 year) and its correlation if any with a modified DAS-28 score and simple erosion narrowing score (SENS).
This study included 30 patients with recent-onset rheumatoid arthritis fulfilling the new American College of Rheumatology/European League Against Rheumatism diagnostic criteria for rheumatoid arthritis and 20 healthy volunteers as controls. All were subjected to a complete blood count, erythrocyte sedimentation rate, C-reactive protein, liver function tests, renal function tests, rheumatoid factor, and plain x-rays of the hands and feet. Dual-energy x-ray absorptiometry DEXA was used to measure bone mineral density (BMD) of the left proximal femur, lumbar spine (L1–L4), and lower distal radius at the time of recruitment.
In the RA patients, 13.3% had osteoporosis, 50% had osteopenia, and 36.7% had normal BMD. The most common site of osteoporosis was the lumbar spine (four patients, 13.3%) followed by the femur (two patients, 6.6%), and forearm (only one patient, 3.3%). There was a significantly higher percentage of osteoporosis among RA males than females and the difference was statistically significant (P = 0.009). Osteoporosis was more common in patients treated with corticosteroids and disease modifying antirheumatic drugs (DMARDs) than in patients treated with only nonsteroidal anti-inflammatory drugs (P = 0.004). Higher disease activity (DAS-28) was found in RA patients with osteoporosis compared to RA patients with normal BMD or osteopenia, but the difference was not statistically significant. Osteoporotic RA patients were found to have a higher SENS score for radiological damage than nonosteoporotic ones.
BMD changes do occur in patients with early RA, and are not necessarily correlated with disease activity (DAS-28). However, a significant negative correlation was found between BMD and the score of radiological damage (SENS). Dual energy x-ray absorptiometry is an important investigation to assess BMD in early RA patients.
PMCID: PMC3201106  PMID: 22084606
BMD; recent onset; rheumatoid arthritis
8.  The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group 
Osteoporosis International  2014;25(5):1439-1443.
Osteoporosis causes an elevated fracture risk. We propose the continued use of T-scores as one means for diagnosis but recommend that, alternatively, hip fracture; osteopenia-associated vertebral, proximal humerus, pelvis, or some wrist fractures; or FRAX scores with ≥3 % (hip) or 20 % (major) 10-year fracture risk also confer an osteoporosis diagnosis.
Osteoporosis is a common disorder of reduced bone strength that predisposes to an increased risk for fractures in older individuals. In the USA, the standard criterion for the diagnosis of osteoporosis in postmenopausal women and older men is a T-score of ≤ −2.5 at the lumbar spine, femur neck, or total hip by bone mineral density testing.
Under the direction of the National Bone Health Alliance, 17 clinicians and clinical scientists were appointed to a working group charged to determine the appropriate expansion of the criteria by which osteoporosis can be diagnosed.
The group recommends that postmenopausal women and men aged 50 years should be diagnosed with osteoporosis if they have a demonstrable elevated risk for future fractures. This includes having a T-score of less than or equal to −2.5 at the spine or hip as one method for diagnosis but also permits a diagnosis for individuals in this population who have experienced a hip fracture with or without bone mineral density (BMD) testing and for those who have osteopenia by BMD who sustain a vertebral, proximal humeral, pelvic, or, in some cases, distal forearm fracture. Finally, the term osteoporosis should be used to diagnose individuals with an elevated fracture risk based on the World Health Organization Fracture Risk Algorithm, FRAX.
As new ICD-10 codes become available, it is our hope that this new understanding of what osteoporosis represents will allow for an appropriate diagnosis when older individuals are recognized as being at an elevated risk for fracture.
PMCID: PMC3988515  PMID: 24577348
Clinical diagnosis; Criteria; Osteoporosis; Position statement
9.  Relationship between blood pressure levels and bone mineral density in postmenopausal Turkish women 
We investigated the association between bone mineral density (BMD) detected by dual-energy X-ray absorptiometric (DXA) method and blood pressure (BP) in a large sample of postmenopausal women.
Material and methods
The current study was based on a retrospective analysis of 586 postmenopausal women with a mean age of 60.8 ±8.8 years, who were screened for osteopenia or osteoporosis by DXA. Patients with hypertension (HT, n= 306) were compared with normotensive (NT, n = 290) individuals. Bone mineral density results for the femur neck and spine were classified into 3 groups according to World Health Organization criteria: normal (T score > –1.0 SD), osteopenia (T score –1.0 to –2.5 SD) and osteoporosis (T score < –2.5 SD). Patients with osteopenia or osteoporosis (T score < –1.0 SD) were grouped as having low bone mass (LBM).
There were no significant differences in femur T score, femur BMD, femur Z score, spinal T score, spinal BMD and spinal Z score between hypertensive and normotensive groups. The group of patients with low bone mass calculated from femur T scores had higher age, systolic BP, duration of hypertension and duration of menopause, but lower BMI. Similarly, patients with low spine BMD had higher age and duration of menopause, but lower BMI. Linear regression analysis showed a significant correlation between systolic BP and femur BMD and T score values. Furthermore, logistic regression analysis revealed that hypertension is an independent predictor of spinal osteopenia and osteoporosis.
The presence of hypertension is an independent predictor of spinal low bone density in Turkish women after menopause.
PMCID: PMC3258724  PMID: 22291766
blood pressure; bone mineral density; dual-energy X-ray absorptiometric
10.  Prevalence of low bone mineral density among HIV patients on long-term suppressive antiretroviral therapy in resource limited setting of western India 
Journal of the International AIDS Society  2014;17(4Suppl 3):19567.
Bone mineral density (BMD) assessment in HIV patients is sparsely done in resource limited settings.
Materials and Methods
We conducted a cross-sectional study of BMD amongst HIV patients following up in our clinic from 1 June to 1 December 2013 by performing dual-energy X-ray absorptiometry scan (Lunar Prodigy Advanced DXA System, GE Healthcare) of lumbar spine and hip. Patients on long term (≥12 months), virologically suppressive antiretroviral therapy (ART) were included. Patients who were ART naïve were included as control population. Virologic failures were excluded. Low BMD was defined by WHO T-score criteria (normal: T score ≥−1;osteopenia: T score between −1 and −2.5 SD; osteoporosis: T score ≤−2.5 SD). Baseline risk factors associated with low BMD like age, low BMI, lipoatrophy, diabetes mellitus, current smoking, current alcohol intake, steroid exposure and menopause were recorded. ART-related factors associated with low BMD like ART duration, exposure to tenofovir and exposure to protease inhibitors (PI) were studied.
A total of 536 patients (66% males, 496 ART experienced and 40 ART naïve) were included in this analysis. Median age was 42 years, mean BMI 23.35 kg/m2 and median CD4 count 146 cells/mm3. All ART experienced patients had plasma viral load<400 copies/ml.
Prevalence of low BMD amongst ART naive and ART experienced patients was 67% (osteopenia: 70.4%, osteoporosis: 29.6%) and 80.4% (osteopenia: 63.4%, osteoporosis: 36.6%), respectively (p=0.05). Mean T scores at lumbar spine and hip for ART naive and ART experienced patients were −1.37 and −0.9 versus −1.56 and −1.48 (p=0.05), respectively. Age, low BMI, current smoking, menopause, baseline CD4 count and exposure to ART were factors significantly associated with low overall BMD on univariate regression analysis. On multivariable logistic regression analysis age (p<0.001), low BMI (p<0.001), current smoking (0.05) and menopause (0.03) were associated with low BMD. BMI decrease of 1 kg/m2 and baseline CD4 decline of 50 cells/mm3 lead to 14% and 4% increased probability of low BMD, respectively. Choice of antiretroviral use (tenofovir vs non-tenofovir, PI vs No PI) did not influence loss of BMD.
Extremely high prevalence of accelerated BMD loss amongst ART naïve and ART experienced patients in our cohort is a matter of deep concern due to its association with pathological fractures. Bone mineral loss was seen irrespective of ART used. Association of low BMD with low baseline CD4 count strengthens the case for early ART.
PMCID: PMC4224871  PMID: 25394074
11.  Radiographic Emphysema Predicts Low Bone Mineral Density in a Tobacco-exposed Cohort 
Rationale: Studies demonstrating an association between chronic obstructive pulmonary disease and low bone mineral density (BMD) implicate factors distinct from treatments and severity of lung disease in the pathogenesis of osteoporosis. Whereas emphysema has been independently associated with vascular disease and other comorbidities, its association with BMD has not been well studied.
Objectives: We explored the associations of BMD with computed tomography (CT) measures of emphysema and other risk factors in current and former smokers.
Methods: One hundred ninety subjects completed a CT scan, pulmonary function testing, questionnaires, and dual x-ray absorptiometry measurements of hip and lumbar spine BMD. Subjects were classified as having normal BMD, osteopenia, or osteoporosis. Demographic, physiologic, and radiographic characteristics were compared and the association of BMD with radiographic emphysema, airflow obstruction, and osteoporosis risk factors was assessed.
Measurements and Main Results: No difference existed in age, tobacco exposure, oral steroid use, or physical activity across BMD categories. Both osteopenia and osteoporosis were associated with the presence of airflow obstruction, inhaled corticosteroid use, and female sex, and demonstrated a significant relationship with the presence of visual emphysema (P = 0.0003). Quantitative emphysema, but not CT-measured indices of airway wall thickness, was inversely associated with BMD. Visual emphysema alone was a significant predictor of osteopenia/osteoporosis (odds ratio = 2.55; 95% confidence interval, 1.24–5.25) in a model including obstruction severity, age, sex, and inhaled and oral steroid use.
Conclusions: Radiographic emphysema is a strong, independent predictor of low BMD in current and former smokers. This relationship suggests a common mechanistic link between emphysema and osteopenia/osteoporosis.
PMCID: PMC3086755  PMID: 20935108
pulmonary disease, chronic obstructive; emphysema; osteoporosis
12.  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
13.  Low bone mineral density linked to colorectal adenomas: a cross-sectional study of a racially diverse population 
Epidemiologic studies suggest that lower bone mineral density (BMD) is associated with an increased risk for colorectal adenoma/cancer, especially in postmenopausal women. The aim of this study is to investigate the association between osteopenia and/or osteoporosis and colorectal adenomas in patients from a New York community hospital.
We performed a cross-sectional observational study on 200 patients who underwent screening colonoscopies and bone density scan (dual-energy X-ray absorptiometry) at Nassau University Medical Center from November 2009 to March 2011. Among these, 83 patients were identified as osteoporosis (T score of −2.5 or below) and 67 were osteopenia (T score between −1.0 and −2.5). Logistic regression model was performed to assess the association between osteopenia and/or osteoporosis and colorectal adenomas.
Among the patients with osteopenia and osteoporosis, the mean ages were 59.1 years [standard deviation (SD) =8.9] and 61.5 (SD =8.9), respectively. There were 94.0%, 85.1% and 74.7% women, respectively, in normal BMD, osteopenia and osteoporosis groups. The prevalence of colorectal adenomas was 17.9% and 25.3% in the osteopenia and osteoporosis groups, respectively, and 18.0% in the normal BMD group. After adjustment for potential confounders including age, sex, race, body mass index (BMI), tobacco use, alcohol use, history of diabetes, hypertension, or dyslipidemia, osteoporosis was found to be associated with presence of colorectal adenomas more than 2, compared to the normal BMD group. No significant associations were found for the prevalence, size, and location of adenomas.
Our study suggests that osteoporosis is significantly associated with the presence of multiple colorectal adenomas. Prospective studies with a larger sample size are warranted in the future.
PMCID: PMC4311102  PMID: 25830036
Bone mineral density (BMD); osteoporosis; colonoscopy; colorectal adenoma
14.  The effect of breast-feeding duration on bone mineral density in postmenopausal Turkish women: a population-based study 
In the present study, we investigated the effects of breast-feeding time on bone mineral density (BMD) later in life.
Material and methods
The current study was based on a retrospective analysis of 586 postmenopausal women with a mean age of 60.8 years, who were screened for osteoporosis by dual energy X-ray absorptiometry (DXA).They were classified into 4 groups with respect to the duration of their breast-feeding as never (group 1), 1-24 months (group 2), 25-60 months (group 3), or > 60 months (group 4). Bone mineral density results for the femur neck and lumbar spine were classified into 3 groups according to WHO criteria as normal (T score > –1.0 SD), osteopenia (T score –1.0 to –2.5 SD), and osteoporosis (T score < –2.5 SD). Patients with osteopenia or osteoporosis (T score < –1.0 SD) were considered as having low bone mass (LBM).
We found a correlation between duration of lactation and femur BMD or spine BMD in the study population (r = 0.116, p < 0.005; r = –0.151, p = 0.001, respectively). Significant differences were found between femur BMD and spine BMD of groups in one-way ANOVA analysis (p = 0.025, p = 0.005, respectively). Additionally, when compared with the other three groups, group 4 was older and had longer duration of menopause (p < 0.01). In logistic regression analysis, age and body mass index were found as independent risk factors of LBM [odds ratio: 1.084 (95% CI 1.031-1.141); odds ratio: 0.896 (95% CI 0.859-0.935)], while duration of lactation was not found as an independent predictor of LBM.
In this study, we have found that changes of bone metabolism during lactation had no effect on postmenopausal BMD measured by DXA. Consequently, it can be suggested that long breast-feeding duration is not a risk factor for low bone mass later in life.
PMCID: PMC3258757  PMID: 22295033
breast-feeding time; bone mineral density; postmenopausal women
15.  Bone-Density Testing Interval and Transition to Osteoporosis in Older Women 
The New England Journal of Medicine  2012;366(3):225-233.
Although bone mineral density (BMD) testing to screen for osteoporosis (BMD T score, −2.50 or lower) is recommended for women 65 years of age or older, there are few data to guide decisions about the interval between BMD tests.
We studied 4957 women, 67 years of age or older, with normal BMD (T score at the femoral neck and total hip, −1.00 or higher) or osteopenia (T score, −1.01 to −2.49) and with no history of hip or clinical vertebral fracture or of treatment for osteoporosis, followed prospectively for up to 15 years. The BMD testing interval was defined as the estimated time for 10% of women to make the transition to osteoporosis before having a hip or clinical vertebral fracture, with adjustment for estrogen use and clinical risk factors. Transitions from normal BMD and from three subgroups of osteopenia (mild, moderate, and advanced) were analyzed with the use of parametric cumulative incidence models. Incident hip and clinical vertebral fractures and initiation of treatment with bisphosphonates, calcitonin, or raloxifene were treated as competing risks.
The estimated BMD testing interval was 16.8 years (95% confidence interval [CI], 11.5 to 24.6) for women with normal BMD, 17.3 years (95% CI, 13.9 to 21.5) for women with mild osteopenia, 4.7 years (95% CI, 4.2 to 5.2) for women with moderate osteopenia, and 1.1 years (95% CI, 1.0 to 1.3) for women with advanced osteopenia.
Our data indicate that osteoporosis would develop in less than 10% of older, post-menopausal women during rescreening intervals of approximately 15 years for women with normal bone density or mild osteopenia, 5 years for women with moderate osteopenia, and 1 year for women with advanced osteopenia. (Funded by the National Institutes of Health.)
PMCID: PMC3285114  PMID: 22256806
16.  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
17.  Osteoporotic profiles in elderly patients with symptomatic lumbar spinal canal stenosis 
Indian Journal of Orthopaedics  2012;46(3):279-284.
The osteoporosis and lumbar canal stenosis, in elderly patients are under diagnosed and under reported. We report a cross sectional study to demonstrate the osteoporotic profile in patients with lumbar spinal stenosis (LSS) and to determine the proportion of patients with LSS who need to be treated for osteoporosis.
Materials and Methods:
One hundred and six postmenopausal patients with symptomatic LSS were evaluated for osteoporotic profile, which included lumbar and hip bone mineral density (BMD), serum vitamin D concentration, bone resorption and formation markers. Demographic and disease related variables were analyzed to identify the association with the risk of osteoporosis or osteopenia. Statistical analysis used were multivariate logistic regression with a forward stepwise procedure.
Twenty-four patients (22.6%) had osteoporosis and 60 (56.6%) had osteopenia. Overall, 84 patients (79.2%) with symptomatic LSS had osteoporosis or osteopenia. Fifty-nine patients (55.6%) had hypovitaminosis D. All bone turnover makers [alkaline phosphatase, osteocalcin, urinary-N-terminal telopeptide (u-NTx)] were demonstrated to be within normal range. Only age was associated with the risk of osteoporosis or osteopenia in the hip region. In the lumbar spine, all variables were not associated with osteoporosis or osteopenia. 44 patients (41.5%) required treatment for osteoporosis as per risk factors for osteoporosis. According to the guidelines from the Health Insurance Review Agency, however, only 20 patients (18.8% required) qualified for reimbursement for osteoporosis medications.
LSS is associated with osteopenia, osteoporosis, and hypovitaminosis D, which should prompt careful screening and treatment in cases of osteoporosis and osteoarthritis.
PMCID: PMC3377137  PMID: 22719113
Bone mineral density; bone turnover marker; hypovitaminosis D; lumbar spinal stenosis; osteoporosis
18.  Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial 
PLoS Medicine  2008;5(10):1-12.
Vitamin K has been widely promoted as a supplement for decreasing bone loss in postmenopausal women, but the long-term benefits and potential harms are unknown. This study was conducted to determine whether daily high-dose vitamin K1 supplementation safely reduces bone loss, bone turnover, and fractures.
Methods and Findings
This single-center study was designed as a 2-y randomized, placebo-controlled, double-blind trial, extended for earlier participants for up to an additional 2 y because of interest in long-term safety and fractures. A total of 440 postmenopausal women with osteopenia were randomized to either 5 mg of vitamin K1 or placebo daily. Primary outcomes were changes in BMD at the lumbar spine and total hip at 2 y. Secondary outcomes included changes in BMD at other sites and other time points, bone turnover markers, height, fractures, adverse effects, and health-related quality of life. This study has a power of 90% to detect 3% differences in BMD between the two groups. The women in this study were vitamin D replete, with a mean serum 25-hydroxyvitamin D level of 77 nmol/l at baseline. Over 2 y, BMD decreased by −1.28% and −1.22% (p = 0.84) (difference of −0.06%; 95% confidence interval [CI] −0.67% to 0.54%) at the lumbar spine and −0.69% and −0.88% (p = 0.51) (difference of 0.19%; 95% CI −0.37% to 0.75%) at the total hip in the vitamin K and placebo groups, respectively. There were no significant differences in changes in BMD at any site between the two groups over the 2- to 4-y period. Daily vitamin K1 supplementation increased serum vitamin K1 levels by 10-fold, and decreased the percentage of undercarboxylated osteocalcin and total osteocalcin levels (bone formation marker). However, C-telopeptide levels (bone resorption marker) were not significantly different between the two groups. Fewer women in the vitamin K group had clinical fractures (nine versus 20, p = 0.04) and fewer had cancers (three versus 12, p = 0.02). Vitamin K supplements were well-tolerated over the 4-y period. There were no significant differences in adverse effects or health-related quality of life between the two groups. The study was not powered to examine fractures or cancers, and their numbers were small.
Daily 5 mg of vitamin K1 supplementation for 2 to 4 y does not protect against age-related decline in BMD, but may protect against fractures and cancers in postmenopausal women with osteopenia. More studies are needed to further examine the effect of vitamin K on fractures and cancers.
Trial registration: (#NCT00150969) and Current Controlled Trials (#ISRCTN61708241)
Angela Cheung and colleagues investigate whether vitamin K1 can prevent bone loss among postmenopausal women with osteopenia.
Editors' Summary
Osteoporosis is a bone disease in which the bones gradually become less dense and more likely to break. In the US, 10 million people have osteoporosis and 18 million have osteopenia, a milder condition that precedes osteoporosis. In both conditions, insufficient new bone is made and/or too much old bone is absorbed. Although bone appears solid and unchanging, very little bone in the human body is more than 10 y old. Old bone is continually absorbed and new bone built using calcium, phosphorous, and proteins. Because the sex hormones control calcium and phosphorous deposition in the bones and thus bone strength, the leading cause of osteoporosis in women is reduced estrogen levels after menopause. In men, an age-related decline in testosterone levels can cause osteoporosis. Most people discover they have osteoporosis only when they break a bone, but the condition can be diagnosed and monitored using bone mineral density (BMD) scans. Treatments can slow down or reverse bone loss (antiresorptive therapies) and some (bone formation therapies) can even make bone and build bone tissue.
Why Was This Study Done?
Although regular exercise and a healthy diet can help to keep bones strong, other ways of preventing osteoporosis are badly needed. Recently, the lay media has promoted vitamin K supplements as a way to reduce bone loss in postmenopausal women. Vitamin K (which is found mainly in leafy green vegetables) is required for a chemical modification of proteins called carboxylation. This modification is essential for the activity of three bone-building proteins. In addition, there is some evidence that low bone density and fractures are associated with a low vitamin K intake. However, little is known about the long-term benefits or harms of vitamin K supplements. In this study, the researchers investigate whether a high-dose daily vitamin K supplement can safely reduce bone loss, bone turnover, and fractures in postmenopausal women with osteopenia in a randomized controlled trial called the “Evaluation of the Clinical Use of Vitamin K Supplementation in Post-Menopausal Women With Osteopenia” (ECKO) trial.
What Did the Researchers Do and Find?
In the study, 440 postmenopausal women with osteopenia were randomized to receive 5mg of vitamin K1 (the type of vitamin K in North American food; the recommended daily adult intake of vitamin K1 is about 0.1 mg) or an inactive tablet (placebo) daily for 2 y; 261 of the women continued their treatment for 2 y to gather information about the long-term effects of vitamin K1 supplementation. All the women had regular bone density scans of their lower back and hips and were examined for fractures and for changes in bone turnover. After 2 y and after 4 y, lower back and hip bone density measurements had decreased by similar amounts in both treatment groups. The women who took vitamin K1 had 10-fold higher amounts of vitamin K1 in their blood than the women who took placebo and lower amounts of a bone formation marker; the levels of a bone resorption marker were similar in both groups. Over the 4-y period, fewer women in the vitamin K group had fractures (nine versus 20 women in the placebo group), and fewer had cancer (three versus 12). Finally, vitamin K supplementation was well tolerated over the 4-y period and adverse health effects were similar in the two treatment groups.
What Do These Findings Mean?
These findings indicate that a high daily dose of vitamin K1 provides no protection against the age-related decline in bone density in postmenopausal women with osteopenia, but that vitamin K1 supplementation may protect against fractures and cancers in these women. The apparent contradiction between the effects of vitamin K1 on bone density and on fractures could mean that vitamin K1 supplements strengthen bone by changing factors other than bone density, e.g., by changing its fine structure rather than making it denser. However, because so few study participants had fractures, the difference in the fracture rate between the two treatment groups might have occurred by chance. Larger studies are therefore needed to examine the effect of vitamin K1 on fractures (and on cancer) and, until these are done, high-dose vitamin K1 supplementation should not be recommended for the prevention of osteoporosis.
Additional Information.
Please access these Web sites via the online version of this summary at
The US National Institute of Arthritis and Musculoskeletal and Skin Diseases provides detailed information about osteoporosis (in English and Spanish) and links to other resources, including an interactive web tool called Check Up On Your Bones
MedlinePlus provides links to additional information about osteoporosis (in English and Spanish)
The MedlinePlus Encyclopedia has a page about vitamin K
The UK Food Standards Agency provides information about vitamin K
Full details about the ECKO trial are available on the Web site
The Canadian Task Force for Preventive Health Care provides recommendations on the prevention of osteoporosis and osteoporotic fractures in postmenopausal women
Osteoporosis Canada provides information on current topics related to osteoporosis
PMCID: PMC2566998  PMID: 18922041
19.  Gender Difference in Bone Loss and Vascular Calcification Associated with Age 
Korean Circulation Journal  2013;43(7):453-461.
Background and Objectives
It is widely known that both bone loss and vascular calcification are age-related processes. The purpose of this study was to investigate the relationship between coronary artery calcium (CAC) score or bone mineral density (BMD) with age and whether there is a gender difference factoring in the two conditions among healthy subjects.
Subjects and Methods
Between March 2009 and August 2011, participants included 1727 subjects (mean age: 55±10 years, M : F=914 : 813) with routine health check-ups. After being categorized into three groups (normal, osteopenia, and osteoporosis) according to the World Health Organization (WHO) diagnostic classification, we estimated BMD by dual energy X-ray absorptiometry (DEXA) and CAC score by dual-source CT (DSCT).
There was a significant gender difference among the risk factors, including total-lumbar spine (1.213±0.176 g/cm2 : 1.087±0.168 g/cm2, p<0.001) and femur (1.024±0.131 g/cm2 : 0.910±0.127 g/cm2, p<0.001) in BMD by DEXA, and CAC score (68±227 : 27±116, p<0.001) in coronary artery calcification by DSCT. Age in male [odds ratio (OR): 1.138 {95% confidence interval (CI): 1.088-1.190}, p<0.001] and menopause in female subjects {OR: 12.370 (95% CI: 3.120-49.047), p<0.001} were, respectively, independently associated with osteopenia.
Although our results do not demonstrate a direct association between CAC score and BMD in both genders, there is a gender difference of CAC score in normal and osteopenia groups according to the WHO diagnostic classification. Additionally, we suggest that more specific therapeutic strategies be considered during any early bone loss period, especially in female subjects.
PMCID: PMC3744732  PMID: 23964291
Gender; Osteoporosis; Coronary vessels; Calcium; Bone density
20.  Low bone mineral density is related to male gender and decreased functional capacity in early spondylarthropathies 
Clinical Rheumatology  2010;30(4):497-503.
The objective of this study was to determine the prevalence and risk factors of low bone mineral density (BMD) in patients with spondylarthropathies (SpA) at an early stage of disease. In this cross-sectional study, the BMD of lumbar spine and hips was measured in 130 consecutive early SpA patients. The outcome measure BMD was defined as (1) osteoporosis, (2) osteopenia, and (3) normal bone density. Logistic regression analyses were used to investigate relations between the following variables: age, gender, disease duration, diagnosis, HLA-B27, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), extra-spinal manifestations and medication, with outcome measure low BMD (osteopenia and/or osteoporosis). The SpA population had a median time since diagnosis of 6.6 months and a disease duration of 6.3 years. In total, 9% of the early SpA patients had osteoporosis, 38% osteopenia, and 53% normal BMD. On univariate analyses, male gender, diagnosis of ankylosing spondylitis, increased CRP, high BASFI, and high BASMI were significantly associated with low BMD. Factors showing a relation with low BMD in the multivariate model were male gender (OR 4.18, 95% confidence interval (CI) 1.73–10.09), high BASMI (OR 1.54, 95% CI 1.14–2.07), and high BASFI (OR 1.18, 95% CI 1.00–1.39). In early SpA patients, a high frequency (47%) of low BMD in femur as well as in lumbar spine was found. Low BMD was associated with male gender and decreased functional capacity. These findings emphasize the need for more alertness for osteoporosis and osteopenia in spondylarthropathy patients at an early stage of the disease.
PMCID: PMC3062761  PMID: 20697764
Ankylosing spondylitis; Bone mineral density; Osteoporosis; Spondylarthropathies
21.  Age effect on bone mineral density changes in breast cancer patients receiving anastrozole: results from the ARBI prospective clinical trial 
We investigated whether age at anastrozole (A) initiation influences the effect of treatment on bone mineral density (BMD). We conducted a post hoc analysis of the dataset of Arimidex Bone Mass Index Oral Bisphosphonates prospective trial, studying the effect of risedronate (R) on BMD of postmenopausal, early breast cancer patients receiving A.
Patients were stratified into those with normal BMD or mild osteopenia (T > −2) receiving A-only and patients with mild or severe osteopenia (T ≤ −2) or osteoporosis (T < −2.5) receiving A and per os R (A + R). Depending on age on treatment initiation, patients were grouped into two age cohorts, above and below 65 years. BMD change in lumbar spine (LS) and hip (HP) was evaluated at 12 months. An analysis of patients with normal BMD at baseline was additionally performed.
Among patients receiving A-only, women ≤65 years were more likely to have a decrease in LS-BMD than older (p = 0.034). HP-BMD decrease at 12 months was not related to age (p = 0.182). In patients with mild or severe osteopenia or osteoporosis, treated with A + R, no age effect was observed for LS or HP (p = 0.099 and p = 0.939, respectively). Among patients with normal BMD at baseline, the age effect on LS-BMD change was more profound (p = 0.026).
Our study suggests that younger postmenopausal women with normal BMD or mild osteopenia receiving A-only face an increased risk of bone loss in LS. Among patients with mild or severe osteopenia or osteoporosis treated with A + R, 12 months LS or HP BMD variations were configured regardless of age group.
PMCID: PMC3418493  PMID: 22552718
Breast cancer; Aromatase inhibitors; Anastrozole; Bisphosphonates; Risedronate; Bone mineral density
22.  Bone mineral density in university aged Saudi females 
The aim of the study was to investigate bone mineral density (BMD) in young Saudi females (20-25 years) using Dual-energy x-ray absorptiometry (DXA), as it is a widely utilized modality for the measurement of BMD, used for the diagnosis of osteoporosis and osteopenia.
BMD measurements were performed in the spine and the neck of the femur in 101 young females.
37% and 34% patients had osteopenia in the spine and the neck of the femur respectively, BMD values = 0.98 and 0.81 gm/cm2 respectively). Whereas 5% had osteoporosis in the spine area, BMD values = 0.82 gm/cm2). Of the 101 subjects, 53 (52.5%) young females did not suffer from osteopenia in either both site, whereas 23 (22.7%) females had osteopenia in both sites, the remaining 25 subjects (25% of the subject included) had either osteopenia or osteoporosis in one of the sites. A strong association between BMD values with weight was found.
We found that one third of the young Saudi females sampled suffer from osteopenia. Additionally, body weight has a positive relationship with bone mineral density.
PMCID: PMC4485270  PMID: 26150843
Bone Mineral Density; Osteopenia; Osteoporosis; T-score; DXA; Young Saudi Females
23.  How Many High Risk Korean Patients with Osteopenia Could Overlook Treatment Eligibility? 
Asian Spine Journal  2014;8(6):729-734.
Study Design
Retrospective study.
To determine the prevalence of high risk patient with osteopenia requiring pharmacologic treatment and investigate the difference of 10-year fracture probability whether bone mineral density (BMD) include or not in Korean FRAX model.
Overview of Literature
Many people with the fracture have osteopenia rather than osteoporosis, and BMD alone could be considered as a chance to prevent fracture.
Three hundred sixty-nine patients who was diagnosed as osteopenia were divided into two groups according to age (group 1, under 65 years; group 2, over 65 years), and 10-year fracture probabilities were calculated by FRAX algorithm with and without femur neck T-score.
The high risk patients of the fracture who had above 3% of 10-year hip fracture probability were 15 cases in group 1 and 121 cases in group 2. In 193 patients of group 1, the mean 10-year fracture probability with BMD was significantly higher than the results without BMD (hip fracture: p=0.04, major osteoporotic fracture: p=0.01). Unlike the results of the group 1, the mean 10-year fracture probability without BMD was significantly higher than the results with BMD in 176 patients of group 2 (hip fracture: p=0.01, major osteoporotic fracture: p=0.01).
Total of 136 cases (36.8%) as a high risk of the fracture with osteopenia could be overlooked treatment eligibility in Korean. The Korean FRAX model without BMD could be effective in predicting fracture risk especially in the individuals who were over 65 years.
PMCID: PMC4278977  PMID: 25558314
Osteopenia; Risk assessment; Bone mineral density; FRAX
24.  Effects of Long-Term Combination Treatment with Valproate and Atypical Antipsychotics on Bone Mineral Density and Bone Metabolism in Premenopausal Patients with Bipolar Disorder: A Preliminary Study 
Psychiatry Investigation  2011;8(3):256-261.
We investigated bone mineral density (BMD) and bone metabolism in female bipolar patients who were undergoing long-term treatment with valproate combined with a low-dose atypical antipsychotic.
Nineteen premenopausal women with bipolar disorder who were treated with valproate combined with atypical antipsycho-tics for at least 2 years were evaluated. The BMD was measured at lumbar spine and femur sites using dual-energy X-ray absorptiometry (DE-XA). The biochemical markers of bone turnover and circulating levels of gonadal hormones were assessed. Subjects with abnormal DEXA scans were compared to those with normal scans.
Nine (47%) of nineteen subjects showed osteopenia or osteoporosis. The T-score for subjects with abnormal DEXA scans was -1.988. Decreased BMD was more prominent in the proximal femur than in the lumbar spine. Subjects with abnormal DEXA scans had high phosphorus and low testosterone levels relative to subjects with normal scans (p=0.008 and p=0.028, respectively). There was a significant negative correlation between phosphorus, osteocalcin, and femur neck BMD (p<0.05). However, multivariate analysis did not show a significant association between femur and lumbar BMD and biochemical markers of bone turnover.
Long-term treatment with valproate combined with low-dose atypical antipsychotics may adversely affect BMD in premenopausal women with bipolar disorder. A prospective, controlled-study with a larger population is warranted, and assessment of BMD and bone metabolism should be taken into consideration in long-term therapy with valproate and atypical antipsychotics.
PMCID: PMC3182392  PMID: 21994514
Bipolar disorder; Bone density; Bone metabolism; Females; Valproate
25.  Risk factors of osteoporosis in healthy Moroccan men 
Although not as common as in women, osteoporosis remains a significant health care problem in men. Data concerning risk factors of osteoporosis are lacking for the male Moroccan population. The objective of the study was to identify some determinants associated to low bone mineral density in Moroccan men.
a sample of 592 healthy men aged 20-79 years was recruited from the area of Rabat, the capital of Morocco. Measurements were taken at the lumbar spine and proximal femurs using DXA (Lunar Prodigy Vision, GE). Biometrical, clinical, and lifestyle determinants were collected. Univariate, multivariate, and logistic regression analyses were performed.
the mean (SD) age of the patients was 49 (17.2) years old. The prevalence of osteoporosis and osteopenia were 8.7% and 52.8%, respectively. Lumbar spine and hip BMD correlated significantly with age, weight and BMI. When comparing the subjects according to the WHO classification, significant differences were revealed between the three groups of subjects for age, weight and BMI, prevalence of low calcium intake and low physical activity. The multiple regression analysis found that only age, BMI, and high coffee consumption were independently associated to the osteoporotic status.
ageing and low BMI are the main risk factors associated with osteoporosis in Moroccan men.
PMCID: PMC2909164  PMID: 20602777

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