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1.  Utilization of DXA Bone Mineral Densitometry in Ontario 
Executive Summary
Issue
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.
Background
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.
Conclusion
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.  Major and minor discordance in the diagnosis of postmenopausal osteoporosis among Indian women using hip and spine dual-energy X-ray absorptiometry 
Journal of Mid-Life Health  2012;3(2):76-80.
Objective:
To determine discordance in the diagnosis of osteoporosis among postmenopausal Indian women using hip and spine Dual-energy X-ray Absorptiometry.
Materials and Methods:
The study included postmenopausal women who underwent bone mineral densitometry (BMD) for suspected osteoporosis at a referral hospital at Hyderabad, India. The BMD measures at the hip and spine were used to derive T-scores and to determine the prevalence of discordance. Factors potentially associated with discordance were explored in univariate and a multivariate regression model.
Results:
The mean age of the 348 postmenopausal women in the study was 53.62 ± 8.94 years (median 53.00 years, range 27.00 to 84.00 years). Major discordance was seen in 16.67% (95% confidence intervals [CI]: 12.73, 20.60) of the study population and minor discordance in 34.48% (95% CI: 29.46, 39.50%) of the study population. Age >50 years (adjusted odds ratios [OR]: 2.60, 95% CI: 1.24, 5.46, P value = 0.01), premature menopause (adjusted OR: 2.94, 95% CI: 1.27, 6.81, P value = 0.03), and multiple pregnancies (adjusted OR: 2.64, 95% CI: 1.28, 5.41, P value = 0.008) were found to be significantly associated with major discordance.
Conclusions:
The large prevalence of discordance may reflect the differences in osteoporosis in different populations and suggests the need to redefine ranges and risk factors used for the diagnosis of osteoporosis in India.
doi:10.4103/0976-7800.104457
PMCID: PMC3555030  PMID: 23372323
Bone mineral density; discordance; dual-energy X-ray absorptiometry; osteoporosis
3.  Differences in Site-Specific Fracture Risk Among Older Women with Discordant Results for Osteoporosis at Hip and Spine: the Study of Osteoporotic Fractures 
To examine the fracture pattern in older women whose bone mineral density (BMD) T-score criteria for osteoporosis at hip and spine disagree, hip and spine BMD were measured in Study of Osteoporotic Fractures participants using dual energy x-ray absorptiometry (DXA). Hip osteoporosis was defined as T-score ≤-2.5 at femoral neck or total hip, and spine osteoporosis as T-score ≤-2.5 at lumbar spine. Incident clinical fractures were self-reported and centrally adjudicated. Incident radiographic spine fractures were defined morphometrically. Compared to women with osteoporosis at neither hip nor spine, those osteoporotic only at hip had a 3.0-fold age and weight-adjusted increased risk for hip fracture (95%CI 2.4-3.6), and smaller increases in risk of nonhip nonspine (HR=1.6), clinical spine (OR=2.2), and radiographic spine fractures (OR=1.5). Women osteoporotic only at spine had a 2.8-fold increased odds of radiographic spine fracture (95%CI 2.1-3.8), and smaller increases in risk of clinical spine (OR=1.4), nonhip nonspine (HR=1.6), and hip fractures (HR=1.2). Discordant BMD results predict different fracture patterns. DXA fracture risk estimation in these patients should be site-specific. Women osteoporotic only at spine would not have been identified from hip BMD measurement alone, and may have a sufficiently high fracture risk to warrant preventive treatment.
doi:10.1016/j.jocd.2007.12.018
PMCID: PMC2724071  PMID: 18296090
Osteoporosis; bone density; fractures; prospective studies; DXA
4.  Assessment of Osteoporosis in Family Medicine Obtained by Ultrasound Densitometry 
Acta Informatica Medica  2013;21(4):274-276.
Introduction:
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.
Objective:
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.
Results:
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.
Conclusion:
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.
doi:10.5455/aim.2013.21.274-276
PMCID: PMC3916165  PMID: 24554805
bone density; early detection; risk factors; quantitative ultrasound densitometry; osteoporosis.
5.  Prevalence and Risk Factors of Discordance between Left- and Right-Hip Bone Mineral Density Using DXA 
ISRN Rheumatology  2012;2012:617535.
To determine the prevalence of significant left-right differences in hip bone mineral density (BMD), and the impact of this difference on osteoporosis diagnosis, we measured bilateral proximal femora using dual energy X-ray absorptiometry (DXA) in 3481 subjects (608 males, 2873 females). The difference between left and right hip was considered significant if it exceeded the smallest detectable difference (SDD) for any of the three hip subregions. Contralateral femoral BMD was highly correlated at all measuring sites (r = 0.92–0.95). However, significant left-right differences in BMD were common: the difference exceeded the SDD for 54% of patients at total hip, 52.1% at femoral neck, and 57.7% at trochanter. The prevalence of left-right differences was greater in participants >65 years. For 1169 participants with normal spines, 22 (1.9%) had discordant left-right hips in which one hip was osteoporotic; for 1349 patients with osteopenic spines, 94 (7%) had osteoporosis in one hip. Participants with BMI < 20 kg/m2 were more likely to show major T-score discordance (osteoporosis in one hip and normal BMD in the other). Multiple regression analysis showed that the only significant statically parameter that persists after adjusting for all potential confounding parameters were age over 65 years.
doi:10.5402/2012/617535
PMCID: PMC3384949  PMID: 22778990
6.  Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 2. The use of bone density measurement in the diagnosis and management of osteoporosis. 
OBJECTIVE: To determine the best method of diagnosing osteoporosis and determining fracture risk and to promote standards in the use of bone densitometry and the reporting of results. OPTIONS: Methods of bone mineral density measurement: dual-energy x-ray absorptiometry (DXA), radiographic absorptiometry, single-photon absorptiometry, dual-photon absorptiometry, quantitative computed tomography, quantitative ultrasound, neutron activation analysis. The options of using bone densitometry in individual patient management and as a mass screening tool are also considered. OUTCOMES: Appropriate use of densitometry to promote accurate diagnosis and assessment of fracture risk and timely, appropriate treatment. EVIDENCE: Relevant clinical studies and reports were examined. Clinical practice in Canada was also considered. VALUES: Accurate assessment of osteoporotic fracture risk and diagnosis of osteoporosis and assuring low exposure to medical radiation were given a high value. BENEFITS, HARMS AND COSTS: Early diagnosis through bone density measurement allows proper management of osteoporosis to minimize injury and disability, improve quality of life and reduce the personal and social costs associated with the condition. Potential harms include radiation exposure and cost. The harms and costs of appropriate use of DXA are minimal compared with the harms and costs associated with osteoporosis. RECOMMENDATIONS: Bone mineral density should be measured only to assist in making a clinical management choice. DXA is the best method of measuring bone density and, thus, the best available indicator of osteoporotic fracture risk. Plain radiographs may supplement DXA if there is a specific reason for their use. Measurement of the lumbar spine and femoral neck is standard, but a different site or a single measurement is recommended in specific cases. Unless accelerated bone loss is suspected, DXA should be repeated every 2 to 4 years for patients receiving ovarian hormone therapy and 1 to 2 years for patients undergoing bisphosphonate therapy. Measurements and reporting of results must be standardized. Reports should refer to the World Health Organization's recommended definitions of osteopenia and osteoporosis and provide actual measurement and its relation to peak bone mass.
PMCID: PMC1335455  PMID: 8837541
7.  Hip Fracture Incidence in Relation to Age, Menopausal Status, and Age at Menopause: Prospective Analysis 
PLoS Medicine  2009;6(11):e1000181.
Using data from the UK Million Women Study, Emily Banks and colleagues investigate the relationships between the incidence of hip fracture and a woman's age, menopausal status, and age at menopause.
Background
Bone mineral density is known to decrease rapidly after the menopause. There is limited evidence about the separate contributions of a woman's age, menopausal status and age at menopause to the incidence of hip fracture.
Methods and Findings
Over one million middle-aged women joined the UK Million Women Study in 1996–2001 providing information on their menopausal status, age at menopause, and other factors, which was updated, where possible, 3 y later. All women were registered with the UK National Health Service (NHS) and were routinely linked to information on cause-specific admissions to NHS hospitals. 561,609 women who had never used hormone replacement therapy and who provided complete information on menopausal variables (at baseline 25% were pre/perimenopausal and 75% postmenopausal) were followed up for a total of 3.4 million woman-years (an average 6.2 y per woman). During follow-up 1,676 (0.3%) were admitted to hospital with a first incident hip fracture. Among women aged 50–54 y the relative risk (RR) of hip fracture risk was significantly higher in postmenopausal than premenopausal women (adjusted RR 2.22, 95% confidence interval [CI] 1.22–4.04; p = 0.009); there were too few premenopausal women aged 55 y and over for valid comparisons. Among postmenopausal women, hip fracture incidence increased steeply with age (p<0.001), with rates being about seven times higher at age 70–74 y than at 50–54 y (incidence rates of 0.82 versus 0.11 per 100 women over 5 y). Among postmenopausal women of a given age there was no significant difference in hip fracture incidence between women whose menopause was due to bilateral oophorectomy compared to a natural menopause (adjusted RR 1.20, 95% CI 0.94–1.55; p = 0.15), and age at menopause had little, if any, effect on hip fracture incidence.
Conclusions
At around the time of the menopause, hip fracture incidence is about twice as high in postmenopausal than in premenopausal women, but this effect is short lived. Among postmenopausal women, age is by far the main determinant of hip fracture incidence and, for women of a given age, their age at menopause has, at most, a weak additional effect.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Anyone can break a hip but most hip fractures occur in elderly people. As people age, their bones gradually lose minerals and become less dense, which weakens the bones and makes them more susceptible to fracture. Because women lose bone density faster than men as they age and because women constitute the majority of the elderly, three-quarters of hip fractures occur in women. Hip fractures can cause long-term health problems and premature death. Thus, although surgical repair of a broken hip usually only requires a hospital stay of about a week, a quarter of elderly people who were living independently before their fracture have to stay in a nursing home for at least a year after their injury and a fifth of elderly people who break a hip die within the year. Most hip fractures are caused by falls. Regular exercise to improve strength and balance combined with review of medicines (to reduce side effects and interactions), regular eye examinations, and the removal of fall hazards from the home can help to prevent hip fractures in elderly people.
Why Was This Study Done?
Bone density decreases very rapidly in women immediately after menopause—the time when menstruation permanently stops—and then continues to decrease more slowly with age. Most women have their menopause in their early 50s but menopause can occur in younger women. Early menopause is thought to be a risk factor for osteoporosis (thinning of the bones) and fractures later in life but little is known about how menopause influences hip fracture risk as women age. In this prospective study (a type of study in which a group of people is followed for several years to see whether they develop a particular condition), the researchers investigate the incidence of hip fractures in relation to age, menopausal status, and age at menopause among the participants of the Million Women Study. This study, which recruited 1.3 million women aged 50–64 years who attended UK breast cancer screening clinics between 1996 and 2001, has been investigating how reproductive and lifestyle factors affect women's health.
What Did the Researchers Do and Find?
At enrollment and three years later, the study participants provided information about their menopausal status and other health and lifestyle factors likely to affect their fracture risk. From these data, the researchers identified more than half a million women who had never used hormone replacement therapy (which reduces fracture risk) and who had given complete information about their menopausal status. They then looked for statistical associations between the occurrence of a first hip fracture in these women over the next few years and their age, menopausal status, and age at menopause. Among women aged 50–54 years, postmenopausal women were twice as likely to have a hip fracture as premenopausal women. Among postmenopausal women, the incidence of hip fractures increased steeply with age and was seven times higher in 70–74-year olds than in 50–54-year olds. Women who had their menopause before age 45 had a slightly increased risk of hip fracture but any effect of age at menopause on the risk of hip fracture was small compared to the effect of age itself, and the slightly increased risk may have been due to other factors that could not be fully accounted for in the analysis.
What Do These Findings Mean?
These findings indicate that around the time of menopause, although hip fractures are rare, the risk of a fracture in postmenopausal women is twice that in premenopausal women. The findings also show that among postmenopausal women, age is the major determinant of hip fracture risk and that for women of a given age, their age at menopause has little effect on hip fracture risk. Women attending breast cancer screening clinics and completing questionnaires about their health may not be representative of the general population. Furthermore, these findings rely on women self-reporting their menopausal status accurately. Nevertheless, the results of this study suggest that clinicians advising women about hip fracture prevention should probably base their advice on the woman's age and on age-related factors such as frailty rather than on factors related to menopause. Clinicians can also now reassure elderly women who had an early menopause that their risk of hip fracture is unlikely to be higher than that of similar women who had a later menopause.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000181.
The American Academy of Orthopaedic Surgeons has detailed information about hip fractures
The US National Institute of Arthritis and Muscoloskeletal and Skin Diseases has an interactive feature called “Check up on your bones and provides detailed information about osteoporosis, including advice on fall prevention
The US Centers for Disease Control and Prevention has a fact sheet about hip fractures among older adults
MedlinePlus has links to resources about hip fracture, osteoporosis, and menopause (in English and Spanish)
More information on the Million Women Study is available
doi:10.1371/journal.pmed.1000181
PMCID: PMC2766835  PMID: 19901981
8.  Increased Levels of Circulating Advanced Glycation End-Products in Menopausal Women with Osteoporosis 
Background: Advanced glycation end-products (AGEs) can accumulate in organs and tissues during ageing and diabetes. Increased levels of AGEs are found in the bone tissue of patients with osteoporosis. The purpose of this study was to evaluate circulating AGEs in patients with osteoporosis.
Methods: We evaluated plasma AGEs, osteoporosis-related biomarkers, and bone mass in 82 menopausal women with osteoporosis or osteopenia, 16 young women with osteopenia, and 43 healthy women without osteoporosis or osteopenia.
Results: Higher levels of serum AGEs were found in the osteoporosis or osteopenia group compared to healthy women (P < 0.0001). A negative correlation was observed between serum AGEs and lumbar spine bone density (BMD of lumbar spine, r = -0.249, P = 0.028; T-score of lumbar spine, r = -0.261, P = 0.021). Women with a increased level of serum AGEs (> 8.12 U/mL) had a 5.34-fold risk of osteopenia regarding lumbar spine T-score and a 3.31-fold risk of osteopenia regarding the hip T-score.
Conclusion: Serum AGEs could be used to monitor the severity and progression of osteoporosis. An increased serum level of AGEs was associated with impaired bone formation and was a risk factor for the development of osteoporosis. Targeting AGEs may represent a novel therapeutic approach for primary or secondary osteoporosis.
doi:10.7150/ijms.8172
PMCID: PMC3970097  PMID: 24688308
Advanced glycation end-products; Osteopenia; Osteoporosis; Biomarker; Osteopontin.
9.  Prevalence and associated factors of osteoporosis in female patients with rheumatoid arthritis  
Background: Osteoporosis (OP) is a common complication of inflammatory arthritis such as rheumatoid arthritis (RA). In this study we evaluated Osteoporosis and its related factors in RA patients.
Methods: This cross - sectional study was carried out from 2010 to 2011 on 121 women with RA aged 45-75 years. These patients were selected and divided in two groups according to their bone mineral densitometry (BMD) status, osteoporotic and non osteoporotic. The data about OP and potential related factors were recorded. T-test for quantitative and X2 for qualitative variables were used for group comparison.
Results: The mean age of the patients was 55.7±10.1 and the duration of the disease was 10.1±9.2 years. Thirty nine (32.3%) of patients had T score≤-2.5 [28 (23.1%) in the lumbar spine and 20 (16.5%) in the femoral neck of regions]. The age and body mass index (BMI) were the most significant factors related to OP (p=0.00, p=0.01). Surgery induced menopause was conversely related to OP in neck of femur (p=0.04). OP in femur was related to overall fracture in patients (p=0.02) and also with seropositivity for RF (p=0.04) and body mass index (p=0.01).
Conclusion: The prevalence of OP in our patients was higher than expected. Old age, menopause, low BMI and seropositivity were the main risk factors of osteoporosis.
PMCID: PMC3755855  PMID: 24009912
Osteoporosis; Rheumatoid arthritis; Bone mineral density; Risk factors
10.  Factors influencing quality of life in Moroccan postmenopausal women with osteoporotic vertebral fracture assessed by ECOS 16 questionnaire 
Objective
The aim of the study was to evaluate factors influencing quality of life (QOL) in Moroccan postmenopausal women with osteoporotic vertebral fracture assessed by the Arabic version of ECOS 16 questionnaire.
Methods
357 postmenopausal women were included in this study. The participants underwent bone mineral density (BMD) measurements by DXA of the lumbar spine and the total hip as well as X-ray examination of the thoraco-lumbar spine to identify subclinical vertebral fractures. Patients were asked to complete a questionnaire on clinical and sociodemographic parameters, and osteoporosis risk factors. The Arabic version of the ECOS16 (Assessment of health related quality of life in osteoporosis questionnaire) was used to assess quality of life.
Results
The mean age was 58 ± 7.8 years, and the mean BMI was 28.3 ± 4.8 kg/m2. One hundred and eight women (30.1%) were osteoporotic and 46.7% had vertebral fractures. Most were categorized as Grade1 (75%). Three independent factors were associated with a poor quality of life: low educational level (p = 0,01), vertebral fracture (p = 0,03), and history of peripheral fracture (p = 0,006). Worse QOL was observed in the group with vertebral fracture in all domains except "pain": Physical functioning (p = 0,002); Fear of illness (p = 0,001); and Psychosocial functioning (p = 0,007). The number of fractures was a determinant of a low QOL, as indicated by an increased score in physical functioning (p = 0,01), fear of illness (p = 0,007), and total score (p = 0,01) after adjusting on age and educational level. Patients with higher Genant score had low QOL in these two domains too (p = 0,002; p = 0,001 respectively), and in the total score (p = 0,01) after adjusting on age and educational level.
Conclusion
Our current data showed that the quality of life assessed by the Arabic version of the ECOS 16 questionnaire is decreased in post menopausal women with prevalent vertebral fractures, with the increasing number and the severity of vertebral fractures.
doi:10.1186/1477-7525-7-23
PMCID: PMC2663551  PMID: 19284667
11.  Vitamin K Supplementation in Postmenopausal Women with Osteopenia (ECKO Trial): A Randomized Controlled Trial 
PLoS Medicine  2008;5(10):1-12.
Background
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.
Conclusions
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: ClinicalTrials.gov (#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
Background.
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 http://dx.doi.org/10.1371/journal.pmed.0050196.
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 ClinicalTrials.gov 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
doi:10.1371/journal.pmed.0050196
PMCID: PMC2566998  PMID: 18922041
12.  The prevalence of vertebral fracture amongst patients presenting with non-vertebral fractures 
Osteoporosis International  2006;18(2):185-192.
Introduction
Despite vertebral fracture being a significant risk factor for further fracture, vertebral fractures are often unrecognised. A study was therefore conducted to determine the proportion of patients presenting with a non-vertebral fracture who also have an unrecognised vertebral fracture.
Methods
Prospective study of patients presenting with a non-vertebral fracture in South Glasgow who underwent DXA evaluation with vertebral morphometry (MXA) from DV5/6 to LV4/5. Vertebral deformities (consistent with fracture) were identified by direct visualisation using the Genant semi-quantitative grading scale.
Results
Data were available for 337 patients presenting with low trauma non-vertebral fracture; 261 were female. Of all patients, 10.4% were aged 50–64 years, 53.2% were aged 65–74 years and 36.2% were aged 75 years or over. According to WHO definitions, 35.0% of patients had normal lumbar spine BMD (T-score −1 or above), 37.4% were osteopenic (T-score −1.1 to −2.4) and 27.6% osteoporotic (T-score −2.5 or lower). Humerus (n=103, 31%), radius–ulna (n=90, 27%) and hand/foot (n=53, 16%) were the most common fractures. For 72% of patients (n=241) the presenting fracture was the first low trauma fracture to come to clinical attention. The overall prevalence of vertebral deformity established by MXA was 25% (n=83); 45% (n=37) of patients with vertebral deformity had deformities of more than one vertebra. Of the patients with vertebral deformity and readable scans for grading, 72.5% (58/80) had deformities of grade 2 or 3. Patients presenting with hip fracture, or spine T-score ≤−2.5, or low BMI, or with more than one prior non-vertebral fracture were all significantly more likely to have evidence of a prevalent vertebral deformity (p<0.05). However, 19.8% of patients with an osteopenic T-score had a vertebral deformity (48% of which were multiple), and 16.1% of patients with a normal T-score had a vertebral deformity (26.3% of which were multiple). Following non-vertebral fracture, some guidelines suggest that anti-resorptive therapy should be reserved for patients with DXA-proven osteoporosis. However, patients who have one or more prior vertebral fractures (prevalent at the time of their non-vertebral fracture) would also become candidates for anti-resorptive therapy—which would have not been the case had their vertebral fracture status not been known. Overall in this study, 8.9% of patients are likely to have had a change in management by virtue of their underlying vertebral deformity status. In other words, 11 patients who present with a non-vertebral fracture would need to undergo vertebral morphometry in order to identify one patient who ought to be managed differently.
Conclusions
Our results support the recommendation to perform vertebral morphometry in patients who are referred for DXA after experiencing a non-vertebral fracture. Treatment decisions will then better reflect any given patient’s future absolute fracture risk. The 'Number Needed to Screen' if vertebral morphometry is used in this way would be seven to identify one patient with vertebral deformity, and 14 to identify one patient with two or more vertebral deformities. Although carrying out MXA will increase radiation exposure for the patient, this increased exposure is significantly less than would be obtained if X-rays of the dorso-lumbar spine were obtained.
doi:10.1007/s00198-006-0211-1
PMCID: PMC1766477  PMID: 17109062
Low trauma fracture; Number needed to screen; Osteoporosis; Vertebral fracture; Vertebral morphometry
13.  Leisure Physical Activity and the Risk of Fracture in Men 
PLoS Medicine  2007;4(6):e199.
Background
Data from previous studies are inconsistent, and it is therefore uncertain whether, to what extent, and at what level leisure physical activity influences the risk of osteoporotic fractures in men.
Methods and Findings
A cohort of 2,205 men, 49–51 y of age, was enrolled in a longitudinal, population-based study. Leisure physical activity and other lifestyle habits were established at baseline and at ages 60, 70, 77, and 82 y. During 35 y of follow-up, 482 men had at least one fracture. Cox's proportional hazards regression was used to determine hazard ratios (HRs) of fracture associated with time-dependent physical activity habits and covariates. Men with a sedentary lifestyle (HR 2.56, 95% confidence interval 1.55–4.24) or men who walked or bicycled only for pleasure (HR 1.61, 95% confidence interval 1.10–2.36) had an increased adjusted risk of hip fracture compared with men who participated in regular sports activities for at least 3 h/wk. At the end of follow-up, 8.4% of the men with a high physical activity, 13.3% of the men with a medium physical activity, and 20.5% of the men with a low physical activity had suffered a hip fracture. According to the estimation of population-attributable risk, one third of all hip fractures could be prevented by participation in regular sports activities. High activity also conferred a reduced overall fracture risk.
Conclusions
Our data indicate that regular sports activities can reduce the risk of fractures in older men.
From a large cohort study with 35 years of follow-up, Michaelsson and colleagues conclude that regular sport activities can reduce the risk of fractures in older men.
Editors' Summary
Background.
One of the hazards of old age is that the bones become less dense—and therefore weaker—so when an elderly person falls, the result is often a broken bone. As many as half of all women and a quarter of men older than 50 y will break a bone because of this, and the consequences can be serious, particularly if the hip is broken. The thinning of bones, which is known as osteoporosis, does affect all people as they age, but the degree to which it occurs varies greatly between individuals. A priority area for medical research is finding ways in which osteoporosis can be reduced, with the aim of improving the lives of older people and reducing their risk of “osteoporotic fractures.” It is known that genetic and environmental factors can both play a part in how rapidly osteoporosis develops, but it is generally agreed that personal lifestyle factors are also important. Osteoporosis develops over many years; in most people bone density starts to decline after the age of about 30 y. Preventive action should therefore begin early.
Most research so far has focused on women, who are more at risk as the thinning of their bones increases after the menopause. (Indeed osteoporosis has sometimes been wrongly described as a “woman's disease.”) It is now accepted that women who are more physically active reduce the rate of decline in their bone density and, as a result, are less likely to break bones when they are elderly. There has been little research in men and the results have not been consistent.
Why Was This Study Done?
In order to provide better evidence as to whether men who do more physical activity have fewer osteoporotic fractures than those with lower activity levels, the researchers wanted to complete a study that was larger and was conducted over a longer period of time than previous research.
What Did the Researchers Do and Find?
Between 1970 and 1973, the researchers invited all those men living in Uppsala, Sweden, who were aged between 49 and 51 y to participate in a health survey. Most of them (2,205) agreed to do so. When the study began, they were asked questions about the amount of physical activity they took outside working hours. They were asked the same questions again when they were aged 60, 70, 77, and 82 y. A record was also kept of the number of fractures the men had suffered during the 35-y study period. (Although some of the men died before the end of the study, about half were still alive at the end.) On the basis of the answers to the questions on physical activity at the start of the study, the researchers divided the men into three categories: those whose lifestyle was considered to be “sedentary,” those whose leisure activities included some walking and cycling, and those who participated in sports for at least 3 h a week. These were referred to as the low, medium, and high activity groups. Over the 35-y period, 428 men had at least one fracture and 134 broke a hip, but there were big differences between the groups—20% of the low-activity men had fractures compared with 13% of those with medium activity and only 8% of those in the high-activity group. In particular, the chance of having a hip fracture was reduced by increased activity.
What Do These Findings Mean?
Taking exercise reduces the risk of an osteoporotic fracture. Participating in sports seems to be particularly effective; the researchers calculate that one-third of fractures could be prevented if men could be persuaded to take part in sports regularly. The researchers do note that the very best evidence always comes from studies where people are assigned at random to receive a particular “treatment” (in this case, it would be exercise) and are compared with others who did not receive the treatment. This is known as a “randomized controlled trial.” Such a trial would be difficult, if not impossible, to organize on this topic, and the approach adopted by the researchers, which is known as a “cohort study,” does provide very strong evidence. There are many other benefits from increased exercise (for example, in reducing the risk of heart attacks and strokes), and most governments are now promoting sports and other active leisure pursuits. This study adds further weight to support such policies.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040199.g002.
There are many free sources of information about osteoporosis on the Web, and many organizations exist to support people with the condition. For example, the National Osteoporosis Society (UK) has useful information about the condition
In the USA, there is the Nationtal Osteoporosis Foundation (USA)
The equivalent organization in Australia is Osteoporosis Australia
The UK National Health Service's NHS Direct Health Encyclopedia has an entry on osteoporosis
MedlinePlus is an excellent source of information
doi:10.1371/journal.pmed.0040199
PMCID: PMC1892039  PMID: 17579509
14.  The utility of clinical decision tools for diagnosing osteoporosis in postmenopausal women with rheumatoid arthritis 
Background
Patients with rheumatoid arthritis have a higher risk of low bone mineral density than normal age matched populations. There is limited evidence to support cost effectiveness of population screening in rheumatoid arthritis and case finding strategies have been proposed as a means to increase cost effectiveness of diagnostic screening for osteoporosis. This study aimed to assess the performance attributes of generic and rheumatoid arthritis specific clinical decision tools for diagnosing osteoporosis in a postmenopausal population with rheumatoid arthritis who attend ambulatory specialist rheumatology clinics.
Methods
A cross-sectional study of 127 ambulatory post-menopausal women with rheumatoid arthritis was performed. Patients currently receiving or who had previously received bone active therapy were excluded. Eligible women underwent clinical assessment and dual-energy-xray absorptiometry (DXA) bone mineral density assessment.
Clinical decision tools, including those specific for rheumatoid arthritis, were compared to seven generic post-menopausal tools to predict osteoporosis (defined as T score < -2.5). Sensitivity, specificity, positive predictive and negative predictive values and area under the curve were assessed. The diagnostic attributes of the clinical decision tools were compared by examination of the area under the receiver-operator-curve.
Results
One hundred and twenty seven women participated. The median age was 62 (IQR 56–71) years. Median disease duration was 108 (60–168) months. Seventy two (57%) women had no record of a previous DXA examination. Eighty (63%) women had T scores at femoral neck or lumbar spine less than -1. The area under the ROC curve for clinical decision tool prediction of T score <-2.5 varied between 0.63 and 0.76. The rheumatoid arthritis specific decision tools did not perform better than generic tools, however, the National Osteoporosis Foundation score could potentially reduce the number of unnecessary DXA tests by approximately 45% in this population.
Conclusion
There was limited utility of clinical decision tools for predicting osteoporosis in this patient population. Fracture prediction tools that include risk factors independent of BMD are needed.
doi:10.1186/1471-2474-9-13
PMCID: PMC2270830  PMID: 18230132
15.  Prevalence of osteoporosis and vertebral fractures in acromegalic patients 
Summary
Growth Hormone (GH) and Insulin-like Growth Factor (IGF-1) stimulate proliferation, differentiation and extracellular matrix production in osteoblastic cells. GH and IGF-1 also stimulate recruitment and bone resorption activity in osteoclastic cells. A chronic systemic GH and IGF-1 excess produces an increased bone turn over in acromegalic patients (pts). Osteoporosis, joint alterations and bone deformities have a great clinical relevance in acromegalic pts and favour mortality and morbility. In the present study we evaluate the still unclear GH/IGF-1 activity on bone, Bone Mineral Density (BMD) and risk of osteoporotic Vertebral Fractures (VF), in relation to gender and gonadal status in acromegalic pts.
Twenty acromegalic pts (12 F, 8 M) ranging 26–64 years were studied. Four pts were hypogonadic (1 F, 3 M), seven women were in post-menopause (PM) and four women eugonadic. The disease was active in twelve pts and inactive in eight pts. Serum and urinary 24/hrs calcium and phosphate and serum PTH, bone formation (P1NP) and resorption (beta-CTX) markers were assayed. BMD was measured using dual energy X ray absorptiometry (DXA) at the lumbar spine and femoral neck and bone quantitative ultrasonography (QUS) at phalanges. Osteoporotic VF were assessed by antero-posterior and lateral x-ray examinations of the thoracic and lumbar spine.
Serum IGF-1, calcium and phosphate and 24-hours urinary calcium were significantly higher in pts with active disease in respect to pts with inactive disease. BMD was reduced in more of 50% of pts, in each skeletal sites measured. Z-score values were lower in males than in females. VF prevalence was 39% (43% in women, 57% in men). Fractured and non-fractured pts were not significantly different for BMD, T-score and Z-score.
In conclusion, VF are frequent in acromegaly and, even mild and asymptomatic, play an important role on life quality and survival, already decreased in acromegalic pts. DXA and QUS methods are not sufficient for identifying pts at risk for fracture, due to the many possible interferences (bone deformities, osteoarthritis, joint rigidity and soft tissue tickening), since BMD is just one determinant of bone fracture. In the screening of acromegalic complications, it is necessary to perform a radiographic study of the spine at the time of diagnosis and during follow up.
PMCID: PMC3279059  PMID: 22461828
acromegaly; osteoporosis
16.  Age-related bone turnover markers and osteoporotic risk in native Chinese women 
Background
The rate of bone turnover is closely related to osteoporosis risk. We investigated the correlation between bone turnover markers and BMD at various skeletal sites in healthy native Chinese women, and to study the effect of changes in the levels of bone turnover markers on the risk of osteoporosis.
Methods
A cross-section study of 891 healthy Chinese women aged 20–80 years was conducted. The levels of serum osteocalcin (OC), bone-specific alkaline phosphatase (BAP), serum cross-linked N-terminal telopeptides of type I collagen (sNTX), cross-linked C-terminal telopeptides of type I collagen (sCTX), urinary NTX (uNTX), urinary CTX (uCTX) and total urinary deoxypyridinoline (uDPD) were determined. BMD at the posteroanterior spine and the hip was measured using DXA.
Results
Pearson’s correlation coefficient found significant negative correlation between bone turnover marker and BMD T-score at different skeletal sites (r = −0.08 to −0.52, all P = 0.038–0.000). After adjustments for age and body mass index, the partial correlation coefficients between the OC, BAP, sNTX, sCTX and uCTX, and the T-scores at various skeletal sites were still significant. After adjustment of height and weight, the correlation coefficients between most BTMs and PA lumbar spine BMD were also significant. Multiple linear regression analysis showed that bone turnover markers were negative determinants of T-scores. BAP and OC accounted for 33.1% and 7.8% of the variations in the T-scores of the PA spine, respectively. Serum OC, BAP, uDPD, and sNTX accounted for 0.4–21.9% of the variations in the femoral neck and total hip T-scores. The bone turnover marker levels were grouped as per quartile intervals, and the T-scores, osteoporosis prevalence and risk were found to markedly and increase with increase in bone turnover marker levels.
Conclusions
This study clarified the relationship between bone turnover markers and osteoporosis risk in native Chinese women. Bone turnover marker levels were found to be important determinants of BMD T-scores. Furthermore, osteoporotic risk significantly increased with increase in the levels of bone turnover markers.
doi:10.1186/1472-6823-14-8
PMCID: PMC3974151  PMID: 24447701
Bone turnover markers; BMD T-scores; Osteoporosis; Osteoporotic risk; Native Chinese women
17.  The Correlation between Phalangeal Quantitative Ultrasonography and Dual Energy X-ray Absorptiometry in Women with Premature Ovarian Failure 
McGill Journal of Medicine : MJM  2008;11(2):132-140.
Objectives
With the growing demand for bone densitometry services there is a need for simple, cost-effective and ideally mobile devices which can identify individuals who are at risk of osteoporotic fracture. When new devices are evaluated, it is useful to examine the correlation with the established ‘gold standard’ technique of dual x-ray absorptiometry (DXA). This study examined the correlation between quantitative ultrasound (QUS) measurements performed at the phalanges and conventional DXA measurements of the spine and hip in women with premature ovarian failure – a known risk factor for osteoporosis.
Methods
Thirteen white Caucasian women suffering from premature ovarian failure and 19 age- and sex-matched controls were recruited into the study. DXA measurements were performed at the spine and hip, followed by quantitative ultrasonography at phalanges II–V of the non-dominant hand.
Results
Significant correlations were observed between the bone transit time (BTT) value from the Bone Profiler and bone mineral density measured at the spine (r=0.66). The spine Z-scores also correlated with many of the ultrasound values (r=0.44 – 0.63). Significant inverse correlations were observed between BMI, weight and ultrasound parameters (r = −0.48 to −0.78).
Conclusion
We have reported moderate but significant correlations between phalangeal QUS and DXA parameters. The strongest correlation was observed between BTT and spine BMD, as well as between the Z-scores from the two devices. QUS parameters also demonstrated an inverse correlation with weight and BMI.
PMCID: PMC2582660  PMID: 19148311
Bone mineral density; osteoporosis; premature ovarian failure; DXA; quantitative ultrasound
18.  Prevalence and predictors of fragility fractures in systemic lupus erythematosus 
Annals of the Rheumatic Diseases  2005;64(1):111-113.
Objective: To establish the prevalence of reduced bone mineral density (BMD) and fractures, and risk factors for fractures, in a cross sectional study of a large cohort of patients with systemic lupus erythematosus (SLE).
Methods: All SLE patients willing to take part in the study had bone densitometry in 1999/2000 and completed a questionnaire on risk factors for osteoporosis and on drugs used. Accumulated damage was scored using the SLICC/ACR damage index (SDI). Only fractures occurring since the onset of SLE and unrelated to trauma were included, and the SDI score was modified to exclude osteoporotic fractures. Statistical analysis was by χ2 test, Fisher's exact test, and binary logistic regression.
Results: 242 patients were studied, median age 39.9 years (range 18 to 80), median disease duration 7.0 years (range 0 to 42). Of these, 123 (50.8%) had reduced BMD (T score <–1.0) and 25 (10.3%) were in the osteoporotic range (T score <–2.5). Fragility fractures had occurred in 22 patients (9.1%) since diagnosis of SLE. Of these, two (9.1%) had normal BMD and 20 (90.9%) had reduced BMD, while seven (31.8%) were within the osteoporotic range. Non-Afro-Caribbean race and exposure to prednisolone >10 mg daily were significantly associated with reduced BMD, while age and menopause were associated with osteoporosis. The risk factors for fractures were reduced BMD and age.
Conclusions: Reduced BMD, osteoporosis, and fragility fractures appear to be prevalent in patients with SLE. Steroids were not an independent risk factor for fractures, although their effect could be mediated through reduced bone mineral density.
doi:10.1136/ard.2003.018127
PMCID: PMC1755180  PMID: 15608308
19.  Controlled HIV Viral Replication, Not Liver Disease Severity Associated with Low Bone Mineral Density in HIV/HCV Co-Infection 
Journal of hepatology  2011;55(4):770-776.
Objective
To evaluate the prevalence and risk factors for low bone mineral density (BMD) in persons co-infected with HIV and Hepatitis C.
Methods
HIV/HCV co-infected study participants (n=179) were recruited into a prospective cohort and underwent dual-energy X-ray absorptiometry (DXA) within 1 year of a liver biopsy. Fibrosis staging was evaluated according to the METAVIR system. Osteoporosis was defined as a T-score ≤ −2.5. Z-scores at the total hip, femoral neck, and lumbar spine were used as the primary outcome variables to assess the association between degree of liver disease, HIV-related variables, and BMD.
Results
The population was 65% male, 85% Black with mean age 50.3 years. The prevalence of osteoporosis at either at the total hip, femoral neck, or lumbar spine was 28%, with 5% having osteoporosis of the total hip, 6% at the femoral neck, 25% at the spine. The mean Z-scores (standard deviation) were −0.42 (1.01) at the total hip, −0.16 (1.05) at the femoral neck, and −0.82 (1.55) at the lumbar spine. In multivariable models, controlled HIV replication (HIV RNA < 400 copies/mL vs ≥400 copies/mL) was associated with lower Z-scores (mean ± standard error) at the total hip (−0.44±0.17, p=0.01), femoral neck (−0.59±0.18, p=0.001), and the spine (−0.98±0.27, p=0.0005). There was no association between degree of liver fibrosis and Z-score.
Conclusion
Osteoporosis was very common in this population of predominately African-American HIV/HCV co-infected patients, particularly at the spine. Lower BMD was associated with controlled HIV replication, but not liver disease severity.
doi:10.1016/j.jhep.2011.01.035
PMCID: PMC3113457  PMID: 21338640
hepatitis C; bone mineral density; hepatic fibrosis; HIV
20.  Significant Differences in UK and US Female Bone Density Reference Ranges 
Summary
In the United Kingdom (UK) T- and Z-scores are usually calculated using reference ranges derived from United States (US) populations. In the UK arm of a recent randomised trial (IBIS-II) substantially fewer women than expected were recruited into the osteopenic (-2.5 < T-score < −1.0) and osteoporotic (T-score < −2.5) arms of the study. Comparison with data from two independent studies showed that UK women aged > 45 years with a typical body mass index of 28 kg m−2 have spine and hip BMD 0.6 SD higher than their US counterparts.
Introduction
Dual energy X-ray absorptiometry (DXA) is widely used for the diagnosis of osteoporosis and to investigate the effect of pharmacological treatments on bone mineral density (BMD). In both routine and research settings it is important that DXA results are correctly interpreted.
Methods
Z-scores for the first 650 UK Caucasian women enrolled in the IBIS-II study were compared with data from two independent studies of unrelated, unselected UK Caucasian women: (1) 2382 women aged 18 to 79 recruited to the Twins UK adult twin registry; (2) 431 women aged 21 to 84 with no risk factors for osteoporosis recruited at Guy’s Hospital. All DXA measurements were performed on Hologic densitometers. Subjects were divided into six age bands and Z-scores calculated using the manufacturer’s US reference range for the spine and the NHANES III reference range for the femoral neck and total hip.
Results
The overall mean Z-scores for the IBIS-II, Twin and Guy’s groups were: spine: 0.61, 0.29, 0.33; femoral neck: 0.42, 0.36, 0.45; total hip: 0.65, 0.38, 0.39 (all p < 0.001 compared with the expected value of 0). The mean body weight of subjects in the three studies was 74.4, 65.5 and 65.4 kg respectively. Analysis revealed a highly significant relationship between Z-score and weight at each BMD site with a slope of 0.03 kg−1.
Conclusions
In general US spine and hip reference ranges are not suitable for the calculation of Z-scores in UK women. For some research study designs the differences may significantly influence the pattern of subject recruitment.
doi:10.1007/s00198-009-1153-1
PMCID: PMC3605787  PMID: 20063090
Dual energy X-ray absorptiometry; Bone mineral density; Z-scores; Reference ranges; body weight
21.  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.
doi:10.1002/jbmr.221
PMCID: PMC3179342  PMID: 20721937
OSTEOPOROSIS; BONE MINERAL DENSITY; HIV; BMI; INNER CITY
22.  Coeliac disease and bone mineral density in adult female patients. 
Gut  1995;37(5):639-642.
A cross sectional study was undertaken to examine the relationship between coeliac disease and bone mineral density. The 135 female coeliac patients registered on the database of the Department of Gastroenterology at Hull Royal Infirmary were approached by letter, advising them of a potential risk of osteoporosis and inviting them to undergo bone densitometry. A total of 81 registered women (60%) attended the Osteoporosis Laboratory, Princess Royal Hospital and underwent dual energy x ray absorptiometry at the lumbar spine (L2-L4) and femoral neck. Historical data relating to the time of diagnosis and adherence to a gluten free diet were obtained. A control group was selected from the local normal population and was first matched for height, weight, and menopausal status. Postmenopausal patients were then further matched to controls of equivalent menopausal age. In coeliac patients, bone mineral density expressed in g/cm2 as mean (SD) was significantly lower at the lumbar spine (1.076 (0.186)) than in the control group (1.155 (0.143), p < 0.001). This was also the case at the femoral neck (0.887 (0.142) versus 0.965 (0.127), p < 0.001). When the coeliac patients were stratified by menopausal status, it was found that femoral neck bone mineral density was significantly below control values in both premenopausal and postmenopausal women. Spinal bone mineral density exhibited a significant decrement only in the postmenopausal group. The age at diagnosis of coeliac disease and adherence to a gluten free diet did not influence bone mineral density at either hip or spine. These results confirm coeliac patients' higher risk of osteopenia. Coeliac disease should be added to the list of medical conditions which constitute an indication for bone densitometry in order that the individual risk of osteoporosis related fracture may be determined.
PMCID: PMC1382867  PMID: 8549938
23.  Osteoporotic profiles in elderly patients with symptomatic lumbar spinal canal stenosis 
Indian Journal of Orthopaedics  2012;46(3):279-284.
Background:
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.
Results:
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.
Conclusions:
LSS is associated with osteopenia, osteoporosis, and hypovitaminosis D, which should prompt careful screening and treatment in cases of osteoporosis and osteoarthritis.
doi:10.4103/0019-5413.96379
PMCID: PMC3377137  PMID: 22719113
Bone mineral density; bone turnover marker; hypovitaminosis D; lumbar spinal stenosis; osteoporosis
24.  Muscle-Bone Interactions Across age in Men 
This study examined the relationship of muscular strength and lean tissue with age-related patterns in bone mineral density (BMD) in men 20-81 years of age. Subjects were assigned to one of three age groups, Young Men (YM), (n = 25, 20-39 yrs), Middle-aged Men (MM) (n = 24, 40-59 yrs), and Older Men (OM) (n = 23, 60-81 yrs). Isotonic and isokinetic strength was assessed for the quadriceps and hamstrings muscle groups. DXA (Lunar DPX-IQ) was used to measure spine, hip, and total body BMD and body composition. OM had significantly lower (p < 0.05) total lean body mass (LBM) than MM and lower leg lean mass (LM) than YM and MM. OM had significantly lower (p < 0.01) BMD than YM and MM at the femoral neck and total hip sites and a higher proportion of OM were osteopenic and osteoporotic at the total hip site. Isotonic and isokinetic strength for both muscle groups was positively related (p < 0.05) with the hip BMD sites (r = 0.38-.67). Leg LM also was positively related to hip BMD (r = 0.37-.58). Multiple Regression analyses determined that age and lean mass (LBM or leg LM) were significant predictors (p < 0.05) of femoral neck, and total hip BMD, while lean mass (LBM or leg LM) was a significant predictor (p < 0.05) of BMD at the spine and trochanter sites. Isotonic and isokinetic leg strength variables were significant predictors (p < 0.05) of the total body, total hip and trochanter BMD. In conclusion, leg strength, leg LM, and total LBM were significant predictors of BMD in men, independent of age. These findings emphasize the importance of maintaining lean body mass for the bone health of aging men.
Key PointsOsteoporosis is an important health problem for men.Bone mineral density for the hip was lower in older men compared to their younger and middle-age counterparts. There were age group differences in the prevalence of osteopenia and osteoporosis for the total hip BMD site.Muscular strength and bone-free lean body mass were significant predictors of hip BMD, independent of age, thus reinforcing the importance of contractile forces on skeletal health.Maintenance of muscle mass and strength should be encouraged in aging men for the reduction of osteoporosis risk.
PMCID: PMC3818673  PMID: 24198680
Lean body mass; osteopenia; osteoporosis; muscle strength; bone density
25.  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.
doi:10.1016/j.jocd.2006.04.116
PMCID: PMC2642644  PMID: 16931341
Spine osteoarthritis; bone mineral density; osteoporosis; elderly

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