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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.  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.
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.
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.
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.
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.
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.
Osteoporosis is a disease characterized by a decrease in bone mineral density, making bones become less rigid, and therefore susceptible to fractures, either spontaneously or with force, which is lower than otherwise needed for healthy bones fractured. Nearly 10% of the world population and 30% of women after menopause, suffer from osteoporosis. Clinical assessment of osteoporosis in family medicine is key to prevention, early detection and treatment of osteoporosis.
To investigate the possibility of early detection and diagnosis of osteoporosis by analyzing the risk factors for osteoporosis and to compare the results with the parameters obtained by ultrasound densitometry of calcaneus, and determine the relationship of calcaneus densitometry with DXA findings, as the gold standard for the diagnosis of osteoporosis.
Patients and methods:
The study included all patients of Family Medicine Kalesija Team 1, aged 50 years and over, a total of 711 patients, of whom 425 were women and 286 men. In all patients we assessed the existence of the following risk factors for osteoporosis: Constitutional: gender, age, weight, constitution, menarche and menopause, loss of height and stooped posture; Living habits: smoking, alcohol consumption, coffee, physical activity, and medications: long-term use corticosteroids, anticonvulsants, antacids, thyroid hormones. Comorbidity: history of fractures, hyperthyroidism, COPD, Chussing’s disease, diabetes. In the group of high-risk patients determined by the clinical assessment, quantitative ultrasound densitometry screening was carried out. Monitoring parameters derived with densitometry: the value of T-score, BUA (Broadband Ultrasound Attenuation), SOS (Speed of Sound), QUI (Quantitative Ultrasound Index). To confirm the diagnosis of osteoporosis, in all patients with positive findings using ultrasound densitometry (T score lower than 2.5), another densitometry was performed by standard DXA method.
The incidence of osteoporosis was 96% in women and 4% in men. Differences in prevalence between men and women are statistically significant. People with and without osteoporosis significantly differ in gender, age, weight, constitution (BMI-Body Mass Index). The parameters that distinguish those with and without osteoporosis: age, weight, height, BMI, gender. Out of the total of 711 patients, in 11% of patients the clinical evaluation showed the existence of high risk of osteoporosis. In 9.8% patients, the values were determined by ultrasound densitometry, where T score was lower than 2.5 what induces a high risk of fractures, and for 8.8% patients the DXA confirmed the diagnosis of osteoporosis.
Clinical assessment of osteoporosis in the family medicine clinic performed in timely and focused history of risk factors for osteoporosis, with additional findings from quantitative densitometry of calcaneus, was sufficient for the early detection and screening of patients with high risk for osteoporosis. With good clinical assessment of osteoporosis it will be necessary to send all patients who enter the high-risk group to undergo ultrasound densitometry of calcaneus, to make it possible to determine the risk of bone fractures and osteoporosis in time, and then refer patients for further processing and DXA measurements according to the guidelines by the WHO.
PMCID: PMC3916165  PMID: 24554805
bone density; early detection; risk factors; quantitative ultrasound densitometry; osteoporosis.
5.  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.
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.  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
8.  Management of osteoporosis and associated quality of life in post menopausal women 
The study aimed to describe the characteristics of women treated for recently-diagnosed osteoporosis, to identify variables associated with different treatment regimens and to assess impact on quality of life.
This is an observational, cross-sectional pharmacoepidemiological study performed in France. A random sample of 684 general practitioners, gynaecologists and rheumatologists included the first three post-menopausal osteoporotic women consulting in the previous six months on the basis of densitometry or fracture. Data on osteoporosis, fracture risk factors, treatments and comorbidities was collected with a physician questionnaire. Data on quality of life was collected using the SF-12.
Data were analysed for 1,306 patients, of whom 1,117 (85.5%) had been evaluated by densitometry within the previous six months and 554 (42.4%) had experienced a fracture, most frequently of the spine or wrist within the previous six months. Osteoporotic fracture risk factors were reported in 1,028 women (78.7%). 746 women (57.1%) were currently receiving treatment, most frequently weekly or monthly bisphosphonates. Five variables were associated with prescription choice: age (p < 0.0001), physician speciality (p < 0.0001), previous fracture history (p = 0.0002), ongoing treatment at the time of consultation (p = 0.0091) and paraclinical investigations performed in the previous six months (p = 0.0060). SF-12 scores were lower in women complaining of pain, with recent fractures and with spine or hip fractures and in women consulting rheumatologists.
A high proportion of women diagnosed with osteoporosis had been evaluated by densitometry, in agreement with national guidelines. Treatment choice varied between physician groups.
PMCID: PMC3034724  PMID: 21226917
9.  Prevalence of Low Bone Mineral Density in a Low-Income Inner-City Population 
Bone mineral density (BMD) is an important factor linked to bone health. Little is known of the prevalence of low BMD and its associated risk factors in an urban underserved population. Between 2001 and 2004, we recruited 338 subjects who completed drug use and medical history questionnaires, underwent hormonal measurements, and underwent whole-body dual-energy X-ray absorptiometry (DXA) for evaluation of BMD and body composition. Of these, 132 subjects had site-specific DXA (lumbar spine and hip) performed. Osteoporosis was defined as a T-score of –2.5 or less for men 50 years of age and older and postmenopausal women and a Z-score of –2.0 or less in men younger than 50 years of age and premenopausal women at either the lumbar spine, total hip, or femoral neck, according to National Osteoporosis Foundation (NOF) guidelines. The cohort consisted of mostly African-American, middle-aged people with a high prevalence of illicit drug use, 50% HIV+, and 39% hepatitis C+. Osteoporosis was identified in 22% of subjects (24 men, 5 women), with the majority of cases (90%) attributable to osteoporosis at the lumbar spine. Osteoporosis was more common in men than in women. Lower whole-body BMD among women was associated with multiple risk factors, but only with lower lean mass among men. Osteoporosis was highly prevalent in men, mainly at the spine. The risk factors for bone loss in this population need to be further clarified. Screening men for osteoporosis starting at age 50 might be warranted in this population given the multiple risk factors and the unexpectedly high prevalence of low BMD. © 2011 American Society for Bone and Mineral Research.
PMCID: PMC3179342  PMID: 20721937
10.  Dual-energy X-ray absorptiometry diagnostic discordance between Z-scores and T-scores in a young Iranian population 
Background: Dual-energy X-ray Absorptiometry (DXA) is considered the gold standard for non-invasive measurement of bone mass. T-scores and Z-scores are used to present the results of bone mass. The present study was designed to evaluate the discordance between T-scores and Z-scores calculated at a same level and its relation with age, gender and body mass index (BMI) in a representative sample of normal population.
Methods: This cross-sectional study was conducted as a part of a comprehensive survey, Iranian Multicenter Osteoporosis Study (IMOS), designed to assess bone health among healthy adults. Each individual underwent both L1–L4 antero-posterior lumbar spine and hip DXA scan. The difference between the T- and Z-scores measured at each of the four skeletal sites was then calculated.
Results: A -1.21 to 1.21 point difference was noted in the Z- and T- scores measured at each site. While the difference between the T-and Z-scores was less than 0.5 SD in most of the cases, the difference was higher than 1 SD in about 5% of the subjects.
Conclusion: Standardization of Z-score definition and calculation techniques as well as developing an ethnicity-matched reference population is needed to improve the reliability of DXA-generated Z-scores.
PMCID: PMC4322344
Osteoporosis; Bone Mineral Density; T-scores; Z-scores; Iran
11.  The utility of clinical decision tools for diagnosing osteoporosis in postmenopausal women with rheumatoid arthritis 
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.
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.
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.
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.
PMCID: PMC2270830  PMID: 18230132
12.  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
13.  Prevalence of osteoporosis and vertebral fractures in acromegalic patients 
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
14.  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.
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.
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.
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).
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
15.  Tibial cortical thickness: A dependable tool for assessing osteoporosis in the absence of dual energy X-ray absorptiopmetry 
Background and Objective:
Bone mineral density measurements with absorptiometry dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing low bone mass and risk for fragility fractures. DXA is not available at every center, and physicians require an alternative method of diagnosis before referring patients. We conducted this study to assess and compare total cortical thickness (TCT) and its relation to the T score by DXA and its correlation-ship in the diagnosis of osteoporosis.
Patients and Methods:
Total cortical thickness was carried out in 50 Saudi Arabian females ≥ 45 years with DXA scans and 25 patients with age of ≤ 35 years whose radiographs of the upper tibia were available for analysis. Postero-medial cortical thickness of the tibia was measured 13 cm from the joint line and an average was calculated. The average T score of the spine and the hip was taken. A comparison was made between age, T score, and the TCT. Inter cortical distance (ICD) was measured and compared in both groups. Data were analyzed for predictive value for diagnosis of osteopenia and osteoporosis.
There was a significant association between the T score and the TCT and age. As the age advanced the T score and TCT was very low (<0.05, 95% confidence interval [CI] <0.2). Forty patients were osteopenic and 10 osteoporotic. The T score in the former was − 1.33 ± 0.71 and the later was − 3.22 ± 0.56 (P < 0.0001 95% CI: <−1.67) and the TCT was 0.655 ± 0.06 versus 0.51 ± 0.05 (P < 0.0001 95% CI: <−0.17). In women ≤35 years the average TCT was 0.804 ± 0.155 cm and IMD was 3.34 ± 0.45 cm.
We conclude that if TCT is less than the threshold value of ≤ 0.5 cm, patients should be referred for further investigations with DXA. We believe that further studies are needed to confirm our findings and in areas where DXA is not available, based on the TCT measurement anti-osteoporotic therapy could be initiated when other risk factors for osteoporosis is present.
PMCID: PMC4318096  PMID: 25664263
Dual-energy X-ray absorptiometry diagnosis; osteoporosis; tibial cortical thickness
16.  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.
To evaluate the prevalence and risk factors for low bone mineral density (BMD) in persons co-infected with HIV and Hepatitis C.
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.
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.
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.
PMCID: PMC3113457  PMID: 21338640
hepatitis C; bone mineral density; hepatic fibrosis; HIV
17.  Significant Differences in UK and US Female Bone Density Reference Ranges 
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.
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.
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.
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.
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.
PMCID: PMC3605787  PMID: 20063090
Dual energy X-ray absorptiometry; Bone mineral density; Z-scores; Reference ranges; body weight
18.  Mutifactorial analysis of risk factors for reduced bone mineral density in patients with Crohn’s disease 
AIM: To determine the prevalence of osteoporosis in a cohort of patients with Crohn’s disease (CD) and to identify the relative significance of risk factors for osteoporosis.
METHODS: Two hundred and fifty-eight unselected patients (92 M, 166 F) with CD were studied. Bone mineral density (BMD) was measured at the lumbar spine and hip by dual X-ray absorptiometry. Bone formation was assessed by measuring bone specific alkaline phosphatase (BSAP) and bone resorption by measuring urinary excretion of deoxypyridinoline (DPD) and N-telopeptide (NTX).
RESULTS: Between 11.6%-13.6% patients were osteoporotic (T score < -2.5) at the lumbar spine and/or hip. NTX levels were significantly higher in the patients with osteoporosis (P < 0.05) but BSAP and DPD levels were not significantly different. Independent risk factors for osteoporosis at either the lumbar spine or hip were a low body mass index (P < 0.001), increasing corticosteroid use (P < 0.005), and male sex (P < 0.01). These factors combined accounted for 23% and 37% of the reduction in BMD at the lumbar spine and hip respectively.
CONCLUSION: Our results confirm that osteoporosis is common in patients with CD and suggest that increased bone resorption is the mechanism responsible for the bone loss. However, less than half of the reduction in BMD can be attributed to risk factors such as corticosteroid use and low BMI and therefore remains unexplained.
PMCID: PMC4088170  PMID: 17007022
Crohn’s disease; Osteoporosis; Osteopenia; Bone mineral density
19.  Factors influencing quality of life in Moroccan postmenopausal women with osteoporotic vertebral fracture assessed by ECOS 16 questionnaire 
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.
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.
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.
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.
PMCID: PMC2663551  PMID: 19284667
20.  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
21.  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.
PMCID: PMC3970097  PMID: 24688308
Advanced glycation end-products; Osteopenia; Osteoporosis; Biomarker; Osteopontin.
22.  The Clinical Utility of Spine Bone Density in Elderly Women 
It is common clinical practice to obtain bone mass measurement at both the hip and spine to evaluate for osteoporosis. With aging, degenerative changes in the lumbar spine may elevate the bone mineral density (BMD) results giving false assurances that the fracture risk at the spine is low. We examined the association of spine osteoarthritis and bone mineral density in 1082 community-dwelling ambulatory older women aged 50–96 years who participated in a 1992–1996 osteoporosis research clinic visit. Bone mineral density (BMD) was measured at the hip, PA and lateral lumbar spine using dual energy x-ray absorptiometry (DXA). Spine osteoarthritis was identified on the PA lumbar spine DXA images by a musculoskeletal radiologist. Forty percent of women had evidence of spine osteoarthritis (OA). Women with spine OA had mean age of 77.4 years (95% CI, 76.5–78.2), were significantly older than women without (mean age 66.8; 95% CI, 65.9–67.7), and were more likely to have prevalent radiographic fractures (14.2% vs. 9.5%, p< 0.05). Age-adjusted BMD at the femoral neck, total hip, PA spine, and lateral spine was significantly higher in women with spine OA. Women with spine OA were more likely to have osteoporosis by WHO classification at the femoral neck and total hip than those without spine OA, but less likely based on the PA spine site (14.4% vs 24.5%). Despite higher BMD levels, women with OA of the lumbar spine had higher prevalence of osteoporosis at the hip and radiographic vertebral fractures. In elderly women 65 years and older who are likely to have spine OA, DXA measurement of the spine may be not useful in assessing fracture risk and DXA of the hip is recommended for identification of osteoporosis.
PMCID: PMC2642644  PMID: 16931341
Spine osteoarthritis; bone mineral density; osteoporosis; elderly
23.  Baseline bone mineral density and bone turnover in pre-operative hip and knee arthroplasty patients 
Bone & Joint Research  2014;3(1):14-19.
Osteoporosis and abnormal bone metabolism may prove to be significant factors influencing the outcome of arthroplasty surgery, predisposing to complications of aseptic loosening and peri-prosthetic fracture. We aimed to investigate baseline bone mineral density (BMD) and bone turnover in patients about to undergo arthroplasty of the hip and knee.
We prospectively measured bone mineral density of the hip and lumbar spine using dual-energy X-ray absorptiometry (DEXA) scans in a cohort of 194 patients awaiting hip or knee arthroplasty. We also assessed bone turnover using urinary deoxypyridinoline (DPD), a type I collagen crosslink, normalised to creatinine.
The prevalence of DEXA proven hip osteoporosis (T-score ≤ -2.5) among hip and knee arthroplasty patients was found to be low at 2.8% (4 of 143). Spinal osteoporosis prevalence was higher at 6.9% (12 of 175). Sixty patients (42% (60 of 143)) had osteopenia or osteoporosis of either the hip or spine. The mean T-score for the hip was -0.34 (sd 1.23), which is within normal limits, and the mean hip Z-score was positive at 0.87 (sd 1.17), signifying higher-than-average BMD for age. The median urinary DPD/creatinine was raised in both female patients at 8.1 (interquartile range (IQR) 6.6 to 9.9) and male patients at 6.2 (IQR 4.8 to 7.5).
Our results indicate hip and knee arthroplasty patients have higher BMD of the hip and spine compared with an age-matched general population, and a lower prevalence of osteoporosis. However, untreated osteoporotic patients are undergoing arthroplasty, which may negatively impact their outcome. Raised DPD levels suggest abnormal bone turnover, requiring further investigation.
Cite this article: Bone Joint Res 2014;3:14–19.
PMCID: PMC3904490  PMID: 24443424
Arthroplasty; Hip; Knee; Bone mineral density; BMD
24.  Fracture risk assessment in postmenopausal women referred to an Italian center for osteoporosis: a single day experience in Messina 
Osteoporosis is a major cause of fragility fractures and these are responsible of large social burden; nevertheless, osteoporosis often remains an underdiagnosed disease.
FRAX is a new and simple validate fracture risk assessment tool helping physicians to select patients at high risk of future fragility fractures.
To promote early diagnosis of osteoporosis, we evaluated fracture risk by FRAX and performed phalangeal quantitative ultrasound (QUS) measurements in a population of postmenopausal women referring to our center during the World Osteoporosis Day on 20th October 2011.
Eighty post-menopausal women (age 60.8±8.6) were screened and the risk of major osteoporotic and hip fractures over ten years was calculated by considering multiple clinical risk factors (CRFs). The median risk of major osteoporotic fracture (%) was 4.9 (3.5–8.6) in women younger than 55 years, 7.3 (5.4–11) in women aged between 55 and 65 years and 17.5 (11–27) in women older than 65 years; the median risk of hip fracture (%) was 0.6 (0.3–1.3), 1.5 (0.9–2.5) and 7.2 (3.1–14) respectively. QUS measurements, were lower in the older women and when multiple CRFs coexisted, and were found to correlate with fracture risk, especially with hip fracture risk (p<0.05).
Within one month from the screening, 75% (44/59) of the women over 55 years came back and received a diagnosis of osteoporosis/osteopenia by dual x-ray absorptiometry (DXA); a positive association between DXA and QUS measurements was observed (p<0.0001).
Adequate treatment of these subjects could reduce fracture rates, improve the quality of life, and reduce the social costs of osteoporosis.
PMCID: PMC3917582  PMID: 24554930
osteoporosis; fragility fractures; prevention; FRAX; quantitative ultrasound
25.  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

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