Thoracic kyphosis assessment in postmenopausal women: an examination of the Flexicurve method in comparison to radiological methods.

The Flexicurve ruler is an alternative method to radiographs for measuring thoracic kyphosis (curvature), but it is not certain that it is comparable. This study shows that Flexicurve can estimate radiographic vertebral centroid angles with less error than Cobb angles but that its accuracy would be inadequate for most clinical purposes. INTRODUCTION: The Flexicurve ruler provides a non-radiological method of measuring thoracic kyphosis (TK) that has moderately strong correlations with the gold-standard radiographic Cobb angle method, while consistently underestimating the TK angle. Cobb angles can include measurement errors that may contribute to poor agreement, particularly in older populations. The vertebral centroid angle could be a better radiographic reference method for the validation of Flexicurve. Using two separate radiographic measurements of TK, we examined the validity of Flexicurve. We aimed to ascertain the level of agreement between measures and to empirically explore reasons for between-method differences. METHODS: TK angles determined using Flexicurve and radiographic Cobb and vertebral centroid methods were compared using data from 117 healthy postmenopausal women (mean (SD) age 61.4 (7.0) years). Bland and Altman plots were used to assess differences between methods. Age, bone mineral density and body mass index were examined as characteristics that might explain any differences. RESULTS: Flexicurve angles were scaled prior to analysis. There was no statistically significant difference between angles produced by Flexicurve and vertebral centroid methods (MD - 2.16°, 95%CI - 4.35° to 0.03°) although differences increased proportionally with TK angles. Flexicurve angles were significantly smaller than radiographic Cobb angles and depending on the scaling method used, systematic error ranged between - 2.48° and - 5.19°. Age accounts for some of the differences observed (R2 < 0.08, p < 0.005). CONCLUSIONS: TK measured using the Flexicurve shows better agreement with the radiographic vertebral centroid method, but inaccuracy of the Flexicurve increases with increasing angle of kyphosis.

Assessment using serum insulin-like growth factor-I and bone mineral density is useful for detecting prevalent vertebral fractures in patients with type 2 diabetes mellitus.

Bone mineral density (BMD) is less useful for evaluating fracture risk in type 2 diabetes. This study showed for the first time that combined evaluation by serum insulin-like growth factor-I and BMD is useful to assess the risk of vertebral fracture in postmenopausal women and men with type 2 diabetes. INTRODUCTION: BMD is less useful for evaluating fracture risk in type 2 diabetes mellitus (T2DM). We aimed to examine the usefulness of combined evaluation by BMD and serum insulin-like growth factor-I (IGF-I) to assess the risk of vertebral fracture (VF) in T2DM. METHODS: In this cross-sectional study, 412 postmenopausal women and 582 men with T2DM, whose BMD, bone turnover markers, and serum IGF-I were measured, were enrolled. The association of BMD alone, serum IGF-I alone, and combined assessment by BMD and IGF-I with the presence of VF was examined. RESULTS: Multiple logistic regression analyses showed that IGF-I as well as BMD T-score at lumbar (L) and femoral neck (FN) were significantly associated with VF except for IGF-I in men, respectively. Receiver operating characteristic curves showed that the cutoff values of IGF-I, L T-score and FN T-score were 127 ng/mL, - 1.78, and - 2.02 in postmenopausal women and 127 ng/mL, - 1.67, and - 1.24 in men. Based on the cutoff vales, the subjects were divided into four categories. The category of lower IGF-I and lower T-scores had a significant increased risk of VF compared to higher IGF-I and higher T-scores both in postmenopausal women and in men. The sensitivity and specificity of the combined assessment to detect VF were better compared to using BMD alone or IGF-I alone. CONCLUSIONS: This is the first study to show that in addition to BMD measurement, the assessment using serum IGF-I is useful to estimate the prevalence of VF in patients with T2DM.

A study of the value of trabecular bone score in fracture risk assessment of postmenopausal women.

OBJECTIVE: Trabecular Bone Score (TBS) is an index of bone microarchitecture that provides additional skeletal information to areal Bone Mineral Density (aBMD). Recently TBS data has been used to optimize the Fracture Risk Assessment Tool (FRAX) predictive value. The aim of this study was to evaluate the clinical value of TBS on FRAX algorithm. MATERIALS AND METHODS: Among total of 358 postmenopausal Iranian women (mean age 61.3 ± 9.5 years) tested for aBMD and TBS, 184 osteopenic women were identified. Thoracolumbar spine X-ray done in all participants revealed twenty-one vertebral fractures. For the osteopenic group, FRAX and TBS adjusted FRAX (FRAX-TBS) were calculated and compared. RESULTS: Mean TBS of the patients was 1.31 (±0.11). A significant correlation was found between TBS and spine aBMD (r = 0.50, p < 0.001) and TBS and femoral neck aBMD (r = 0.37, p < 0.0001). A strong positive correlation was observed between aBMD adjusted FRAX and FRAX-TBS in predicting the risk of major osteoporotic fracture (r = 0.90, p < 0.0001), and hip fracture (r = 0.97, p < 0.0001). According to the area under the receiver operating characteristics curve, the predictive value of the three different models using aBMD, TBS, and combination of aBMD and TBS were similar (0.765, 0.776, and 0.781, respectively; p = 0.19). The proportion of the women needed treatment remained unchanged using FRAX or FRAX-TBS. CONCLUSION: This study showed no clinical benefit for TBS in postmenopausal women. Adding TBS data to aBMD or FRAX neither improved aBMD predictive value for vertebral fracture nor changed the decision on treatment based on FRAX.

Changes in bone mineral density after kidney transplantation: 2-year assessment of a French cohort.

INTRODUCTION: In renal transplant patients, bone loss may be related to the drugs patients are taking but also to their past history of chronic kidney disease. The purpose of this study was to assess changes in BMD 2 years after an initial assessment (performed 9 months post transplantation) and the factors associated with these changes. METHODS: This longitudinal study included patients who had undergone a renal transplantation between 2005 and 2011, and who were followed up at the Lille Regional University Hospital. Patients were included if they had a first bone evaluation (including bone densitometry, spine X-rays and biological assessment) and at least another BMD assessment. The first assessment was performed on average 9 months post transplantation. A second assessment was performed at 2 years. RESULTS: Two hundred fifty-nine out of 366 patients satisfied the inclusion criteria. The population included 96 women. Mean age at transplantation was 49.7 ± 12.1 years. Mean duration of dialysis was 3.2 ± 3.3 years. For 75 patients (29.0%), corticosteroid treatment was discontinued 7 days after transplantation without subsequent resumption during follow-up. Vertebral fractures assessed by X-rays at baseline were found in 28 patients (10.8%). According to the WHO classification, 106 patients (40.9%) patients had osteoporosis and 111 patients (42.8%) had osteopenia at the first assessment. Oral bisphosphonates were prescribed for 95 patients. The decision to prescribe bisphosphonates was taken jointly by rheumatologists and nephrologists based on BMD assessment, past history of fracture and corticosteroid management. In all patients, BMD gains at the second evaluation (2.2 ± 0.79 years) compared with baseline were significant (3.9 ± 6.6, 2.6% ± 7.6, 3.0 ± 7.2% at the lumbar spine, femoral neck and total hip respectively; p < 0.0001). The difference in gain between bisphosphonate-treated and untreated patients was significant (+ 5.0 ± 0.8% (p < 0.0001), + 2.5 ± 1.0% (p = 0.01) and + 2.7 ± 0.9% (p < 0.01) at the lumbar spine, femoral neck and total hip respectively. The patients who benefited early corticosteroid discontinuation had higher gains in BMD at the lumbar spine (+ 2.1 ± 0.9%; p = 0.02) and total hip (+ 2.0 ± 1.0%; p = 0.04) compared to those for whom corticosteroid therapy was maintained. Stepwise regression analysis (patients without bisphosphonates) showed associations between change in BMD (femoral neck) and duration of corticosteroid therapy, bone alkaline phosphatase level at baseline, and absence of vertebral fracture. No correlation was found between change in BMD and duration of dialysis or renal function. CONCLUSION: Kidney transplant recipients have an increased risk of bone fragility in the year following transplantation. Bisphosphonates and early corticosteroid discontinuation can improve BMD.

Bone health assessment in older people with or without muscle health impairment.

This study investigated the relationship between muscle and bone status in elderly individuals. Our results suggested links between sarcopenia and osteoporosis; impairment in muscle status (i.e., muscle mass, muscle strength, and physical performance) is associated with deterioration in bone mass and texture subsequently leading to an increased risk of fracture. INTRODUCTION: Accumulating evidence has shown associations between sarcopenia and osteoporosis, but existing studies face inconsistencies in the clinical definition of both conditions. Thus, we sought to investigate bone health among older individuals with or without muscle health impairment. METHODS: We conducted an analysis of cross-sectional data available from the Sarcopenia and Physical Impairment with Advancing Age (SarcoPhAge) study. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People (EWGSOP) (i.e., a low muscle mass plus either low muscle strength or low physical performance). Muscle mass and areal bone mineral density (aBMD) were determined using dual-energy X-ray absorptiometry (DEXA). Muscle strength was assessed using a hand dynamometer, and physical performance was assessed with the Short Physical Performance Battery test. Using the cutoff limits proposed by the EWGSOP, we have classified women in the "low SMI group" when its value was < 5.50 kg/m2, in the "low muscle strength group" when strength was < 20 kg, and in the "low physical performance group" when SPPB < 8 points. The thresholds of < 7.26 kg/m2 (for SMI), < 30 kg (for muscle strength), and SPPB < 8 points were used for men. The 10-year fracture risk was obtained using the FRAX® tool. Moreover, bone texture was determined using the trabecular bone score (TBS) method. RESULTS: The study sample consisted of 288 older subjects aged 74.7 ± 5.7 years, and 59.0% of the subjects were women. Sarcopenia was diagnosed in 43 individuals (14.9%), and osteoporosis was diagnosed in 36 subjects (12.5%). Moreover, aBMD values were, most of the time, lower in older men and women with muscle impairment (i.e., low muscle mass, low muscle strength, and low physical performance). For these subjects, we also noted a higher probability of fracture. When comparing bone quality, there were no significant differences in the TBS values between sarcopenic and non-sarcopenic older men and women or between those with low and high muscle mass. However, when controlling for confounders (i.e., age, BMI, number of co-morbidities, smoking status, and nutritional status), TBS values were lower in older women with low muscle strength (p = 0.04) and in older men with low physical performance (p = 0.01). CONCLUSIONS: Our study showed interrelationships between components of sarcopenia and osteoporosis, with older subjects with muscle impairment having poorer bone health.

Bone Mass Assessment in a Cohort of Adults With Down Syndrome: A Cross-Sectional Study.

Differences in bone mineral density (BMD) have been observed between adults with Down syndrome (DS) and the general population. The purpose of this article is to describe the prevalence of bone mass disorders in a cohort of adults with DS and their predisposing factors. We performed a cross-sectional study of 104 consecutively recruited adults with DS from an outpatient clinic of a tertiary care hospital in Madrid, Spain. We recorded epidemiological and anthropometric data, nutritional variables, coexisting clinical conditions, and laboratory variables. BMD was measured at the lumbar spine, total hip, and femoral neck using dual-energy X-ray absorptiometry. The prevalence of osteopenia ranged from 48% to 52%, and that of osteoporosis ranged from 19% to 22% depending on the site of measurement (femoral neck or lumbar spine, respectively). Age was the greatest risk factor associated for lower BMD, with similar bone mass accrual curve but with lower peak of BMD than the general population. We conclude that low bone mass is an extremely prevalent condition in adult patients with DS.

Pre-fracture individual characteristics associated with high total health care costs after hip fracture.

Older women with pre-fracture slow walk speed, high body mass index, and/or a high level of multimorbidity have significantly higher health care costs after hip fracture compared to those without those characteristics. Studies to investigate if targeted health care interventions for these individuals can reduce hip fracture costs are warranted. INTRODUCTION: The aim of this study is to estimate the associations of individual pre-fracture characteristics with total health care costs after hip fracture, using Study of Osteoporotic Fractures (SOF) cohort data linked to Medicare claims. METHODS: Our study population was 738 women age 70 and older enrolled in Medicare Fee for Service (FFS) who experienced an incident hip fracture between January 1, 1992 and December 31, 2009. We assessed pre-fracture individual characteristics at SOF study visits and estimated costs of hospitalizations, skilled nursing facility and inpatient rehabilitation stays, home health care visits, and outpatient utilization from Medicare FFS claims. We used generalized linear models to estimate the associations of predictor variables with total health care costs (2010 US dollars) after hip fracture. RESULTS: Median total health care costs for 1 year after hip fracture were $35,536 (inter-quartile range $24,830 to $50,903). Multivariable-adjusted total health care costs for 1 year after hip fracture were 14 % higher ($5256, 95 % CI $156 to $10,356) in those with walk speed <0.6 m/s compared to ≥1.0 m/s, 25 % higher ($9601, 95 % CI $3314 to $16,069) in those with body mass index ≥30 kg/m2 compared to 20 to 24.9 mg/kg2, and 21 % higher ($7936, 95 % CI $346 to $15,526) for those with seven or more compared to no comorbid medical conditions. CONCLUSIONS: Pre-fracture poor mobility, obesity, and multiple comorbidities are associated with higher total health care costs after hip fracture in older women. Studies to investigate if targeted health care interventions for these individuals can reduce the costs of hip fractures are warranted.

Targeted assessment of fracture risk in women at midlife.

UNLABELLED: This study establishes a profile for women at midlife, referred for a dual energy X-ray absorptiometry (DXA), most likely to have osteoporosis, and from this, a pre-DXA screening tool has been developed. These findings inform much needed evidence-based guidelines for targeted and effective screening for osteoporosis and osteoporotic fracture prevention in women at midlife. INTRODUCTION: There is no consensus as to whether women at midlife should undergo screening dual energy X-ray absorptiometry (DXA) to identify osteoporosis (T-score < -2.5). METHODS: We investigated the prevalence of osteoporosis in women, aged 40-65 years, referred to 42 community-based Australian radiology centres, and identified the characteristics that best predict osteoporosis in women having a screening DXA. RESULTS: One thousand four hundred and two women completed the study questionnaire and had DXA reports available. After excluding women with an established indication for a DXA (58 %), users of bone-specific medication (10.5 %) and cancer (7.6 %), 466 women were classified as having a screening DXA. Forty of these women had osteoporosis at the lumbar spine (n = 32, 6.9 %) or femoral neck (n = 17, 3.6 %). Three predictors of osteoporosis (postmenopausal, nonuse of hormonal therapy and body mass index) were identified and incorporated into the Monash Osteoporosis Risk Score for women at midlife (MORS). In the screened study population, the MORS had a sensitivity of 70 % and specificity of 66 %, with a positive predictive value of 16.2 % and negative predictive value of 95.9 % for osteoporosis. CONCLUSIONS: Very few women referred for a screening DXA scan will be found to have osteoporosis. The MORS, a simple decision tool, would have identified 70 % of the women in our screening DXA study population and would have eliminated over 60 % of the screening DXA studies. Hence, use of the MORS may reduce unnecessary DXA scans and facilitate identification of the majority of cases of osteoporosis in women aged 40 to 65 years.

Lumbar spine texture enhances 10-year fracture probability assessment.

UNLABELLED: We found that lumbar spine texture analysis using trabecular bone score (TBS) is a risk factor for MOF and a risk factor for death in a retrospective cohort study from a large clinical registry for the province of Manitoba, Canada. INTRODUCTION: FRAX® estimates the 10-year probability of major osteoporotic fracture (MOF) using clinical risk factors and femoral neck bone mineral density (BMD). Trabecular bone score (TBS), derived from texture in the spine dual X-ray absorptiometry (DXA) image, is related to bone microarchitecture and fracture risk independently of BMD. Our objective was to determine whether TBS provides information on MOF probability beyond that provided by the FRAX variables. METHODS: We included 33,352 women aged 40-100 years (mean 63 years) with baseline DXA measurements of lumbar spine TBS and femoral neck BMD. The association between TBS, the FRAX variables, and the risk of MOF or death was examined using an extension of the Poisson regression model. RESULTS: During the mean of 4.7 years, 1,754 women died and 1,872 sustained one or more MOF. For each standard deviation reduction in TBS, there was a 36 % increase in MOF risk (HR 1.36, 95 % CI 1.30-1.42, p < 0.001) and a 32 % increase in death (HR 1.32, 95 % CI 1.26-1.39, p < 0.001). When adjusted for significant clinical risk factors and femoral neck BMD, lumbar spine TBS was still a significant predictor of MOF (HR 1.18, 95 % CI 1.12-1.23) and death (HR 1.20, 95 % CI 1.14-1.26). Models for estimating MOF probability, accounting for competing mortality, showed that low TBS (10th percentile) increased risk by 1.5-1.6-fold compared with high TBS (90th percentile) across a broad range of ages and femoral neck T-scores. CONCLUSIONS: Lumbar spine TBS is able to predict incident MOF independent of FRAX clinical risk factors and femoral neck BMD even after accounting for the increased death hazard.

Use of a performance algorithm improves utilization of vertebral fracture assessment in clinical practice.

SUMMARY: A performance algorithm can be successfully used by bone density technologists at the time of a bone density test to identify patients with an indication for vertebral fracture assessment (VFA). Doing so appropriately increases physician prescription of fracture prevention medication. INTRODUCTION: Densitometric spine imaging (vertebral fracture assessment, VFA) can identify prevalent vertebral fracture but is underutilized. We developed an algorithm by which DXA technologists identify patients for whom VFA should be performed. Following this algorithm, VFA was performed in patients whose lowest T-score (lumbar spine, total hip, or femoral neck) was between -1.5 and -2.4 inclusive and with one of the following: age, ≥ 65 years; height loss, ≥ 1.5 in.; or current systemic glucocorticoid therapy. Our main objectives were to assess change in VFA utilization at two other healthcare organizations after algorithm implementation, and to estimate the association of VFA results with prescription of fracture prevention medication. METHODS: The proportions of patients with an indication for VFA who had one performed before and after algorithm implementation were compared. Logistic regression was used to estimate the multivariable-adjusted association of VFA results with subsequent prescription of fracture prevention medication adjusted for healthcare organization (study site). RESULTS: After algorithm introduction, appropriate VFA use rose significantly Patients with a VFA positive for vertebral fracture had an odds ratio of 3.2 (95 % C.I., 2.1- 5.1) for being prescribed new fracture prevention medication, adjusted for age, sex, prior clinical fracture, use of glucocorticoid medication, femoral neck bone mineral density T-score, and study site. CONCLUSIONS: An algorithm to identify those for whom VFA is indicated can successfully be implemented by DXA technologists. Documentation of vertebral fracture increases prescription of fracture prevention medication for patients who otherwise lack an apparent indication for such therapy.

Is lower income associated with an increased likelihood of qualification for treatment for osteoporosis in Canadian women?

UNLABELLED: We examined whether low income was associated with an increased likelihood of treatment qualification for osteoporotic fracture probability determined by Canada FRAX in women aged ≥50 years. A significant negative linear association was observed between income and treatment qualification when FRAX included bone mineral density (BMD), which may have implications for clinical practice. INTRODUCTION: Lower income has been associated with increased fracture risk. We examined whether lower income in women was associated with an increased likelihood of treatment qualification determined by Canada FRAX®. METHODS: We calculated 10-year FRAX probabilities in 51,327 Canadian women aged ≥50 years undergoing baseline BMD measured by dual energy x-ray absorptiometry 1996-2001. FRAX probabilities for hip fracture ≥3% or major osteoporotic fracture (MOF) ≥20 % were used to define treatment qualification. Mean household income from Canada Census 2006 public use files was used to categorize the population into quintiles. Logistic regression analyses were used to model the association between income and treatment qualification. RESULTS: Percentages of women who qualified for treatment based upon high hip fracture probability increased linearly with declining income quintile (all p trend <0.001), but this was partially explained by older age among lower income quintiles (p trend <0.001). Compared to the highest income quintile, women in the lowest income quintile had a greater likelihood of treatment qualification based upon high hip fracture probability determined with BMD (age-adjusted odds ratio [OR], 1.34; 95% confidence intervals (CI), 1.23-1.47) or high MOF fracture probability determined with BMD (age-adjusted OR, 1.31; 95% CI, 1.18-1.46). Differences were nonsignificant when FRAX was determined without BMD, implying that BMD differences may be the primary explanatory factor. CONCLUSIONS: FRAX determined with BMD identifies a larger proportion of lower income women as qualifying for treatment than higher income women.

Cost-effectiveness of strontium ranelate in the treatment of male osteoporosis.

UNLABELLED: The results of this study suggest that, under the assumption of same relative risk reduction of fractures in men as for women, strontium ranelate could be considered a cost-effective strategy compared with no treatment for the treatment of osteoporotic men from a Belgian healthcare payer perspective. INTRODUCTION: This study was conducted to estimate the cost-effectiveness of strontium ranelate in the treatment of osteoporotic men. METHODS: A previously validated Markov microsimulation model was adapted to estimate the cost (2,010) per quality-adjusted life-year (QALY) gained of strontium ranelate compared with no treatment. Similar efficacy data on lumbar spine and femoral neck bone mineral density (BMD) between men with osteoporosis at high risk of fracture (MALEO Trial) and postmenopausal osteoporotic women (pivotal SOTI, TROPOS trials) supports the assumption, in the base-case analysis, of the same relative risk reduction of fractures in men as for women. Analyses were conducted, from a Belgian healthcare payer perspective, in the population from the MALEO Trial who is a men population with a mean age of 73 years, and BMD T-score ≤-2.5 or prevalent vertebral fracture (PVF). RESULTS: In the MALEO population, strontium ranelate compared with no treatment was estimated at 49,798 and 25,584 per QALY gained using efficacy data from the intent-to-treat analysis and the per-protocol analysis including only adherent patients, respectively. In men with a BMD T-score ≤-2.5 or with PVF, the cost per QALY gained of strontium ranelate fall below thresholds of 45,000 and 25,000 per QALY gained based on efficacy data from the entire population of the clinical trial and from the per-protocol analyses, respectively. CONCLUSIONS: The results of this study suggest that, under the assumption of same relative risk reduction of fractures in men as for women, strontium ranelate could be considered cost-effective compared with no treatment for male osteoporosis.

The Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) study: 2-year nonvertebral fragility fracture results.

UNLABELLED: This observational study evaluated the occurrence of nonvertebral fragility fractures (NVFX) in over 4,000 men and women with osteoporosis treated with teriparatide (TPTD). The incidence of new NVFX decreased for patients receiving TPTD treatment for greater than 6 months. No new significant safety findings were observed in this large trial. INTRODUCTION: The Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) study evaluated the occurrence of NVFX in patients receiving TPTD for osteoporosis in a real-world setting. METHODS: DANCE is a multicenter, prospective, observational trial that examined the long-term effectiveness of TPTD in men and women with osteoporosis whom study physicians judged to be suitable for TPTD therapy. Patients received 20 µg TPTD per day by subcutaneous injection for up to 24 months and were followed for 24 months after treatment cessation. The incidence of patients experiencing a new NVFX, defined as a fracture associated with low trauma, was evaluated during four 6-month periods in both the treatment and cessation phases with >0 to ≤6 months serving as the reference. We also observed the spectrum and occurrence of serious adverse events. RESULTS: Of the 4,167 patients enrolled, 4,085 took one or more doses of TPTD (safety population); 3,720 were included in the efficacy analysis. The incidence of patients experiencing a NVFX was 1.42, 0.91, 0.70, and 0.81 % for the four treatment periods, respectively, and 0.80, 0.68, 0.33, and 0.33 % for the four periods after treatment cessation. Differences for each period were statistically significant compared with the reference period (first 6-month interval, each p < 0.05). No new significant safety findings were observed. CONCLUSIONS: In this study, the incidence of NVFX decreased for patients receiving TPTD for all three treatment periods >6 months compared to 0 to ≤6 months, and this trend persisted throughout the cessation phase. TPTD was generally well tolerated.

Associations between adverse social position and bone mineral density in women aged 50 years or older: data from the Manitoba Bone Density Program.

UNLABELLED: We examined the independent contribution of income to low bone mineral density in women aged 50 years and older. A significant dose-response association was observed between low income and low (bone mineral density) BMD, which was not explained by clinical risk factors or osteoporotic treatment in the year prior. INTRODUCTION: The association between social disadvantage and osteoporosis is attracting increased attention; however, little is known of the role played by income. We examined associations between income and bone mineral density (BMD) in 51,327 women aged ≥50 years from Manitoba, Canada. METHODS: Low BMD was defined as a T-score ≥2.5SD (femoral neck or minimum) measured by dual energy X-ray absorptiometry (DXA) 1996-2001. Mean household income was extracted from Canada Census 2006 public use files and categorized into quintiles. Age, weight and height were recorded at time of DXA. Parental hip fracture was self-reported. Diagnosed comorbidities, including osteoporotic fracture and rheumatoid arthritis, were ascertained from hospital records and physician billing claims. Chronic obstructive pulmonary disease was used as a proxy for smoking and alcohol abuse as a proxy for high alcohol intake. Corticosteroid use was obtained from the comprehensive provincial pharmacy system. Logistic regression was used to assess relationships between income (highest income quintile held as referent) and BMD, accounting for clinical risk factors. RESULTS: Compared to quintile 5, the adjusted odds ratio (OR) for low BMD at femoral neck for quintiles 1 through 4 were, respectively, OR1.41 (95%CI 1.29-1.55), OR1.32 (95%CI 1.20-1.45), OR1.19 (95%CI 1.08-1.30) and OR1.10 (95%CI 1.00-1.21). Similar associations were observed when further adjustment was made for osteoporotic drug treatment 12 months prior and when low BMD was defined by minimum T-score. CONCLUSIONS: Lower income was associated with lower BMD, independent of clinical risk factors. Further work should examine whether lower income increases the likelihood of treatment qualification.

Dose-related effect of urinary cotinine levels on bone mineral density among Korean females.

UNLABELLED: To evaluate the dose-dependent relationship between smoking and bone mineral density (BMD), the present study used the BMD dataset of the Korean National Health and Nutrition Examination Survey IV (KNHANES IV). The linearity of BMD for urinary cotinine levels was demonstrated with statistical significance in postmenopausal females. INTRODUCTION: It is well established that smoking is an important lifestyle risk factor for bone health (bone loss, osteoporosis, and fracture). However, several studies demonstrated conflicting evidence for a dose-dependent relationship between smoking and bone health. To evaluate the dose-dependent relationship between smoking and BMD, the present study estimated dose-related effects of smoking (urinary cotinine level) on BMD at various sites (femur neck, total femur, and lumbar spine) in females with controlling menopausal status. METHODS: The present study used the BMD dataset of the KNHANES IV, which was performed in 2008 and 2009. A total of 4,260 pre- and postmenopausal females were included in the present study. Dose-response relationships between BMD and urinary cotinine levels were estimated using analysis of covariance in pre-menopausal females and postmenopausal females, respectively. RESULTS: In postmenopausal females, the regression coefficients for BMD with urinary cotinine levels were -0.006, -0.006, and -0.008 (g/cm2 per ng/ml) at femur neck, total femur, and lumbar spine, respectively (p value<0.05). Thus, the linearity of BMD for urinary cotinine levels was demonstrated with statistical significance in postmenopausal females. CONCLUSION: Our findings suggested a significant dose-related effect of urinary cotinine level with BMD at femur neck, total femur, and lumbar spine among postmenopausal females.

Competing mortality and fracture risk assessment.

SUMMARY: Failure to account for competing mortality gave higher estimates of 10-year fracture probability than if appropriate adjustment is made for competing mortality, particularly among subgroups with higher mortality. A modified Kaplan-Meier method is easy to implement and provides an alternative approach to existing methods for competing mortality risk adjustment. INTRODUCTION: A unique feature of FRAX(®) is that 10-year fracture probability accounts for mortality as a competing risk. We compared the effect of competing mortality adjustment on nonparametric and parametric methods of fracture probability estimation. METHODS: The Manitoba Bone Mineral Density (BMD) database was used to identify men and women age ≥50 years with FRAX probabilities calculated using femoral neck BMD (N = 39,063). Fractures were assessed from administrative data (N = 2,543 with a major osteoporotic fracture, N = 549 with a hip fracture during mean 5.3 years follow-up). RESULTS: The following subgroups with higher mortality were identified: men, age >80 years, high fracture probability, and presence of diabetes. Failure to account for competing mortality in these subgroups overestimated fracture probability by 16-56 % with the standard nonparametric (Kaplan-Meier) method and 15-29 % with the standard parametric (Cox) model. When the outcome was hip fractures, failure to account for competing mortality overestimated hip fracture probability by 18-36 % and 17-35 %, respectively. A simple modified Kaplan-Meier method showed very close agreement with methods that adjusted for competing mortality (within 2 %). CONCLUSIONS: Failure to account for competing mortality risk gives considerably higher estimates of 10-year fracture probability than if adjustment is made for this competing risk.

Magnitude and consequences of misclassification of incident hip fractures in large cohort studies: the Study of Osteoporotic Fractures and Medicare claims data.

UNLABELLED: In the Study of Osteoporotic Fractures (SOF), 18.5 % of incident hip fractures identified in Medicare Fee-for-Service claims data were not reported to or confirmed by the cohort. Cognitive impairment was a modest risk factor for false-negative hip fracture ascertainment via self-report. INTRODUCTION: Prospective cohort studies of fractures that rely on participant self-report to be the initial signal of an incident fracture could be prone to bias if a significant proportion of fractures are not self-reported. METHODS: We used data from the SOF merged with Medicare Fee-for-Service claims data to estimate the proportion of participants who had an incident hip fracture identified in Medicare claims that was either not self-reported or confirmed (by review of radiographic reports) in SOF. RESULTS: Between 1/1/1991 and 12/31/2007, 647 SOF participants had a hip fracture identified in Medicare claims, but 120 (18.5 %) were either not reported to or confirmed by the cohort. False-negative hip fracture ascertainment was associated with a reduced modified Mini-Mental State Exam (MMSE) score (odds ratio 1.31 per SD decrease, 95 % C.I. 1.06-1.63). Point estimates of associations of predictors of incident hip fracture were changed minimally when the misclassification of incident hip fracture status was corrected with use of claims data. CONCLUSIONS: A substantial minority of incident hip fractures were not reported to or confirmed in the SOF. Cognitive impairment was modestly associated with false-negative hip fracture ascertainment. While there was no evidence to suggest that misclassification of incident hip fracture status resulted in biased associations of potential predictors with hip fracture in this study, false-negative incident fracture ascertainment in smaller cohort studies with limited power may increase the risk of type 2 error (not finding significant associations of predictors with incident fractures).

Glutamine repeat variants in human RUNX2 associated with decreased femoral neck BMD, broadband ultrasound attenuation and target gene transactivation.

RUNX2 is an essential transcription factor required for skeletal development and cartilage formation. Haploinsufficiency of RUNX2 leads to cleidocranial displaysia (CCD) a skeletal disorder characterised by gross dysgenesis of bones particularly those derived from intramembranous bone formation. A notable feature of the RUNX2 protein is the polyglutamine and polyalanine (23Q/17A) domain coded by a repeat sequence. Since none of the known mutations causing CCD characterised to date map in the glutamine repeat region, we hypothesised that Q-repeat mutations may be related to a more subtle bone phenotype. We screened subjects derived from four normal populations for Q-repeat variants. A total of 22 subjects were identified who were heterozygous for a wild type allele and a Q-repeat variant allele: (15Q, 16Q, 18Q and 30Q). Although not every subject had data for all measures, Q-repeat variants had a significant deficit in BMD with an average decrease of 0.7SD measured over 12 BMD-related parameters (p = 0.005). Femoral neck BMD was measured in all subjects (-0.6SD, p = 0.0007). The transactivation function of RUNX2 was determined for 16Q and 30Q alleles using a reporter gene assay. 16Q and 30Q alleles displayed significantly lower transactivation function compared to wild type (23Q). Our analysis has identified novel Q-repeat mutations that occur at a collective frequency of about 0.4%. These mutations significantly alter BMD and display impaired transactivation function, introducing a new class of functionally relevant RUNX2 mutants.

Fracture risk assessment without bone density measurement in routine clinical practice.

UNLABELLED: Fracture probability assessed without bone mineral density (BMD) could potentially be sufficient for clinical decision making in many individuals categorized as low or high fracture risk. For individuals falling in a moderate risk range, there is incremental value in using BMD in the probability calculation as this appropriately reclassifies risk in over one third of the individuals. INTRODUCTION: A new fracture risk assessment tool from the World Health Organization (FRAX) estimates 10-year major osteoporotic and hip fracture probabilities from multiple clinical risk factors with or without hip BMD. The objective of this study is to determine whether fracture probability derived without BMD can be used to identify individuals who would be designated for treatment. METHODS: A historical cohort of 36,730 women and 2,873 men aged 50 years and older drawn from the Manitoba Bone Density Program database, which contains clinical BMD results for the Province of Manitoba, Canada, was included in the study. RESULTS: When 10-year probability for major osteoporotic fracture estimated without knowledge of BMD was high (≥ 20%), the vast majority (92.8%) qualified for intervention under the National Osteoporosis Foundation (NOF) guidelines, whereas among those at low risk (<10%), the vast majority (80.5%) did not satisfy any NOF intervention criteria. The benefit of including BMD in the risk assessment was greatest among those initially at moderate risk (10-19%) when fracture probability was derived without BMD, but this represented only 29.4% of the cohort (9.3% of those aged < 65 years and 48.7% of those ≥ 65 years). CONCLUSIONS: Fracture probability derived without BMD is able to risk stratify women in terms of future fracture risk and could potentially be sufficient for clinical decision making in many of those designated at low or high fracture risk.

Gender differences for initiating teriparatide therapy: baseline data from the Direct Assessment of Nonvertebral Fracture in the Community Experience (DANCE) study.

UNLABELLED: The prospective, observational Direct Assessment of Nonvertebral Fracture in the Community Experience (DANCE) study shows that, among patients with risk factors for osteoporosis, women are more likely to be screened and to receive appropriate treatment than men. There needs to be greater awareness that osteoporosis affects both men and women. INTRODUCTION: The prospective, observational DANCE study evaluated teriparatide use in the mainland USA and Puerto Rico in patients with osteoporosis in a community setting. This analysis compares baseline characteristics of women and men that may contribute to differences in initiation of teriparatide therapy. METHODS: Investigators prescribed teriparatide 20 µg/day subcutaneous injection for ≤24 months to 3,698 patients (3,342 women, 356 men) whom they considered appropriate candidates for therapy. Study entry was guided by product labeling. Specific timing and frequency of office visits were not mandated. Treatment decisions were based on the clinical judgment of study investigators and local standards of care. RESULTS: At baseline, similar proportions of women and men had prior fragility fractures (57% and 59%, respectively) and comorbid conditions that increase fracture risk (83% and 84%, respectively). Women were older than men (mean age 68 vs. 65 year; P < 0.0001) and more likely to have received prior osteoporosis therapy (88% vs. 62%; P < 0.0001). Investigators prescribed teriparatide more often for women than men based on general frailty (21% vs. 16%; P = 0.0151), low body mass index (17% vs. 10%; P = 0.0005), and an inadequate response (58% vs. 36%; P < 0.0001) or intolerance to previous therapy (23% vs. 12%; P < 0.0001). Chronic glucocorticoid therapy was the reason investigators cited most frequently for initiating therapy more often in men than in women (17% vs. 10%; P < 0.0001) CONCLUSIONS: These results suggest that patients' gender may influence the reasons physicians initiate teriparatide therapy in a community setting.