A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX.

Trabecular bone score (TBS) is a gray-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual-level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow-up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR = 1.32, 95% CI 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65-1.87 versus 1.70, 95% CI 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. © 2015 American Society for Bone and Mineral Research.

The human cost of fracture

In this population-based, observational study, we document the personal burden of fracture and utilization of community and health services for women during the 12-month period following a fracture. Participants were 598 women (aged 35-92 years) with incident fracture in the years 1994-1996 who were enrolled in the Geelong Osteoporosis Study. Almost all hip fracture cases and 27% of nonhip fracture cases were hospitalized. Homes were modified in 14% of cases, and 32% of the women purchased or hired equipment to assist with activities of daily living. Three-quarters of women with hip, pelvis, or lower limb fractures were confined to the home, had to walk with a walking aid, or could walk only short distances for several weeks. After a year, nearly one-half had not regained prefracture mobility. One-seventh of women with upper-limb fractures did not venture outside the home for at least 6 weeks. Nearly half of all fracture cases needed help with personal care and housework during the first 6 weeks. After 6 months, 3.4% of all patients and 19.6% of hip, 12.8% of humeral, and 4.7% of spine fracture patients required assistance with bathing and showering. After a year, more than half of the hip fracture cases remained restricted regarding housework, gardening, and transport. These findings have important implications for rehabilitation therapy. A fracture, regardless of site, had a major impact on a woman's lifestyle and well-being. Most women were restricted in their activities of daily living and suffered loss of confidence and independence. Short-term morbidity was common for all fractures, with varying degrees of prolonged morbidity often extending to at least a year postfracture.

Fracture rates lower in rural than urban communities : the Geelong Osteoporosis Study

Background: Urban and rural communities differ in the incidence of several diseases including coronary heart disease and some cancers. Lower hip fracture rates among rural than urban populations have been reported but few studies have compared rural and urban fractures at sites other than the hip.

Objective: To compare total and site specific fracture rates among adult residents of rural and urban communities within the same population.

Design and setting: This is a population based study on osteoporosis in Australia. All fractures occurring in adult residents over a two year period were ascertained using radiological reports. The rural and urban areas are in close proximity, with the same medical, hospital, and radiological facilities permitting uniform fracture ascertainment.

Main outcome measures: All fracture rates were age adjusted and sex adjusted to the Australian population according to the 1996 census of the Australian Bureau of Statistics and described as the rate per 10 000 person years. The p values refer to the adjusted rate difference.

Results: The hip fracture rate (incidence per 10 000 person years) was 32% lower (39 v 57, p<0.001), and the total fracture rate 15% lower (160 v 188, p=0.004) among rural than urban residents, respectively. The lower fracture rates in the rural population were also apparent for pelvic fractures.

Conclusion: In the older rural population, lower fracture rates at sites typically associated with osteoporosis suggest environmental factors may have a different impact on bone health in this community. If the national rate of hip fracture could be reduced to that of the rural population, the projected increase in hip fracture number attributable to aging of the population could be prevented.

Alleles of RUNX2/CBFA1 gene are associated with differences in bone mineral density and risk of fracture

The aim of this study was to determine if DNA polymorphism within runt-related gene 2 (RUNX2)/core binding factor A1 (CBFA1) is related to bone mineral density (BMD). RUNX2 contains a glutamine-alanine repeat where mutations causing cleidocranial dysplasia (CCD) have been observed. Two common variants were detected within the alanine repeat: an 18-bp deletion and a synonymous alanine codon polymorphism with alleles GCA and GCG (noted as A and G alleles, respectively). In addition, rare mutations that may be related to low BMD were observed within the glutamine repeat. In 495 randomly selected women of the Geelong Osteoporosis Study (GOS), the A allele was associated with higher BMD at all sites tested. The effect was maximal at the ultradistal (UD) radius (p = 0.001). In a separate fracture study, the A allele was significantly protective against Colles' fracture in elderly women but not spine and hip fracture. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture, suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis.

Forearm bone mineral density and incidence of hip fractures in Swedish urban and rural men 1987-2002

Background: It is not known whether the recently described break in the trend in hip fracture incidence in many settings applies in both women and men, depends on changes in bone mineral density (BMD) or changes in other risk factors, or whether it is apparent in both urban and rural settings. Methods: We evaluated changes in annual hip fracture incidence from 1987 to 2002 in Swedish men aged ≥60 years in one urban (n=25,491) and one rural population (n=16,432) and also secular differences in BMD, measured by single-photon absorptiometry at the distal radius and multiple other risk factors for hip fracture in a population-based sub-sample of the urban and the rural men aged 60–80 years in 1988/89 (n=202 vs. 121) and in 1998/99 (n=79 vs. 69). Results: No statistically significant changes in the annual age-adjusted hip fracture incidence per 10,000 were apparent from 1987 to 2002 in urban (0.38 per year, 95% CI-0.12 to 0.88) or rural men (-0.05 per year, 95% CI -0.63 to 0.53). BMD was similar in 1988/89 and 1998/99 when examining both urban (-19.6 mg/cm², 95% CI -42.6 to 3.5) and rural (-23.0 mg/cm², 95% CI -52.1 to 6.1) men. Conclusions: Since no secular change in age-adjusted hip fracture incidence was found during the study period, a levelling off in hip fracture incidence is present also in Swedish men. Because BMD on a group level was similar in 1988/89 and 1998/99, changes in other risk factors ought to be either of minor importance or counteracted by changes in different risk factors.

The contributions of first nations ethnicity, income, and delays in surgery on mortality post-fracture : a population-based analysis

Summary We examined the independent contributions of First Nations ethnicity and lower income to post-fracture mortality. A similar relative increase in mortality associated with fracture appears to translate into a larger absolute increase in post-fracture mortality for First Nations compared to non-First Nations peoples. Lower income also predicted increased mortality post-fracture.

Introduction First Nations peoples have a greater risk of mortality than non-First Nations peoples. We examined the independent contributions of First Nations ethnicity and income to mortality post-fracture, and associations with time to surgery post-hip fracture.

Methods Non-traumatic fracture cases and fracture-free controls were identified from population-based administrative data repositories for Manitoba, Canada (aged ≥50 years). Populations were retrospectively matched for sex, age (within 5 years), First Nations ethnicity, and number of comorbidities. Differences in mortality post-fracture of hip, wrist, or spine, 1996–2004 (population 1, n = 63,081), and the hip, 1987–2002(Population 2, n = 41,211) were examined using Cox proportional hazards regression to model time to death. For hip fracture, logistic regression analyses were used to model the probability of death within 30 days and 1 year.

Results Population 1: First Nations ethnicity was associated with an increased mortality risk of 30–53 % for each fracture type. Lower income was associated with an increased mortality risk of 18–26 %. Population 2: lower income predicted mortality overall (odds ratio (OR) 1.15, 95 % confidence interval (CI) 1.07–1.23) and for hip fracture cases (OR 1.18, 95%CI 1.05–1.32), as did older age, male sex, diabetes, and >5 comorbidities (all p ≤ 0.01). Higher mortality was associated with pertrochanteric fracture (OR 1.14, 95 % CI 1.03–1.27), or surgery delay of 2–3 days (OR 1.34, 95 % CI 1.18–1.52) or ≥4 days (OR 2.35, 95 % CI 2.07–2.67).

Conclusion A larger absolute increase in mortality post-fracture was observed for First Nations compared to non-First Nations peoples. Lower income and surgery delay >2 days predicted mortality post-fracture. These data have implications regarding prioritization of healthcare to ensure targeted, timely care for First Nations peoples and/or individuals with lower income.

Personal and psychosocial impacts of clinical fracture in men

Background : Little is known about the personal burden of fracture across the age spectrum, particularly in men. This study aimed to document the impact of clinical fracture on men's participation in employment, sports and outdoor recreation, mobility, handiwork, activities of daily living, home modification, and utilisation of community and health services.

Methods : This prospective study followed 196 men with incident fracture identified from radiology reports at the Geelong Hospital during the period July 2006 to December 2007 and examined personal and psychosocial impacts 12 months post-fracture, using a self-report questionnaire.

Results : Of all men identified with fracture, 40% took time off work. All fractures, except those to the upper limbs, had considerable impact on mobility. Inability to drive was associated with all fractures, but was most common with ankle fractures and most prolonged with hip fractures. Loss of confidence was reported by over one-third of all fracture cases, even 12 months after the fracture event. All fractures affected activities of daily living, and this was generally most prolonged for fractures of the hip. Similarly, all men with fracture utilised community and health services, even for the relatively minor fractures of the finger/thumb.

Conclusions : This study supports previous reports of the personal impact of hip fracture, and presents data about the consequences of upper and lower limb fractures and the generally poorly described sequelae of fractures of the finger/thumb and foot/toe. These observations have important implications for post-fracture care and rehabilitation in men.

Is there an interaction between socioeconomic status and FRAX 10-year fracture probability determined with and without bone density measures? Data from the Geelong Osteoporosis Study of female cohort.

FRAX(©) evaluates 10-year fracture probabilities and can be calculated with and without bone mineral density (BMD). Low socioeconomic status (SES) may affect BMD, and is associated with increased fracture risk. Clinical risk factors differ by SES; however, it is unknown whether aninteraction exists between SES and FRAX determined with and without the BMD. From the Geelong Osteoporosis Study, we drew 819 females aged ≥50 years. Clinical data were collected during 1993-1997. SES was determined by cross-referencing residential addresses with Australian Bureau of Statistics census data and categorized in quintiles. BMD was measured by dual energy X-ray absorptiometry at the same time as other clinical data were collected. Ten-year fracture probabilities were calculated using FRAX (Australia). Using multivariable regression analyses, we examined whether interactions existed between SES and 10-year probability for hip and any major osteoporotic fracture (MOF) defined by use of FRAX with and without BMD. We observed a trend for a SES * FRAX(no-BMD) interaction term for 10-year hip fracture probability (p = 0.09); however, not for MOF (p = 0.42). In women without prior fracture (n = 518), we observed a significant SES * FRAX(no-BMD) interaction term for hip fracture (p = 0.03) and MOF (p = 0.04). SES does not appear to have an interaction with 10-year fracture probabilities determined by FRAX with and without BMD in women with previous fracture; however, it does appear to exist for those without previous fracture.

The effect of surgical timing on the outcome of patients with neck of femur fracture

Aims: To investigate the effect of surgical timing (in hours versus after hours and weekdays versus weekends) on the outcome of patients with neck of femur fracture. Methods: Patients who were admitted to a single tertiary referral hospital for surgical management of femoral neck fractures over a continuous period from 1/11/2002 to 12/7/2012 were identified from medical records and the operating theatre database. Results: A consecutive series of 2334 patients were included in the study. Of the patients who underwent surgery during the weekday and during usual hours, 18 % (207/1135) experienced an adverse event, compared to 16 % (193/1199) outside of these times. The difference between the two groups was not significant (p = 0.17). The same conclusion was made for the comparison between those who had surgery during the week with those who had surgery on the weekend (17 %, 267/1546 and 17 %, 133/788, respectively, p > 0.05). The proportion of patients who underwent surgery during hours that experienced an adverse event was significantly higher than those undergoing surgery out of hours (18 %, 327/1789 and 13 %, 73/545, respectively, p = 0.0081). When adjusted for age, ASA score and pre-operative stay, there was no statistical difference between those different sub-groups. Conclusions: There was no difference in the rates of adverse events between patients who had surgery during hours and weekdays with those who had surgery after hours or weekends. The careful selection of patients with appropriate hospital staff, resources and adequate theatre access, surgery during after hours and weekends may be safely considered to prevent a delay in surgical treatment for patient with neck of femur fracture.

Fracture prediction from repeat BMD measurements in clinical practice

Summary: We investigated whether repeat BMD measurements in clinical populations are useful for fracture risk assessment. We report that repeat BMD measurements are a robust predictor of fracture in clinical populations; this is not affected by preceding BMD change or recent osteoporosis therapy. Introduction: In clinical practice, many patients selectively undergo repeat bone mineral density (BMD) measurements. We investigated whether repeat BMD measurements in clinical populations are useful for fracture risk assessment and whether this is affected by preceding change in BMD or recent osteoporosis therapy. Methods: We identified women and men aged ≥50 years who had a BMD measurement during 1990–2009 from a large clinical BMD database for Manitoba, Canada (n = 50,215). Patient subgroups aged ≥50 years at baseline with repeat BMD measures were identified. Data were linked to an administrative data repository, from which osteoporosis therapy, fracture outcomes, and covariates were extracted. Using Cox proportional hazards models, we assessed covariate-adjusted risk for major osteoporotic fracture (MOF) and hip fracture according to BMD (total hip, lumbar spine, femoral neck) at different time points. Results: Prevalence of osteoporosis therapy increased from 18 % at baseline to 55 % by the fourth measurement. Total hip BMD was predictive of MOF at each time point. In the patient subgroup with two repeat BMD measurements (n = 13,481), MOF prediction with the first and second measurements was similar: adjusted-hazard ratio (HR) per SD 1.45 (95 % CI 1.34–1.56) vs. 1.64 (95 % CI 1.48–1.81), respectively. No differences were seen when the second measurement results were stratified by preceding change in BMD or osteoporosis therapy (both p-interactions >0.2). Similar results were seen for hip fracture prediction and when spine and femoral neck BMD were analyzed. Conclusion: Repeat BMD measurements are a robust predictor of fracture in clinical populations; this is not affected by preceding BMD change or recent osteoporosis therapy.

Depression as a risk factor for fracture in women: a 10 year longitudinal study

BACKGROUND: Previous research has demonstrated deficits in bone mineral density (BMD) among individuals with depression. While reduced BMD is a known risk for fracture, a direct link between depression and fracture risk is yet to be confirmed. METHODS: A population-based sample of women participating in the Geelong Osteoporosis Study was studied using both nested case-control and retrospective cohort study designs. A lifetime history of depression was identified using a semi-structured clinical interview (SCID-I/NP). Incident fractures were identified from radiological reports and BMD was measured at the femoral neck using dual energy absorptiometry. Anthropometry was measured and information on medication use and lifestyle factors was obtained via questionnaire. RESULTS: Among 179 cases with incident fracture and 914 controls, depression was associated with increased odds of fracture (adjusted odds ratio (OR) 1.57, 95%CI 1.04-2.38); further adjustment for psychotropic medication use appeared to attenuate this association (adjusted OR 1.52, 95%CI 0.98-2.36). Among 165 women with a history of depression at baseline and 693 who had no history of depression, depression was associated with a 68% increased risk of incident fracture (adjusted hazard ratio (HR) 1.68, 95%CI 1.02-2.76), with further adjustment for psychotropic medication use also appearing to attenuate this association (adjusted HR 1.58, 95%CI 0.95-2.61). LIMITATIONS: Potential limitations include recall bias, unrecognised confounding and generalizability. CONCLUSIONS: This study provides both cross-sectional and longitudinal evidence to suggest that clinical depression is a risk factor for radiologically-confirmed incident fracture, independent of a number of known risk factors. If there is indeed a clinically meaningful co-morbidity between mental and bone health, potentially worsened by psychotropic medications, the issue of screening at-risk populations needs to become a priority.

Handgrip strength predicts pressure ulcers in patients with hip fractures

Objective: Pressure ulcer (PU) is a frequent complication of hip fracture. Studies were carried out to identify the risk factors of PU development after hip fractures. The objective of the study was to determine the role of anthropometric measurements and handgrip strength as predictors of PUs in patients with hip fractures during their hospital stay and 30 d after discharge, which has not yet been established.Methods: Ninety-two consecutive patients with hip fractures who were older than 65 y old and admitted to an orthopedic unit were prospectively evaluated. Within the first 72 h of admission, each patient's characteristics were recorded, anthropometric measurements were taken (circumferences of the arm, waist, thigh, calf, triceps, and biceps and subscapular and suprailiac skinfolds), handgrip strength was measured, and blood samples were collected. PU evaluations were performed during the hospital stay and 30 d after hospital discharge.Results: Three patients were excluded because of PUs before hospitalization. Eighty-nine patients (average age 80.6 +/- 7.5 y) were studied; 70.8% were women, and 49.4% developed PUs during their hospital stay. In a univariate analysis, length of hospital stay (P = 0.001) and handgrip strength (P = 0.02), but not body circumferences and skinfolds, were associated with PUs during a hospital stay. Only handgrip strength (P = 0.007) was associated with PUs 30 d after hospital discharge. In a multivariate analysis, only handgrip strength was found to predict PU development at these points.Conclusion: Handgrip strength was found to predict PU development in patients with hip fractures during their hospital stay and 30 d after discharge. (C) 2012 Elsevier B.V. All rights reserved.

Fracture hospitalizations between years 2000 and 2007 in Switzerland: a trend analysis

In Switzerland, the total number and incidence of hospitalizations for major osteoporotic fractures increased between years 2000 and 2007, while hospitalizations due to hip fracture decreased. The cost impact of shorter hospital stays was offset by the increasing cost per day of hospitalization.

Effect of once-yearly zoledronic acid 5 mg on fracture risk and change in femoral neck bone mineral density

Context: In the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg significantly reduced fracture risk. Objective: To identify factors associated with greater efficacy during ZOL 5 mg treatment. Design, Setting and Patients: Subgroup analysis (preplanned and post hoc) of a multicenter, double-blind, placebo-controlled, 36-month trial in 7765 women with postmenopausal osteoporosis. Intervention: Single infusion of ZOL 5 mg or placebo at baseline, 12 and 24 months. Main Outcome Measures: Primary endpoints: new vertebral fracture and hip fracture. Secondary endpoints: non-vertebral fracture, change in femoral neck bone mineral density (BMD). Baseline risk factor subgroups: age, BMD T-score and vertebral fracture status, total hip BMD, race, weight, geographical region, smoking, height loss, history of falls, physical activity, prior bisphosphonates, creatinine clearance, body mass index (BMI), concomitant osteoporosis medications. Results: Greater ZOL induced effects on vertebral fracture risk with younger age (treatment-by-subgroup interaction P=0.05), normal creatinine clearance (P=0.04), and BMI >/=25 kg/m(2) (P=0.02). There were no significant treatment-factor interactions for hip or non-vertebral fracture or for change in BMD. Conclusions: ZOL appeared more effective in preventing vertebral fracture in younger women, overweight/obese women and women with normal renal function. ZOL had similar effects irrespective of fracture risk factors or femoral neck BMD.