The epidemiology of incident fracture from cradle to senescence

To reduce the burden of fracture, not only does bone fragility need to be addressed, but also injury prevention. Thus, fracture epidemiology irrespective of degree of trauma is informative. We aimed to determine age-and-sex-specific fracture incidence rates for the Barwon Statistical Division, Australia, 2006-2007. Using radiology reports, incident fractures were identified for 5342 males and 4512 females, with incidence of 210.4 (95 % CI 204.8, 216.2) and 160.0 (155.3, 164.7)/10,000/year, respectively. In females, spine (clinical vertebral), hip (proximal femoral) and distal forearm fractures demonstrated a pattern of stable incidence through early adult life, with an exponential increase beginning in postmenopausal years for fractures of the forearm followed by spine and hip. A similar pattern was observed for the pelvis, humerus, femur and patella. Distal forearm, humerus, other forearm and ankle fractures showed incidence peaks during childhood and adolescence. For males, age-related changes mimicked the female pattern for fractures of the spine, hip, ribs, pelvis and humerus. Incidence at these sites was generally lower for males, particularly among the elderly. A similar childhood-adolescent peak was seen for the distal forearm and humerus. For ankle fractures, there was an increase during childhood and adolescence but this extended into early adult life; in contrast to females, there were no further age-related increases. An adolescent-young adult peak incidence was observed for fractures of the face, clavicle, carpal bones, hand, fingers, foot and toe, without further age-related increases. Examining patterns of fracture provides the evidence base for monitoring temporal changes in fracture burden, and for identifying high-incidence groups to which fracture prevention strategies could be directed.

Changes in gait performance over several years are associated with recurrent falls status in community-dwelling older women at high risk of fracture

Background: gait analysis is a recommended geriatric assessment for falls risk and sarcopenia; however, previous research utilises measurements at a single time point only. It is presently unclear how changes in gait over several years influence risk of recurrent falls in older adults.Methods: we investigated 135 female volunteers (mean age ± SD: 76.7 ± 5.0 years; range: 70-92 years) at high risk of fracture. Gait parameters (speed, cadence, step length, step width, swing time and double support phase) were assessed using the GAITRite Electronic Walkway System at four annual clinics over ?3.7 ± 0.5 years. Participants reported incident falls monthly for 3.7 ± 1.2 years.Results: increasing gait speed (odds ratio: 0.96; 95% confidence interval 0.93, 0.99) and step length (0.87; 0.77, 0.98) from baseline to final follow-up was associated with reduced likelihood of being a recurrent faller over the study period. No significant associations were observed for baseline gait parameters (all P ≥ 0.05). At the second follow-up (2.8 ± 0.6 years), an increase in swing time (0.65; 0.43, 0.98) was associated with reduced likelihood, while an increase in double support phase (1.31; 1.04, 1.66) was associated with increased likelihood, for being a recurrent faller in the subsequent 1.3 years following this time point.Conclusion: changes in gait parameters over several years are significantly associated with the likelihood of being a recurrent faller among community-dwelling older women at high risk of fracture. Further research is required to develop gait monitoring guidelines and gait parameter decline cut points that may be utilised by clinicians to identify older adults at risk of incident falls and sarcopenia.

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.

Reliability, validity, and responsiveness of the Western Ontario and McMaster Universities osteoarthritis index for elderly patients with a femoral neck fracture

Background: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) has been extensively evaluated in groups of patients with osteoarthritis, yet not in patients with a femoral neck fracture. This study aimed to determine the reliability, construct validity, and responsiveness of the WOMAC compared with the Short Form-12 (SF-12) and the EuroQol 5D (EQ-5D) questionnaires for the assessment of elderly patients with a femoral neck fracture.

Methods: Reliability was tested by assessing the Cronbach alpha. Construct validity was determined with the Pearson correlation coefficient. Change scores were calculated from ten weeks to twelve months of follow-up. Standardized response means and floor and ceiling effects were determined. Analyses were performed to compare the results for patients less than eighty years old with those for patients eighty years of age or older.

Results: The mean WOMAC total score was 89 points before the fracture in the younger patients and increased from 70 points at ten weeks to 81 points at two years postoperatively. In the older age group, these scores were 86, 75, and 78 points. The mean WOMAC pain scores before the fracture and at ten weeks and two years postoperatively were 92, 76, and 87 points, respectively, in the younger age group and 92, 84, and 93 points in the older age group. Function scores were 89, 68, and 79 points for the younger age group and 84, 71, and 73 points for the older age group. The Cronbach alpha for pain, stiffness, function, and the total scale ranged from 0.83 to 0.98 for the younger age group and from 0.79 to 0.97 for the older age group. Construct validity was good, with 82% and 79% of predefined hypotheses confirmed in the younger and older age groups, respectively. Responsiveness was moderate. No floor effects were found. Moderate to large ceiling effects were found for pain and stiffness scales at ten weeks and twelve months in younger patients (18% to 36%) and in the older age group (38% to 53%).

Conclusions: The WOMAC showed good reliability, construct validity, and responsiveness in both age groups of elderly patients with a femoral neck fracture who had been physically and mentally fit before the fracture. The instrument is suitable for use in future clinical studies in these populations.

DNA methylation and the social gradient of osteoporotic fracture: a conceptual model

INTRODUCTION: Although there is a documented social gradient for osteoporosis, the underlying mechanism(s) for that gradient remain unknown. We propose a conceptual model based upon the allostatic load theory, to suggest how DNA methylation (DNAm) might underpin the social gradient in osteoporosis and fracture. We hypothesise that social disadvantage is associated with priming of inflammatory pathways mediated by epigenetic modification that leads to an enhanced state of inflammatory reactivity and oxidative stress, and thus places socially disadvantaged individuals at greater risk of osteoporotic fracture. METHODS/RESULTS: Based on a review of the literature, we present a conceptual model in which social disadvantage increases stress throughout the lifespan, and engenders a proinflammatory epigenetic signature, leading to a heightened inflammatory state that increases risk for osteoporotic fracture in disadvantaged groups that are chronically stressed. CONCLUSIONS: Our model proposes that, in addition to the direct biological effects exerted on bone by factors such as physical activity and nutrition, the recognised socially patterned risk factors for osteoporosis also act via epigenetic-mediated dysregulation of inflammation. DNAm is a dynamic modulator of gene expression with considerable relevance to the field of osteoporosis. Elucidating the extent to which this epigenetic mechanism transduces the psycho-social environment to increase the risk of osteoporotic fracture may yield novel entry points for intervention that can be used to reduce individual and population-wide risks for osteoporotic fracture. Specifically, an epigenetic evidence-base may strengthen the importance of lifestyle modification and stress reduction programs, and help to reduce health inequities across social groups. MINI ABSTRACT: Our conceptual model proposes how DNA methylation might underpin the social gradient in osteoporotic fracture. We suggest that social disadvantage is associated with priming of inflammatory signalling pathways, which is mediated by epigenetic modifications, leading to a chronically heightened inflammatory state that places disadvantaged individuals at greater risk of osteoporosis.

Rapidly cured out-of-autoclave laminates: understanding and controlling the effect of voids on laminate fracture toughness

Voids are one of the most significant defects found within composites and have been demonstrated to reduce the performance of composite structures. The understanding of the impact of the size and distribution of voids on laminate properties is still limited because voids have proven difficult to deliberately control. This study aims to understand the mechanisms by which voids are generated within out-of-autoclave cured laminates. In this study, a process of prepreg conditioning was developed to control the level of voids within test laminates. Non-conditioned laminates highlighted signs of void growth (1.5%), while conditioned laminates showed consistently low levels of voids (<0.3%). Mass spectrometry indicated higher levels of aqueous and solvent volatiles within the non-conditioned prepreg. Finally, Mode II fracture testing revealed a 21% improvement in toughness for the non-voided laminates. A model on the effect of voids within the Mode II stress state has also been proposed.

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.