Search

Summary: Vertebral fracture (VF) is a strong predictor of subsequent fracture. In this study of older women, VF, identified by dual-energy X-ray absorptiometry (DXA) vertebral fracture assessment (VFA), were associated with an increased risk of incident fractures and had a substantial impact on fracture probability, supporting the utility of VFA in clinical practice. Purpose: Clinical and occult VF can be identified using VFA with dual-energy X-ray absorptiometry (DXA). The aim of this study was to investigate to what extent VFA-identified VF improve fracture risk prediction, independently of bone mineral density (BMD) and clinical risk factors used in FRAX. Methods: A total of 2852 women, 75–80 years old, from the prospective population-based study SUPERB cohort, were included in this study. At baseline, BMD was measured by DXA, VF diagnosed by VFA, and questionnaires used to collect data on risk factors for fractures. Incident fractures were captured by X-ray records or by diagnosis codes. An extension of Poisson regression was used to estimate the association between VFA-identified VF and the risk of fracture and the 5- and 10-year probability of major osteoporotic fracture (MOF) was calculated from the hazard functions for fracture and death. Results: During a median follow-up of 5.15 years (IQR 4.3–5.9 years), the number of women who died or suffered a MOF, clinical VF, or hip fracture was 229, 422, 160, and 124, respectively. A VFA-identified VF was associated with an increased risk of incident MOF (hazard ratio [HR] = 1.78; 95% confidence interval [CI] 1.46–2.18), clinical VF (HR = 2.88; 95% [CI] 2.11–3.93), and hip fracture (HR = 1.67; 95% [CI] 1.15–2.42), adjusted for age, height, and weight. For women at age 75 years, a VFA-identified VF was associated with 1.2–1.4-fold greater 10-year MOF probability compared with not taking VFA into account, depending on BMD. Conclusion: Identifying an occult VF using VFA has a substantial impact on fracture probability, indicating that VFA is an efficient method to improve fracture prediction in older women. [ABSTRACT FROM AUTHOR]

Summary: We compared, for women in Pakistan, the utility of intervention thresholds either at a T-score ≤ − 2.5 or based on a FRAX probability equivalent to women of average body mass index (BMI) with a prior fragility fracture. Whereas the FRAX-based intervention threshold identified women at high fracture probability, the T-score threshold was less sensitive, and the associated fracture risk decreased markedly with age. Purpose: The fracture risk assessment algorithm FRAX® has been recently calibrated for Pakistan, but guidance is needed on how to apply fracture probabilities to clinical practice. Methods: The age-specific 10-year probabilities of a major osteoporotic fracture were calculated in women with average BMI to determine fracture probabilities at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of − 2.5. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without bone mineral density (BMD). The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing. Results: When a BMD T-score ≤ − 2.5 was used as an intervention threshold, FRAX probabilities in women aged 50 years were approximately two-fold higher than in women of the same age but with no risk factors and average BMD. The relative increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T-score of − 2.5 was actually protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture, rose with age from 2.1% at the age of 40 years to 17%, at the age of 90 years, and identified women at increased risk at all ages. Conclusion: Intervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a 'fracture threshold' target women at high fracture risk. [ABSTRACT FROM AUTHOR]

Summary: In women of ages 75–80 years, a low one leg standing time (OLST) was associated with an increased risk of incident fractures, independently of bone mineral density and clinical risk factors. OLST contributed substantially to fracture probability, indicating that the test should be considered when evaluating fracture risk in older women. Introduction: Physical function and risk of falls are important risk factors for fracture. A few previous studies have suggested that a one leg standing time (OLST) less than 10 s predicts fracture risk, but the impact of OLST, in addition to known clinical risk factors, for fracture probability is unknown. The aim of this study was to determine the independent contribution of OLST to fracture probability in older women. Methods: The Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study of 3028 women 75–80 years old, recruited from the greater Gothenburg area in Sweden. At baseline, information on risk factors was collected using questionnaires, bone mineral density was measured with dual-energy X-ray absorptiometry (DXA), and OLST was performed. Results: During a median follow-up of 3.6 years (IQR 1.5 years), X-ray-verified incident fractures were identified using health records. OLST was available in 2405 women. OLST less than 10 s was associated with an increased risk for incident hip fracture (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) [1.49–6.10]), major osteoporotic fracture (HR 95% CI 1.76 [1.34–1.46]), and nonvertebral fracture (HR 95% CI 1.61 [1.26–2.05]) in Cox regression analyses adjusted for age, height, and weight. Depending on BMD, the 4-year fracture probability increased by a factor of 1.3 to 1.5 in a 75-year-old woman with a low OLST (<10 s). Conclusion: A low OLST has a substantial impact on fracture probability and should be considered when evaluating fracture risk in older women. [ABSTRACT FROM AUTHOR]

Summary: In a simulated population of older women, we demonstrate that an upward shift in the population distribution of BMD by approximately 0.3SD may decrease the risk of incident fractures to the same extent as an intervention targeted to those with T-score less than −2.5. Introduction: To investigate the impact of population level or targeted alterations to BMD on the incidence of fractures. Methods: We used a simulated cohort of 49,242 women with age and body mass index distribution from the UK, and prevalence of other clinical risk factors based on European FRAX® cohorts. Using FRAX probabilities of major osteoporotic fracture (MOF: hip, clinical vertebral, distal forearm, proximal humerus) and hip fracture, calculated with femoral neck BMD, we determined the expected number of fractures over 10 years, stratified by 10-year age band from 50 years. We then investigated the effect of (i) uplifting all individuals with T-score below −2.5 to be exactly −2.5 (high-risk strategy) and (ii) shifting the entire BMD distribution upwards (population strategy). Results: Overall, the high-risk strategy prevented 573 MOF including 465 hip fractures. Moving the BMD T-score distribution upward by 0.27SD gave an equivalent reduction in numbers of MOF; for hip fractures prevented, this was 0.35SD. A global upward 0.25SD BMD shift prevented 524 MOF including 354 hip fractures, with corresponding figures for an increase of 0.5SD being 973 MOF prevented and 640 hip fractures prevented. The ratio of hip fracture to MOF prevented differed by the two approaches, such that for the high-risk strategy, the ratio was 0.81, and for the population strategy was 0.68 (0.25SD BMD uplift) and 0.66 (0.5SD BMD uplift). The numbers of fractures prevented by the high-risk strategy increased with age. In contrast, the age-related increase in numbers of fractures prevented with the population strategy rose with age, but peaked in the 70–79-year age band and declined thereafter. Conclusions: Both strategies reduced the numbers of expected incident fractures, with contrasting relative impacts by age and fracture site. Whilst the current analysis used UK/European anthropometric/risk factor distributions, further analyses calibrated to the distributions in other settings globally may be readily undertaken. Overall, these findings support the investigation of both population level interventions and those targeted at high fracture risk groups. [ABSTRACT FROM AUTHOR]

Summary: The National Osteoporosis Guideline Group (NOGG) has developed intervention thresholds based on FRAX® to characterise patients at high and very high risk of fracture. Introduction: Guidelines for the assessment of fracture risk have begun to categorise patients eligible for treatment into high and very high risk of fracture to inform choice of therapeutic approach. The aim of the present study was to develop intervention thresholds based on the hybrid assessment model of NOGG. Methods: We examined the impact of intervention thresholds in a simulated cross-sectional cohort of women age 50 years or more from the UK with the distribution of baseline characteristics based on that in the FRAX cohorts. The prevalence of very high risk using the hybrid model was compared with age-dependent thresholds used by the International Osteoporosis Foundation and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (IOF/ESCEO). The appropriateness of thresholds was tested based on the populations treated with anabolic agents. Results: With an upper intervention threshold using the IOF/ESCEO criteria, 56% of women age 50 years or more would be characterised at very high risk. This compares with 36% using the IOF/ESCEO criteria and an age-specific intervention threshold over all ages. With an upper intervention threshold of 1.6 times the pre-existing intervention threshold, 10% of women age 50 years or more would be characterised at very high risk. The data from phase 3 studies indicate that most trial participants exposed to romosozumab or teriparatide would fall into the very high-risk category. Conclusions: Proposals for FRAX-based criteria for very high risk for the NOGG hybrid model categorise a small proportion of women age 50 years or more (10%) in this highest risk stratum. The level of risk identified was comparable to that of women enrolled in trials of anabolic agents. [ABSTRACT FROM AUTHOR]

Summary: This study aimed to determine the interaction between baseline FRAX® fracture probability and romosozumab efficacy. Using an ITT approach, it was determined that the efficacy of romosozumab on clinical fracture, osteoporotic fracture, and major osteoporotic fracture is significantly greater in patients at high baseline fracture risk, when compared with placebo. Introduction: Post hoc analyses of placebo-controlled osteoporosis treatment studies have shown significantly greater reductions of fracture incidence for higher fracture risk patients. This study determined the interaction between baseline FRAX® fracture probability and romosozumab efficacy in the placebo-controlled first year of the phase 3 FRAME study (NCT01575834). Methods: Using an ITT approach, an extension of Poisson regression analysis studied the relationship between treatment, FRAX® 10-year probability of major osteoporotic fracture (MOF, calculated without BMD) and risk of first incident fracture (adjusting for age and follow-up time). Treatment interactions considered outcomes of all clinical fractures, osteoporotic fractures, MOF, clinical vertebral fractures, and morphometric vertebral fractures. Two-sided p value of < 0.1 for the interaction between treatment and FRAX® was considered significant. Results: Compared with placebo, romosozumab reduced the incidence of all fracture outcomes in the first year (range: 32% reduction in MOF [p = 0.07] to 80% reduction in clinical vertebral fractures [p = 0.038]). Significant interactions were observed between efficacy and baseline FRAX® probability for composite outcomes of clinical fractures, osteoporotic fractures, and MOF (p = 0.064–0.084), but not vertebral fractures (p > 0.3). For example, romosozumab decreased all clinical fractures by 22% at the 25th centile of FRAX® probability but the reduction was 41% at the 75th centile. Exclusion of vertebral fractures from each composite fracture outcome (i.e. only nonvertebral fractures included) showed even stronger interactions with baseline FRAX® probability (p = 0.036–0.046). Conclusions: Efficacy of romosozumab on clinical fracture, osteoporotic fracture, and MOF is significantly greater in patients at high baseline fracture risk compared with placebo. [ABSTRACT FROM AUTHOR]

The authors reflect on the risk factors for future fracture, particularly prior fragility fracture, and the short time horizons for fracture prediction tools. Topics include the risks of osteoporotic fractures, the heterogeneity of fracture risk between countries, the studies using machine learning methods, as well as the use of the FRAX tool to estimate the probability of a major osteoporotic fracture.

Summary: Vertebral fractures are independent risk factors for vertebral and nonvertebral fractures. Since vertebral fractures are often missed, the relatively new introduction of vertebral fracture assessment (VFA) for imaging of the lateral spine during DXA-measurement of the spine and hips may contribute to detect vertebral fractures. We advocate performing a VFA in all patients with a recent fracture visiting a fracture liaison service (FLS). Fracture liaison services (FLS) are important service models for delivering secondary fracture prevention for older adults presenting with a fragility fracture. While commonly age, clinical risk factors (including fracture site and number of prior fracture) and BMD play a crucial role in determining fracture risk and indications for treatment with antiosteoporosis medications, prevalent vertebral fractures usually remain undetected. However, vertebral fractures are important independent risk factors for future vertebral and nonvertebral fractures. A development of the DXA technology, vertebral fracture assessment (VFA), allows for assessment of the lateral spine during the regular DXA bone mineral density measurement of the lumbar spine and hips. Recent approaches to the stratification of antiosteoporosis medication type according to baseline fracture risk, and differences by age in the indication for treatment by prior fracture mean that additional information from VFA may influence initiation and type of treatment. Furthermore, knowledge of baseline vertebral fractures allows reliable definition of incident vertebral fracture events during treatment, which may modify the approach to therapy. In this manuscript, we will discuss the epidemiology and clinical significance of vertebral fractures, the different methods of detecting vertebral fractures, and the rationale for, and implications of, use of VFA routinely in FLS. Summary points: • Vertebral fracture assessment is a tool available on modern DXA instruments and has proven ability to detect vertebral fractures, the majority of which occur without a fall and without the signs and symptoms of an acute fracture. • Most osteoporosis guidelines internationally suggest that treatment with antiosteoporosis medications should be considered for older individuals (e.g., 65 years +) with a recent low trauma fracture without the need for DXA. • Younger individuals postfracture may be risk-assessed on the basis of FRAX® probability including DXA and associated treatment thresholds. • Future fracture risk is markedly influenced by both site, number, severity, and recency of prior fracture; awareness of baseline vertebral fractures facilitates definition of true incident vertebral fracture events occurring during antiosteoporosis treatment. • Detection of previously clinically silent vertebral fractures, defining site of prior fracture, might alter treatment decisions in younger or older FLS patients, consistent with recent IOF-ESCEO guidance on baseline-risk-stratified therapy, and provides a reliable baseline from which to define new, potentially therapy-altering, vertebral fracture events. [ABSTRACT FROM AUTHOR]

Summary: This paper explores use of metrics that combine fracture outcomes that add power to phase 3 studies and provide a surrogate outcome for regulatory agencies. Introduction: The aim of this study was to develop an analytic framework that would combine information from all fracture outcomes (including radiographic vertebral fractures) in phase 3 studies to provide a metric for the assessment of treatment efficacy. Methods: Data from the phase 3 study of denosumab were used as an exemplar comparing the effects of active intervention with placebo on the risk of all fractures associated with osteoporosis. Fracture outcomes were assigned utility weights drawn from the published literature and applied to age-specific health state values of the general population. For each fracture outcome in each arm of the study, cumulative disutility was computed to serve as the principal end point. The hypothesis tested was that treatment with denosumab results in a significant reduction in mean fracture-related disutility. Results: Treatment with denosumab was associated with significantly lower utility loss compared with placebo. For patients treated with denosumab, mean utility loss was 42% less than with placebo (4.5 vs. 7.5 QALYs/1000 patient years, respectively, p < 0.001). Conclusions: Denosumab significantly decreased utility loss. The use of metrics that combine fracture outcomes may provide added power to phase 3 studies and provide a surrogate outcome for regulatory agencies. [ABSTRACT FROM AUTHOR]

Summary: The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. In older women, TUG time predicts the risk of major osteoporotic fracture and hip fracture independently of clinical risk factors and bone mineral density, and has a substantial impact on fracture probabilities. Introduction: The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. A slow TUG has been associated with an increased fracture risk, but it is unclear whether the association is independent of clinical risk factors and bone mineral density (BMD). The aim of this study was to investigate if TUG time was associated with fracture risk independently of clinical risk factors and BMD and to determine its impact on fracture probabilities in older women. Methods: A standardized questionnaire was used to assess information regarding clinical risk factors in the large population-based SUPERB study of 3028 older women (75–80 years). At baseline, the TUG test was performed and BMD measured with DXA. The association between TUG time and the risk of hip fracture and major osteoporotic fracture (MOF) was examined using an extension of Poisson regression. Results: Fracture incidence increased steeply with increasing TUG time up to 12 s and subsequently started to level off. A slow TUG time was therefore defined as TUG > 12 s, a cutoff level then used in Cox models to study the association between slow TUG and fracture risk. A slow TUG time was associated with an increased risk of fracture (MOF 2.39 [1.80–3.18] and hip fracture 2.96 [1.62–5.40]). These associations were slightly attenuated but remained significant after adjustment for clinical risk factors and femoral neck BMD. Depending on BMD, the 4-year fracture probability of MOF increased by a factor of 1.5–1.9 in a 75-year-old woman with slow TUG (> 12 s). Conclusion: The TUG time predicts the risk of MOF and hip fracture independently of clinical risk factors and BMD and has a substantial impact on fracture probabilities, indicating that inclusion of the TUG test in patient evaluation should be considered in order to improve fracture prediction in older women. [ABSTRACT FROM AUTHOR]

An editorial is presented regarding FRAX and ethnicity. It mentions the key messages from the epidemiology of fracture globally, key considerations in building risk assessment tools, the specific contribution of race/ethnicity and practical considerations related to any move to alter race/ethnicity categorization or remove them entirely.

Objective Following breast cancer surgery with lymph node removal, women are at risk of developing lymphedema in the upper extremity or trunk. Currently, trunk lymphedema diagnosis relies on a clinical assessment because no quantifiable standard method exists. Tissue dielectric constant (TDC) values are quantifiable measures of localized skin tissue water and may be able to detect trunk lymphedema. The goal of this study was to (1) compare parameters derived from TDC measurements with those derived from clinically accepted criteria for trunk lymphedema in women following breast cancer surgery and (2) explore the potential utility of TDC to detect trunk lymphedema early in its progression. Methods This prospective longitudinal study, a secondary analysis from a larger study, observed women with and without clinically determined truncal lymphedema following breast cancer surgery. TDC was measured on the lateral trunk wall at post-surgery weeks 2, 4, 12, and 78 in women who had surgical breast cancer treatment with lymph node removal. Clinical assessment for trunk lymphedema was determined at 78 weeks by a lymphedema expert. Comparison of TDC measurements in women with and without clinical trunk lymphedema was analyzed. Results Clinical assessment identified trunk lymphedema in 15 out of 32 women at 78 weeks. These women had TDC ratios statistically higher than women without truncal lymphedema. Conclusion The overall findings indicate that TDC has the ability to quantify trunk lymphedema and might be valuable in early detection. Impact TDC may be a beneficial tool in the early detection of breast cancer–related trunk lymphedema, which could trigger intervention. Lay Summary A new device may help recognize trunk lymphedema in patients with breast cancer so they could receive appropriate treatment. [ABSTRACT FROM AUTHOR]

Summary: Prior high-trauma fractures identified through health services data are associated with low bone mineral density (BMD) and future fracture risk to the same extent as fractures without high-trauma. Introduction: Some have questioned the usefulness of distinguishing high-trauma fractures from low-trauma fractures. The aim of this study is to compare BMD measurements and risk of subsequent low-trauma fracture in patients with prior high- or low-trauma fractures. Methods: Using a clinical BMD registry for the province of Manitoba, Canada, we identified women and men age 40 years or older with fracture records from linked population-based healthcare data. Age- and sex-adjusted BMD Z-scores and covariate-adjusted hazard ratios (HR) with 95% confidence intervals (CI) for incident fracture were studied in relation to prior fracture status, categorized as high-trauma if associated with external injury codes and low-trauma otherwise. Results: The study population consisted of 64,428 women and men with no prior fracture (mean age 63.7 years), 858 with prior high-trauma fractures (mean age 65.1 years), and 14,758 with prior low-trauma fractures (mean age 67.2 years). Mean Z-scores for those with any prior high-trauma fracture were significantly lower than in those without prior fracture (P < 0.001) and similar to those with prior low-trauma fracture. Median observation time for incident fractures was 8.8 years (total 729,069 person-years). Any prior high-trauma fracture was significantly associated with increased risk for incident major osteoporotic fracture (MOF) (adjusted HR 1.31, 95% CI 1.08–1.59) as was prior low-trauma fracture (adjusted HR 1.55, 95% CI 1.47–1.63), and there was no significant difference between the two groups (prior trauma versus low-trauma fracture P = 0.093). A similar pattern was seen when incident MOF was studied in relation to prior hip fracture or prior MOF, or when the outcome was incident hip fracture or any incident fracture. Conclusions: High-trauma and low-trauma fractures showed similar relationships with low BMD and future fracture risk. This supports the inclusion of high-trauma fractures in clinical assessment for underlying osteoporosis and in the evaluation for intervention to reduce future fracture risk. [ABSTRACT FROM AUTHOR]

Summary: Using data from the Hertfordshire cohort study, this study examined the effect of breastfeeding and bottle feeding on adult lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD). The type of infant milk feeding was significantly associated with lumbar spine BMD in males. Introduction: Using data from the Hertfordshire cohort study (HCS), this study aims to examine the effect of infant milk feeding on bone health in later life by comparing the effect of breastfeeding and bottle feeding on lumbar spine and femoral neck BMC and BMD. Methods: Information about infant milk feeding, birth weight (kg) and weight at 1 (kg) was collected by health visitors between 1931 and 1939 in Hertfordshire. BMC and BMD measurements were taken by DXA scan between 1998 and 2004. Linear regression models adjusted for conditional weight at 1, age at DXA scan, sex, adult BMI, smoking behaviour, alcohol consumption, physical activity, dietary calcium, and prudent diet score. Results: Infant milk feeding was significantly associated with lumbar spine BMD (b = − 0.028; 95% CI, − 0.055; − 0.000; p value, 0.047) in males. On average, males who consumed breastmilk alternatives in infancy had lower lumbar spine BMD measurements than those who were fed only breastmilk. These associations remained significant in fully adjusted models. There were no significant associations between infant milk feeding and bone health for females. Conclusions: Significant associations between infant milk feeding and lumbar spine BMD in males indicate that breastmilk may be protective for the bone health of male babies. The evidence presented here underscores the potential lifelong benefits of breastfeeding and may highlight the differences between osteoporotic risk factors for males and females. [ABSTRACT FROM AUTHOR]

Summary: A reduction in hip fracture incidence following population screening might reflect the effectiveness of anti-osteoporosis therapy, behaviour change to reduce falls, or both. This post hoc analysis demonstrates that identifying high hip fracture risk by FRAX was not associated with any alteration in falls risk. Introduction: To investigate whether effectiveness of an osteoporosis screening programme to reduce hip fractures was mediated by modification of falls risk in the screening arm. Methods: The SCOOP study recruited 12,483 women aged 70–85 years, individually randomised to a control (n = 6250) or screening (n = 6233) arm; in the latter, osteoporosis treatment was recommended to women at high risk of hip fracture, while the control arm received usual care. Falls were captured by self-reported questionnaire. We determined the influence of baseline risk factors on future falls, and then examined for differences in falls risk between the randomisation groups, particularly in those at high fracture risk. Results: Women sustaining one or more falls were slightly older at baseline than those remaining falls free during follow-up (mean difference 0.70 years, 95%CI 0.55–0.85, p < 0.001). A higher FRAX 10-year probability of hip fracture was associated with increased likelihood of falling, with fall risk increasing by 1–2% for every 1% increase in hip fracture probability. However, falls risk factors were well balanced between the study arms and, importantly, there was no evidence of a difference in falls occurrence. In particular, there was no evidence of interaction (p = 0.18) between baseline FRAX hip fracture probabilities and falls risk in the two arms, consistent with no impact of screening on falls in women informed to be at high risk of hip fracture. Conclusion: Effectiveness of screening for high FRAX hip fracture probability to reduce hip fracture risk was not mediated by a reduction in falls. [ABSTRACT FROM AUTHOR]

Summary: Guidance is provided in an international setting on the assessment and specific treatment of postmenopausal women at low, high and very high risk of fragility fractures. Introduction: The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2019. This manuscript seeks to apply this in an international setting, taking additional account of further categorisation of increased risk of fracture, which may inform choice of therapeutic approach. Methods: Clinical perspective and updated literature search. Results: The following areas are reviewed: categorisation of fracture risk and general pharmacological management of osteoporosis. Conclusions: A platform is provided on which specific guidelines can be developed for national use to characterise fracture risk and direct interventions. [ABSTRACT FROM AUTHOR]

Summary: The present study, drawn from a sample of the Icelandic population, quantified high immediate risk and utility loss of subsequent fracture after a sentinel fracture (at the hip, spine, distal forearm and humerus) that attenuated with time.Introduction: The risk of a subsequent osteoporotic fracture is particularly acute immediately after an index fracture and wanes progressively with time. The aim of this study was to quantify the risk and utility consequences of subsequent fracture after a sentinel fracture (at the hip, spine, distal forearm and humerus) with an emphasis on the time course of recurrent fracture.Methods: The Reykjavik Study fracture registration, drawn from a sample of the Icelandic population (n = 18,872), recorded all fractures of the participants from their entry into the study until December 31, 2012. Medical records for the participants were manually examined and verified. First sentinel fractures were identified. Subsequent fractures, deaths, 10-year probability of fracture and cumulative disutility using multipliers derived from the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) were examined as a function of time after fracture, age and sex.Results: Over 10 years, subsequent fractures were sustained in 28% of 1498 individuals with a sentinel hip fracture. For other sentinel fractures, the proportion ranged from 35 to 38%. After each sentinel fracture, the risk of subsequent fracture was highest in the immediate post fracture interval and decreased markedly with time. Thus, amongst individuals who sustained a recurrent fracture, 31-45% did so within 1 year of the sentinel fracture. Hazard ratios for fracture recurrence (population relative risks) were accordingly highest immediately after the sentinel fracture (2.6-5.3, depending on the site of fracture) and fell progressively over 10 years (1.5-2.2). Population relative risks also decreased progressively with age. The utility loss during the first 10 years after a sentinel fracture varied by age (less with age) and sex (greater in women). In women at the age of 70 years, the mean utility loss due to fractures in the whole cohort was 0.081 whereas this was 12-fold greater in women with a sentinel hip fracture, and was increased 15-fold for spine fracture, 4-fold for forearm fracture and 8-fold for humeral fracture.Conclusion: High fracture risks and utility loss immediately after fracture suggest that treatment given as soon as possible after fracture would avoid a higher number of new fractures compared with treatment given later. This provides the rationale for very early intervention immediately after a sentinel fracture. [ABSTRACT FROM AUTHOR]

Summary: We aimed to study the risk of hip fracture and risk of hip arthroplasty among farmers in Sweden. Our results indicate that farming, representing an occupation with high physical activity, in men is associated with a lower risk of hip fracture but an increased risk of hip arthroplasty.Introduction: The risks of hip fracture and hip arthroplasty are influenced by factors including socioeconomic status, education, urbanization, latitude of residence, and physical activity. Farming is an occupation encompassing rural living and high level of physical activity. Therefore, we aimed to study the risk of hip fracture and risk of hip arthroplasty among farmers in Sweden.Methods: We studied the risk of hip fracture, and hip arthroplasty due to primary osteoarthritis, in all men and women aged 35 years or more in Sweden between 1987 and 2002. Documented occupations were available in 3.5 million individuals, of whom 97,136 were farmers. The effects of age, sex, income, education, location of residence, and occupation on risk of hip fracture or hip arthroplasty were examined using a modification of Poisson regression.Results: A total of 4027 farmers and 93,109 individuals with other occupations sustained a hip fracture, while 5349 farmers and 63,473 others underwent a hip arthroplasty. Risk of hip fracture was higher with greater age, lower income, lower education, higher latitude, and urban area for all men and women. Compared to all other occupations, male farmers had a 20% lower age-adjusted risk of hip fracture (hazard ratio (HR) 0.80, 95%CI 0.77-0.84), an effect that was not seen in female farmers (HR 0.96, 95% CI 0.91-1.01). Both male and female farmers had a higher age-adjusted risk for hip arthroplasty.Conclusions: Our results indicate that farming, representing an occupation with high physical activity, in men is associated with a lower risk of hip fracture but an increased risk of hip arthroplasty. [ABSTRACT FROM AUTHOR]

Summary: Lumbar spine trabecular bone score (TBS) can be used to modify the output from the fracture risk assessment tool, FRAX, to enhance fracture prediction. An alternative approach for using TBS in clinical practice, based upon an adjustment to the bone mineral density (BMD) T-score, may be helpful in regions where intervention guidelines and/or reimbursement are primarily based on BMD T-score.Introduction: The aim of this study is to develop an approach for using TBS in clinical practice based upon a “risk-equivalent” adjustment to the BMD T-score.Methods: We identified 45,185 women age 40 years and older with baseline spine and hip DXA, TBS, and FRAX probabilities including femoral neck BMD. Incident major osteoporotic fractures (MOF, n = 3925) were identified from population-based health services data (mean follow-up 7.4 years comprising 335,910 person-years). Cox proportional hazards models adjusted for age and BMI were first used to estimate the risk for MOF from BMD T-score alone, then after including TBS and a multiplicative age interaction term. From the parameter estimates, we developed a TBS offset to the BMD T-score based upon change in TBS that would give the same risk as a unit change in BMD T-score for the femoral neck, total hip, and lumbar spine.Results: All BMD measurements, TBS, and the age interaction term independently predicted MOF (p < 0.001). Measures of risk stratification and model fit were improved for the TBS-adjusted BMD T-score versus the unadjusted BMD T-score (p < 0.001). There was a high level of agreement between MOF probability estimated from TBS-adjusted MOF FRAX probability and FRAX probability using the “risk-equivalent” femoral BMD T-score: MOF probability r2 = 0.98, slope = 1.02, intercept = − 0.3; hip probability r2 = 0.95, slope = 1.07, intercept = 0.0.Conclusions: The BMD-independent effect of lumbar spine TBS on fracture risk can be estimated as a simple offset to the BMD T-score. [ABSTRACT FROM AUTHOR]

Summary: Many current guidelines for the assessment of osteoporosis, including those in Kuwait, initiate fracture risk assessment in men and women using BMD T-score thresholds. We compared the Kuwaiti guidelines with FRAX-based age-dependent intervention thresholds equivalent to that in women with a prior fragility fracture. FRAX-based intervention thresholds identified women at higher fracture probability than fixed T-score thresholds, particularly in the elderly. Purpose: A FRAX® model been recently calibrated for Kuwait, but guidance is needed on how to utilise fracture probabilities in the assessment and treatment of patients. Methods: We compared age-specific fracture probabilities, equivalent to women with no clinical risk factors and a prior fragility fracture (without BMD), with the age-specific fracture probabilities associated with femoral neck T-scores of −2.5 and −1.5 SD, in line with current guidelines in Kuwait. Upper and lower assessment thresholds for BMD testing were additionally explored using FRAX. Results: When a BMD T-score of −2.5 SD was used as an intervention threshold, FRAX probabilities of a major osteoporotic fracture in women aged 50 years were approximately twofold higher than those in women of the same age but with an average BMD. The increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 83 years or more, a T-score of −2.5 SD was associated with a lower probability of fracture than that of the age-matched general population with no clinical risk factors. The same phenomenon was observed from the age of 66 years at a T-score of −1.5 SD. A FRAX-based intervention threshold, defined as the 10-year probability of a major osteoporotic fracture in a woman of average BMI with a previous fracture, rose with age from 4.3% at the age of 50 years to 23%, at the age of 90 years, and identified women at increased risk at all ages. Qualitatively comparable findings were observed in the case of hip fracture probability and in men. Conclusion: Intervention thresholds based on BMD alone do not optimally target women at higher fracture risk than those on age-matched individuals without clinical risk factors, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a 'fracture threshold' consistently target women at higher fracture risk, irrespective of age. [ABSTRACT FROM AUTHOR]

Background Evidence that atopic eczema partly originates in utero is increasing, with some studies linking the risk of developing the condition with aspects of maternal diet during pregnancy. Nicotinamide, a naturally occurring nutrient that is maintained through the dietary intakes of vitamin B3 and tryptophan, has been used in the treatment of some skin conditions including atopic eczema. Objective To examine the relation of maternal serum concentrations of nicotinamide and related tryptophan metabolites to the risk of atopic eczema in the offspring. Methods Within the UK Southampton Women Survey, infantile atopic eczema at ages 6 and 12 months was ascertained (modified UK Working Party Criteria for the Definition of Atopic Dermatitis). Maternal serum levels of kynurenine, kynurenic acid, anthranilic acid, tryptophan, nicotinamide and N1-methylnicotinamide were measured in late pregnancy by mass spectrometry ( n = 497) and related to the odds ratio of infantile atopic eczema. Results Maternal nicotinamide and related metabolite concentrations were not associated with offspring atopic eczema at age 6 months. Higher concentrations of nicotinamide and anthranilic acid were, however, associated with a lower risk of eczema at age 12 months (odds ratios 0.69, 95% CI 0.53-0.91/ SD change, P = 0.007 and 0.63, 0.48-0.83, P = 0.001, respectively). The associations were robust to adjustment for potentially confounding variables. Conclusion and clinical relevance This is the first study linking maternal serum concentrations of nicotinamide and related metabolites to the risk of atopic eczema in the offspring. The findings point to potentially modifiable maternal influences on this complex and highly prevalent condition. [ABSTRACT FROM AUTHOR]

Summary: In this retrospective cohort study using the Clinical Practice Research Datalink (CPRD), patients with sarcoidosis have an increased risk of clinical vertebral fractures and when on recent treatment with oral glucocorticoids, also an increased risk of any fractures and osteoporotic fractures. Introduction: Sarcoidosis is a chronic inflammatory disease, in which fragility fractures have been reported despite normal BMD. The aim of this study was to assess whether patients with sarcoidosis have an increased risk of clinical fractures compared to the general population. Methods: A retrospective cohort study was conducted using the CPRD. All patients with a CPRD code for sarcoidosis between January 1987 and September 2012 were included. Cox proportional hazards models were used to derive adjusted relative risks (RRs) of fractures in all sarcoidosis patients compared to matched controls, and within the sarcoidosis group according to use and dose of systemic glucocorticoids. Results: Five thousand seven hundred twenty-two sarcoidosis patients (mean age 48.0 years, 51 % females, mean follow-up 6.7 years) were identified. Compared to 28,704 matched controls, the risk of any fracture was not different in patients with sarcoidosis. However, the risk of clinical vertebral fractures was significantly increased (adj RR 1.77; 95 % CI 1.06-2.96) and the risk of non-vertebral fractures was decreased although marginally significant (adj RR 0.87; 95 % CI 0.77-0.99). Compared to sarcoidosis patients not taking glucocorticoids, recent use of systemic glucocorticoids was associated with an increased risk of any fracture (adj RR 1.50; 95 % CI 1.20-1.89) and of an osteoporotic fracture (adj RR 1.47; 95 % CI 1.07-2.02). Conclusions: Patients with sarcoidosis have an increased risk of clinical vertebral fractures, and when using glucocorticoid therapy, an increased risk of any fractures and osteoporotic fractures. In contrast, the risk of non-vertebral fractures maybe decreased. Further investigation is needed to understand the underlying mechanisms of these contrasting effects on fracture risk. [ABSTRACT FROM AUTHOR]