Prospective Association of the Portfolio Diet with All-Cause and Cause-Specific Mortality Risk in the Mr. OS and Ms. OS Study.

The Portfolio Diet has demonstrated its cardiovascular benefit from interventions, but the association between Portfolio Diet adherence and the risk of all-cause and cause-specific mortality has not been examined in Chinese population. The present study has collected Portfolio Diet adherence (assessed by food frequency questionnaire), lifestyle factors and mortality status of 3991 participants in the Mr. Osteoporosis (OS) and Ms. OS Study. Cox regression models were used to examine the association between the Portfolio Diet adherence and mortality risk (all-cause, cardiovascular disease or cancer). The highest quartile of the Portfolio Diet score was associated with a 28% lower risk of all-cause (hazard ratio, HR: 0.72) and cancer (HR: 0.72) mortality, respectively. The association between Portfolio Diet adherence and cardiovascular disease mortality did not reach statistical significance (HR: 0.90, 95% CI = 0.64, 1.26). Among male participants, the highest adherence to the Portfolio Diet was also associated with a lower risk of all-cause (HR: 0.63) and cancer mortality (HR: 0.59), and there was an inverse association between food sources of plant protein and the risk of cardiovascular mortality (HR: 0.50). However, most associations between the Portfolio Diet and mortality were not significant among females. The protection for cancer mortality risk might reach the plateau at the highest adherence to the Portfolio Diet for females. To conclude, greater adherence to the Portfolio Diet was significantly associated with a lower risk of mortality in Hong Kong older adults, and the associations appeared stronger among males.

Management of bone fragility in type 2 diabetes: Perspective from an interdisciplinary expert panel.

AIM: Bone fragility is increasingly recognized as a relevant complication of type 2 diabetes (T2D) and diabetic patients with fragility fractures have higher mortality rates than non diabetic individuals or diabetic patients without fractures. However, current diagnostic approaches for fracture risk stratification, such as bone mineral density measurement or the use of risk assessment algorithms, largely underestimate fracture risk in T2D patients. A multidisciplinary expert panel was established in order to in order to formulate clinical consensus recommendations on bone health assessment and management of fracture risk in patients with T2D. DATA SYNTHESIS: The following key questions were addressed: a) which are the risk factors for bone fragility in T2D?, b) which diagnostic procedures can be currently used to stratify fracture risk in T2D patients?, c) which are the effects of antidiabetic treatments on bone?, and d) how to prevent and treat bone fragility in T2D patients? Based on the available data members of this panel suggest that the stratification of fracture risk in patients with diabetes should firstly rely on the presence of a previous fragility fracture and on the individual risk profile, with the inclusion of T2D-specific risk factors (namely T2D duration above 10 yrs, presence of chronic T2D complications, use of insulin or thiazolidinediones and persistent HbA1c levels above 8% for at least 1 year). Two independent diagnostic approaches were then suggested in the presence or the absence of a prevalent fragility fracture, respectively. CONCLUSIONS: Clinical trials in T2D patients at risk for fragility fractures are needed to determine the efficacy and safety of available antiresorptive and anabolic agents in this specific setting.

Co-morbidities and mortality associated with transfusion-dependent beta-thalassaemia in patients in England: a 10-year retrospective cohort analysis.

A retrospective cohort analysis to explore 10-year mortality and prevalence of transfusion-dependent ß-thalassaemia (TDT)-associated co-morbidities in patients with TDT was undertaken using Hospital Episode Statistics (HES) data from the National Health Service (NHS) in England. A 10-year forward-looking cohort analysis for the period 2009-2018 was completed using HES admitted patient care (APC), outpatient data, and linked HES/Office of National Statistics mortality data for patients with ß-thalassaemia (ICD-10 diagnosis code D56.1). TDT-associated co-morbidity rates were high in the 612 patients with TDT, with 76% having at least one co-morbidity, 54% suffering from two of more, and 37% three or more. The three most common TDT-associated co-morbidities, occurring in more than one third of patients were: endocrine disorders (excluding diabetes) 40%, osteoporosis 40%, and diabetes 34%. Cardiac disease was observed in 18% of patients overall, with atrial fibrillation and heart failure being the most common with a prevalence of 11% and 9%, respectively. The crude 10-year mortality rate in the TDT cohort was 6·2% (38/612), significantly greater than the 1·2% age/sex-adjusted mortality rate of the general population (P < 0·001). These data support the notion that the unmet need in TDT remains significant, with high rates of co-morbidity and mortality.

Breast cancer outcome in relation to bone mineral density and bisphosphonate use: a sub-study of the DATA trial.

PURPOSE: The phase III DATA study compared 6 and 3 years of adjuvant anastrozole following 2-3 years of tamoxifen in postmenopausal breast cancer patients. This pre-planned side-study assessed the relationship between a reduced bone mineral density (BMD) and distant recurrence-free survival (DRFS), and evaluated the effect of bisphosphonates on DRFS. METHODS: We selected all patients with a BMD measurement within 3 years after randomisation (landmark) without any DRFS events. Kaplan-Meier methods and Cox proportional hazards models were used for analyses. RESULTS: Of 1860 eligible patients, 1142 had a DEXA scan before the landmark. The BMD was normal in 436 (38.2%) and showed osteopenia in 565 (49.5%) and osteoporosis in 141 (12.3%) patients. After a median follow-up of 5.0 years from the landmark, neither osteopenia nor osteoporosis (compared with normal BMD) were associated with DRFS in both the 6-year [osteopenia HR 0.82 (95% CI 0.45-1.49), osteoporosis HR 1.10 (95% CI 0.26-4.67)] and the 3-year arm [osteopenia HR 0.75 (95% CI 0.40-1.42), osteoporosis HR 1.86 (95% CI 0.43-8.01)]. Moreover, bisphosphonate use did not impact DRFS. CONCLUSION: No association was observed between a reduced BMD and DRFS. Neither did we observe an impact of bisphosphonates on DRFS.

Adherence to anti-osteoporosis medication associated with lower mortality following hip fracture in older adults: a nationwide propensity score-matched cohort study.

BACKGROUND: We investigated the association of anti-osteoporosis medication with mortality risk in older adults with hip fractures and evaluated the influence of medication adherence on mortality. METHODS: We conducted a population-based cohort study and identified a total of 13,123 patients aged 65 years or older with hip fracture from the Taiwan National Health Insurance Database during the period 2001-2010. Individuals with (n = 2092) and without (n = 2092) receiving anti-osteoporosis medication were matched using propensity score matching (1:1 ratio). The 1-, 3- and 5-year survival rates after the index fracture were compared between patients with and without treatment. In the treated group, survival rate was compared between those with good and non-adherence. Good adherence was defined as the medication possession ratio of ≥80% and non-adherence as a ratio < 80%. RESULTS: The 1-, 3- and 5-year mortality rates were significantly lower in the treated vs. the non-treated group (all p < 0.0001). In the treated group, the estimated 1-, 3- and 5-year survival rates were higher in those with good adherence than in those with non-adherence (all p < 0.0001). Regarding all-cause mortality, the adjusted hazard ratio in the treated vs. the non-treated group was 0.63 (95% confidence interval 0.58-0.68, p < 0.0001). The good adherence subgroup showed a significantly lower mortality risk than that in the non-adherence subgroup (hazard ratio 0.41, 95% confidence interval 0.32-0.51, p < 0.0001). CONCLUSIONS: The 1-, 3- and 5-year survival rates were significantly higher in patients receiving anti-osteoporosis medication than in the untreated group. All-cause mortality rates were lower in patients with good adherence to anti-osteoporosis medication.

Reduced Bone Loss Is Associated With Reduced Mortality Risk in Subjects Exposed to Nitrogen Bisphosphonates: A Mediation Analysis.

Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates and mortality is mediated by a reduction in the rate of bone loss. Participants from the population-based Canadian Multicentre Osteoporosis Study were followed prospectively between1996 and 2011. Comorbidities and lifestyle factors were collected at baseline and bone mineral density (BMD) at baseline and at years 3 (for those aged 40 to 60 years), 5, and 10. Rate of bone loss was calculated using linear regression. Information on medication use was obtained yearly. Bisphosphonate users grouped into nitrogen bisphosphonates (nBP; alendronate or risedronate) and etidronate and non-users (NoRx) were matched by propensity score, including all baseline factors as well as time of treatment. Cox's proportional hazards models, unadjusted and adjusted for annual rate of bone loss, were used to determine the association between nBP and etidronate versus NoRx. For the treatment groups with significant mortality risk reduction, the percent of mortality reduction mediated by a reduction in the rate of bone loss was estimated using a causal mediation analysis. There were 271 pairs of nBP and matched NoRx and 327 pairs of etidronate and matched NoRx. nBP but not etidronate use was associated with significant mortality risk reduction (hazard ratios [HR] = 0.61 [95% confidence interval 0.39-0.96] and 1.35 [95% CI 0.86-2.11] for nBP and etidronate, respectively). Rapid bone loss was associated with more than 2-fold increased mortality risk compared with no loss. Mediation analysis indicated that 39% (95% CI 7%-84%) of the nBP association with mortality was related to a reduction in the rate of bone loss. This finding provides an insight into the mechanism of the relationship between nBP and survival benefit in osteoporotic patients. © 2019 American Society for Bone and Mineral Research.

The major causes and risk factors of total and cause-specific mortality during 5.4-year follow-up: the Shanghai Changfeng Study.

To investigate the major causes and predictive factors of death in a middle-aged and elderly Chinese population. A total of 6591 residents aged ≥ 45 years from Shanghai Changfeng community were followed up for an average of 5.4 years. The causes of death were coded according to the 10th Revision of International Classification of Diseases. The mortality rate was calculated by person-years of follow up and age-standardized according to the 2010 Chinese census data. Multivariable-adjusted Cox proportional hazards model was performed to investigate the predictors of all-cause and cause-specific mortality. During the total follow-up of 35,739 person-years, 370 deaths were documented (157 from malignant neoplasms, 70 from heart diseases, 68 from cerebrovascular diseases, 75 from other causes). The age-standardized all-cause mortality rate was 798.2 per 100,000 person-years (927.9 among men and 716.7 among women). Results from multivariable analyses showed that aging, diabetes, and osteoporosis at baseline were independent predictors of all-cause mortality, with hazard ratios (HR) of 1.11 (95% CI 1.10-1.13), 1.91 (1.51-2.42), and 1.71 (1.24-2.35), respectively. The population attributable risk percent of diabetes and osteoporosis was 19.7% and 11.7%, respectively. Cigarette smoking was associated with a higher risk of all-cause mortality in men (HR and 95%CI 1.44, 1.01-2.06). In women, diabetes and osteoporosis were related to a higher risk of cardiovascular mortality (3.27, 1.82-5.88 and 1.89, 1.04-3.46, respectively). While in men, osteoporosis was related to a higher risk of malignant neoplasms mortality (2.39, 1.07-5.33). Malignant neoplasms, heart diseases, and cerebrovascular diseases are the leading causes of death. Aging, smoking, underweight, diabetes, and osteoporosis are independent predictors of premature death among middle-aged and elderly Chinese community population. Moreover, there may have been some differences in the causes and predictors of premature death between men and women.

Bisphosphonates and mortality: confounding in observational studies?

Numerous observational studies suggest that bisphosphonates reduce mortality. This study showed that bisphosphonate use is associated with lower mortality within days of treatment, although the association was not significant until the second week. Such an early association is consistent with confounding, although an early treatment effect cannot be ruled out. INTRODUCTION: The purpose of this study was to examine whether confounding explains why numerous observational studies show that bisphosphonate use is associated with lower mortality. To this end, we examined how soon after treatment initiation a lower mortality rate can be observed. We hypothesized that, due to confounding, the association would be observed immediately. METHODS: This was a retrospective cohort study of hip fracture patients discharged from Swedish hospitals between 1 July 2006 and 31 December 2015. The data covered 260,574 hip fracture patients and were obtained from the Swedish Hip Fracture Register and national registers. Of the 260,574 patients, 49,765 met all eligibility criteria and 10,178 were pair matched (bisphosphonate users to controls) using time-dependent propensity scores. The matching variables were age, sex, diagnoses, prescription medications, type of hip fracture, type of surgical procedure, known or suspected dementia, and physical functioning status. RESULTS: Over a median follow-up of 2.8 years, 2922 of the 10,178 matched patients died. The mortality rate was 7.9 deaths per 100 person-years in bisphosphonate users and 9.4 deaths in controls, which corresponded to a 15% lower mortality rate in bisphosphonate users (hazard ratio 0.85, 95% confidence interval 0.79-0.91). The risk of death was lower in bisphosphonate users from day 6 of treatment, although the association was not significant until the second week. CONCLUSION: Bisphosphonate use was associated with lower mortality within days of treatment initiation. This finding is consistent with confounding, although an early treatment effect cannot be ruled out.

Osteoporosis in patients with dementia is associated with high morbidity and mortality: Findings from a single orthogeriatric unit.

BACKGROUND AND OBJECTIVES: Osteoporosis and dementia are common and associated with a high healthcare burden. The aim of this paper was to assess the impact of dementia on treatment, morbidity and mortality in osteoporosis. METHOD: Data were collected on 502 prospective orthogeriatric admissions for fracture. Fisher's exact chi-square was used to compare treatment stratified by dementia status. RESULTS: Of the 502 patients, 281 (56%) had osteoporosis, 226 (45%) had dementia,  and 156 (31%) had dementia and osteoporosis diagnosed before they sustained fractures. Patients with dementia were more likely to have osteoporosis but less likely to be receiving treatment. Although there was a significant improvement in discharge versus admission rates of osteoporosis treatment, those with dementia were less likely to be treated with antiresorptive therapy (36%, compared with 59%, P <0.001) or combined therapy (32%, compared with 56%, P <0.001) and had double the 90-day mortality (17.3%, compared with 9.6%) and six times the 30-day mortality (6.4%, compared with 1.6%). DISCUSSION: Patients with dementia and osteoporosis have a higher risk of recurrent fractures and mortality. Prevention may be the key strategy.

Association of Bone Density Monitoring in Routine Clinical Practice With Anti-Osteoporosis Medication Use and Incident Fractures: A Matched Cohort Study.

Routine bone mineral density (BMD) monitoring of individuals during the initial 5 years of anti-osteoporosis treatment is controversial. Using a registry-based cohort from the Province of Manitoba, Canada, we compared anti-osteoporosis medication use and fracture outcomes in women with versus without BMD monitoring receiving anti-osteoporosis medication. We identified 4559 women aged 40 years and older receiving anti-osteoporosis therapy with serial BMD testing (monitoring) within 5 years (mean interval 3.2 years) and 4559 propensity score-matched women without BMD monitoring. We assessed anti-osteoporosis medication use over 5 years from a population-based retail pharmacy database. Incident fractures to 10 years from health services data. During median 10 years observation, 1225 (13.4%) women developed major osteoporotic fracture, including 382 (4.2%) with hip fractures. Monitored women had significantly better fracture-free survival for major osteoporotic fracture (p = 0.040; 10-year cumulative risk 1.9% lower, 95% confidence interval [CI] 0.3-3.6%) and hip fracture ( p = 0.001; 10-year cumulative risk 1.8% lower, 95% CI 0.7-2.8%) compared with women who were not monitored. Hazard ratios (HRs) were significantly lower in monitored versus not monitored women for major osteoporotic fracture (HR = 0.89, 95% CI 0.80-0.98) and hip fracture (HR = 0.74, 95% CI 0.63-0.87). Days of medication use, medication persistence ratio, and treatment switching over 5 years were greater in monitored versus not monitored women. At the end of 5 years, more women in the monitored group persisted on treatment and more switched treatment, with switching behavior associated with an observed interval reduction in BMD. In conclusion, our findings suggest a possible role for BMD monitoring after initiating anti-osteoporosis therapy in the routine clinical practice setting. © 2019 American Society for Bone and Mineral Research.

A join point regression analysis of trends in mortality due to osteoporosis in Spain.

Osteoporosis is a major health problem in terms of fracture probability and disability. The aim of this ecological study is to identify the temporal trends in osteoporosis mortality in Spain from 1999 to 2015. Data on the Spanish population and number of deaths due to osteoporosis were obtained from the Spanish National Institute for Statistics. Age-adjusted mortality rates were estimated. Join point regression was used to identify the years when changes in mortality s and annual percentage change in mortality rates took place. Women presented a greater mortality rate decrease (p < 0.001), though this mortality difference by sex was reduced by half at the end of the period. The higher the age, the faster the mortality rate declined in women, while no clear pattern could be identified in men. In women, significant changes in trends were identified in three age groups (50-54, 60-64 and 80-84 years old). A sustained decrease in osteoporosis-associated mortality was found in women aged 75-79 and ≥85 years and men aged 60-64. In conclusion, mortality caused by osteoporosis in Spain is decreasing faster in the older age ranges especially in women.

Predictors of Nephrolithiasis, Osteoporosis, and Mortality in Primary Hyperparathyroidism.

CONTEXT: Primary hyperparathyroidism (PHPT) has a prevalence of 0.86% and is associated with increased risk of nephrolithiasis and osteoporosis. PHPT may also be associated with increased risk of cardiovascular disease and mortality. OBJECTIVE: To identify risk factors for nephrolithiasis, osteoporosis, and mortality in PHPT. DESIGN: Retrospective cohort study. SETTING: University teaching hospital. PATIENTS: Presented with PHPT between 2006 and 2014 (n = 611). MAIN OUTCOME MEASURE: Assessment of nephrolithiasis, osteoporosis, and mortality. RESULTS: Of patients with PHPT, 13.9% had nephrolithiasis. Most had previously documented stone disease, and only 4.7% of asymptomatic patients who were screened for renal stones had calculi identified, not very dissimilar to the rate in the non-PHPT population. Younger age (P < 0.001) and male sex (P = 0.003) were the only independent predictors of nephrolithiasis. Of patients with dual-energy X-ray absorptiometry data, 48.4% had osteoporosis (223/461). Older age (P < 0.001), lower body mass index (P = 0.002), and lower creatinine (P = 0.006) were independently associated with a diagnosis of osteoporosis. Higher PTH was independently associated with lower z score at the hip (P = 0.009); otherwise, calcium and PTH were not associated with lower z scores. Mortality in PHPT was associated with older age (P < 0.008), social deprivation (P = 0.028), and adjusted calcium (P = 0.009) but not independently with PTH at diagnosis. CONCLUSIONS: Screening for nephrolithiasis has a low yield, particularly in lower risk patients. Osteoporosis is only minimally associated with biochemical indices of PHPT. Mortality is associated with higher calcium (and possibly vitamin D deficiency) but not PTH.

Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study.

In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. INTRODUCTION: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. METHODS: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. RESULTS: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]. CONCLUSION: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.

Lower baseline value and greater decline in BMD as independent risk factors for mortality in community dwelling elderly.

Skeleton plays diverse roles via crosstalk between others, thus it is conceivable that lower BMD per se may reflect negative influences on health status and threats to life independent of fracture events. We investigated investigate the association between BMD and mortality, and to examine whether the rate of bone loss can predict future mortality in an elderly population. This study was conducted as a part of the Korean Longitudinal Study on Health and Aging, a community-based prospective study of Korean people aged 65 years and older that began in 2005. A total of 648 people (318 men and 330 women) were included. Dual energy X-ray absorptiometry were conducted at baseline and at 5 years. Mortality data were collected until the date of death or the last follow-up in December 2014. Osteoporosis in all skeletal sites significantly related to increased risk of mortality in men and women, but the associations were stronger for BMD in the femur neck and total hip than in the lumbar spine. A multivariable Cox proportional-hazards model showed that baseline BMD level was a significant independent predictor of increased all-cause mortality for all three skeletal sites in men, and for lumbar spine and total hip in women. Furthermore, faster bone loss of BMDs, as shown by the decline in BMD in the lumbar spine, femur neck, and total hip, was significantly related to increased risk of mortality after adjusting for all covariates in men. Faster BMD loss at femur neck was also related to the increased risks of mortality in women. Conclusively, both a lower baseline values and greater decline in BMD were associated with excess morality in community-dwelling elderly population; there associations were stronger in men than in women. This study emphasizes the importance of skeletal health for healthy aging, revealing lower bone mass and faster bone loss may be markers of poorer health that are driving excess mortality.

Cost-effectiveness of single-dose zoledronic acid for nursing home residents with osteoporosis in the USA.

OBJECTIVE: To evaluate the cost-effectiveness of routine administration of single-dose zoledronic acid for nursing home residents with osteoporosis in the USA. DESIGN: Markov cohort simulation model based on published literature from a healthcare sector perspective over a lifetime horizon. SETTING: Nursing homes. PARTICIPANTS: A hypothetical cohort of nursing home residents aged 85 years with osteoporosis. INTERVENTIONS: Two strategies were compared: (1) a single intravenous dose of zoledronic acid 5 mg and (2) usual care (supplementation of calcium and vitamin D only). PRIMARY AND SECONDARY OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER), as measured by cost per quality-adjusted life year (QALY) gained. RESULTS: Compared with usual care, zoledronic acid had an ICER of $207 400 per QALY gained and was not cost-effective at a conventional willingness-to-pay threshold of $100 000 per QALY gained. The results were robust to a reasonable range of assumptions about incidence, mortality, quality-of-life effects and the cost of hip fracture and the cost of zoledronic acid. Zoledronic acid had a potential to become cost-effective if a fracture risk reduction with zoledronic acid was higher than 23% or if 6-month mortality in nursing home residents was lower than 16%. Probabilistic sensitivity analysis showed that the zoledronic acid would be cost-effective in 14%, 27% and 44% of simulations at willingness-to-pay thresholds of $50 000, $100 000 or $200 000 per QALY gained, respectively. CONCLUSIONS: Routine administration of single-dose zoledronic acid in nursing home residents with osteoporosis is not a cost-effective use of resources in the USA but could be justifiable in those with a favourable life expectancy.

Osteoporosis and osteopenia in the distal forearm predict all-cause mortality independent of grip strength: 22-year follow-up in the population-based Tromsø Study.

Low bone mineral density (BMD) gives an increased risk of fractures, which can lead to premature death. Can BMD of the wrist predict mortality? BMD consistent with osteopenia and osteoporosis gave a significantly increased risk of death for both men and women in a general population in Tromsø, Norway. INTRODUCTION: To investigate if bone mineral density (BMD) levels of the distal forearm, consistent with osteopenia and osteoporosis, can predict mortality and if grip strength is an effect modifier. METHODS: The study population constituted 6565 participants aged 50-79 years at baseline in the Tromsø Study wave 4 conducted in 1994-1995. Forearm BMD measured by SXA was categorized as "normal," "osteopenia," or "osteoporosis" following WHO's definition. Cox regression with all-cause mortality as the outcome over 22 years of follow-up was performed for men and women separately, adjusting for health-related factors, as well as BMD by grip strength interaction. A secondary analysis with a 15-year follow-up also adjusted for hip fractures and osteoporotic fractures. RESULTS: During follow-up, 3176 of participants died (47%). Those categorized as osteoporotic had higher mortality hazard ratio (HR) compared to those with normal BMD; men HR = 1.37 (95% confidence interval (CI) 1.19, 1.58) and women HR = 1.32 (1.14, 1.53) were adjusted for age, body mass index, physical activity, smoking habits, education, health status, chronic diseases, and grip strength. Corresponding HRs for osteopenia were men HR = 1.13 (1.00, 1.27) and women HR = 1.17 (1.01, 1.35). Further adjustments for fractures did only marginally attenuate the results, and HRs were still significant. There was no grip strength by BMD interaction. CONCLUSION: Men and women with low distal forearm BMD values, consistent with osteoporosis or osteopenia, had an increased mortality compared to normal BMD participants. High grip strength did not modify this association, and the association remained after adjustment for a range of health-related factors.

Nonlinear association between bone mineral density and all-cause mortality: the Dong-gu study.

There was a U-shaped association between hip BMD and all-cause mortality, with the lowest mortality in the 90th percentile in males. However, there was an inverse linear relationship in females. In contrast, the association between lumbar spine BMD and mortality was less evident in males, with no association in females. INTRODUCTION: Bone mineral density (BMD) is reported inversely associated with mortality. Although some previous studies provided evidence for nonlinear associations, these were not adequately assessed in most previous works. METHODS: We evaluated the nonlinear relationship between BMD and mortality in Asians. Our study involved 8629 participants in the Dong-gu study from 2007 to 2010. Cox proportional hazard regression was used to calculate hazard ratios (HRs) according to BMD categories after adjusting for potential confounders. During a follow-up of 6.7 ± 1.4 years, 712 participants died. RESULTS: There was a U-shaped association between hip BMD and all-cause mortality, with the lowest mortality in the 90th percentile in males. However, there was an inverse linear relationship in females. In males, compared with the 75th to 95th percentile group, the < 2.5th percentile group had a 3.89 (95% CI 2.41-6.28)-fold higher risk and the 2.5th to 5th percentile group had a 2.51 (95% CI 1.25-5.04)-fold higher risk. The HR was 2.51 (95% CI 1.25, 5.04) in the > 97.5th percentile group. In females, compared with that in the 75th to 95th percentile group, the HR was 2.33 (95% CI 1.24, 4.39) in the < 2.5th percentile group. In contrast, the association between lumbar spine BMD and mortality was less evident in males, with no association in females. CONCLUSION: In conclusion, this study shows that the association between BMD and mortality varies by gender and that high and low BMD are predictors of all-cause mortality in males.

Volumetric bone mineral density of the spine predicts mortality in African-American men with type 2 diabetes.

The study showed that in African-American men with type 2 diabetes mellitus (T2D), vertebral volumetric bone mineral density (vBMD) predicts all-cause mortality, independent of other risk factors for death. INTRODUCTION: Compared to European Americans, African Americans have lower rates of osteoporosis and higher rates of T2D. The relationships between BMD and fractures with mortality are unknown in this population. The aim of this study was to determine relationships between vertebral fractures and vertebral vBMD and mortality in African Americans with T2D. METHODS: Associations between vertebral fractures and vBMD with all-cause mortality were examined in 675 participants with T2D (391 women and 284 men) in the African American-Diabetes Heart Study (AA-DHS). Lumbar and thoracic vBMD were measured using quantitative computed tomography (QCT). Vertebral fractures were assessed on sagittal CT images. Associations of vertebral fractures and vBMD with all-cause mortality were determined in sex-stratified analyses and in the full sample. Covariates in a minimally adjusted model included age, sex, BMI, smoking, and alcohol use; the full model was adjusted for those variables plus cardiovascular disease, hypertension, coronary artery calcified plaque, hormone replacement therapy (women), African ancestry proportion, and eGFR. RESULTS: After mean 7.6 ± 1.8-year follow-up, 59 (15.1%) of women and 58 (20.4%) of men died. In men, vBMD was inversely associated with mortality in the fully adjusted model: lumbar hazard ratio (HR) per standard deviation (SD) = 0.70 (95% CI 0.52-0.95, p = 0.02) and thoracic HR per SD = 0.71 (95% CI 0.54-0.92, p = 0.01). Only trends toward association between vBMD and mortality were observed in the combined sample of men and women, as significant associations were absent in women. Vertebral fractures were not associated with mortality in either sex. CONCLUSIONS: Lower vBMD was associated with increased all-cause mortality in African-American men with T2D, independent of other risk factors for mortality including subclinical atherosclerosis.

Surviving ectopic Cushing's syndrome: quality of life, cardiovascular and metabolic outcomes in comparison to Cushing's disease during long-term follow-up.

OBJECTIVE: Aim of our study was to analyze long-term outcome of patients with the ectopic Cushing's syndrome (ECS) compared to patients with Cushing's disease (CD) regarding cardiovascular, metabolic, musculoskeletal and psychiatric comorbidities. DESIGN: Cross-sectional study in patients with ECS and CD in two German academic tertiary care centers. METHODS: Standardized clinical follow-up examination was performed including health-related quality of life (QoL) in 21 ECS patients in long-term remission (≥18 months since successful surgery). Fifty-nine patients with CD in remission served as controls. RESULTS: Time from first symptoms to diagnosis of Cushing's syndrome (CS) was shorter in ECS than in CD (8.5 (IQR: 30.3) vs 25 (IQR: 39.0) months, P = 0.050). ECS patients had lower self-reported psychiatric morbidity compared to CD (19% vs 43%, P = 0.050) at follow-up. Moreover, female ECS patients reported favorable scores for QoL in the SF-36 questionnaire (mental health: 92 (IQR: 30) vs 64 (IQR: 32) in CD, P = 0.010) and a Cushing-specific QoL questionnaire (73 (IQR: 18) vs 59 (IQR: 36) in CD, P = 0.030). In a pooled analysis of ECS and CD patients, QoL correlated with time from first symptoms until diagnosis of CS, but not with urinary free cortisol levels or serum cortisol after dexamethasone at the time of diagnosis. Long-term outcomes regarding hypertension, metabolic parameters, bone mineral density and grip strength were comparable in ECS and CD. CONCLUSIONS: Our data support the concept that time of exposure to glucocorticoid excess appears to be a better predictor than peak serum cortisol levels at the time of diagnosis regarding long-term psychiatric morbidity and QoL.