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Summary: We analyzed the association of proton pump inhibitors (PPIs) with mortality after osteoporosis-related hip fracture in Austria. PPIs were associated with reduced 90-day mortality but elevated mortality after half a year when initiated pre-fracture. Inpatients and discharged patients on PPIs showed lowered in-hospital and 90-day mortality, respectively. Introduction: We herein investigated use of proton pump inhibitors (PPIs) and mortality among hip fracture patients in a nationwide study in Austria. Methods: In this retrospective cohort study, data on use of PPIs were obtained from 31,668 Austrian patients ≥50 years with a hip fracture between July 2008 and December 2010. All-cause mortality in patients without anti-osteoporotic drug treatment who had received their first recorded PPI prescription in the study period either before or after fracture was compared with hip fracture patients on neither PPIs nor anti-osteoporotic medication using logistic and Cox regression analysis. Results: With PPI use, 90-day mortality was significantly reduced, both at initiation before (OR 0.66; p < 0.0001) and after hip fracture (OR 0.23; p < 0.0001). 90-day mortality was also reduced when PPIs were prescribed not until after discharge from the last recorded hip fracture-related hospital stay (OR 0.49; p < 0.0001) except for patients aged <70 years. In a sub-cohort of patients beginning PPIs during hospital stay, in-hospital mortality (0.2%) was substantially reduced relative to matched control patients (3.5%) ( p < 0.0001). Longer-term mortality significantly increased after half a year post-fracture only among those who started PPI prescription before fracture. Conclusions: PPI use during and after hospital stay due to hip fracture is associated with a considerable decrease in mortality. These findings could have implications for hip fracture treatment. [ABSTRACT FROM AUTHOR]

Summary: We analyzed the association of bisphosphonate therapy with mortality and hip refracture incidence among osteoporosis-related hip fracture patients in Austria. Mortality was lower in primarily female bisphosphonate users, while hip refracture incidence was generally elevated relative to controls, indicating beneficial effects of bisphosphonates other than on bone. Introduction: The purpose of this study was to analyze mortality and hip refracture risk in osteoporotic hip fracture patients with and without antiosteoporotic medication. Methods: We retrospectively analyzed data on 31,668 Austrian patients ≥50 years with a hip fracture between July 2008 and December 2010 for antiosteoporotic drug treatment with respect to outcome parameters all-cause mortality, hip refracture incidence, and hip refracture-free days. Outcomes when bisphosphonate (BP) treatment was begun before or after fracture were compared with an age- and sex-matched hip fracture control without antiosteoporotic medication. Results: 27.69 % of patients (33.01 % of women, 13.13 % of men) were prescribed antiosteoporotic medication, primarily BPs. Females having initiated BP treatment before first fracture had lower odds for mortality 1 and 3 year(s) post-fracture, whereas hip refracture incidence under pre-fracture BP initiation was generally higher. Treatment that was started after fracture, however, entailed significantly lower mortality hazards for both genders (HR 0.43, 95 %CI 0.36-0.52, p < 0.0001 after 1 year) but significantly higher hip refracture incidence except for patients aged 50-69 years and more hip refracture free days for females. Hip refractures overall amounted to 29.22/1000 patient years differing significantly between women and men (31.03 vs. 23.89, respectively, p < 0.0001), and longer hip refracture free survival was observed for women than for men (499 vs. 466 median days, respectively, p < 0.0001). Conclusions: Although BP use is associated with reduced mortality after hip fracture, notably among women, hip refracture incidences are likewise elevated, which is most likely accounted for by a high probability of BP prescription to more comorbid patients suffering from more severe osteoporosis. Concomitantly, through possible effects other than on bone, BPs might be able to curtail mortality. Male hip fracture patients' low treatment frequency in particular reflects underdiagnosis and undertreatment of osteoporosis in Austria. [ABSTRACT FROM AUTHOR]

Summary: Raman microspectroscopic analysis of iliac crest from patients that were treated with alendronate (ALN) for 10 years revealed minimal, transient alterations in bone material properties confined to actively forming bone surfaces compared to patients that were on ALN for 5 years. These changes were not encountered in the bulk tissue. Introduction: Alendronate (ALN) and other bisphosphonates (BPs) are the most widely prescribed therapy for postmenopausal osteoporosis. Despite their overall excellent safety record and efficacy in reducing fractures, questions have been raised regarding potential detrimental effects that may be related to prolonged bone turnover reduction, although no definite cause-effect relationship has been established to date. The purpose of the present study was to evaluate bone material properties in patients that were receiving ALN for 5 or 10 years. Methods: Raman microspectroscopic analysis was used to analyze iliac crest biopsies from postmenopausal women with osteoporosis who had been treated with ALN for 5 years and were then re-randomized to placebo (PBO, N = 14), 5 mg/day ALN ( N = 10), or 10 mg/day ALN ( N = 6) for another 5 years. The parameters monitored and expressed as a function of tissue age were (i) the mineral/matrix ratio (MM), (ii) the relative proteoglycan content (PG), (iii) the relative lipid content (LPD), (iv) the mineral maturity/crystallinity (MMC), and (v) the relative pyridinoline content (PYD). Results: The obtained data indicate that 10-year ALN use results in minimal, transient bone tissue composition changes compared to use for 5 years, confined to actively forming trabecular surfaces, implying potential differences in bone matrix maturation that nevertheless did not result in differences of these values in bulk tissue. Conclusions: The data suggest that prolonged reduction in bone turnover during 10 years of therapy with ALN by itself is unlikely to be associated with adverse effects on bone material properties. [ABSTRACT FROM AUTHOR]

Summary: The results of the present study, involving analysis of biopsies from patients who received teriparatide for 2 years and were previously either treatment-naïve or on long-term alendronate therapy, suggest that prior alendronate use does not blunt the favorable effects of teriparatide on bone quality. Introduction: Examine the effect of 2 years of teriparatide (TPTD) treatment on mineral and organic matrix properties of the newest formed bone in patients who were previously treatment-naïve (TN) or on long-term alendronate (ALN) therapy. Methods: Raman and Fourier transform infrared microspectroscopic analyses were used to determine the mineral/matrix (M/M) ratio, the relative proteoglycan (PG) content, and the mineral maturity/crystallinity (MMC; determined by three methods: carbonate content, full width at half height of the vPO band [FWHH], and wavelength at maxima of the vPO band), as well as collagen maturity (ratio of pyridinoline/divalent cross-links), in paired iliac crest biopsies at trabecular, endosteal, and osteonal surfaces of newly formed bone in postmenopausal osteoporotic women who were previously either TN ( n = 16) or receiving long-term ALN treatment ( n = 24). Results: Trabecular M/M ratio increased and matrix content decreased significantly in the ALN pretreated group. Collagen maturity decreased in both patient groups. Endosteal M/M ratio increased significantly in the TN group. Trabecular M/M ratio was higher at endpoint in the ALN pretreated group than in the TN group. Overall, no changes from baseline were observed in PG content, except that PG content was higher in the ALN pretreated group than in the TN group at endosteal surfaces at endpoint. The ability of TPTD treatment to reduce MMC in both patient groups and at the different bone surfaces depended on the measurement tool (relative carbonate content or wavelength at maxima of the vPO band). None of the changes in MMC were different between the two patient groups. Conclusions: The results suggest some favorable impact of TPTD on bone mineral and organic matrix properties of in situ forming bone in terms of increased initial mineralization and decreased MMC and collagen maturity. Moreover, prior long-term ALN administration may have only limited influence on these properties in bone newly formed after 2 years of TPTD treatment. [ABSTRACT FROM AUTHOR]

Summary: Once-yearly administration of intravenous zoledronic acid for 3 years in humans affects the kinetics of matrix filling in by mineral, independent of bone turnover. Introduction: Yearly 5-mg infusions of zoledronic acid (ZOL) for 3 years have shown pronounced antifracture efficacy. The purpose of the present study was to test whether ZOL affects the kinetics of forming bone material properties maturation. Methods: Iliac crest biopsies from the HORIZON-PFT clinical trial were analyzed by Raman microspectroscopy in actively bone-forming surfaces as a function of tissue age in trabecular and osteonal bone, to determine ZOL's effect on bone material quality indices maturation kinetics. Results: Mineral/matrix ratio increased in both groups as a function of tissue age, at both osteonal- and trabecular-forming surfaces; ZOL exhibiting the greatest increase in the trabecular surfaces only. The proteoglycan content showed a dependency on tissue age in both trabecular and osteonal surfaces, with ZOL exhibiting lower values in the tissue age 8-22 days in the trabecular surfaces. Mineral crystallinity (crystallite length and thickness) showed a dependence on tissue age, with ZOL exhibiting lower crystallite length compared with placebo only in the 8- to 22-day-old tissue at trabecular surfaces, while crystal thickness was lower in the 1- to 5-day-old tissue at both osteonal and trabecular surfaces. Conclusions: The results of the present study suggest that once-yearly administration of intravenous ZOL for 3 years in humans does not exert any adverse effects on the evolution of bone material properties at actively forming osteonal and trabecular surfaces, while it may have a beneficial effect on the progression of the mineral-to-matrix ratio and mineral maturity bone quality indices. [ABSTRACT FROM AUTHOR]

Abstract Background Because there is reason to assume that also in Austria calcium and vitamin D malnutrition is wide-spread, we initiated a comprehensive study on calcium and vitamin D status in relation to bone health in a large group of the normal adult population. Subjects and methods We assessed dietary calcium and vitamin D intake, serum concentrations of Ca2+ , phosphate, alkaline phosphatase, 25(OH)D, 1,25(OH) 2 D, parathyroid hormone (PTH), follicle-stimulating hormone (FSH), sex hormones and bone mineral density (BMD) by double-energy X-ray absorptiometry at five different skeletal sites in 648 females and 400 males (age 21–76 years). Results Mean daily intake of vitamin D (101 IU, range 0·2–320) and calcium (569 mg, range 40–2170) was significantly less than the respective recommended dietary allowances. Two hundred and seventy-one (26%) individuals had hypovitaminosis D with serum 25(OH)D < 12 ng mL-1 , while serum Ca 2+ was less than normal in 82 (7·8%) subjects. Multiple regression analysis revealed significant correlations between mean calcium intake and BMD in the femoral region in the men ( r = 0·13, P < 0·05) though not in the women. No consistent data could be obtained for associations between BMD and vitamin D status, except for 25(OH)D and BMD at the spine in the men ( r = 0·10, P < 0·05). 25(OH)D correlated negatively ( P < 0·05) with age in the women ( r = -0·11) and with PTH in the women ( r = -0·11) and men ( r = -0·16). Inversely, a significant ( P < 0·001) age-related increase in PTH was observed in both sexes (men, r = 0·19; women, r = 0·14). Conclusions Prevalence of hypovitaminosis D in adult Austrians is an imminent risk for development of secondary hyperparathyroidism with advancing age, and requires timely correction of nutritional deficits. [ABSTRACT FROM AUTHOR]

Objective: Patients with diabetes have an increased risk of osteoporosis and shorter life expectancy. Hip fracture (HF) is the most serious consequence of osteoporosis and is associated with increased mortality risk. We aimed to assess the association of antidiabetic medications with HF and the post-hip fracture mortality risk among diabetic patients ≥50 years., Design: In this nationwide case-control study 53 992 HF cases and 112 144 age-, sex- and region-matched non-hip fracture controls were analyzed. A cohort of hip-fractured diabetic patients were followed-up for an all-cause mortality., Methods: We defined three groups of diabetic patients based on a prescription of antidiabetic medications: group 1 treated with insulin monotherapy (G1DM), group 2 (G2DM) treated with blood glucose-lowering drugs (BGLD) only, group 3 on a combined BGLD and insulin therapy (G3DM). We applied logistic regression and Cox regression., Results: We identified 2757 G1DM patients, 15 310 G2DM patients, 3775 G3DM patients and 144 294 patients without any antidiabetic treatment. All three groups of diabetic patients had increased odds of HF compared to controls. G1DM patients aged 50-64 years (aOR: 4.80, 95% CI: 3.22-7.17) and G3DM patients (aOR: 1.39, 95% CI: 1.02-1.88) showed the highest HF odds, whereas G2DM patients had 18% decrease in HF odds than their non-diabetic controls (aOR: 0.82, 95% CI: 0.69-0.99). All diabetic patients had increased post-hip fracture mortality risk compared to non-diabetic controls. The highest mortality hazard was observed in G1DM patients, being greater for women than men (HR: 1.71, 95% CI: 1.55-1.89 and HR: 1.44, 95% CI: 1.27-1.64, respectively)., Conclusions: Antidiabetic medications increase the probability of HF. Diabetic patients, who sustained HF have a higher mortality risk than non-diabetic patients.

Background and Aims: With rising rates of inflammatory bowel diseases [IBD] in older adults, management of comorbidities such as osteoporosis is becoming increasingly important. Hip fracture [HF] is the most serious consequence of low bone mineral quality and is associated with excess risk of mortality. For older IBD patients, there are only limited data available. Therefore, we aimed to assess the association of IBD with HF, and all-cause mortality risk after HF, among IBD patients older than 50 years., Methods: In a national database-registered case-control study, 56 821 HF cases aged ≥50 years, and 113 718 age-, sex- and region-matched non-hip-fracture controls, were analysed between 2012 and 2016. A history of IBD was assessed from data from Austrian social health insurance funds. Logistic regression and Cox proportional multivariate models were used to test the association of IBD with HF and post-hip fracture mortality risk., Results: A total of 531 patients were identified with IBD (25.0% men, mean age 81.2 years, standard deviation [SD] 9.7). Analysis, adjusted for anti-osteoporotic treatment, use of glucocorticoids, and selected medications, showed that IBD patients had an increased odds of HF (odds ratio [[OR] 2.22, 95% confidence interval [CI] 1.86-2.64). Patients with Crohn's disease [CD] revealed a higher HF odds in contrast to patients with ulcerative colitis [OR 2.91, 95% CI 2.17-3.89 and OR 1.89, 95% CI 1.52-2.35, respectively]. Overall mortality risk after HF was higher among female CD patients [HR 1.75, 95% CI 1.28-2.41] than in the general population., Conclusions: IBD was strongly associated with HF in older patients. Post-hip fracture mortality risk was elevated particularly in women with CD., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Osteoporosis-related hip fractures represent a substantial cause of mortality and morbidity in industrialized countries like Austria. Identification of groups at high risk for mortality after hip fracture is crucial for health policy decisions. To determine in-hospital, long-term, and excess mortality after osteoporosis-related hip fracture in Austrian patients, we conducted a retrospective cohort analysis of pseudonymized invoice data from Austrian social insurance authorities covering roughly 98 % of the entire population. The data set included 31,668 subjects aged 50 years and above sustaining a hip fracture between July 2008 and December 2010 with follow-up until June 2011, and an age-, gender-, and regionally matched control population without hip fractures (56,320 subjects). Kaplan-Meier and Cox hazard regression analyses served to determine unadjusted and adjusted mortality rates: Unadjusted all-cause 1-year mortality amounted to 20.2 % (95 % CI: 19.7-20.7 %). Males had significantly higher long-term, in-hospital, and excess mortality rates than females, but younger males exhibited lower excess mortality than their female counterparts. Advanced age correlated with increased long-term and in-hospital mortality, but lower excess mortality. Excess mortality, particularly in males, was highest in the first 6 months after hip fracture, but remained statistically significantly elevated throughout the observation period of 3 years. Longer hospital stay per fracture was correlated with mortality reduction in older patients and in patients with more subsequent fractures. In conclusion, more efforts are needed to identify causes and effectively prevent excess mortality especially in male osteoporosis patients.

A 44 yr-old female with osteoporosis had no relevant gastrointestinal symptoms and did not avoid any specific food. However, after prescription of a lactose-rich calcium supplementation, clinical symptoms suspicious for lactose intolerance occurred, which were thereafter confirmed by a lactose tolerance test. Lactose intolerance may present with only slight or subtle symptoms. Drugs containing lactose may induce or increase gastrointestinal symptoms in patients with lactose intolerance. In case of gastrointestinal symptoms occurring after the initiation of drugs containing lactose, the possibility of lactose intolerance should be considered and tested by lactose tolerance test or genetic testing for the LCT (-13910) polymorphism. Due to the prevalence of about 15-25% lactose intolerance in the Austrian population, lactose free drugs should be prescribed as widely as possible.

Osteoporosis is a systemic skeletal disease characterized by diminished bone mass and deterioration of bone microarchitecture, leading to increased fragility and subsequent increased fracture risk. Therapeutic measures therefore aim at reducing individual fracture risk. In Austria, the following drugs, all of which have been proven to reduce fracture risk, are currently registered for the treatment of postmenopausal osteoporosis: alendronate, risedronate, etidronate, ibandronate, raloxifene, teriparatide (1-34 PTH), 1-84 PTH, strontium ranelate and salmon calcitonin. Fluorides are still available, but their role in daily practice has become negligible. Currently, there is no evidence that a combination of two or more of these drugs could improve anti-fracture potency. However, treatment with PTH should be followed by the treatment with an anticatabolic drug such as bisphosphonates. Calcium and vitamin D constitute an important adjunct to any osteoporosis treatment.

Background: There is increasing evidence that correct interpretation of bone mineral density (BMD) measurements by dual energy X-ray absorptiometry (DEXA) requires a population-specific reference range. We therefore collected data on age-related BMD in a random sample of the normal adult Austrian population to establish an appropriate normative database., Methods: We measured BMD by DEXA at five different skeletal sites in 1089 subjects, i.e. 654 females and 435 males, aged between 21-76 years, who had been recruited by 17 centres across Austria., Results: Age-related bone loss was observed until age 65 years with significant changes at the lumbar spine (r = -0.23), total hip (r = -0.07), trochanter (r = -0.10), femoral neck (r = -0.30) and Ward's triangle (r = -0.40) in the women but only at the femoral neck (r = -0.23) and at Ward's triangle (r = -0.40) in the men. When we calculated T scores from the BMD data of the young normal adult study population and used the T score set points according to the WHO classification of osteopenia and osteoporosis, we found that, depending on the skeletal site measured, 7.6-27.4% of the women and 16-41% of the men in our study group had low bone mass, whereas 0.6-2.7% of the female and 0.2-1.0% of the male study population were osteoporotic. However, osteoporosis was indicated in 4-9-fold more females and 5-15-fold more males when we based our estimates on the normative data provided by the manufacturers of the DEXA systems., Conclusion: Our data underscore the importance of using a population-specific reference range for DEXA measurements to avoid overdiagnosis of osteoporosis.

This study is an investigation into the epidemiologic and socioeconomic impact of osteoporosis-associated hip fractures in Austria. We determined age- and gender-specific incidence rates of osteoporosis-associated hip fractures for all patients treated in hospitals in 1995 and calculated mortality rates, hospitalization days and direct costs of hospitalization. The data were obtained from the hospital discharge statistics for all general hospitals and for all hospitals of the General Austrian Accident Insurance. To calculate the portion of hip fractures attributable to osteoporosis in a given age-group, a basic, non-osteoporotic incidence of hip fractures was determined for ages 20-39, using gender-specific regression models. 11,379 patients with osteoporotic hip fractures underwent treatment in Austrian hospitals in 1995, accounting for 79 percent of all hip fracture patients treated. 82 percent of those were female, with the highest incidence among women aged 95 years and older with a rate of 3,000/100,000. For male patients the highest incidence was observed for the age-group of 90-94 years with 1,743/100,000. International comparisons indicate these incidence rates to be similar to those reported for the Swiss population. In 1995, 778 patients or 6.8 percent of all patients with osteoporotic hip fractures died during hospitalization. Hospital care of patients with osteoporotic hip fractures required an overall 250,268 bed-days with an age-group-specific length of stay between 8.5-27 days for female and 16-23 days for male patients. The total cost of hospital treatment of osteoporotic hip fractures in Austria was ATS 1,043,379,000 (US$ 103,509,800), with average costs per patient of ATS 91,700 (US$ 9,097). Due to the aging of the population in the years to come, an increase of osteoporotic hip fractures among individuals aged 50 years and older must be expected. The economic importance of this development and its impact on the health care system must be considered as significant.