Association between recurrent fracture risk and implementation of fracture liaison services in four Swedish hospitals: A cohort study

Structured secondary preventions programs, called fracture liaison services (FLSs), increase the rate of evaluation with bone densitometry and use of osteoporosis medication after fracture. However, the evidence regarding the effect on the risk of recurrent fracture is insufficient. The aim of this study was to investigate if implementation of FLS was associated with reduced risk of recurrent fractures. In this retrospective cohort study, electronic health records during 2012 to 2017 were used to identify a total of 21,083 patients from four hospitals in Western Sweden, two with FLS (n = 15,449) and two without (n = 5634). All patients aged 50 years or older (mean age 73.9 [SD 12.4] years, 76% women) with a major osteoporotic index fracture (hip, clinical spine, humerus, radius, and pelvis) were included. The primary outcome was recurrent major osteoporotic fracture. All patients with an index fracture during the FLS period (n = 13,946) were compared with all patients in the period before FLS implementation (n = 7137) in an intention‐to‐treat analysis. Time periods corresponding to the FLS hospitals were used for the non‐FLS hospitals. In the hospitals with FLSs, there were 1247 recurrent fractures during a median follow‐up time of 2.2 years (range 0–6 years). In an unadjusted Cox model, the risk of recurrent fracture was 18% lower in the FLS period compared with the control period (hazard ratio = 0.82, 95% confidence interval [CI] 0.73–0.92, p = .001), corresponding to a 3‐year number needed to screen of 61, and did not change after adjustment for clinical risk factors. In the hospitals without FLSs, no change in recurrent fracture rate was observed. Treatment decisions were made according to the Swedish treatment guidelines. In conclusion, implementation of FLS was associated with a reduced risk of recurrent fracture, indicating that FLSs should be included routinely at hospitals treating fracture patients. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research

Type 2 diabetes and risk of hip fractures and non-skeletal fall injuries in the elderly: A study from the Fractures and Fall Injuries in the Elderly Cohort (FRAILCO)

Questions remain about whether the increased risk of fractures in patients with type 2 diabetes (T2DM) is related mainly to increased risk of falling or to bone‐specific properties. The primary aim of this study was to investigate the risk of hip fractures and non‐skeletal fall injuries in older men and women with and without T2DM. We included 429,313 individuals (aged 80.8 ± 8.2 years [mean ± SD], 58% women) from the Swedish registry “Senior Alert” and linked the data to several nationwide registers. We identified 79,159 individuals with T2DM (45% with insulin [T2DM‐I], 41% with oral antidiabetics [T2DM‐O], and 14% with no antidiabetic treatment [T2DM‐none]) and 343,603 individuals without diabetes. During a follow‐up of approximately 670,000 person‐years, we identified in total 36,132 fractures (15,572 hip fractures) and 20,019 non‐skeletal fall injuries. In multivariable Cox regression models where the reference group was patients without diabetes and the outcome was hip fracture, T2DM‐I was associated with increased risk (adjusted hazard ratio (HR) [95% CI] 1.24 [1.16–1.32]), T2DM‐O with unaffected risk (1.03 [0.97–1.11]), and T2DM‐none with reduced risk (0.88 [0.79–0.98]). Both the diagnosis of T2DM‐I (1.22 [1.16–1.29]) and T2DM‐O (1.12 [1.06–1.18]) but not T2DM‐none (1.07 [0.98–1.16]) predicted non‐skeletal fall injury. The same pattern was found regarding other fractures (any, upper arm, ankle, and major osteoporotic fracture) but not for wrist fracture. Subset analyses revealed that in men, the risk of hip fracture was only increased in those with T2DM‐I, but in women, both the diagnosis of T2DM‐O and T2DM‐I were related to increased hip fracture risk. In conclusion, the risk of fractures differs substantially among patients with T2DM and an increased risk of hip fracture was primarily found in insulin‐treated patients, whereas the risk of non‐skeletal fall injury was consistently increased in T2DM with any diabetes medication. © 2016 American Society for Bone and Mineral Research

Development of a novel method to measure bone marrow fat fraction in older women using high-resolution peripheral quantitative computed tomography

Bone marrow adipose tissue (BMAT) has been implicated in a number of conditions associated with bone deterioration and osteoporosis. Several studies have found an inverse relationship between BMAT and bone mineral density (BMD), and higher levels of BMAT in those with prevalent fracture. Magnetic resonance imaging (MRI) is the gold standard for measuring BMAT, but its use is limited by high costs and low availability. We hypothesized that BMAT could also be accurately quantified using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods: In the present study, a novel method to quantify the tibia bone marrow fat fraction, defined by MRI, using HR-pQCT was developed. In total, 38 postmenopausal women (mean [standard deviation] age 75.9 [3.1] years) were included and measured at the same site at the distal (n = 38) and ultradistal (n = 18) tibia using both MRI and HR-pQCT. To adjust for partial volume effects, the HR-pQCT images underwent 0 to 10 layers of voxel peeling to remove voxels adjacent to the bone. Linear regression equations were then tested for different degrees of voxel peeling, using the MRI-derived fat fractions as the dependent variable and the HR-pQCT-derived radiodensity as the independent variables. Results: The most optimal HR-pQCT derived model, which applied a minimum of 4 layers of peeled voxel and with more than 1% remaining marrow volume, was able to explain 76% of the variation in the ultradistal tibia bone marrow fat fraction, measured with MRI (p < 0.001). Conclusion: The novel HR-pQCT method, developed to estimate BMAT, was able to explain a substantial part of the variation in the bone marrow fat fraction and can be used in future studies investigating the role of BMAT in osteoporosis and fracture prediction

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation

Association between alendronate use and hip fracture risk in older patients using oral prednisolone

Importance Oral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids. Objective To investigate whether alendronate treatment in older patients using oral prednisolone is associated with decreased hip fracture risk and adverse effects. Design, Setting, and Participants Retrospective cohort study using a national database (N = 433 195) of patients aged 65 years or older undergoing a health evaluation (baseline) at Swedish health care facilities; 1802 patients who were prescribed alendronate after at least 3 months of oral prednisolone treatment (≥5 mg/d) were identified. Propensity score matching was used to select 1802 patients without alendronate use from 6076 patients taking prednisolone with the same dose and treatment time criteria. Follow-up occurred between January 2008 and December 2014. Exposures Alendronate vs no alendronate use; no patients had previously taken alendronate at the time of prednisolone initiation. Main Outcomes and Measures The primary outcome was incident hip fracture. Results Of the 3604 included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34 years), there were 27 hip fractures in the alendronate group and 73 in the no-alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and 27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate difference of −17.6 (95% CI, −24.8 to −10.4). The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3-18.0] per 1000 person-years; P = .40) or peptic ulcers (10.9 [95% CI, 7.7-15.5] vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years; P = .86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group. Conclusions and Relevance Among older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group

Association between cortical bone microstructure and statin use in older women

Context Treatment with statins has been associated with increased bone mineral density, but whether this association depends on differences in cortical or trabecular volumetric bone microstructure is unknown. Objective The aim of this study was to investigate if treatment with statins is associated with bone microstructure and geometry in older women. Design Setting and Participants Older women were included in a population-based study of 3028 women (mean age ± SD, 77.8 ± 1.6 years) from the greater Gothenburg area in Sweden. Information regarding medical history, medication, and lifestyle factors was obtained from validated questionnaires. Main Outcome Bone geometry and microstructure were measured at the ultradistal and distal (14%) site of radius and tibia using high-resolution peripheral quantitative computed tomography. Results The 803 women in the cohort who used statins had higher body weight, worse physical function, and more frequent cardiovascular disease and diabetes than nonusers (P < 0.05). Statin users had lower cortical porosity (radius, 2.2 ± 1.9 vs 2.5 ± 2.0%; tibia, 5.2 ± 2.4 vs 5.4 ± 2.5; P = 0.01), higher cortical bone density (radius, 1008 ± 39.1 vs 1001 ± 38.4 mg/cm3; tibia, 919 ± 42.6 vs 914 ± 41.5; P < 0.01), and greater cortical area (radius, 60.5 ± 9.6 vs 58.6 ± 9.7 mm2; tibia, 150.0 ± 23.6 vs 146.7 ± 23.8; P < 0.01) than nonusers after adjustment for a large number of confounders, including age, weight, smoking, other medications, and prevalent diseases. Conclusions Use of statins was associated with better cortical bone characteristics in older women

Fracture risk after gastric bypass surgery: A retrospective cohort study

Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone loss, but fracture risk following surgery has been insufficiently studied. Furthermore, the association between gastric bypass and fracture risk has not been studied in patients with diabetes, which is a risk factor for fracture and affected by surgery. In this retrospective cohort study using Swedish national databases, 38,971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31,213 without. An equal amount of well‐balanced controls were identified through multivariable 1:1 propensity score matching. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation 1‐year postsurgery was investigated. During a median follow‐up time of 3.1 (interquartile range [IQR], 1.7 to 4.6) years, gastric bypass was associated with increased risk of any fracture, in patients with and without diabetes using a multivariable Cox model (hazard ratio [HR] 1.26; 95% CI, 1.05 to 1.53; and HR 1.32; 95% CI, 1.18 to 1.47; respectively). Using flexible parameter models, the fracture risk appeared to increase with time. The risk of fall injury without fracture was also increased after gastric bypass. Larger weight loss or poor calcium and vitamin D supplementation after surgery were not associated with increased fracture risk. In conclusion, gastric bypass surgery is associated with an increased fracture risk, which appears to be increasing with time and not associated with degree of weight loss or calcium and vitamin D supplementation following surgery. An increased risk of fall injury was seen after surgery, which could contribute to the increased fracture risk. © 2018 American Society for Bone and Mineral Research

Analysis of comorbidities, clinical outcomes, and parathyroidectomy in adults with primary hyperparathyroidism

Importance: patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials.Objective: to investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes.Design, Setting, and Participants: this cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022.Main Outcomes and Measures: the primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs).Results: a total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pHPT group and 803 522 person-years for the control group. Compared with the control group, the pHPT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65).Conclusions and Relevance Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery

Hemoglobin levels improve fracture risk prediction in addition to FRAX® clinical risk factors and bone mineral density

Context: anemia and decreasing levels of hemoglobin (Hb) have previously been linked to increased fracture risk, but the added value to FRAX®, the most utilized fracture prediction tool worldwide, is unknown.Objectives: to investigate the association between anemia, Hb levels, bone microstructure, and risk of incident fracture and to evaluate if Hb levels improve fracture risk prediction in addition to FRAX clinical risk factors (CRFs).Methods: a total of 2778 community-dwelling women, aged 75-80 years and part of a prospective population-based cohort study in Sweden were included. At baseline, information on anthropometrics, CRFs and falls was gathered, blood samples were collected, and skeletal characteristics were investigated using dual energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. At the end of follow-up, incident fractures were retrieved from a regional x-ray archive.Results: the median follow-up time was 6.4 years. Low Hb was associated with worse total hip and femoral neck bone mineral density (BMD), lower tibia cortical and total volumetric BMD, and anemia was associated with increased risk of major osteoporotic fracture (MOF; hazard ratio 2.04; 95% CI 1.58-2.64). Similar results were obtained for hip fracture and any fracture, also when adjusting for CRFs. The ratio between 10-year fracture probabilities of MOF assessed in models with Hb levels included to not included, ranged from 1.2 to 0.7 at the 10th and 90th percentile of Hb, respectively.Conclusions: anemia and decreasing levels of Hb are associated with lower cortical BMD and incident fracture in older women. Considering Hb levels may improve the clinical evaluation of patients with osteoporosis and the assessment of fracture risk.</p

Effects of glucose availability in <i>Lactobacillus sakei</i>; metabolic change and regulation of the proteome and transcriptome

<div><p>Effects of glucose availability were investigated in <i>Lactobacillus sakei</i> strains 23K and LS25 cultivated in anaerobic, glucose-limited chemostats set at high (<i>D</i> = 0.357 h^-1) and low (<i>D</i> = 0.045 h^-1) dilution rates. We observed for both strains a shift from homolactic towards more mixed acid fermentation when comparing high to low growth rates. However, this change was more pronounced for LS25 than for 23K, where dominating products were lactate>formate>acetate≥ethanol at both conditions. A multivariate approach was used for analyzing proteome and transcriptome data from the bacterial cultures, where the predictive power of the omics data was used for identifying features that can explain the differences in the end-product profiles. We show that the different degree of response to the same energy restriction revealed interesting strain specific regulation. An elevated formate production level during slow growth, more for LS25 than for 23K, was clearly reflected in correlating pyruvate formate lyase expression. With stronger effect for LS25, differential expression of the Rex transcriptional regulator and NADH oxidase, a target of Rex, indicated that maintainance of the cell redox balance, in terms of the NADH/NAD⁺ ratio, may be a key process during the metabolic change. The results provide a better understanding of different strategies that cells may deploy in response to changes in substrate availability.</p></div