Birth weight and birth length affect future fracture risk differently in men and women.

We wanted to determine if there are any associations between birth factors and adult fracture risk. For women only, shorter birth length was associated with lower relative fracture risk. For women and men, individuals who were long at birth as well as tall in adulthood had a substantially higher relative fracture risk. PURPOSE: We aimed to examine associations between birth anthropometry and adult fracture risk and to investigate if developmental mismatch is associated with fracture risk. METHODS: We included 4635 participants (476 women and 4159 men; born 1921-1950) with hospital and national registry-based data on birth anthropometry and adult fractures (≥ 50 years). We tested associations by Cox proportional hazards regressions and present hazard ratios (HR) with 95% confidence intervals. RESULTS: In total, 1215 (26%) suffered ≥ 1 fracture during a mean observation period of 26 years. In women, unadjusted analyses indicated that both higher birth weight (HR 1.42 per kg (1.10-1.84)) and birth length (1.10 per cm (1.05-1.17)) were associated to higher adult fracture risk. After adjustment (year of birth and gestational age), statistical significance remained only for birth length, HR 1.10 per cm (1.04-1.17). For men, no associations were apparent. We found no associations between developmental mismatch (lower birth weight followed by higher adult weight) and adult fracture risk. However, for both sexes, being born tall and staying tall into adulthood was associated with a markedly higher (55-105%) relative fracture risk (HR women 2.09 (1.18-3.68), men 1.55 (1.19-2.03)) compared to being born short and remaining short in adulthood. CONCLUSION: In this study, being born shorter and lighter was associated with a lower risk for fractures ≥ 50 years in women. However, analyses indicated that tall adults who were also long at birth may be at markedly higher risk of fractures; this warrants further examinations.

3D Finite Element Models Reconstructed From 2D Dual-Energy X-Ray Absorptiometry (DXA) Images Improve Hip Fracture Prediction Compared to Areal BMD in Osteoporotic Fractures in Men (MrOS) Sweden Cohort.

Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed a method to reconstruct the 3D hip anatomy from a 2D DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a population-based cohort (Osteoporotic Fractures in Men [MrOS] Sweden). We defined two subcohorts: (i) hip fracture cases and controls cohort: 120 men with a hip fracture (<10 years from baseline) and two controls to each hip fracture case, matched by age, height, and body mass index; and (ii) fallers cohort: 86 men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE-predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, ΔAUROC = 0.06) and fallers (ΔAUROC = 0.22) cohorts. This is the first time that FE models outperformed aBMD in predicting incident hip fractures in a population-based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Time Trends in Trajectories of Forearm Mineral Content and Bone Size during Childhood-Results from Cross-Sectional Measurements with the Same Apparatus Four Decades Apart.

Evidence suggests that single photon absorptiometry (SPA)-measured forearm bone mineral density (BMD) is lower in contemporary children in Malmö than it was four decades ago, but the fracture incidence in the at-risk population (all Malmö children) has been stable during the same period. The aim of this study was to evaluate if improvements in skeletal structure over time may explain this observation. In 2017-2018 we measured distal forearm bone mineral content (BMC; mg/cm) and periosteal diameter (mm) in 238 boys and 204 girls aged 7-15 using SPA. Based on the SPA measurements, we calculated forearm BMD (mg/cm2), bone mineral apparent density (BMAD, mg/cm3), section modulus, and strength index (BMAD × section modulus). The results were compared with those derived from measurements of 55 boys and 61 girls of the same ages using the same scanner in 1979-1981. We used log-linear regression with age, sex, and cohort as predictors to investigate differences in trait trajectories (trait versus age slopes [mean percent difference in beta values (95% confidence interval)]). SPA-measured forearm BMC was lower at each age in 2017-2018 compared to 1979-1981 (a mean age and sex adjusted relative difference of 9.1%), the forearm BMC trajectory was similar in 2017-2018 to that in 1979-1981 (reference) [0.0%/year (-1.0%, 1.0%)], while the 2017-2018 forearm periosteal diameter trajectory was steeper [1.1%/year (0.3%, 2.0%)]. Since bone size influences both BMD (BMC divided by scanned area) and mechanical characteristics, the forearm BMD trajectory was flatter in 2017-2018 [-1.1%/year (-2.0%, -0.2%)] and the forearm section modulus trajectory steeper [3.9%/year (1.4%, 6.4%)]. Forearm strength index trajectory was similar [1.8%/year (-0.5%, 4.1%)]. The lower SPA-measured forearm BMD trajectory in contemporary children compared to four decades ago may be offset by changes in forearm bone structure, resulting in similar overall bone strength. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Prevalence and morbidity of neck pain: a cross-sectional study of 3000 elderly men.

BACKGROUND: The purpose of this study is to determine the prevalence and morbidity of neck pain with or without cervical rhizopathy, upper extremity motor deficit and/or thoracolumbar pain in elderly men. METHODS: We conducted a cross-sectional questionnaire study of 3,000 community-dwelling older men with a mean age of 75.4 ± 3.2 years (range 69-81) to determine if they had experienced neck pain with or without cervical rhizopathy/upper extremity motor deficit/thoracolumbar pain (yes/no) during the preceding 12 months, and if so, morbidity with the condition (no/minor/moderate/severe). RESULTS: Among the participants, 865 (29%) reported they had experienced neck and 1,619 (54%) thoracolumbar pain. Among the men with neck pain, 59% had experienced only neck pain, 17% neck pain and cervical rhizopathy and 24% neck pain, rhizopathy and motor deficit. For men with only neck pain, the morbidity was severe in 13%, for men with neck pain and rhizopathy it was 24%, and for men with pain, rhizopathy and motor deficit it was 46% (p < 0.001). Among the men with neck pain, 23% had experienced only neck pain and no thoracolumbar pain; the remaining 77% had both neck and thoracolumbar pain. The morbidity was severe in 10% of the men with neck pain but no thoracolumbar pain and 30% in men with neck and thoracolumbar pain (p < 0.001). CONCLUSION: Neck pain in elderly men is common but symptoms and morbidity vary. For men who only have neck pain, 1/8 rated their morbidity as severe, while almost half who also had cervical rhizopathy and motor deficit and almost 1/3 of those who also had thoracolumbar pain reported severe morbidity.

Outcomes of trabecular metal total ankle replacement: a longitudinal observational cohort study of 239 consecutive cases from the Swedish Ankle Registry.

BACKGROUND AND PURPOSE: Information on outcomes after some modern total ankle replacement (TAR) designs is scarce. We therefore examined outcomes after trabecular metal (TM) TAR in Sweden by use of data from the national registry. PATIENTS AND METHODS: On December 31, 2020, 239 primary TM TARs had been reported to the Swedish Ankle Registry. We analyzed prosthesis survival probability, using exchange or permanent extraction of components as endpoint for 239 protheses with mean follow-up of 2.2 years (0.1-6.6), risk of revision, as well as patient-reported outcome measures (SEFAS/EQ-5D/EQ-VAS) and satisfaction with surgery. RESULTS: 7/239 prostheses (3%) had been revised by December 31, 2020. We found an overall prosthesis survival probability of 95% (95% CI 89-98) after 3 years. 2 years after surgery 81% of the answering patients were satisfied or very satisfied with surgery and patients reported median SEFAS 36 (max 48), EQ-5D 0.90 (max 1), and EQ-VAS 80 (max 100). INTERPRETATION: We found short- to mid-term outcomes after TM TAR to be at least as good as after other TAR designs regarding prosthesis survival and patient-reported satisfaction.

Physical Activity in Late Prepuberty and Early Puberty Is Associated With High Bone Formation and Low Bone Resorption.

Background: Physical activity (PA) increases bone mass, especially in late prepuberty and early puberty, but it remains unclear if and how PA affects both bone formation and bone resorption. Materials and Methods: We included 191 boys and 158 girls aged 7.7 ± 0.6 (mean ± SD) in a population-based PA intervention study. The intervention group (123 boys and 94 girls) received daily physical education (PE) in school (40 min/day; 200 min/week) from study start and during the nine compulsory school years in Sweden. The controls (68 boys and 64 girls) received the national standard of 1-2 classes PE/week (60 min/week). During the intervention, blood samples were collected at ages 9.9 ± 0.6 (n = 172; all in Tanner stages 1-2) and 14.8 ± 0.8 (n = 146; all in Tanner stages 3-5) and after termination of the intervention at age 18.8 ± 0.3 (n = 93; all in Tanner stage 5) and 23.5 ± 0.7 (n = 152). In serum, we analyzed bone formation markers [bone-specific alkaline phosphatase (bALP), osteocalcin (OC), and N-terminal propeptide of collagen type 1 (PINP)] and bone resorption markers [C-terminal telopeptide cross links (CTX) and tartrate-resistant acid phosphatase (TRAcP 5b)]. Linear regression was used to compare age and sex-adjusted mean differences between intervention children and controls in these markers. Results: Two years after the intervention was initiated (at Tanner stages 1-2), we found higher serum levels of bALP and OC, and lower serum levels of TRAcP 5b in the intervention compared with the control group. The mean difference (95% CI) was for bALP: 13.7 (2.1, 25.3) µg/L, OC: 9.1 (0.1, 18.1) µg/L, and TRAcP 5b: -2.3 (-3.9, -0.7) U/L. At Tanner stages 3-5 and after the intervention was terminated, bone turnover markers were similar in the intervention and the control children. Conclusion: Daily school PA in the late prepubertal and early pubertal periods is associated with higher bone formation and lower bone resorption than school PA 1-2 times/week. In late pubertal and postpubertal periods, bone formation and resorption were similar. Termination of the intervention is not associated with adverse bone turnover, indicating that PA-induced bone mass benefits gained during growth may remain in adulthood.

Downturn in Childhood Bone Mass: A Cross-Sectional Study Over Four Decades.

Screen time and physical inactivity have increased among children. As physical activity is a determinant of bone mass, there is a concern that children today have lower bone mass than earlier. If this is true, fractures may become more common in the future. In 2017-2018, we used single-photon absorptiometry (SPA) to measure distal forearm bone mineral density (BMD; mg/cm2) in a normative cohort of 238 boys and 204 girls aged 7 to 15 years. We compared these results to BMD in a normative cohort collected in 1979-1981 (55 boys and 61 girls aged 7 to 15 years) measured by the same scanner. To investigate difference between the two cohorts, we used multiple linear regression with age, sex, and cohort as predictors. Predicted bone density at age 16 years was estimated through the slope values. The bone density-age slope was flatter in the cohort measured in 2017-2018 than in the cohort measured 1979-1981 (-5.6 mg/cm2/yr [95% confidence interval -9.6 to -1.5]). Predicted bone density was at age 16 years in 2017-2018 in boys was 10% lower (-0.9 SD) and in girls 11% lower (-1.1 SD) than in their counterparts measured in 1979-1981. We found indications that children nowadays develop lower bone mass than four decades ago, giving concern that they may have a higher risk of osteoporosis and fragility fractures as they grow old. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Physical Activity at Growth Induces Bone Mass Benefits Into Adulthood - A Fifteen-Year Prospective Controlled Study.

Daily school physical activity (PA) improves musculoskeletal traits. Whether or not benefits remain in adulthood is debated. We included in this study 131 children that took part in an intervention with 40 minutes of PA per school day (200 minutes per week) from age 6 to 9 years (grade one) to age 14 to 16 years (grade nine), whereas 78 children continued with national recommended school physical education of 60 minutes per week. Measurements were done with dual-energy X-ray absorptiometry (bone mineral content [BMC], bone mineral density [BMD], and bone area), and a computerized knee dynamometer (peak torque muscle strength) at study start, at the end of the intervention, and 7 years after the intervention. Group differences from study start and end of the intervention to 7 years thereafter were estimated by analyses of covariance (adjusted for sex and follow-up time). Musculoskeletal gains from study start to 7 years after termination of the intervention were higher in the intervention group (total body less head BMC +182.5 g [95% confidence interval {CI}, 55.1-309.9] and BMD +0.03 g/cm2 [95% CI, 0.003-0.05], femoral neck area + 0.2 cm2 [95% CI, 0.1-0.4], and knee flexion peak torque muscle strength at 60 degrees per second +9.2 Nm [95% CI, 2.9-15.5]). There was no attenuation during the 7 years that followed termination of the intervention (all group comparisons p > 0.05). Benefits in musculoskeletal gains remain 7 years after termination of a daily school-based PA program, without attenuation after termination of the program. Daily school PA may counteract low bone mass and inferior muscle strength in adulthood. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Childhood Distal Forearm Fracture Incidence in Malmö, Sweden 1950 to 2016.

Background Distal forearm fracture is the most common pediatric fracture. As studies have indicated time trends in fracture incidence, we wanted to update the epidemiology and estimate time trends between 1950 and 2016 in Malmö, Sweden. Methods The city of Malmö, Sweden, had 318,107 inhabitants (58,585 of the population was aged <16 years) in 2014 and one hospital. We, therefore, used the hospital diagnosis registry and hospital medical records to identify and classify distal forearm fractures 2014 to 2016 in children aged 0 to 15 years. For long-term trend calculations, we also included published data from 1950 to 2006 (resulting in 17 evaluated years) and used joinpoint regression to estimate annual percent changes (APC). To describe differences in incidence between two periods, we calculated incident rate ratios (IRR) with 95% confidence intervals (95% CI) to describe uncertainty. Results Childhood distal forearm fracture incidence in 2014 to 2016 was 546/100,000 person-years (660 in boys and 427 in girls). The age-adjusted incidence in 2014 to 2016 and in 2005 to 2006 was similar (boys IRR 1.0, 95% CI: 0.9-1.2 and girls IRR 1.1, 95% CI: 0.9-1.3). Time-trend analyses from 1950 to 2016 revealed increasing age-adjusted incidence in both boys (APC +0.9%, 95% CI: 0.7-1.2) and girls (APC +0.6%, 95% CI: 0.3-0.9). Conclusion Distal forearm fracture incidence was similar in 2014 to 2016 and in 2005 to 2006. Age-adjusted incidence had increased in both sexes from 1950 to 2016. Level of Evidence This is a Level III b study.

Time trends in pediatric hand fracture incidence in Malmö, Sweden, 1950-2016.

BACKGROUND: The hand is the second most fractured region in children. It is therefore important to update fracture epidemiology to be able to identify time trends for adequate health care planning. This study reports pediatric hand fracture incidence 2014-2016 and, using published data, also long-term time trends in 1950-2016. PATIENTS AND METHODS: The Swedish city of Malmö, with 328,494 inhabitants in 2016, has only one hospital. We used the hospital radiological archive, medical charts, and diagnosis registry to identify hand fractures in city residents < 16 years in 2014-2016. These data were compared to those from three published studies that evaluated periods in 1950-2006. Differences between two periods were calculated as both unadjusted and age- and sex-adjusted incident rate ratios (IRR) with 95% confidence intervals (95% CI). We used joinpoint regression to estimate time trends during the entire period and present annual percent changes (APC) with 95% CI. RESULTS: In 2014-2016 phalangeal fractures accounted for 71% of all hand fractures, metacarpal fractures for 24%, and carpal fractures for 5%. We identified 615 hand fractures (419 in boys and 196 in girls) during 181,617 person-years in 2014-2016, resulting in an unadjusted pediatric hand fracture incidence of 339/100,000 person-years (boys 452/100,000 person-years and girls 220/100,000 person-years). The age-adjusted incidence 2014-2016 was similar to 2005-2006, the most recently evaluated period (IRR in boys 0.9; 95% CI 0.8 to 1.01, and in girls 1.0; 95% CI 0.8 to 1.2). Looking at the entire period 1950-2016, we found that age-adjusted incidence increased in 1950-1979, in boys by APC + 3.8%; 95% CI 3.0 to 4.5 and in girls by + 3.9%; 95% CI 2.8 to 5.0, but decreased in 1979-2016, in boys by - 0.7%; 95% CI - 1.4 to - 0.003, and girls by - 1.3%; 95% CI - 2.4 to - 0.1. CONCLUSIONS: Phalangeal fractures accounted for about three quarters of all hand fractures. The age-adjusted hand fracture incidence increased in both sexes in 1950-1979 and decreased in 1979-2016. LEVEL OF EVIDENCE: III.

Musculoskeletal Benefits from a Physical Activity Program in Primary School are Retained 4 Years after the Program is Terminated.

Daily school physical activity (PA) improves musculoskeletal traits. This study evaluates whether the benefits remain 4 years after the intervention. We followed 45 boys and 36 girls who had had 40 min PA/school day during the nine compulsory school years and 21 boys and 22 girls who had had 60 min PA/school week (reference), with measurements at baseline and 4 years after the program terminated. Bone mineral content (BMC; g) and bone mineral density (BMD; g/cm2) were measured by dual-energy X-ray absorptiometry and knee flexion peak torque relative to total body weight (PTflexTBW) at a speed of 180 degrees/second with a computerized dynamometer. Group differences are presented as mean differences (adjusted for sex and duration of follow-up period) with 95% confidence intervals. The total gain bone mass [mean difference in spine BMC +32.0 g (14.6, 49.4) and in arms BMD of +0.06 g/cm2 (0.02, 0.09)] and gain in muscle strength [mean difference in PTflex180TBW +12.1 (2.0, 22.2)] were greater in the intervention than in the control group. There are still 4 years after the intervention indications of benefits in both bone mass and muscle strength gain. Daily school PA may counteract low bone mass and inferior muscle strength in adult life. ClinicalTrials.gov.NCT000633828 retrospectively registered 2008-11-03.

Severe alpha-1-antitrypsin deficiency increases the risk of venous thromboembolism.

BACKGROUND: Severe alpha-1-antitrypsin deficiency (AATD), phenotype PiZZ, is associated with increased risk of liver disease and chronic obstructive pulmonary disease (COPD), but the risk of venous thromboembolism (VTE) is unknown. Our aim was to evaluate the risk of VTE in individuals with severe AATD compared with control subjects from the general population. METHODS: Individuals with severe AATD (n = 1577) were recruited from the Swedish national AATD register. Control subjects (n = 5969) were selected from the OLIN (Obstructive Lung Disease in Northern Sweden) studies, that include a random general population sample. Longitudinal data on VTE and diagnoses were obtained from the Swedish National Patient Registry. Associations were analyzed using multivariable Cox regression. RESULTS: At inclusion, 46% of the AATD individuals and 53% of the controls were never-smokers. COPD was present in 46% of the AATD individuals compared with 4% of the controls. During a median follow-up of 18 years, 116 (7%) of the AATD individuals and 89 (1%) of the control subjects developed VTE, unadjusted hazard ratio 6.5 (95% confidence interval 4.9-8.6). Risk factors for incident VTE were male gender, age, COPD, cancer, and liver disease. Adjusting for these factors, the AATD individuals had a significantly higher risk of incident VTE, adjusted hazard ratio 4.2 (95% confidence interval 2.9-6.2) as compared with the controls. CONCLUSION: Subjects with severe AATD have considerably increased risk of developing VTE compared with the general population, even after accounting for risk factors. This calls for optimized risk factor management and clinical follow-up of this patient group.

Association between circulating furin levels, obesity and pro-inflammatory markers in children.

AIM: To, in children, investigate the associations between serum furin, obesity, overweight, body fat and circulating markers reflecting adipose tissue or systemic inflammation. METHODS: We analysed furin, leptin, adipocyte fatty acid-binding protein, triglycerides, interleukin (IL)-6, IL-8 and C-reactive protein in serum from 166 children in the Pediatric Osteoporosis Prevention (POP) study collected at mean age (SD) 9.9 (0.6) years. Children were classified as low-to-normal weight, overweight or obese. Total body fat mass (kg), trunk fat mass (kg) and total body lean mass (kg) were measured by dual-energy X-ray absorptiometry. Body fat percentage (%) was calculated. RESULTS: We found that circulating furin levels were higher in children with obesity and overweight compared with children with low-to-normal weight (p < 0.001 and p = 0.006, respectively). Also, there were positive correlations between circulating furin, total body fat mass, trunk fat mass, body fat percentage, triglycerides, adipokines and pro-inflammatory markers. CONCLUSION: This study indicates associations between furin, adiposity and a pro-inflammatory milieu in children. We suggest that future studies investigate the role of furin in fat tissue inflammation and associated increased risk of cardiometabolic diseases in children. Studies should also investigate whether higher furin levels could be a link between obesity and severe coronavirus disease 2019 in children.

Better implant survival with modern ankle prosthetic designs: 1,226 total ankle prostheses followed for up to 20 years in the Swedish Ankle Registry.

Background and purpose - We have previously reported on the prosthetic survival of total ankle replacements (TAR) in Sweden performed between 1993 and 2010. Few other reports have been published on 5- and 10-year survival rates. Furthermore, there is a lack of long-term outcome data on modern prosthetic designs. Therefore, we compared early and current prosthetic designs after a mean 7-year follow-up.Patients and methods - On December 31, 2016, 1,230 primary TARs had been reported to the Swedish Ankle Registry. We analyzed prosthetic survival, using exchange or permanent extraction of components as endpoint for 1,226 protheses with mean follow-up of 7 years (0-24). Differences between current (Hintegra, Mobility, CCI, Rebalance, and TM Ankle) and early prosthetic designs (STAR, BP, and AES) were examined by log rank test.Results - 267/1,226 prostheses (22%) had been revised by December 31, 2016. We found an overall prosthetic survival rate at 5 years of 0.85 (95% CI 0.83-0.87), at 10 years 0.74 (CI 0.70-0.77), at 15 years 0.63 (CI 0.58-0.67), and at 20 years 0.58 (CI 0.52-0.65). For early prosthetic designs the 5- and 10-year survival rates were 0.81 (CI 0.78-0.84) and 0.69 (CI 0.64-0.73) respectively, while the corresponding rates for current designs were 0.88 (CI 0.85-0.91) and 0.84 (CI 0.79-0.88). Current prosthetic designs had better survival (log rank test p < 0.001).Interpretation - Our results point to a positive time trend of prosthetic survival in Sweden; use of current prosthetic designs was associated with better prosthetic survival. Improved designs and instrumentation, more experienced surgeons, and improved patient selection may all have contributed to the better outcome.

Serum Renin Levels Increase With Age in Boys Resulting in Higher Renin Levels in Young Men Compared to Young Women, and Soluble Angiotensin-Converting Enzyme 2 Correlates With Renin and Body Mass Index.

Background: Age, sex, and body constitution may affect the shedding of membrane bound angiotensin-converting enzyme 2 (mACE2) and lead to a relative mACE2 deficiency. However, it is unclear if differences, reflected by serum renin levels, exist in the basal renin-angiotensin-system (RAS) between children and adults, boys, and girls as well as young women and young men. Furthermore, it remains to be investigated if renin and soluble ACE2 (sACE2) levels are correlated with body mass index (BMI) in children and young adults. The aim of this observational study was to assess age-and sex differences in serum renin, and the relationship between renin, soluble angiotensin-converting enzyme 2, and body mass index in a prospectively followed population-based cohort of children which were followed into young adulthood. Study Design: We analyzed renin and sACE2 in serum in a prospectively followed population-based cohort at 9.9 (0.6) [mean (SD)] (n = 173), 11.7 (0.6) (n = 156), 14.8 (0.8) (n = 149), 18.8 (0.3) (n = 93), and 23.5 (0.7) (n = 152) years of age. Height (cm) and weight (kg) was measured and body mass index (BMI) was calculated as weight (kg)/height (m)2. Sex-related differences in renin levels were calculated using analysis of covariance, adjusted for age. Correlations were assessed by calculating the correlation coefficient (R 2) using a multivariable linear mixed model. Results: Both sexes had low renin levels up to 12 years of age. Thereafter renin levels increased more in boys than in girls. Males from the age of 15 had significantly higher levels than females (p < 0.001). There was a positive linear relationship between renin and sACE2 levels in male and female subjects (p < 0.001), and between sACE2 levels and BMI in males (p < 0.001). Conclusion: Renin levels increase with age, are higher in men than in women since around puberty, and are correlated with sACE2 levels. Furthermore, sACE2 levels are correlated with body mass index in males. These findings indicate that high renin levels in males and females and a high BMI in males may activate pathways which increase the shedding of mACE2, with possible implications for the risk of severe coronavirus disease 2019.

Decline in FEV1 and hospitalized exacerbations in individuals with severe alpha-1 antitrypsin deficiency.

Background and aim: The value of the forced expiratory volume in one second (FEV1) is useful in the diagnosis and prognosis of chronic obstructive pulmonary disease (COPD). Previous studies on lung function in individuals with severe alpha-1 antitrypsin deficiency (AATD) have shown a variable annual decline in FEV1 (∆FEV1). The aim of this study was to analyze ∆FEV1 and to identify risk factors for ∆FEV1 in individuals with severe AATD. Material and methods: Data on smoking habits, symptoms, results of lung function tests and exacerbations were obtained from the Swedish AATD Register and the Swedish National Patient Register (SNPR). The ∆FEV1 was analyzed by random-effects modeling and adjusted for age and FEV1 at baseline. Results: One hundred and four (9%) current smokers, 539 (48%) ex-smokers and 489 (43%) never-smokers were included in the study and followed-up from 1991 to 2016. A total of 584 (52%) individuals with severe AATD had COPD at inclusion. The median (IQR) annual severe exacerbation rate was 0.66 (1.4). The adjusted mean ∆FEV1 was significantly higher in the current smokers compared with the ex-smokers and never-smokers (70 [95% CI 56-83] vs 42 [95% CI 36-48] and 32 [95% CI 25-38) mL·yr-1], in the middle-aged individuals compared with the young individuals (48 [95% CI 41-55] vs 32 [95% CI 18-45] mL·yr-1), in the individuals with respiratory symptoms at inclusion compared with the asymptomatic individuals (46 [95% CI 40-52] vs 30 [95% CI 22-38]mL·yr-1), and in the individuals with frequent exacerbations compared with those with infrequent exacerbations (57 [95% CI 47-68] vs 27 [95% CI 17-37] mL·yr-1). Conclusion: Active smoking, age, respiratory symptoms at baseline and repeated severe exacerbations of COPD are factors associated with an accelerated decline of lung function in individuals with severe AATD.

Re-arthrodesis after primary ankle fusion: 134/1,716 cases from the Swedish Ankle Registry.

Background and purpose - Arthrodesis is the most common treatment of severe ankle arthritis. Large studies on the occurrence of re-arthrodesis are few, especially with information in terms of risk. We used the National Swedish Ankle Registry to assess incidence and risk factors for re-arthrodesis. Patients and methods - In the Registry, we examined the occurrence of re-arthrodesis in 1,716 patients with a primary ankle arthrodesis. We also analyzed associations between the re-arthrodesis risk and sex, diagnosis, and surgical method. Results - The risk of first re-arthrodesis at 2.5 years was 7.4% and the rate at 9 years 7.8%. The risk following arthroscopic surgery with fixation by screws was 15%, which is statistically significantly higher than the 8% following the gold standard technique with open screw fixation, the 5% following fixation by intramedullary nailing, and the 3% following fixation by plate and screws. Patients with either idiopathic osteoarthritis or posttraumatic arthritis had a higher risk of re-arthrodesis than patients with rheumatoid arthritis. We could not find that the risk of re-arthrodesis was associated with sex. Interpretation - In Sweden, the re-arthrodesis risk varied by primary technique and was especially high after arthroscopic surgery. Reasons are unknown but poor surgical technique and/or surgeon inexperience may contribute, as may patient selection.