Prevalence of denosumab-induced hypocalcemia: a retrospective observational study of patients routinely monitored with ionized calcium post-injection.

We assessed the prevalence of hypocalcemia after denosumab injections in a real-world cohort routinely monitored for calcium during up to 7.5 years of treatment. Among 1096 injections in 242 patients, 6.3% resulted in hypocalcemia, and was independent of the injection number. Severe hypocalcemia was rare (1%). PURPOSE: To assess the prevalence of and risk factors for hypocalcemia after administration of denosumab in a patient cohort routinely monitored for ionized calcium after each dose. METHODS: In this retrospective observational study, we analyzed denosumab-induced hypocalcemia in a real-world cohort who were routinely followed up with ionized calcium pre- and post-injection (within 31 days after injection) during the period 2011 to 2020. RESULTS: In total, we included data from 1096 denosumab injections in 242 individuals (1-15 injections per patient). The mean age for the first injection was 74 ± 10 years, and 88% were female. Post-injection hypocalcemia occurred after 6.3% of all injections (4.6% mild, 0.6% moderate, and 1.1% severe) and was independent of the number of injections (rate of hypocalcemia varied from 3-8%). Risk factors for hypocalcemia were male sex, severe renal failure, pre-injection hypocalcemia, hypomagnesemia, hypophosphatemia, and vitamin D insufficiency. Furthermore, older age was not associated with an increased hypocalcemia risk. CONCLUSIONS: Denosumab-induced hypocalcemia is a prevalent adverse event, which occurs independently of the number of injections. However, severe hypocalcemia is a rare occurrence, and severe renal failure and nutritional status appear to be important predictive factors. Magnesium and phosphate might add value in the pre-injection risk assessment; however, this observation needs to be confirmed in larger cohorts.

Vitamin D status in longstanding type 1 diabetes and controls. Association with upper extremity impairments.

Background: Patients with type 1 diabetes have a high prevalence of upper extremity impairments (UEIs), such as frozen shoulder, carpal tunnel syndrome, and trigger finger. The UEIs are strongly associated with activity limitations and impaired quality of life. The etiology of the UEI is not clear. Vitamin D deficiency has been considered to play a role in the pathogenesis of type 1 diabetes and in the development of macro- and microvascular complications in diabetes. Aim: To characterize vitamin D status in a large population of patients with type 1 diabetes, if vitamin D deficiency is associated with metabolic factors and possible association with UEI. Material and methods: Patients who diagnosed before 35 years of age, whose diabetes duration >20 years, and who are not older than 65 years were invited to participate in this cross-sectional case-control, multicenter study. Controls matched for age and sex were obtained from the national population registry. Fasting blood samples were collected and stored at -80°C until analyzed regarding 25-hydroxy-vitamin D (25(OH)D3) by a liquid chromatographic-mass spectrometric method (LC-MS/MS). Results: Vitamin D levels varied with season as expected in the northern hemisphere. The association between 25(OH)D3 and clinical variables was analyzed in a univariate general linear model, which indicated no difference in 25(OH)D3 in men with and without diabetes but higher values in women with diabetes. About 30% of both patients and controls had vitamin D deficiency (≤50 nmol/L). Analyzed by binary logistic regression UEIs was not associated with 25(OH)D3 levels. In both patients and controls, 25(OH)D3 was correlated to apolipoprotein A1 (r = 0.153; 0.220, P < 0.001). Conclusion: In patients with type 1 diabetes and a duration of 20 years or more, vitamin D level is not lower than in nondiabetic controls and is not associated with UEIs.

Patient Education Improves Pain and Health-Related Quality of Life in Patients with Established Spinal Osteoporosis in Primary Care-A Pilot Study of Short- and Long-Term Effects.

Fragility fractures, in particular vertebral fractures, are associated with high morbidity, including chronic pain and reduced health-related quality of life. We aimed to investigate the short- and long-term effects of patient education, including interdisciplinary themes, with or without physical training or mindfulness/medical yoga for patients with established spinal osteoporosis in primary care. Osteoporotic persons aged sixty years or older with one or more vertebral fractures were randomized to theory only, theory and physical exercise, or theory and mindfulness/medical yoga and were scheduled to once a week for ten weeks. Participants were followed up by clinical tests and questionnaires. Twenty-one participants completed the interventions and the one-year follow-up. Adherence to interventions was 90%. Pooled data from all participants showed significant improvements after intervention on pain during the last week and worst pain, and reduced painkiller use (any painkillers at baseline 70% [opioids 25%] vs. post-intervention 52% [opioids 14%]). Significant improvements were seen regarding RAND-36 social function, Qualeffo-41 social function, balance, tandem walking backwards, and theoretical knowledge. These changes were maintained at the 1-year follow-up. Patient group education combined with supervised training seems to have positive effects on pain, and physical function in persons with established spinal osteoporosis. The improved quality of life was maintained at the 1-year follow-up.

Trabecular bone microstructure analysis on data from a novel twin robotic X-ray device.

BACKGROUND: Bone strength is related to both mineral density (BMD) and the bone microstructure. However, only the assessment of BMD is available in clinical routine care today. PURPOSE: To analyze and study the correlation of trabecular bone microstructure from the imaging data of a prototype Multitom Rax system, using micro-computed tomography (CT) data as the reference method (Skyscan 1176). MATERIAL AND METHODS: Imaging data from 14 bone samples from the human radius were analyzed regarding six bone structure parameters, i.e. trabecular nodes, separation, spacing, and thickness as well as bone volume (BV/TV) and structural model index (SMI). RESULTS: All six structure parameters showed strong correlations to micro-CT with Spearman correlation coefficients in the range of 0.83-0.93. BV/TV and SMI had a correlation >0.90. Two of the parameters, namely, separation and number, had mean values in the same range as micro-CT. The other four were either over- or underestimated. CONCLUSION: The strong correlation between micro-CT and the clinical imaging system, indicates the possibility for analyzing bone microstructure with potential to add value in fracture assessment using the studied device in a clinical workflow.

The impact of imaging time and contrast agent dose on screening for osteoporosis with contrast-enhanced CT.

BACKGROUND: Screening for osteoporosis with contrast-enhanced computed tomography (CT) is promising for identifying high-risk osteoporotic patients. Our aims were (1) to investigate the estimated volume bone mineral density (vBMD) change over time after contrast injection (CT perfusion imaging, CTPI); and (2) to examine the influence of contrast dose on vBMD. METHODS: Fifteen patients, aged 71 ± 9 years (mean ± standard deviation, range 55-86) underwent a CTPI examination (28 scans within 63 s) of the upper body followed (after a waiting time of 10 min) by a full 4-phase CT examination (4 scans within 4 min). The contrast dose for CTPI was 0.38-0.83 mL/kg, and for 4-phase CT was 0.87-1.29 mL/kg. Vertebrae L1-L3 were analysed totalling 43 vertebrae, using Mindways qCT Pro. RESULTS: After contrast injection, vBMD showed a near-horizontal line until 17.5 s (non-contrast phase), followed by a steep increase 17.5-41.5 s after contrast injection, i.e., in the arterial phase, which plateaued 41.5 s after, i.e., in the early venous phase. A higher contrast dose per kg yielded significantly higher vBMD increase in both the arterial and venous phase (p < 0.003). CONCLUSIONS: Both time from contrast administration and contrast dose per kg affected vBMD results. In arterial phase, the steepness of the curve makes vBMD estimation unsure. However, as values plateaued in the venous phase it might be possible to predict the correct vBMD values. Furthermore, contrast dose is a factor that needs to be adjusted for when using such a formula.

Selection of risk assessment methods for osteoporosis screening in postmenopausal women with low-energy fractures: A comparison of fracture risk assessment tool, digital X-ray radiogrammetry, and dual-energy X-ray absorptiometry.

OBJECTIVES: Fracture liaison services are designed to identify patients needing osteoporosis treatment after a fracture. Some fracture liaison service designs involve a prescreening step, for example, fracture risk assessment tool (FRAX®). Another possible prescreening tools are bone mass density assessment in the acute setting. The aim of this study was to assess the effectiveness of prescreening tools. METHODS: In the present prospective cohort study, women aged >55 years with a radius fracture were included. Patients were recruited at the emergency department after experiencing their fracture. All patients performed fracture risk assessment by fracture risk assessment tool, and bone mass density assessment by digital X-ray radiogrammetry and dual-energy X-ray absorptiometry (prescreening steps) as well as full routine evaluation at the osteoporosis unit (endpoint). The main outcome measures were sensitivity, specificity, predictive values, and area under the curve. RESULTS: Forty-one women were recruited (mean age: 70 ± 8 years). Of these, 54% fulfilled the treatment indication criteria of osteoporosis after a full examination. Fracture risk assessment tool without bone mass density (cutoff ⩾ 15%) for prescreening patients had a high sensitivity (90%) but a low area under the curve (0.50) and specificity (16%). The highest area under the curve (0.73) was found prescreening with bone mass density assessment (dual-energy X-ray absorptiometry or digital X-ray radiogrammetry) having a sensitivity of 59%-86% and specificity of 61%-90%. CONCLUSION: This study, though small, raises questions regarding the effectiveness of using a prescreening step in fracture liaison services for high-risk individuals. In this cohort, FRAX® without bone mass density had a low precision, with a risk of both underestimating and overestimating patients requiring treatment. Bone mass density assessment in the acute setting could improve the precision of prescreening. Further investigations on the effectiveness and health economics of prescreening steps in fracture liaison services are needed.

Total Hip Bone Mineral Density as an Indicator of Fracture Risk in Bisphosphonate-Treated Patients in a Real-World Setting.

Bone mineral density (BMD) is an established measure used to diagnose patients with osteoporosis. In clinical trials, change in BMD has been shown to provide a reliable estimate of fracture risk reduction, and achieved BMD T-score has been shown to reflect the near-term risk of fracture. We aimed to test the association between BMD T-score and fracture risk in patients treated for osteoporosis in a real-world setting. This retrospective, observational cohort study included Swedish females aged ≥55 years who had a total hip BMD measurement at one of three participating clinics. Patients were separated into two cohorts: bisphosphonate-treated and bisphosphonate-naïve prior to BMD measurement, stratified by age and prior nonvertebral fracture status. The primary outcome was cumulative incidence of clinical fractures within 24 months of BMD measurement, with other fracture types included as secondary outcomes. Associations between T-score and fracture risk were estimated using proportional hazards regression and restricted cubic splines. A total of 15,395 patients were analyzed: 11,973 bisphosphonate-naïve and 3422 bisphosphonate-treated. In the 24 months following BMD measurement, 6.3% (95% confidence interval [CI], 5.9-6.7) of bisphosphonate-naïve and 8.4% (95% CI, 7.5-9.4) of bisphosphonate-treated patients experienced a clinical fracture. Strong inverse relationships between BMD T-score and fracture incidence were observed in both cohorts. Among bisphosphonate-naïve patients, this relationship appeared to plateau around T-score -1.5, indicating smaller marginal reductions in fracture risk above this value; bisphosphonate-treated patients showed a more consistent marginal change in fracture risk across the evaluated T-scores (-3.0 to -0.5). Trends remained robust regardless of age and prior fracture status. This real-world demonstration of a BMD-fracture risk association in both bisphosphonate-naïve and bisphosphonate-treated patients extends evidence from clinical trials and recent meta-regressions supporting the suitability of total hip BMD as a meaningful outcome for the clinical management of patients with osteoporosis. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Computed tomography-based opportunistic osteoporosis assessment: a comparison of two software applications for lumbar vertebral volumetric bone mineral density measurements.

BACKGROUND: We aimed to compare two volumetric bone mineral density (vBMD) analysis programs, regarding (I) agreement of vBMD values based on mono- and dual-energy computed tomography (MECT and DECT) scans and (II) suitability for analyzing DECT data obtained at different energies. METHODS: We retrospectively analyzed two abdominal CT datasets: one performed in a MECT scan (vertebrae L1-L3) and one in a DECT scan (vertebrae L1-L4). Each dataset included different individuals [MECT 15 patients (45 vertebrae) and DECT 12 patients (48 vertebrae), respectively]. vBMD analysis was conducted using Philips IntelliSpace (IP) and Mindways qCT Pro (MW). Regarding the DECT scans, vBMD analysis was done at three different energies: 80, 150 and synthetic 120 kVp and for MECT scan at 120 kVp. For comparison of vBMD results between different software (aim 1) MECT 120 kVp and DECT synthetic 120 kVp data was used. For analyzing suitability of using different DECT energies for vBMD assessment (aim 2) all three DECT energies were used and results from each software was analyzed separately. RESULTS: vBMD assessed with MW and IP, respectively correlated significantly for both the MECT (r=0.876; P<0.001) and DECT (r=0.837; P<0.001) scans, but the vBMD values were lower in using IP for vBMD assessment (8% and 14% lower for MECT and DECT, respectively; P=0.001). Regarding the different DECT energies, using MW for vBMD assessment showed significant correlations in vBMD results between 120 kVp and the two other energies (r=0.988 and r=0.939) and no significant differences in absolute vBMD values (P>0.05). The IP analysis as well showed significant correlation between 120 kVp and the other energies (r=0.769 and r=0.713, respectively), but differences in absolute vBMD values between the energies (P≤0.001). CONCLUSIONS: We show that the correlations between the vBMD derived from the two investigated software solutions were generally good but that absolute vBMD value did differ and might impact the clinical diagnosis of osteoporosis. Though small, our study data indicate that vBMD might be assessed in energies other than 120 kVp when using MW but not when using IP.

Weight loss with or without intragastric balloon causes divergent effects on ghrelin cell expression.

OBJECTIVE: The mechanism of action of intragastric balloons in the treatment of obesity is not fully understood. One of the hypotheses is that balloons might have an effect on the fundus, the area of ghrelin production. METHODS: Participants were randomized to a 13-week period of sham or balloon treatment followed by a 13-week period of balloon therapy in everyone. Blood samples for ghrelin levels were taken in the fasting state and after a breakfast at the start, after 13 and 26 weeks. Biopsies for ghrelin cell immunohistochemistry were taken from the fundus at endoscopy. RESULTS: Seven participants entered the balloon-balloon (BB) group and 11 the sham-balloon (SB) group. Despite a considerable weight loss, a median -17.9 kg (interquartile ranges -23.8 to -0.5) in the BB group and -18.3 kg (-22.7 to -14.7) in the SB group, fasting ghrelin and meal-induced ghrelin response did not change. In the SB group, the number of ghrelin cells increased significantly (p 0.001) from 110.6 (83.6-118.9) to 160.2 (128.5-223.0) while on sham treatment and returned to initial levels, 116.3 (91.7-146.9) (p 0.001), when they received their first balloon. No significant changes in ghrelin cell numbers were observed in the BB group. CONCLUSION: In participants without a balloon, weight loss induced an increase in ghrelin cell numbers in the fundus, which was annulled by the subsequent placement of a balloon. The effect of a balloon might be explained by effects on ghrelin cell numbers or ghrelin cell activity.

Low health-related quality of life is strongly linked to upper extremity impairments in type 1 diabetes with a long duration.

PURPOSE: To compare health-related quality of life (HRQOL) in type 1 diabetes and non-diabetic controls and possible links to upper extremity impairments (UEIs). Prevalence of sick-leave and causes were investigated. MATERIALS AND METHODS: This Swedish population-based case-control study included type 1 diabetes patients <67 years old and with a diabetes duration ≥20 years. Participants completed a postal questionnaire including Short Form 36, and questions regarding UEIs, and sick-leave. RESULTS: In total, 773 patients, aged 50 ± 10 years (diabetes duration 35 ± 10 years), and 708 non-diabetic controls, aged 54 ± 9 years, completed the study. Patients reported significantly lower HRQOL compared with controls. The difference was greatest for general health, vitality, and bodily pain. Patients with shoulder or hand but not finger impairments scored significantly lower than asymptomatic patients. The prevalence of sick leave was higher in patients vs. controls (23% vs. 9%, p < 0.001), and nearly half cited impairments from back, muscles, or joints as the main reason. CONCLUSIONS: Health-related quality of life is lower in type 1 diabetes than controls and in patients with shoulder and hand impairments than in asymptomatic. Musculoskeletal impairments (back/muscle/joints) have impact on work ability. Identification of UEIs is important for initiating preventative-, therapeutic-, and rehabilitative interventions.Implications for rehabilitationUpper extremity impairments (UEIs) that are common in type 1 diabetes, and associated with reduced health-related quality of life, should preferably be screened for on a regular basis along with other known diabetes complications.Early identification of UEIs is important to improve health by initiating preventive as well as therapeutic multi-professional rehabilitative interventions.Sick leave is higher in type 1 diabetes than in controls. Musculoskeletal impairments, including the back, muscles, and joints, are a common cause for sick leave warranting further studies.

Mindfulness and Modified Medical Yoga as Intervention in Older Women with Osteoporotic Vertebral Fracture.

Background: People with osteoporotic vertebral compression fractures (VCFs) have decreased health-related quality of life (HRQoL). Yoga and mindfulness are methods that can promote well-being. Objective: The aim of this article was to explore the effect of mindfulness and modified medical yoga on HRQoL, stress, sleep, and pain in people 60 years or older with a diagnosed osteoporotic VCF. Design: The School of Osteoporosis in Linköping (SOL) is a pilot study with randomized groups. Materials and Methods: The SOL-study was scheduled to once a week for 10 weeks. Ten people were randomized to a theory (T) group, and ten people were randomized to a theory and mindfulness/medical yoga (MMY) group. The educational sessions lasted 60 min and were similar for the groups, but they took place at different facilities. An experienced physiotherapist supervised the MMY sessions for 60 min. Sleep quality and present stress experience were measured on a symmetric Likert scale. The numeric rating scale was used for pain, and EQ-5D, RAND-36, and Qualeffo-41 were used for HRQoL. The patient enablement instrument (PEI) was used to reflect how the participants coped with their illness. Results: Eight women in the MMY-group and seven women in the T-group completed the SOL study interventions. The adherence to the intervention program was 89% in the MMY-group and 87% in the T-group. There was no adverse consequence of the MMY training. After the 10-week intervention period, sleep quality (p = 0.018) and present stress (p = 0.043), but not perceived pain were improved in the MMY-group. The social function (SF) domain was improved in the MMY-group that was measured by both RAND-36 (p = 0.028) and Qualeffo-41 (p = 0.012). There was a trend toward a better PEI-score in the MMY-group compared with the T-group postintervention (p = 0.089). Conclusion: This article suggests that mindfulness and modified medical yoga supervised by a skilled physiotherapist may be a feasible way to improve SF, sleep, and stress in older women with osteoporotic VCFs.

Adherence to and persistence with zoledronic acid treatment for osteoporosis-reasons for early discontinuation.

This retrospective study reports 81% long-term (> 3 years) adherence to and 77% persistence with zoledronic acid (ZA) treatment in osteoporosis patients, with ZA being costfree for patients. Eight percent of patients discontinued treatment because of adverse events (AEs), with a tendency of higher discontinuation rate in older patients. PURPOSE: This study investigated (1) long-term adherence to and persistence with ZA treatment in a real-world setting, (2) extent to which an adverse reaction to ZA impacted on adherence and persistence, and (3) whether there were sex or age differences in patients that had early treatment termination (ETT) due to AEs and those who adhered to the regimen. METHODS: All patients treated with ZA at the Endocrinology Department at Linköping University Hospital, Linköping, Sweden between 2012 and 2017 were included. ETT was defined as < 3 ZA infusions, which was confirmed from patients' medical records. RESULTS: A total of 414 patients were treated with ZA, with 81% receiving > 3 ZA infusions. Three-year persistence was 77% for a treatment window of 365 days ± 90 days (75% with 365 days ± 60 days window). The most common reason for ETT was AEs (8%), followed by medical conditions (5%), biological aging (3%), and other (e.g., lost to follow-up [3%]). Most patients who discontinued treatment because of AEs reported symptoms of acute-phase reaction, and tended to be older than those who adhered to treatment (74 ± 9 vs 70 ± 13 years, p = 0.064). There was no difference in sex ratio between the 2 groups (85% vs 90% females, p = 0.367). CONCLUSION: Rates of long-term adherence to and persistence with ZA treatment were high with a pre-scheduled 3-year treatment regimen in the tax-financed Swedish healthcare system. AEs-mainly acute-phase reaction-were the most common reason for ETT, occurring in nearly 1 out of 10 patients.

Clinical Examination and Self-Reported Upper Extremity Impairments in Patients with Long-Standing Type 1 Diabetes Mellitus.

AIM: The aims of the current study were (1) to determine the prevalence of upper extremity impairments (UEIs) in patients with type 1 diabetes by clinical investigation; (2) to investigate if self-reported impairments were concordant with clinical findings and if key questions could be identified; and (3) to investigate if answers to our self-reported questionnaire regarding UEIs are reliable. METHODS: Patients with type 1 diabetes were invited to participate in a cross-sectional study of clinical and self-reported (12 items) UEIs in adjunction to ordinary scheduled clinical visit. Before the visit, a questionnaire on UEIs was filled in twice (test-retest) followed by clinical testing at the planned visit. RESULTS: In total, 69 patients aged 45 ± 14 years and with diabetes duration 26 ± 15 were included in the study. In the clinical examination, two-thirds (65%) of the patients showed one or more UEI, with failure to perform hand against back as the most common clinical finding (40%) followed by positive Phalen's test (27%), Tinel's test (26%), and Prayer's sign (24%). UEIs observed by clinical examination were often bilateral, and multiple impairments often coexisted. Self-reported shoulder stiffness was associated with impaired shoulder mobility and with Prayer's sign. Self-reported reduced hand strength was associated to lower grip force, Prayer's sign, trigger finger, fibrosis string structures, and reduced thenar strength as well as reduced shoulder mobility. In addition, self-reporting previous surgery of carpal tunnel and trigger finger was associated with several clinical UEIs including shoulder, hand, and finger. The test-retest of the questionnaire showed a high agreement of 80-98% for reported shoulder, hand, and finger impairments. CONCLUSION: UEIs are common in type 1 diabetes. Self-reported shoulder stiffness and reduced hand strength might be used to capture patients with UEIs in need of clinical investigation and enhanced preventive and therapeutic strategies, as well as rehabilitative interventions.

Toe brachial index predicts major acute cardiovascular events in patients with type 2 diabetes independently of arterial stiffness.

OBJECTIVE: Our aim was to analyze the predictive value of toe brachial index (TBI) as a risk marker for future major adverse cardiovascular events (MACE) and all-cause mortality in patients with type 2 diabetes (T2D). METHODS: TBI was measured in 741 patients with T2D in 2005-2008. Conventional risk factors for vascular disease as well as non-invasive measurements such as pulse-wave velocity (PWV) and intima-media thickness (IMT) of the carotid arteries were estimated. MACE was defined as cardiovascular death or hospitalization for non fatal myocardial infarction or non fatal stroke. Patients were followed for incidence of MACE using the national Swedish Cause of Death Registry and the Inpatient Register. RESULTS: During the follow-up for a period of 9 years MACE occurred in 97 patients and 85 patients died. TBI tertile, 1 versus 3, was significantly related to MACE (HR 2.67, 95%CI 1.60-4.50; p < 0.001) and to all-cause mortality (HR 1.98, 95%CI 1.16-3.83; p = 0.01). TBI tertile 1 as compared to TBI tertile 3 predicted MACE, but not all-cause mortality, independently of age, sex, diabetes duration and treatment, antihypertensive treatment, previous cardiovascular diseases, office systolic blood pressure, HbA1c, LDL cholesterol, estimated glomerular filtration rate, body mass index, current smoking PWV, IMT and carotid plaque presence (HR 3.39, 95%CI 1.53-7.51; p = 0.003 and HR 1.81, 95%CI 0.87-3.76; p = 0.1, respectively). CONCLUSIONS: Low TBI predicts an increased risk for MACE independently of arterial stiffness in patients with type 2 diabetes. TRIAL REGISTRATION: Clinical Trials.gov number NCT01049737. Registered January 14, 2010.

Risk of major osteoporotic fracture after first, second and third fracture in Swedish women aged 50 years and older.

BACKGROUND: Osteoporosis affects approximately one in five European women and leads to fragility fractures, which result in poor health, social and economic consequences. Fragility fractures are a strong risk factor for subsequent major osteoporotic fracture (MOF), with risk of MOF being elevated in the 1-2 years following an earlier fracture, a concept described as "imminent risk". This study examines risk of subsequent MOF in patients with one, two or three prior fractures by age and type of fracture. METHODS: In this retrospective, observational cohort study, Swedish women aged ≥50 years with ≥1 any clinical fragility fracture between July 1, 2006 and December 31, 2012 were identified from Sweden's National Patient Register. Each patient was age- and sex-matched to three controls without history of fracture. Group 1 women included those with one fragility fracture during the study period; Group 2 included those with two fragility fractures; and Group 3 included those with three fragility fractures. "Index fracture" was defined as the first fracture during the study period for Group 1; the second for Group 2; and the third for Group 3. Patients in each cohort and matched controls were followed for up to 60 months or until subsequent MOF (hip, vertebra, forearm, humerus), death or end of data availability. RESULTS: 231,769 women with at least one fracture were included in the study and therefore constituted Group 1; of these, 39,524 constituted Group 2 and of those, 7656 constituted Group 3. At five years, cumulative incidence of subsequent MOF was higher in patients with a history of fracture as compared to controls (Group 1: 20.7% vs 12.3%; Group 2: 32.0% vs 15.3%). Three-year cumulative incidence for Group 3 was 12.1% (vs 10.7% for controls). After adjusting for baseline covariates, risk of subsequent MOF was highest within 0-24 months following an index fracture, then decreased but remained elevated as compared to controls. Having two prior fractures, vertebral fractures and younger age at time of index fracture were associated with greater relative risk. CONCLUSIONS: Women with a history of osteoporotic fracture are at increased risk of subsequent fracture, which is highest during the first 24 months following a fracture. Younger women and those with vertebral fractures are at greatest relative risk, suggesting that treatment should target these patients and be timely enough to impact the period of imminent risk.

History of Previous Fracture and Imminent Fracture Risk in Swedish Women Aged 55 to 90 Years Presenting With a Fragility Fracture.

The term "fracture cascade" refers to the sequence of fragility fractures resulting from the increased fracture risk that occurs with aging and following fractures. Here, we evaluate the sequence of previous fractures in women aged 55 to 90 years presenting with a fragility fracture and subsequent (12 to 24 months) fracture incidence. In this retrospective, observational study, women aged 55 to 90 years with an "index" fragility fracture in 2013 were identified from Swedish national registries. A history of previous fractures (2001 to 2012) and osteoporosis treatment was used to characterize fracture cascade patterns. Cumulative incidence of new fractures within 12 to 24 months following the index fracture, based on index fracture type and age, were used to describe the risk of subsequent fractures. A total of 35,146 women with a mean age of 73.8 years were included (7180 hip, 2786 clinical vertebral, and 25,180 nonhip/nonvertebral [NHNV] index fractures); 38% of women with hip, 38% with clinical vertebral, and 25% with NHNV index fractures had one or more previous fractures. Across all index fracture types, the proportion of women with any previous fracture increased with age; 34% to 46% of index hip or clinical vertebral fractures in women ≥70 years were not their first fracture. Following any index fracture, cumulative incidence of a new fracture over 24 months was over 11% (index clinical vertebral 18%; index hip 14%). Osteoporosis treatment rates were low both in patients with (27%) and without (18%) a previous fracture. These descriptive data demonstrate that almost one-third of women aged 55 to 90 years suffering a new fracture have had a previous fragility fracture. Fracture location influences incidence and type of subsequent fracture during the 24 months following a fragility fracture, with clinical vertebral fractures carrying the greatest imminent fracture risk. These data highlight the clinical impact and need for early, effective treatment soon after any fragility fracture. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Mobile learning device increased study efficiency for radiology residents but with risk of temporary novelty effect.

BACKGROUND: Digital resources in learning are increasingly available and offer new possibilities in education. Mobile learning devices (MLD) such as tablets provide easy and flexible access for users. PURPOSE: To investigate whether the introduction of MLDs in radiology education affected time spent on studies over a longer time frame and whether learning behavior and attitudes changed. MATERIAL AND METHODS: The radiology residents employed during 2015-2016 were invited to participate in this 12-month MLD intervention study. Results were evaluated using online questionnaires at six months (6 m) and 12 months (12 m). RESULTS: Thirty-one residents were included, of whom half were in the early stages of residency (<2 years). After the MLD introduction, most participants (91% [6 m] and 83% [12 m]) estimated increased time spent on studies. Of these, 32% stated "a lot more" at 6 m but only 8% at 12 m (P = 0.12). The MLDs showed positive effects on the experience of radiology studies, as a majority of participants stated better quality and effectiveness in their studies (100% [6 m]-92% [12 m]), that MLD facilitated access to educational materials to a high degree (83% [6 m]-75% [12 m]), and that studies had become better and more fun (96% [6 m]-100% [12 m]). CONCLUSION: The use of MLDs seems to facilitate learning effectively for radiologic residents. However, a larger scale study is required as a trend of decreasing figures in the longer term was seen, but our results did not show a significant reduction of time spent on radiology studies.

Differing impact of clinical factors on the risk of fracture in younger and older women in the general population and an osteoporosis clinic population.

This study assesses the impact of risk factors for fracture in women aged 80+ and 60-79. The results suggest that risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort. PURPOSE: This study assesses whether the impact of classical risk factors for fracture due to osteoporosis is different in women aged 80+ and women aged 60-79. Since most prior research on the contribution of risk factors is based on patients below 80 years of age, this study aims to fill this knowledge gap to increase the accuracy of risk assessment in the oldest old. METHODS: Retrospective, observational cohort study using Swedish national health register data and BMD data from osteoporosis clinics. Women aged at least 60 were identified from a random sample of the general population and from the BMD databases and allocated to two populations representing patients at different stages of risk assessment. The relative impact of risk factors on fracture risk was assessed using multivariate competing risk regression with fracture as outcome and death as competing event. RESULTS: A total of 163,329 women were included from the general population (52,499 aged 80+) and 22,378 from the BMD databases (4563 aged 80+). The clinical risk factors with relatively highest effect on fracture risk in the older patients were prior fracture and hip T-score below - 2.5 SD. Other included risk factors showed lower impact in the older compared to the younger strata. CONCLUSIONS: This study confirms our understanding of the key risk factors for fracture: age, prior fracture, and a low T-score. Regarding remaining risk factors, risk assessment which fits younger women may not be suited for the 80+ strata as many common risk factors are less predictive in the older compared to the younger cohort.

Upper extremity impairments in type 1 diabetes with long duration; common problems with great impact on daily life.

PURPOSE: To investigate the prevalence, activity limitations and potential risk factors of upper extremity impairments in type 1 diabetes in comparison to controls. METHODS: In a cross-sectional population-based study in the southeast of Sweden, patients with type 1 diabetes <35 years at onset, duration ≥20 years, <67 years old and matched controls were invited to answer a questionnaire on upper extremity impairments and activity limitations and to take blood samples. RESULTS: Seven hundred and seventy-three patients (ages 50 ± 10 years, diabetes duration 35 ± 10 years) and 708 controls (ages 54 ± 9 years) were included. Shoulder pain and stiffness, hand paraesthesia and finger impairments were common in patients with a prevalence of 28-48%, which was 2-4-folds higher than in controls. Compared to controls, the patients had more bilateral impairments, often had coexistence of several upper extremity impairments, and in the presence of impairments, reported more pronounced activity limitations. Female gender (1.72 (1.066-2.272), p = 0.014), longer duration (1.046 (1.015-1.077), p = 0.003), higher body mass index (1.08 (1.017-1.147), p = 0.013) and HbA1c (1.029 (1.008-1.05), p = 0.007) were associated with upper extremity impairments. CONCLUSIONS: Compared to controls, patients with type 1 diabetes have a high prevalence of upper extremity impairments, often bilateral, which are strongly associated with activity limitations. Recognising these in clinical practise is crucial, and improved preventative, therapeutic and rehabilitative interventions are needed. Implications for rehabilitation Upper extremity impairments affecting the shoulder, hand and fingers are common in patients with type 1 diabetes, the prevalence being 2-4-fold higher compared to non-diabetic persons. Patients with diabetes type 1 with upper extremity impairments have more pronounced limitations in daily activities compared to controls with similar impairments. Recognising upper extremity impairments and activity limitations are important and improved preventive, therapeutic and rehabilitation methods are needed.

Dysregulated growth hormone-insulin-like growth factor-1 axis in adult type 1 diabetes with long duration.

CONTEXT: In type 1 diabetes (T1D), dysregulation of the GH-IGF-1 axis has been reported. Whether this is related to upper extremity impairments (UEI) is unknown. OBJECTIVE: Examine differences in GH-IGF-1 axis between T1D on subcutaneous insulin treatment and matched controls without diabetes and possible associations between GH-IGF-1 axis and UEI. DESIGN: Cross-sectional population-based study. Patients with T1D, onset <35 years, duration ≥ 20 years, <67 years old and controls were invited to answer questionnaires and take blood samples. SUBJECTS: A total of 605 patients with T1D and 533 controls accepted to participate. OUTCOMES: Fasting levels of IGF-1, IGF-1 Z-score, IGFBP-1, IGFBP-3, C-peptide, GH and UEI. RESULTS: Patients with T1D had lower IGF-1 and IGFBP-3 and higher IGFBP-1 and GH than controls. The difference in IGF-1 persisted with age. Insulin dose was associated with increasing IGF-1 Z-score but even at a very high insulin dose (>1U/kg) IGF-1 Z-score was subnormal compared to controls. IGF-1 Z-score was unaffected by glycaemic control (HbA1c) but increased with residual insulin secretion, (C-peptide 1-99 pmol/L). IGFBP-1 was associated with fasting blood glucose, negatively in controls and positively in patients with T1D probably reflecting insulin resistance and insulin deficiency, respectively. There was no association between lower IGF-1 Z-score and UEI in T1D. CONCLUSION: In adult T1D with fair glycaemic control, the GH-IGF-1 axis is dysregulated exhibiting GH resistance, low IGF-1 and elevated IGFBP-1. Subcutaneous insulin cannot normalize these changes while endogenous insulin secretion has marked effects on IGF-1 pointing to a role of portal insulin.