Opportunistic Identification of Vertebral Compression Fractures on CT Scans of the Chest and Abdomen, Using an AI Algorithm, in a Real-Life Setting.

This study evaluated the performance of a vertebral fracture detection algorithm (HealthVCF) in a real-life setting and assessed the impact on treatment and diagnostic workflow. HealthVCF was used to identify moderate and severe vertebral compression fractures (VCF) at a Danish hospital. Around 10,000 CT scans were processed by the HealthVCF and CT scans positive for VCF formed both the baseline and 6-months follow-up cohort. To determine performance of the algorithm 1000 CT scans were evaluated by specialized radiographers to determine performance of the algorithm. Sensitivity was 0.68 (CI 0.581-0.776) and specificity 0.91 (CI 0.89-0.928). At 6-months follow-up, 18% of the 538 patients in the retrospective cohort were dead, 78 patients had been referred for a DXA scan, while 25 patients had been diagnosed with osteoporosis. A higher mortality rate was seen in patients not known with osteoporosis at baseline compared to patients known with osteoporosis at baseline, 12.8% versus 22.6% (p = 0.003). Patients receiving bisphosphonates had a lower mortality rate (9.6%) compared to the rest of the population (20.9%) (p = 0.003). HealthVCF demonstrated a poorer performance than expected, and the tested version is not generalizable to the Danish population. Based on its specificity, the HealthVCF can be used as a tool to prioritize resources in opportunistic identification of VCF's. Implementing such a tool on its own only resulted in a small number of new diagnoses of osteoporosis and referrals to DXA scans during a 6-month follow-up period. To increase efficiency, the HealthVCF should be integrated with Fracture Liaison Services (FLS).

Development of a program theory for osteoporosis patient education in Denmark: a qualitative study based on realist evaluation.

BACKGROUND: Osteoporosis patient education is offered in many countries worldwide. When evaluating complex interventions like these, it is important to understand how and why the intervention leads to effects. This study aimed to develop a program theory of osteoporosis patient education in Danish municipalities with a focus on examining the mechanisms of change i.e. what is about the programs that generate change. METHODS: The program theory was developed in an iterative process. The initial draft was based on a previous published systematic review, and subsequently the draft was continually refined based on findings from observations (10 h during osteoporosis patient education) and interviews (individual interviews with six employees in municipalities and three health professionals at hospitals, as well as four focus group interviews with participants in patient education (in total 27 informants)). The transcribed interviews were analyzed using thematic analysis and with inspiration from realist evaluation the mechanisms as well as the contextual factors and outcomes were examined. RESULTS: Based on this qualitative study we developed a program theory of osteoporosis patient education and identified four mechanisms: motivation, recognizability, reassurance, and peer reflection. For each mechanism we examined how contextual factors activated the mechanism as well as which outcomes were achieved. For instance, the participants' motivation is activated when they meet in groups, and thereafter outcomes such as more physical activity may be achieved. Recognizability is activated by the participants' course of disease, which may lead to better ergonomic habits. Reassurance may result in more physical activity, and this mechanism is activated in newly diagnosed participants without previous fractures. Peer reflection is activated when the participants meet in groups, and the outcome healthier diet may be achieved. CONCLUSIONS: We developed a program theory and examined how and why osteoporosis patient education is likely to be effective. Understanding these prerequisites is important for future implementation and evaluation of osteoporosis patient education.

The Postprandial Calcium Absorption of a Milk-Derived Calcium Permeate - The Acute RENEW Double-Blinded Randomized Controlled Cross-Over Study.

BACKGROUND: Studies suggest that dairy-derived calcium supplements have additional beneficial properties compared with other calcium supplements in relation to bone health. OBJECTIVES: We investigated the postprandial calcium absorption from a milk-derived calcium permeate (CP) compared with calcium carbonate (CC). METHODS: In this randomized double-blinded cross-over study, 10 healthy postmenopausal females (age 50-65 y) received maltodextrin (placebo), 800 mg calcium from CP or from CC provided in 6 capsules on separate days. A fasting blood sample was collected at baseline, 60, 120, 240, and 360 min after ingestion. At baseline and 360 min, spot-urine samples were collected. Serum-ionized calcium, intact parathyroid hormone, phosphorus, and magnesium were analyzed, as were urinary calcium, phosphorus, and magnesium. A linear mixed model was applied. RESULTS: Serum-ionized calcium concentration after the CC supplement was higher at 240 min compared with the CP supplement [between-group difference; 95% confidence interval (CI): 0.039 mmol/L; 95% CI: 0.017-0.061; P = 0.00078]. Serum-ionized calcium concentration after the CC supplement was significantly higher than placebo at all postprandial time points except at 60 min. Urinary calcium concentration in 360 min spot urine was higher after intake of CC compared with CP [between-group difference; 95% CI: 2.47 mmol/L; 95% CI: 1.90-3.03; P = 0.0042]. CONCLUSIONS: Postprandial calcium absorption from CP was lower than that of CC, and concurrently, urinary concentration reflected increased serum appearance by CC compared with CP, highlighting different metabolic responses. The long-term and clinical implications should be studied further.

The effect of parathyroidectomy compared to non-surgical surveillance on kidney function in primary hyperparathyroidism: a nationwide historic cohort study.

BACKGROUND: Patients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) < 60 mL/min) are offered parathyroidectomy (PTX) to protect them from further complications. Surprisingly, two recent uncontrolled cohort studies have suggested a further decrease in kidney function following PTX. We aimed to examine the effects of PTX compared to non-surgical surveillance on kidney function in pHPT patients. METHODS: Historic cohort study. From the Danish National Patient Registry (NPR) and major medical biochemistry laboratories in Denmark, we identified 3585 patients with biochemically confirmed pHPT among whom n = 1977 (55%) were treated with PTX (PTX-group) whereas n = 1608 (45%) were followed without surgery (non-PTX group). Baseline was defined as time of diagnosis and kidney function was re-assessed 9-15 months after PTX (PTX group) or 9-15 months after diagnosis (non-PTX group). RESULTS: At follow-up, eGFR had decreased significantly in the PTX- compared to the non-PTX-group (median - 4% vs. - 1%, p < 0.01). Stratification by baseline eGFR showed that the decrease was significant for those with a baseline eGFR value of 80-89 and > 90 mL/min, but not for those with lower eGFR values. Findings did not differ between patients with mild compared to moderate/severe hypercalcemia. However, after mutual adjustments, we identified baseline levels of calcium, PTH, and eGFR as well as age and treatment (PTX vs. no-PTX) as independent predictors for changes in kidney function. CONCLUSION: Compared to non-surgical surveillance, PTX is associated with a small but significant decrease in kidney function in pHPT patients with an initial normal kidney function.

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial-Protocol and statistical analysis plan.

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists. METHODS: The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals. DISCUSSION: The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

Evaluation of an mHealth App on Self-Management of Osteoporosis: Prospective Survey Study.

BACKGROUND: Mobile health (mHealth) technologies can be used for disease-specific self-management, and these technologies are experiencing rapid growth in the health care industry. They use mobile devices, specifically smartphone apps, to enhance and support medical and public health practices. In chronic disease management, the use of apps in the realm of mHealth holds the potential to improve health outcomes. This is also true for mHealth apps on osteoporosis, but the usage and patients' experiences with these apps are underexplored. OBJECTIVE: This prospective survey study aimed to investigate the eHealth literacy of Danish patients with osteoporosis, as well as the usability and acceptability of the app "My Bones." METHODS: Data on patient characteristics, disease knowledge, eHealth literacy, usability, and acceptability were collected using self-administered questionnaires at baseline, 2 months, and 6 months. The following validated questionnaires were used: eHealth Literacy Questionnaire, System Usability Scale, and Service User Technology Acceptability Questionnaire. RESULTS: Mean scores for eHealth literacy ranged from 2.6 to 3.1, with SD ranging from 0.5 to 0.6 across the 7 domains. The mean (SD) System Usability Scale score was 74.7 (14.4), and the mean (SD) scores for domains 1, 2, and 6 of the Service User Technology Acceptability Questionnaire were 3.4 (1.2), 4.5 (1.1), 4.1 (1.2), respectively. CONCLUSIONS: Danish patients with osteoporosis are both motivated and capable of using digital health services. The app's usability was acceptable, and it has the potential to reduce visits to general practitioner clinics, enhance health outcomes, and serve as a valuable addition to regular health or social care services.

Postoperative Chronic Hypoparathyroidism and Quality of Life After Total Thyroidectomy.

Chronic hypoparathyroidism (HypoPT) is a common complication after total thyroidectomy and it impacts affected patients' quality of life (QoL). This study aimed to assess the QoL in patients with chronic HypoPT independently from their concurrent hypothyroidism and other comorbidities. For this purpose a follow-up study was performed, including 14 patients who developed chronic HypoPT after total thyroidectomy and 28 age- and sex-matched patients who had intact parathyroid function after total thyroidectomy. We used the RAND Short Form 36 Health Survey (SF-36) to compare the QoL between patients with or without chronic HypoPT. Chronic HypoPT patients had lower QoL scores in all domains of the RAND-SF-36 questionnaire and significant impairment in six of eight domains after adjustment for relevant confounders. They were more often operated because of a toxic diagnosis (p = .01), often being Graves disease. Additionally adjusting for surgical indications resulted in three of eight domains being significant affected. Chronic HypoPT is associated with significantly impairment of QoL, independently of the concurrent disease of hypothyroidism, comorbidities, and prospective values of TSH and serum (se)-ionized-Ca++. There is a need for more focus and better treatment of patients experiencing chronic HypoPT after surgery. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Deficiency of 25-hydroxyvitamin D in male HIV-positive patients: a descriptive cross-sectional study.

The aim of this descriptive cross-sectional study was to describe the prevalence of hypovitaminosis D in a cohort of HIV-seropositive males. Blood samples were collected in November and December 2004 and analyzed in the hospital laboratory. The concentration of 25-hydroxyvitamin D (25(OH)D) was defined as excellent when >75 nmol/l, normal when >50 nmol/l, insufficient when <50 nmol/l, deficient when <25 nmol/l and severely deficient when <12.5 nmol/l. Patient information was extracted from the medical records. A total of 115 males, median age 44 y (range 19-63 y), were included in the study. The median 25(OH)D concentration was 43.0 nmol/l (range 8-163 nmol/l) and the 25(OH)D level was excellent in 13%, normal in 27%, insufficient in 36%, deficient in 20%, and severely deficient in 4% of the cases. Vitamin D level was not associated with age, y with HIV infection, highly active antiretroviral therapy (HAART) or CD4 count. Compared to patients not in treatment, patients on HAART (n = 71) had higher levels of total alkaline phosphatase (median 83.0 vs 75.5 U/l; p = 0.031) and lower, though not significantly, total body mineral density (1.055 vs 1.107 g/cm(2); p = 0.077). This study confirms that the prevalence of hypovitaminosis is high among HIV-infected patients.

High incidence of chronic hypoparathyroidism secondary to total thyroidectomy.

INTRODUCTION: Hypoparathyroidism (HypoPT) is the most common complication after total thyroidectomy (TT). Recent literature report incidences of HypoPT that are higher than previously anticipated. This study aimed to assess the incidence of transient and chronic HypoPT in patients undergoing TT and to specify risk factors and recovery time. METHODS: This was a retrospective review of patients undergoing TT in the period from 2013 to 2018 due to benign thyroid disease in a Danish university hospital. In total, 187 patients were eligible for inclusion. Data were collected from internal medical files, the Thykir database sheets and patient records. HypoPT was defined as SE-ionised-Ca2+ levels (Less than 1.16 mmol/l) and inappropriately low parathyroid hormone levels. RESULTS: The incidence of transient and chronic HypoPT was 81 (43.3%) and 25 (13.4%), respectively. Younger ages and toxic indication for surgery were independent risk factors for transient and chronic HypoPT. Incidences in Graves' disease population were 70.5% and 27.3%, respectively. Resolution within the first months was seen in 48.2% of the patients with acute transient HypoPT. CONCLUSIONS: The incidence of chronic HypoPT after TT is higher than previously reported. This is primarily due to a lack of consistency in the definition and follow-up time between studies. Younger patients and those with a toxic indication for surgery are at higher risk of HypoPT after TT than other patients. FUNDING: none. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (REG-015-2019) and The Ethical Committee of Central Denmark (No. 66792).

Outcome of osteoporosis evaluation, treatment, and follow-up in patients referred to a specialized outpatient clinic compared to patients in care of general practitioners.

In Denmark, osteoporosis treatment is either handled by general practitioners or at more resource demanding specialist clinics. We evaluated the treatment adherence and persistence in the two settings, which were overall similar. The type of medical support did, however, differ and was provided to two very different patient populations. PURPOSE: The study aimed to investigate the effect of patient care by general practitioners (GPs) or specialists on treatment adherence among osteoporosis patients initiating treatment with oral bisphosphonates (OB). METHODS: Dual-energy X-ray absorption (DXA)-scanning data from 2005 to 2013 were extracted. Treatment naïve patients with a T-score ≤ - 2.5 (spine or hip) were included. Information on medical treatment, comorbidities, and socio-economic status was extracted from Danish registries. Scanning results were evaluated by a specialist. Subsequent treatment initiation and follow-up was either handled by GPs or specialists: GP population (GPP) vs. specialist population (SP). Primary adherence was defined as treatment initiating within 12 months from diagnosis and secondary adherence as days with medicine possession rates (MPR) > 80%. RESULTS: Of 11,201 DXA-scanned patients, 3685 met the inclusion criteria (GPP = 2177, SP = 1508). The GPP consisted of relatively more men, was older, had shorter education, lower income, and more comorbidities. There was no difference in baseline T-score or prior incidence of major osteoporotic fractures (MOFs). The GPP was primarily treated with OB and had better primary adherence (adjusted ORGPP/SP = 1.52 [1.31-1.75], p < 0.0001) than the SP that to a higher degree received another treatment. Secondary adherence was similar (adjusted ORGPP/SP: OR12 months = 1.02 [0.83-1.26]; OR24 months = 0.90 [0.73-1.10]; OR4 years = 0.88 [0.71-1.07]; OR5 years = 0.91 [0.74-1.13]. CONCLUSION: Patients in care of specialists were most likely to receive a treatment other than OB. Primary adherence was highest in the GPP, whereas short- and long-term persistence was similar for up to 5 years whether treated by a specialist or a GP.

[Bilateral atypical femoral fractures after prolonged antiresorptive treatment].

In this case report, two cases of bilateral atypical femoral fractures after prolonged bisphosphonate therapy are described. Two elderly females had more than ten years of antiresorptive treatment with bisphosphonate, and they were diagnosed with bilateral atypical femoral fracture (AFF) after a dual energy X-ray absorptiometry scanning of the entire femoral shaft. They were both subjected to intramedullary nails and anabolic treatment. Currently, bisphosphonate treatment of osteoporosis has been reduced because of side effects such as AFF.

Markers of bone turnover are reduced in patients with CF related diabetes; the role of glucose.

BACKGROUND: Cystic fibrosis(CF) related diabetes(CFRD) and osteoporosis are prevalent in adult patients with CF. We aimed to evaluate if CFRD and markers of glucose metabolism and inflammation are associated with bone turnover in CF. METHODS: Cross sectional study at the adult section at the Copenhagen CF Center from January-October 2017. Fasting blood samples, including bone turnover markers(BTMs) and cytokines, Dual-x-ray absorptiometry scan and oral glucose tolerance test were performed. Lung-transplanted participants and patients in antiosteoporotic treatment were excluded from analyses. RESULTS: 102 patients were included of whom 19 had a prior CFRD diagnosis. CFRD patients had lower procollagen type 1 N-terminal propeptide(P1NP) and C-Terminal cross-linked Telopeptide(CTX) levels compared to CF patients without diabetes (median[IQR]) 49.5 µg/l [29.6,57.1] vs 56.9 µg/l [38.2,74.3], p = .03 and 0.2 µg/l [0.1,0.3] vs 0.4 µg/l [0.3,0.6], p < .01, respectively. Fasting plasma glucose(FPG) was negatively associated with the bone formation markers P1NP and osteocalcin and bone resorption marker CTX. In multivariate linear regression FPG remained a significant predictor of P1NP -1.07 [-1.09;-0.01] and CTX -1.13 [-1.21;-1.06]. Bone mineral density Z-score was not different between patients with and without CFRD but FPG was negatively associated with hip and femoral neck Z-score. There was no consistent association between inflammatory cytokines and BTMs. CONCLUSIONS: Bone turnover markers are reduced in CF patients with CFRD and negatively associated with glucose levels. Extra attention towards frequent hyperglycemia in CF patients should be taken when evaluating decreased BMD. Glycemia may be a future target for improving outcome in CFBD.

Osteoporosis Is Associated with Deteriorating Clinical Status in Adults with Cystic Fibrosis.

BACKGROUND: Cystic fibrosis (CF) patients are in increased risk of osteoporosis. We aimed to determine the osteoporosis prevalence in an adult CF cohort and investigate calcium metabolic parameters and clinical status' association with bone mineral density evaluated by dual X-ray absorptiometry scan. METHODS: We performed a cross section database study of adults at a tertiary CF Center. Z scores were applied for patients < 50 years of age and T scores for patients > 50 years of age. RESULTS: One hundred twenty-five patients were included. Compared to nonosteoporotic patients, osteoporotic patients (15%) had significantly lower percent predicted forced expiratory volume in 1 second (ppFEV1), lower body mass index, higher frequency of CF-related diabetes and chronic lung infection, and higher high-sensitive C-reactive protein and glycated hemoglobin levels. Vitamin D was not associated with any outcome. In multivariate analyses, only ppFEV1 and female gender were independently associated with Z scores. CONCLUSIONS: Osteoporosis in CF occurs with deteriorating clinical status while the role of calcium metabolism seems minor. Gender specific and dysglycemic impact on bone status should be investigated further.

[Potentially beneficial effects of climate changes]. / Potentielt gunstige effekter af klimaforandringer.

Climate changes have many unbeneficial effects on human health, but may also have beneficial effects. An increased mean temperature reduces the incidence of death due to hypothermia and cardiovascular disease and may increase exercise frequency. As the ozone layer decreases, the synthesis of vitamin D in the organism will also increase. An increased level of plasma vitamin D has beneficial effects on bone- and muscle health, seems to reduce cancer incidence and mortality and reduces the prevalence of autoimmune- and cardiovascular disease.

Bone mineral density in patients with growth hormone deficiency: does a gender difference exist?

OBJECTIVE: The aim of the study was to clarify whether a gender difference exists with respect to bone mineral density (BMD) and bone mineral content (BMC) in adult patients with growth hormone deficiency (GHD). DESIGN: A case-control design. METHODS: Blood sampling for measurements of calcium, phosphate, creatinine, PTH, vitamin D, IGF-1, markers of bone formation and bone resorption, and dual energy X-ray absorptiometry (DEXA), to determine BMD and BMC of the lumbar spine, hip, distal arm and total body, were performed in 34 patients with GHD (19 females) and 34 sex-, age- and weight-matched healthy control subjects. The patients were well substituted on all pituitary axes, apart from GH. RESULTS: GH-deficient males had significantly lower BMD in the lumbar spine (P = 0.02), hip (P = 0.01) and total body (P = 0.003) than healthy males while GH-deficient females compared to healthy females had identical BMD values at all regions. This gender difference was even more obvious when BMD values were expressed as Z-scores or as three-dimensional BMD of the total body. The bone formation and bone resorption markers, as well as calcium and vitamin D, were all at the same levels in GH-deficient and healthy males, indicating identical bone turnover. The GH-deficient females, however, had significantly lower levels of bone markers compared to healthy females, indicating a reduced bone turnover. Oestrogen substitution of the GH-deficient females could explain this difference. CONCLUSIONS: Compared to healthy control subjects GH-deficient males had, in contrast to GH-deficient females, significantly reduced BMD and BMC. This obvious gender difference seems to be caused by the oestrogen substitution given to the females, compensating for the lack of GH, an effect testosterone does not seem to possess.