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Folkestad L.,University of Southern Denmark | Folkestad L.,Hospital of Southwest Denmark | Hald J.D.,Aarhus University Hospital | Hansen S.,University of Southern Denmark | And 5 more authors.
Journal of Bone and Mineral Research | Year: 2012

Osteogenesis imperfecta (OI) is a hereditary disorder characterized by decreased biosynthesis or impaired morphology of type I collagen that leads to decreased bone mass and increased bone fragility. We hypothesized that patients with OI have altered bone microstructure and bone geometry. In this cross-sectional study we compared patients with type I OI to age- and gender-matched healthy controls. A total of 39 (13 men and 26 women) patients with OI, aged 53 (range, 21-77) years, and 39 controls, aged 53 (range, 21-77) years, were included in the study. Twenty-seven of the patients had been treated with bisphosphonates. High-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia and dual-energy X-ray absorptiometry of total hip, femoral neck, trochanteric region, and the lumbar spine (L1-L4) were performed. The patients were shorter than the controls (159 ± 10 cm versus 170 ± 9 cm, p < 0.001), but had similar body weight. In OI, areal bone mineral density (aBMD) was 8% lower at the hip (p < 0.05) and 13% lower at the spine (p < 0.001) compared with controls. The trabecular volumetric bone mineral density (vBMD) was 28% lower in radius (p < 0.001) and 38% lower in tibia (p < 0.001) in OI compared with controls. At radius, total bone area was 5% lower in OI than in controls (p < 0.05). In the tibia, cortical bone area was 18% lower in OI (p < 0.001). In both radius and tibia the number of trabeculae was lower in patients compared to the controls (35% and 38%, respectively, p < 0.001 at both sites). Furthermore, trabecular spacing was 55% higher in OI in both tibia and radius (p < 0.001 at both sites) when compared with controls. We conclude that patients with type I OI have lower aBMD, vBMD, bone area, and trabecular number when compared with healthy age- and gender-matched controls. Copyright © 2012 American Society for Bone and Mineral Research.


Bouteldja N.,Hospital of Southwest Denmark | Andersen L.T.,Aarhus University Hospital | Moller N.,Aarhus University Hospital | Gormsen L.C.,Aarhus University Hospital
Metabolism: Clinical and Experimental | Year: 2014

Ketone bodies - 3-hydroxybutyrate and acetoacetate - are important fuel substrates, which can be oxidized by most tissues in the body. They are synthesized in the liver and are derived from fatty acids released from adipose tissue. Intriguingly, under conditions of stress such as fasting, arterio-venous catheterization studies have shown that the brain switches from the use of almost 100% glucose to the use of > 50-60% ketone bodies. A similar adaptive mechanism is observed in the heart, where fasting induces a shift toward ketone body uptake that provides the myocardium with an alternate fuel source and also favorably affects myocardial contractility. Within the past years there has been a renewed interest in ketone bodies and the possible beneficial effects of fasting/semi-fasting/exercising and other "ketogenic" regimens have received much attention. In this perspective, it is promising that positron emission tomography (PET) techniques with isotopically labeled ketone bodies, fatty acids and glucose offer an opportunity to study interactions between ketone body, fatty acid and glucose metabolism in tissues such as the brain and heart. PET scans are non-invasive and thus eliminates the need to place catheters in vascular territories not easily accessible. The short half-life of e.g. 11C-labeled PET tracers even allows multiple scans on the same study day and reduces the total radiation burden associated with the procedure. This short review aims to give an overview of current knowledge on ketone body metabolism obtained by PET studies and discusses the methodological challenges and perspectives involved in PET ketone body research. © 2014 Elsevier Inc.


Skov V.,University of Southern Denmark | Cangemi C.,University of Southern Denmark | Gram J.,Hospital of Southwest Denmark | Christensen M.M.,University of Southern Denmark | And 5 more authors.
Diabetes Care | Year: 2014

OBJECTIVE The extracellular matrix protein fibulin-1 is upregulated in the arterial wall in type 2 diabetes (T2D) and circulates in increased concentrations in diabetes. Metformin is an antidiabetic drug with beneficial cardiovascular disease effects in diabetes.We hypothesized thatmetformin would influence the increased level of plasma fibulin-1 in diabetes. RESEARCH DESIGN AND METHODS After a 4-week run-in period, 371 eligible patients with T2D were randomized to treatment groups in a factorial design including insulin alone (control), +metformin, +rosiglitazone, or +both metformin and rosiglitazone. Plasma fibulin-1 was analyzed at the beginning of the study and after 18 and 24 months. RESULTS Plasma fibulin-1 increased in all groups throughout the 2-year period; however, the increase was strongly attenuated among patients treated with metformin. A highly significant difference was observed when the mean change in plasma fibulin-1 was compared between metformin- and non-metformin-treated individuals both at 18 and 24 months of treatment, but rosiglitazone had no effect. Metformin and rosiglitazone alone reduced the HbA1c levels to comparable levels and in combination even further. CONCLUSIONS Metformin attenuates the increase in plasma fibulin-1 concentrations in T2D, independently of glycemic effects. Changes in fibulin-1 may reflect an important element in diabetic arteriopathy that can be influenced by metformin.© 2014 by the American Diabetes Association.


Gram B.,University of Southern Denmark | Christensen R.,University of Southern Denmark | Christensen R.,Statistics Denmark | Christiansen C.,Hospital of Southwest Denmark | Gram J.,Hospital of Southwest Denmark
Clinical Journal of Sport Medicine | Year: 2010

Objective: Both Nordic walking and Exercise on Prescription have potential as elements in the management of type 2 diabetes mellitus. These programs are recommended, but their effectiveness has not yet been established. The aim was to evaluate the efficacy of these 2 interventions compared with standard information on physical activity. DESIGN:: Single-blinded, randomized, controlled intervention study. SETTING:: Sixty-eight patients (37 men and 31 women) were randomized into 3 groups: Nordic walking (NW; n = 22), Exercise on Prescription (EP; n = 24), and control (CG; n = 22). PATIENTS:: Patients were recruited from a diabetes outpatient clinic and via newspaper advertisement. INTERVENTIONS:: Consisted of a 4-month intervention period followed by an 8-month follow-up, during which the participants were recommended to train on their own. MAIN OUTCOME MEASURES:: HbA1c. RESULTS:: There was no difference in HbA1c when comparing the intervention groups relative to the control group: ΔNW = -0.4% [95% confidence intervals (CI), -0.9% to 0.1%] and ΔEP = -0.2% (95% CI, -0.6% to 0.2%) after 4 months; ΔNW = 0.0% (95% CI, -0.6% to 0.5%) and ΔEP = 0.3% (95% CI, -0.3% to 0.9%) after 12 months. However, fat mass assessed by dual energy X-ray absorptiometry (DXA) decreased significantly in the NW group after 4 months [-1.0 kg (95% CI, -1.7 to 0.1)] and after 12 months in both NW [-1.8 kg (95% CI, -3.2 to -0.4)] and EP [-1.5 kg (95% CI, -2.9 to -0.05)] groups. No significant changes in other variables. CONCLUSIONS:: Four-month exercise programs at moderate intensity of either Nordic walking or Exercise on Prescription did not significantly improve HbA1c in patients with type 2 diabetes either at the end of the program or at the follow-up. © 2010 by Lippincott Williams & Wilkins.


Hallas P.,Copenhagen University | Brabrand M.,Hospital of Southwest Denmark | Folkestad L.,Hospital of Southwest Denmark
Western Journal of Emergency Medicine | Year: 2013

Introduction: Intraosseous access (IO) is indicated if vascular access cannot be quickly established during resuscitation. Complication rates are estimated to be low, based on small patient series, model or cadaver studies, and case reports. However, user experience with IO use in real-life emergency situations might differ from the results in the controlled environment of model studies and small patient series. We performed a survey of IO use in real-life emergency situations to assess users' experiences of complications. Methods: An online questionnaire was sent to Scandinavian emergency physicians, anesthesiologists and pediatricians. Results: 1,802 clinical cases of IO use was reported by n=386 responders. Commonly reported complications with establishing IO access were patient discomfort/pain (7.1%), difficulties with penetration of periosteum with IO needle (10.3%), difficulties with aspiration of bone marrow (12.3%), and bended/broken needle (4.0%). When using an established IO access the reported complications were difficulties with injection fluid and drugs after IO insertion (7.4%), slow infusion (despite use of pressure bag) (8.8%), displacement after insertion (8.5%), and extravasation (3.7%). Compartment syndrome and osteomyelitis occurred in 0.6% and 0.4% of cases respectively. Conclusion: In users' recollection of real-life IO use, perceived complications were more frequent than usually reported from model studies. The perceived difficulties with using IO could affect the willingness of medical staff to use IO. Therefore, user experience should be addressed both in education of how to use, and research and development of IOs.


Andersen S.,University of Southern Denmark | Frederiksen K.D.,University of Southern Denmark | Hansen S.,University of Southern Denmark | Hansen S.,Hospital of Southwest Denmark | And 4 more authors.
Calcified Tissue International | Year: 2014

Obesity is associated with high bone mineral density (BMD), but whether obesity-related higher bone mass increases bone strength and thereby protect against fractures is uncertain. We estimated effects of obesity on bone microarchitecture and estimated strength in 36 patients (12 males and 24 females, age 25-56 years and BMI 33.2-57.6 kg/m2) matched with healthy controls (age 25-54 years and BMI 19.5-24.8 kg/m2) in regard to gender, menopausal status, age (±6 years) and height (±6 cm) using high resolution peripheral quantitative computed tomography and dual energy X-ray absorptiometry. In radius, total bone area and trabecular area were significantly higher in obese patients (both p < 0.04). In tibia, cortical area was larger in obese patients (p < 0.001) compared with controls. Total BMD was higher in tibia (p = 0.03) but not in radius. Trabecular integrity was strengthened in obese patients compared with controls in radius and tibia with higher trabecular number (p = 0.002 and p < 0.001) and lower trabecular spacing (p = 0.01 and p < 0.001). Finite element analysis estimated failure load (FL) was higher in tibia (p < 0.001), but not in radius in obese patients. FL was significantly lower per kg body weight in radius and tibia in obese patients compared with controls (p = 0.007 and p < 0.001). Furthermore, the ratios of FLs between groups were comparable in both sites. These findings suggest that mechanical loading is not the primary mediator of the effects of obesity on estimated FL, and suggest that bone strength adaptations in morbid obesity may be inadequate with respect to the increased mechanical demands. © 2014 Springer Science+Business Media.


Shanbhogue V.V.,University of Southern Denmark | Hansen S.,University of Southern Denmark | Folkestad L.,University of Southern Denmark | Brixen K.,University of Southern Denmark | And 2 more authors.
Journal of Bone and Mineral Research | Year: 2015

Hypophosphatemic rickets (HR) is characterized by a generalized mineralization defect. Although densitometric studies have found the patients to have an elevated bone mineral density (BMD), data on bone geometry and microstructure are scarce. The aim of this cross-sectional in vivo study was to assess bone geometry, volumetric BMD (vBMD), microarchitecture, and estimated bone strength in adult patients with HR using high-resolution peripheral quantitative computed tomography (HR-pQCT). Twenty-nine patients (aged 19 to 79 years; 21 female, 8 male patients), 26 of whom had genetically proven X-linked HR, were matched with respect to age and sex with 29 healthy subjects. Eleven patients were currently receiving therapy with calcitriol and phosphate for a median duration of 29.1 years (12.0 to 43.0 years). Because of the disproportionate short stature in HR, the region of interest in HR-pQCT images at the distal radius and tibia were placed in a constant proportion to the entire length of the bone in both patients and healthy volunteers. In age- and weight-Adjusted models, HR patients had significantly higher total bone cross-sectional areas (radius 36%, tibia 20%; bothp<0.001) with significantly higher trabecular bone areas (radius 49%, tibia 14%; both p<0.001) compared with controls. In addition, HR patients had lower total vBMD (radius-20%, tibia-14%; both p<0.01), cortical vBMD (radius-5%, p<0.001), trabecular number (radius -13%, tibia-14%; both p<0.01), and cortical thickness (radius-19%; p<0.01) compared with controls, whereas trabecular spacing (radius 18%, tibia 23%; p<0.01) and trabecular network inhomogeneity (radius 29%, tibia 40%; both p<0.01) were higher. Estimated bone strength was similar between the groups. In conclusion, in patients with HR, the negative impact of lower vBMD and trabecular number on bone strength seems to be compensated by an increase in bone diameter, resulting in HR patients having normal estimates of bone strength. © 2014 American Society for Bone and Mineral Research.


Hansen C.T.,University of Southern Denmark | Pedersen P.T.,Hospital of Southwest Denmark | Nielsen L.C.,Hospital of Southwest Denmark | Abildgaard N.,University of Southern Denmark
European Journal of Haematology | Year: 2014

Background: Observational data from clinical studies indicate that the goal of first-line therapy in newly diagnosed patients with symptomatic multiple myeloma (MM) should be very good partial response (VGPR) or better, preferably before high-dose treatment. We evaluated the value of early measurements of involved free light chains (iFLC) in prediction of high-quality responses. Measuring iFLC has a potential advantage due to a short half-life compared to the half-life of the M-protein. Methods: In 36 multiple myeloma (MM) patients, we measured serial changes in iFLC and M-protein after start of treatment. iFLC and M-protein were measured before treatment, the following 5 wk days, 2, 3 and 6 wks after start of treatment. Results: Median iFLC and M-protein half-life was 2.75 and 11.9 d, respectively. All patients with an iFLC >75 mg/L had an initial significant reduction (>20%) in iFLC, even patients with no response to treatment. The mean per cent reduction in iFLC 3 d after start of treatment was 52.3% and 23.6% (P = 0.021) in patients achieving ≥VGPR and PR, respectively. The mean per cent reduction in M-protein in patients achieving ≥VGPR and PR was not significantly different in the 6-wk study period. As a predictor of VGPR, an 80% reduction in iFLC at day 21 resulted in a sensitivity of 87.5% and a specificity of 100%. Conclusion: Changes in iFLC could be a tool for early identification of responders to anti-myeloma therapy. Early, sequential measurements of iFLC within the first week after start of treatment are not meaningful. © 2014 John Wiley & Sons A/S.


Beck-Nielsen S.S.,Hospital of Southwest Denmark
Danish medical journal | Year: 2012

Rickets is a heterogeneous group of diseases of the growing child caused by defect mineralization of bone. Nutritional rickets is caused by deficiency of vitamin D, calcium or both. Several hereditary forms of rickets exist where the disease proceeds into adulthood. Nutritional rickets was common in the past, but by introduction of preventative administration of cod liver oil and vitamin D supplementation, nutritional rickets became a rarity. During the last decades, case reports of nutritional rickets reappear in the industrialized countries. It is the general conception that in the industrialized countries, hereditary rickets is the most prevalent cause of rickets today. However, the incidence of nutritional rickets and the incidence and prevalence of hereditary rickets in Scandinavia are unknown. The most common form of hereditary rickets is hypophosphatemic rickets (HR). The geno- and phenotype among Scandinavian patients have not been characterized. Especially, the disease in adult patients is not well described. Moreover, there are conflicting reports of the benefits of medical treatment throughout childhood, and in addition on gender differences in disease severity.


Mrgan M.,Hospital of Southwest Denmark | Mohammed A.,Hospital of Southwest Denmark | Gram J.,Hospital of Southwest Denmark
Journal of Clinical Densitometry | Year: 2013

We performed a retrospective study to assess if vertebral fracture assessment (VFA) after routine bone mineral density (BMD) measurement on a dual-energy X-ray absorptiometry (DXA) machine had increased the number of patients diagnosed with osteoporosis and revealed previous unknown incident vertebral fractures. A total of 3275 patients were referred to bone densitometry by DXA to be screened for osteoporosis or evaluation of ongoing antiosteoporotic treatment. All spine X-rays obtained at our hospital from the same patients in the period from 3mo before to 3mo after the date of DXA scans were reviewed. Among the 3275 patients, 85% were females and 15% were males. In total, 68% of the patients had normal BMD, and 32% had osteoporosis. Vertebral fractures diagnosed by VFA were seen in 7.9% patients, of which 3.2% had normal BMD and 4.8% had osteoporosis assessed by BMD. The relative number of patients diagnosed with osteoporosis increased 9.79% and in absolute terms from 32.4% to 35.6% of patients referred to DXA. Addition of VFA to routine BMD measurement increased clinically significant the number of patients diagnosed with osteoporosis as well as the number of patients with fractures and thereby altered the severity and prognosis. © 2013 The International Society for Clinical Densitometry.

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