Search

Brown tumors (BTs) are manifestations of osteitis fibrosa cystica that develops due to increased osteoclast activity secondary to hyperparathyroidism (HPTH). The name comes from its characteristic brown color due to high hemosiderin level and hemorrhage surrounded by osteoclastic giant cells, fibrous tissue, and bone fragments. Presentation can be either unifocal or rarely multifocal. Misdiagnosis of BT compared to malignant giant cell tumor is not uncommon. Early diagnosis and intervention may prevent destructive bone changes. Treatment of BTs due to chronic renal failure should be aimed primarily at its prevention with phosphate binders, vitamin D (analogues), calcimimetics, and prolonged dialysis sessions. Parathyroidectomy can be the option in nonresponsive cases. In this report, we present an unusual case of multiple brown tumors in a 54-year-old female renal transplant patient involving the spine, jaw, and scapula, initially misdiagnosed as giant cell tumor. Five years later, the patient was diagnosed with BT because of the medical history, morphology, and negative p63 staining in combination with secondary/tertiary hyperparathyroidism. The patient subsequently underwent subtotal parathyroidectomy. [ABSTRACT FROM AUTHOR]

Precise staging of breast cancer-related lymphedema (BCRL) is important to guide treatment-decision making. Recent studies have suggested staging of BCRL using indocyanine green lymphangiography (ICG-L) based on the extent of lymphatic injury and dermal backflow patterns. Currently, the benefits of ICG-L compared to conventional clinical staging are unknown. For this study, we included 200 patients with unilateral BCRL. All BCRL patients were staged using ICG-L and clinical exam. The amounts of excess arm volume, fat mass and lean mass were compared between stages using Dual Energy X-Ray Absorptiometry. Multivariate regression models were used to adjust for confounders. For each increase in the patient's ICG-L stage, the excess arm volume, fat mass and lean mass was increased by 8, 12 and 6.5 percentage points respectively (P < 0.001). For each increase in the patient's clinical ISL stage, the volume was increased by 3.5 percentage points (P < 0.05), however no statistically significant difference in the lean and fat mass content of the arm was observed for ascending stages. However, the residual plots showed a high degree of variance for both ICG-L and clinical staging. This study found that ICG-L staging of BCRL was superior to clinical staging in forecasting BCRL excess arm volume, fat mass, and lean mass. However, there was a high degree of variance in excess arm volume, fat mass, and lean mass within each staging system, and neither the ICG-L nor clinical staging forecasted perfectly. [ABSTRACT FROM AUTHOR]

This study investigated changes in body weight, lean body mass (LBM), fat mass (FM), muscle strength and functional performance during radiation treatment in head and neck cancer (HNSCC) patients. Secondly, it investigated the impact of cisplatin-based chemoradiation (CCRT) on LBM loss compared with radiation alone. 48 patients (all tumor sites) received either 6 weeks of radiation alone (n = 16) with 66–68 Gy in 33–34 Fx, 5-6 Fx/week or CCRT, adding weekly cisplatin or carboplatin (n = 32). LBM and FM was evaluated using Dual-energy X-ray Absorptiometry bi-weekly from pre- to two weeks post-treatment. Maximal muscle strength (knee extension, leg - and chest press) and functional performance (stair climb, chair rise, and arm curl) were assessed pre- and post-treatment. Body weight and LBM had declined significantly already week 2 into treatment and declined significantly further through week 4 and 6 before leveling off after week 6. Bi-weekly, from treatment start to week 2, 2–4, and 4–6, LBM declined 1.2 ± 0.4 kg (p =.002; 95% CI: 0.4;2.0), 2.0 ± 0.4 kg (p <.0001; 1.2;2.8) and 1.4 ± 0.4 kg (p =.001; 0.6;2.2). With a two-week delay, FM declined significantly from week 2–8. All measures of muscle strength declined significantly from pre- to post-treatment. Functional performance was unchanged. LBM loss from pre- to post-treatment was significantly associated with impaired muscle strength (R2 = 0.3–0.5). CCRT patients lost 3.1 ± 0.8 kg of LBM (p =.0001; 1.5;4.7) more from pre- to post-treatment compared with patients receiving radiation alone. Analyses adjusting for nimorazole, tumor stage, baseline BMI, mean radiation dose to constrictor muscles and oral cavity confirmed this. Accelerated and substantial LBM loss was already initiated within the first two weeks of treatment - before the onset of radiation-induced mucositis. LBM loss was associated with muscle strength impairment. Patients receiving CCRT experienced significantly larger LBM loss than patients receiving radiation alone. Registered on clinincaltrials.gov (Identifier: NCT05890859). [ABSTRACT FROM AUTHOR]

Bisphosphonates are widely used globally as the main treatment for osteoporosis. Both safety and efficacy have only been rigorously evaluated in studies of relatively short duration (3–5 years), with smaller extension studies. The evidence for benefit beyond five years in intervention studies is limited and does not include proven efficacy against nonvertebral fractures. Observational studies suggest a sustained benefit against hip fractures. Bisphosphonates are stored in the skeleton for months to years, depending on the degree of bone turnover and the binding properties of the bisphosphonate in question. The effects of continued treatment on bone strength is not known but there are concerns that osteonecrosis of the jaw and atypical femur fractures may stem from long term bisphosphonate use. [ABSTRACT FROM AUTHOR]

Objective: To investigate possible effects of insulin-sensitizing treatment on cortisol metabolism in insulin-resistant patients with polycystic ovary syndrome (PCOS). Design: Randomized placebo-controlled study. Setting: Academic tertiary care medical center. Patient(s): Thirty insulin-resistant PCOS patients. Intervention(s): Sixteen weeks of pioglitazone (30 mg/day) or placebo treatment. Main Outcome Measure(s): Twenty-four-hour 20 min integrated blood sampling for measurement of cortisol and 24 h urinary excretion of steroid metabolites. Relative 5α-reductase activity was evaluated by allotetrahydrocortisol (alloTHF)/THF and androsterone/etiocholanolone (A/E) ratios. Delta values denoted changes during the treatment period (16 weeks − basal). Pyridostigmine growth hormone (GH) stimulation tests were performed, and testosterone (T), dihydrotestosterone (DHT), DHEA, DHEAS, adiponectin, and insulin-like growth factor I (IGF-I) were measured before and after intervention. Result(s): Insulin sensitivity, GH, adiponectin, and IGF-I significantly increased during pioglitazone treatment, whereas alloTHF/THF levels significantly decreased. Delta alloTHF/THF levels inversely correlated with Δ adiponectin levels. Δ A/E ratio inversely correlated with Δ IGF-I and Δ peak GH during GH stimulation tests. No significant changes were measured in T, DHT, DHEA, DHEAS, 24 h mean cortisol, or urinary excretion of steroid metabolites. Conclusion(s): Pioglitazone decreased relative 5α-reductase activity, whereas no significant changes were measured in cortisol levels or urinary cortisol excretion. [Copyright &y& Elsevier]

Objective: To thoroughly examine the mechanisms for insulin resistance in polycystic ovary syndrome (PCOS) and to evaluate the effects of pioglitazone treatment on insulin resistance, β-cell function, LH secretion, and glucose metabolism. Design: Randomized, blinded, placebo-controlled study. Setting: Outpatient clinic, at a university hospital in Denmark. Patient(s): Thirty obese women with PCOS and 14 weight-matched healthy females. Intervention(s): Sixteen weeks of blinded treatment with pioglitazone (30 mg/d) or placebo. Main Outcome Measure(s): Fasting blood samples, 24-hour 20-minute integrated blood sampling (LH, insulin, and C-peptide), euglycemic hyperinsulinemic clamps including 3-3H glucose, and indirect calorimetry were performed before and after the intervention period. Result(s): Patients with PCOS had significantly lower insulin sensitivity compared with controls, including significantly decreased insulin-stimulated oxidative and nonoxidative glucose metabolism. Pioglitazone treatment resulted in significantly lower levels of fasting insulin and significantly higher insulin sensitivity, increased insulin-stimulated glucose oxidation, and increased insulin-stimulated inhibition of lipid oxidation. During 24-hour blood sampling, significantly lower area under-the-curve insulin and lower median insulin levels were observed. Secretion profiles of LH and E2 and T levels did not change significantly. Conclusion(s): Insulin resistance in PCOS was characterized by hyperinsulinemia, impaired insulin-stimulated oxidative and nonoxidative glucose metabolism, which was partly reversed by pioglitazone treatment. [Copyright &y& Elsevier]

Objectives: To study the effects of hormonal replacement on hot flushes, other symptoms linked to menopause, and blood pressure. Methods: The study included 1006 early postmenopausal women aged 45–58 years, participating in the Danish Osteoporosis Prevention Study (DOPS) randomised to Hormonal replacement therapy (HRT) (n=502) or no HRT (n=504) in an open label trial. Symptom scores were recorded at baseline, after 6 month, 1, 2, and 5 years on a modified Greene scale (range 0–4 with 0 equalling no symptoms, and 4 maximal symptoms). Results: HRT efficiently alleviated hot flushes (mean±S.E.M. score 0.48±0.04 in HRT vs. 0.83±0.05 in no HRT after 5 years, P<0.01 by repeated measures ANOVA), sleeping difficulties associated with hot flushes (0.21±0.60 vs. 0.37±0.86, P<0.01), vaginal dryness (0.45±0.04 vs. 0.73±0.05, P<0.01), dyspareunia (0.27±0.04 vs. 0.39±0.04, P<0.01), and libido (0.48±0.05 vs. 0.59±0.05, P=0.08). In the untreated group the occurrence of mood swings (from 0.77±0.05 at baseline to 0.45±0.04 after 5 years, 2P<0.01) and oedemas (from 0.59±0.04 to 0.43±0.04, 2P=0.02) decreased with age while the occurrence of incontinence increased (from 0.43±0.03 to 0.52±0.04, 2P<0.01). These changes were not influenced by HRT. Furthermore, HRT had no influence on presence of headache (0.54±0.05 vs. 0.58±0.05 after 5 years), voiding pattern (0.49±0.04 vs. 0.53±0.04), or blood pressure (mean systolic pressure 123±18 vs. 123±19, diastolic pressure 77±10 vs. 77±11). Conclusions: HRT is efficient in controlling hot flushes and vaginal dryness, and symptoms related to these conditions. However, no effect on blood pressure or other menopause symptoms was recorded. [Copyright &y& Elsevier]

Simple Summary: Cellulitis is a common complication in Breast Cancer-Related Lymphedema (BCRL); however, it is not known whether cellulitis is associated with the severity and biocompositon of BCRL. This study showed that cellulitis was associated with more excess volume, fat, and lean arm mass. Treatments should aim to prevent cellulitis in BCRL to possibly avoid the condition exacerbating. Cellulitis is a common complication in Breast Cancer-Related Lymphedema (BCRL). The excess amount of fat and lean mass in BCRL is a vital factor in patient stratification, prognosis, and treatments. However, it is not known whether cellulitis is associated with the excess fat and lean mass in BCRL. Therefore, this prospective observational study was designed to fundamentally understand the heterogonous biocomposition of BCRL. For this study, we consecutively enrolled 206 patients with unilateral BCRL between January 2019 and February 2020. All patients underwent Dual-Energy X-Ray Absorptiometry scans, bioimpedance spectroscopy, indocyanine green lymphangiography comprehensive history of potential risk factors, and a clinical exam. Multivariate linear and beta regression models were used to determine the strength of association and margins effect. Sixty-nine patients (33%) had at least one previous episode of cellulitis. Notably, a previous episode of cellulitis was associated with 20 percentage points more excess fat and 10 percentage points more excess lean mass compared to patients without cellulitis (p < 0.05). Moreover, each 1 increase in the patients BMI was associated with a 0.03 unit increase in the fat mass proportion of the lymphedema arm. Cellulitis was associated with more excess fat and lean arm mass in BCRL. In addition, patients BMI affect the proportion of fat mass in the arm. [ABSTRACT FROM AUTHOR]

Background: One in three women and one in five men over the age of 50 will experience an osteoporotic fracture. Vertebral fractures can be very painful, affect patients' daily function, and in severe cases require hospitalization. Traditionally, fracture pain is treated conservatively with analgesics, and bracing. Vertebral augmentation, also known as vertebroplasty, has been used during the last three decades as a minimally invasive treatment option for vertebral compression fractures, but the evidence base for its efficacy is weak. We describe a double-blind randomized sham-controlled clinical trial to assess the impact of vertebroplasty on self-reported clinical outcomes in patients with painful osteoporotic vertebral compression fractures and vertebral oedema. Methods: Two hundred and forty patients with painful osteoporotic vertebral fractures and MRI verified oedema will be randomized in a prospective, double-blind, single-center, clinical trial to either vertebroplasty or a sham procedure, with the possibility of crossover 12 weeks after randomization and operation. The primary outcome will be difference in self-reported pain 12 weeks after treatment between the vertebroplasty and sham group. Secondary outcomes will be patient-reported disability, health-related quality of life, societal costs of treatment and complications. Analysis will be based on intention-to-treat. Repeated measures ANCOVA with baseline ODI, Numerical Pain Rating Scale, EQ-5D-5 L, and number of levels involved as co-variates will be performed. Discussion: With an aging population, the prevalence of osteoporosis and related complications such as vertebral compression fractures is expected to increase. Therefore, there is a growing need for evidence-based fracture treatments. This study fills a gap in the evidence base for treatment of painful osteoporotic vertebral fractures and will likely influence future treatment guidelines. Trial registration: The study has been evaluated and approved by the Regional Committees on Health Research for Southern Denmark October 9 2023 (Projekt-ID S-20230058) and the Danish Data Protection Agency 23/40,938. The protocol has been registered at ClinicalTrials.gov with trial registration number NCT06141187 November 21, 2023. [ABSTRACT FROM AUTHOR]

Background: One in three women and one in five men over the age of 50 will experience an osteoporotic fracture. Vertebral fractures can be very painful, affect patients' daily function, and in severe cases require hospitalization. Traditionally, fracture pain is treated conservatively with analgesics, and bracing. Vertebral augmentation, also known as vertebroplasty, has been used during the last three decades as a minimally invasive treatment option for vertebral compression fractures, but the evidence base for its efficacy is weak. We describe a double-blind randomized sham-controlled clinical trial to assess the impact of vertebroplasty on self-reported clinical outcomes in patients with painful osteoporotic vertebral compression fractures and vertebral oedema. Methods: Two hundred and forty patients with painful osteoporotic vertebral fractures and MRI verified oedema will be randomized in a prospective, double-blind, single-center, clinical trial to either vertebroplasty or a sham procedure, with the possibility of crossover 12 weeks after randomization and operation. The primary outcome will be difference in self-reported pain 12 weeks after treatment between the vertebroplasty and sham group. Secondary outcomes will be patient-reported disability, health-related quality of life, societal costs of treatment and complications. Analysis will be based on intention-to-treat. Repeated measures ANCOVA with baseline ODI, Numerical Pain Rating Scale, EQ-5D-5 L, and number of levels involved as co-variates will be performed. Discussion: With an aging population, the prevalence of osteoporosis and related complications such as vertebral compression fractures is expected to increase. Therefore, there is a growing need for evidence-based fracture treatments. This study fills a gap in the evidence base for treatment of painful osteoporotic vertebral fractures and will likely influence future treatment guidelines. Trial registration: The study has been evaluated and approved by the Regional Committees on Health Research for Southern Denmark October 9 2023 (Projekt-ID S-20230058) and the Danish Data Protection Agency 23/40,938. The protocol has been registered at ClinicalTrials.gov with trial registration number NCT06141187 November 21, 2023. [ABSTRACT FROM AUTHOR]

Reduced physical function caused by bone destruction, pain, anemia, infections, and weight loss is common in multiple myeloma (MM). Myeloma bone disease challenges physical exercise. Knowledge on the effects and safety of physical exercise in newly diagnosed patients with MM is limited. In a randomized, controlled trial, we studied the effect of a 10‐week individualized physical exercise program on physical function, physical activity, lean body mass (LBM), bone mineral density (BMD), quality of life (QoL), and pain in patients newly diagnosed with MM. Lytic bone disease was assessed, and exercise was adjusted accordingly. Primary outcome: knee extension strength. Secondary outcomes: Six‐Minute‐Walk‐Test, 30‐s Sit‐to‐Stand‐Test (SST), grip strength, level of physical activity, LBM, BMD, QoL, and pain. Measurements were conducted pre‐ and post‐intervention, and after 6 and 12 months. We included 100 patients, 86 were evaluable; 44 in the intervention group (IG) and 42 in the control group (CG). No statistically significant differences between groups were observed. Knee extension strength declined in the IG (p =.02). SST, aerobic capacity, and global QoL improved in both groups. Pain decreased consistently in the IG regardless of pain outcome. No significant safety concerns of physical exercise in newly diagnosed patients with MM were observed. [ABSTRACT FROM AUTHOR]

Identifying comorbidities in polymyalgia rheumatica/giant cell arteritis (PMR/GCA) is crucial for patients' outcomes. The present study aimed to evaluate the impact of the inflammatory process and glucocorticoid treatment on aortic arterial stiffness and body composition in PMR/GCA. 77 patients with newly diagnosed PMR/GCA were treated with oral glucocorticoids and followed for 40 weeks. Aortic pulse wave velocity (PWV) was measured at baseline and during the follow-up period and compared to the results of temporal artery biopsy (TAB) and 18F-FDG PET/CT. Body composition was assessed by total body DXA at baseline and the end of the study. Of 77 patients (49 (63.6%) female, mean of age: (71.8 ± 8.0)), 64 (83.1%) had pure PMR, 10 (13.0%) concomitant PMR and GCA, and 3 (3.9%) pure GCA. Compared to baseline values, aortic PWV was initially decreased at week 16 (p = 0.010) and remained lower than baseline at week 28 (p = 0.002) and week 40 (p < 0.001), with no association with results of TAB and 18F-FDG PET/CT. Aortic PWV was significantly associated with age, male gender, left systolic and diastolic blood pressure, right diastolic blood pressure, and CRP. Total bone mineral content (BMC) was decreased in both genders (p < 0.001), while fat mass (FM) was significantly increased (p < 0.001). However, lean body mass did not significantly change during the study. Changes in FM were correlated with cumulative prednisolone dose (rho: 0.26, p = 0.031). Glucocorticoid treatment of patients with PMR/GCA had several prognostic impacts. Arterial stiffness was decreased due either to the treatment or a reduction in the inflammatory load. Additionally, treatment led to changes in body composition, including a decrease in BMC and FM excess. [ABSTRACT FROM AUTHOR]

Objective: Roux-en-Y-gastric bypass (RYGB) surgery is an effective treatme nt for morbid obesity. A possible overlooked side effect is negative bone metabolic consequences. Design: A seven-year prospective study following ten women and seven m en after RYGB (baseline mean age 43 ± 8 years, BMI 42 ± 6 kg/m²). Methods: Lumbar spine and total hip bone mineral density (BMD) using dual energy x-ray absorptiometry, distal radius and tibia bone geometry, volumetric BMD, microarchitecture and finite element estimated bone strength using highresolution peripheral quantitative CT and biochemical markers of bone remodelling were assessed at baseline, 2 and 7 years. Results: Compared to baseline, body weight was 24 ± 10% lower after 2 years and 21 ± 11% after 7 years. During the 7 years of follow-up, radius and tibia vBMD had declined 13 ± 8% and 8 ± 7% from baseline to 2 years and further 10 ± 7% and 7 ± 8% from 2 to 7 years (all P < 0.001). At both radius and tibia, cortical thickness declined and cortical porosity increased. From baseline to 7 years, there were clear indications of deteriorations of the trabecular network with fewer, more widely spaced and more in-homogeneously distri buted trabeculae in both radius and tibia. Overall, declines in estimated bone strength of 16 ± 9% in radius and 16 ± 7% in tibia were observed (both P < 0.001). Conclusion: Seven years after RYGB, evidence of continuous declines in BMD and ongoing deterioration of bone microarchitecture and reduced estimated bone strength compared to baseline and 2 years post-surgery results were found. These findings emphasize the need for regular assessment of bone health in patients with prior RYGB. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple endocrine neoplasia 2A (MEN 2A) is a rare hereditary cancer syndrome, in which primary hyperparathyroidism (PHPT) is reported in up to 35% of affected individuals. Recent studies suggest a lower frequency and a milder course of PHPT in MEN 2A, but these studies often lack a strict definition of PHPT and are frequently carried out at smaller research centers. This could result in diverging and incomplete data. Consequently, we aimed to investigate PHPT in a complete nationwide cohort of MEN 2A to suggest a representative frequency and clinical course of PHPT. This may alter the information given to MEN 2A patients by their caretakers on the likelihood of developing PHPT and on the clinical course of PHPT. Studies of primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia type 2A (MEN 2A) shows divergence in frequency, disease definition, reporting of clinical characteristics and traces of selection bias. This is a nationwide population-based retrospective study of PHPT in MEN 2A, suggesting a representative frequency, with complete reporting and a strict PHPT definition. The Danish MEN 2A cohort 1930–2021 was used. Of 204 MEN 2A cases, 16 had PHPT, resulting in a frequency of 8% (CI, 5–12). Age-related penetrance at 50 years was 8% (CI, 4–15). PHPT was seen in the American Thyroid Association moderate (ATA-MOD) and high (ATA-H) risk groups in 62% and 38% of carriers, respectively. Median age at PHPT diagnosis was 45 years (range, 21–79). A total of 75% were asymptomatic and 25% were symptomatic. Thirteen underwent parathyroid surgery, resulting in a cure of 69%, persistence in 8% and recurrence in 23%. In this first study with a clear PHPT definition and no selection bias, we found a lower frequency of PHPT and age-related penetrance, but a higher age at PHPT diagnosis than often cited. This might be affected by the Danish RET p.Cys611Tyr founder effect. Our study corroborates that PHPT in MEN 2A is often mild, asymptomatic and is associated with both ATA-MOD and ATA-H variants. Likelihood of cure is high, but recurrence is not infrequent and can occur decades after surgery. [ABSTRACT FROM AUTHOR]

Summary: The incidence of hip and major osteoporotic fracture was increased in patients with primary hyperparathyroidism even in patients not referred for parathyroidectomy. The risk of death was also increased which attenuated an effect on fracture probabilities. The findings argue for widening the indications for parathyroidectomy in mild primary hyperparathyroidism. Introduction: Primary hyperparathyroidism (PHPT) is associated with an increase in the risk of fracture. In FRAX, the increase in risk is assumed to be mediated by low bone mineral density (BMD). However, the risk of death is also increased and its effect on fracture probability is not known. Objective: The aim of this study was to determine whether PHPT affects hip fracture and major osteoporotic fracture risk independently of bone mineral density (BMD) and whether this and any increase in mortality affects the assessment of fracture probability. Methods: A register-based survey of patients with PHPT and matched controls in Denmark were identified from hospital registers. The incidence of death, hip fracture, and major osteoporotic fracture were determined for computing fracture probabilities excluding time after parathyroidectomy. The gradient of risk for fracture for differences in BMD was determined in a subset of patients and in BMD controls. The severity of disease was based on serum calcium and parathyroid hormone levels. Results: We identified 6884 patients with biochemically confirmed PHPT and 68,665 matched population controls. On follow-up, excluding time after parathyroidectomy in those undergoing surgery, patients with PHPT had a higher risk of death (+52%), hip fracture (+48%), and major osteoporotic fracture (+36%) than population controls. At any given age, average 10-year probabilities of fracture were higher in patients with PHPT than population controls. The gradient of fracture risk with differences in BMD was similar in cases and controls. Results were similar when confined to patients not undergoing parathyroidectomy. Fracture probability decreased with the severity of disease due to an increase in mortality rather than fracture risk. Conclusion: The risk of hip and other major osteoporotic fracture is increased in PHPT irrespective of the disease severity. Fracture probability was attenuated due to the competing effect of mortality. The increased fracture risk in patients treated conservatively argues for widening the indications for parathyroidectomy in mild PHPT. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery has adverse effects on the muscular-skeletal system with loss of bone mass and muscle mass and an increase in the risk of fracture. Zoledronic acid is widely used in osteoporosis and prevents bone loss and fracture. Bisphosphonates may also have positive effects on skeletal muscle. The aim of this study is to investigate the effects of zoledronic acid for the prevention of bone and muscle loss after bariatric surgery.  METHODS/DESIGN: This is a randomized double-blind placebo-controlled study. Sixty women and men with obesity aged 35 years or older will complete baseline assessments before randomization to either zoledronic acid (5 mg in 100 ml isotonic saline) or placebo (100 ml isotonic saline only) 3 weeks before surgery with Roux-en-Y-gastric bypass (RYGB) or sleeve gastrectomy (SG). Follow-up assessments are performed 12 and 24 months after surgery. The primary outcome is changes in lumbar spine volumetric bone mineral density (vBMD) assessed by quantitative computed tomography (QCT). Secondary bone outcomes are changes in proximal femur vBMD assessed by QCT. Changes in cortical and trabecular bone microarchitecture and estimated bone strength will be assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical material bone strength at the mid-tibia diaphysis will be assessed using microindentation and fasting blood samples will be obtained to assess biochemical markers of bone turnover and calcium metabolism.  Secondary muscle outcomes include whole body lean mass assessed using dual-energy X-ray absorptiometry. Dynamometers will be used to assess handgrip, shoulder, ankle, and knee muscle strength. Short Physical Performance Battery, 7.6-m walking tests, 2-min walking test, and a stair climb test will be assessed as biomarkers of physical function. Self-reported physical activity level is assessed using International Physical Activity Questionnaire (IPAQ).Discussion: Results from this study will be instrumental for the evidence-based care of patients undergoing bariatric surgery.Trial Registration: ClinicalTrials.gov NCT04742010. Registered on 5 February 2021. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the performance of the Swedish version of Fracture Risk Assessment Tool (FRAX)) without bone mass density (BMD) in a Danish population to examine the possibility of applying this version to Danish women. Methods: From the Danish National Register of social security numbers, we randomly selected 5000 women living in the region of Southern Denmark aged 40—90 years to receive a mailed questionnaire concerning risk factors for osteoporosis based on FRAX. The predicted 10-year probability of hip fractures was calculated for each woman returning a complete questionnaire using the Swedish version of FRAX. The observed 10-year hip fracture risk was also calculated for each woman using age-specific hip fracture rates from the National Hospital Discharge Register and National survival tables. Results: A total of 4194 (84%) women responded to the questionnaire and 3636 (73%) gave complete information and were included in the analysis. Using FRAX, the predicted 10-year fracture risk was 7.6%, ranging from 0.3 to 25.0% at the age of 41—50 and 81—90, respectively, while the corresponding observed fracture risk was 7.6%, ranging from 0.4 to 24.0%, respectively and not significantly different from the predicted risk (p = 0.92). Conclusions: The Swedish version of FRAX without BMD is applicable to Danish women. [ABSTRACT FROM PUBLISHER]

Aim: To investigate the efficacy and safety of a non‐calorie–restricted low‐carbohydrate diet (LCD) on glycaemic control, body composition, and cardiovascular risk factors in patients with type 2 diabetes (T2D) instructed to maintain their non‐insulin antidiabetic medication and physical activity. Materials and Methods: In an open‐label randomized controlled trial, patients with T2D were randomized 2:1 to either a LCD with a maximum of 20 E% (percentage of total energy intake) from carbohydrates (n = 49) or a control diet with 50‐60 E% from carbohydrates (n = 22) for 6 months. Examinations at enrolment and after 3 and 6 months included blood sample analyses, anthropometrics, blood pressure, accelerometer‐based assessment of physical activity, and food diaries. Total fat mass and lean mass were determined by dual‐energy x‐ray absorptiometry scan. The mean difference in change between groups from baseline are reported. Results: The LCD group decreased carbohydrate intake to 13.4 E% and increased fat intake to 63.2 E%, which was −30.5 ± 2.2 E% lower for carbohydrates and 30.6 ± 2.2 E% higher for fat, respectively, compared with the control group (all P <.001). The LCD reduced HbA1c after 3 months (−8.9 ± 1.7 mmol/mol; P <.0001), and this was maintained after 6 months (−7.5 ± 1.8 mmol/mol; P <.0001) compared with the control diet. The LCD also reduced weight (−3.9 ± 1.0 kg), body mass index (−1.4 ± 0.4 kg/m2), and waist circumference (−4.9 ± 1.3 cm) compared with the control diet (all P <.01), accompanied by reductions in total fat mass (−2.2 ± 1.0 kg; P =.027) and lean mass (−1.3 ± 0.6 kg; P =.017). No changes in blood lipids or blood pressure were seen after 6 months. The level of physical activity was maintained, and there were no episodes of severe hypoglycaemia. Conclusion: A non‐calorie–restricted LCD high in fat has significant beneficial effects on glycaemic control and body composition, and does not adversely affect cardiovascular risk factors in patients with T2D. Reducing carbohydrate intake to 10‐25 E% appears to be an effective and safe nutritional approach with respect to classical cardiovascular risk factors and hypoglycaemia. [ABSTRACT FROM AUTHOR]

Summary background and objectives Reduced bone mineral content (BMC) and bone mineral density (BMD) have previously been reported in Turner's syndrome, although appropriate GH treatment and early induction of puberty seem to permit normal bone mass accumulation. Furthermore, an increased risk of fractures and osteoporosis have been reported in a registry study. The aim of the present study was to further characterize the risk of fractures in TS and to explore risk factors, in a historical follow-up survey based on a self-administered questionnaire. study groups The questionnaire was issued to all females with TS (n = 632) in Denmark and to 1888 randomly selected controls (C) matched for age and geographical region. A total of 322 patients (51%) and 1169 controls (62%) returned the questionnaire. results TS women were younger than C (30 years, range: 1–73 years vs. 34 years, range 2–82 years, P < 0·0005), smoked less often (17%vs. 27%, P < 0·0005), and had less frequent spontaneous menstruation (18%vs. 86%, P < 0·0005). In contrast, they used hormonal replacement therapy (HRT) more often (71%vs. 7%, P < 0·0005). The median age at start of HRT was 16 years (range 8–59 years) in TS vs. 42 years (range 12–53 years) in C (P < 0·0005). Above the age of 15 years, 83% of TS and 8% of C used HRT. GH had been used by 37% of TS but only 0·2% of C. Both type 1 and 2 diabetes were increased sevenfold among TS. Altogether, 77 individuals with TS had 109 fractures. The fracture risk was increased in TS [hazard ratio (HR, status) 1·35, confidence interval (CI) 1·04–1·75, P = 0·025]. Time to first fracture was reduced in TS (53 ± 2 vs. 63 ± 1; log-rank P = 0·03). Spontaneous menstruation was protective in females above 13 years of age (HR: 0·70, CI 0·54–0·93, P = 0·012). A history of parental fractures increased the risk (HR 1·92, CI... [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Hyperthyroidism is associated with bone mass reduction and increased fracture risk, but the effects on other important bone parameters have been sparsely examined. Therefore, we investigated bone microarchitecture and estimated bone strength by high-resolution peripheral quantitative computed tomography (HR-pQCT) in hyperthyroid patients at diagnosis and after being euthyroid for at least one year. Methods: Two approaches were used: (A) a case–control study comparing 61 hyperthyroid women with 61 euthyroid women matched for age and menopause status; (B) a follow-up study, in which 46 of the 61 women were re-examined after having been euthyroid for one year. HR-pQCT of the distal radius and tibia, and dual-energy X-ray absorptiometry (DXA) of the lumbar spine and the hip were performed. Results: In analysis A: In the radius, compared with the healthy controls, hyperthyroid patients had higher total area (16.9% ± 29.5%; p < 0.001), trabecular area (28.6% ± 45.7%; p < 0.001), and lower cortical area (−11.7% ± 23.2%; p < 0.001). Total volumetric bone mineral density (vBMD) (−13.9% ± 26.5%; p < 0.001), cortical vBMD (−5.8% ± 7.9%; p < 0.001), cortical thickness (−16.7% ± 26.0%; p < 0.001), and estimated bone strength (−6.6% ± 19.5%; p < 0.01) were lower. No significant differences were found in the tibia or in the DXA parameters. In analysis B: In the radius, significant improvements were observed in the cortical area (2.1% ± 4.6%; p < 0.01), cortical thickness (2.5% ± 5.1%; p < 0.001), and total vBMD (0.8% ± 3.0%; p < 0.05). Trabecular area decreased (−0.5% ± 1.0%; p < 0.01) and trabecular separation increased (2.0% ± 8.3%; p < 0.05). In the tibia, cortical area (3.6% ± 7.3%; p < 0.01) and cortical thickness (3.8% ± 7.6%; p < 0.01) increased, and trabecular area decreased (−0.5% ± 1.1%; p < 0.01). Areal BMD, measured by DXA, increased in the spine (1.1% ± 3.4%; p < 0.05) and in the hip (2.0% ± 3.8%; p < 0.01). Conclusions: Compared with the healthy control group, hyperthyroid women had lower vBMD, lower estimated bone strength, and compromised cortical microarchitecture in the radius. After restoration of euthyroidism, significant improvements in vBMD and cortical microarchitecture were observed, highlighting the importance of achieving and maintaining euthyroidism. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is associated with decreased bone mineral density and increased risk of fracture. The aim of this study was to assess bone geometry, volumetric bone mineral density (vBMD), trabecular microarchitecture and estimated failure load in weight-bearing vs. non-weight-bearing bones in AN. We included twenty-five females with AN, and twenty-five female controls matched on age and height. Bone geometry, vBMD and trabecular microarchitecture were assessed using high-resolution peripheral quantitative computed tomography of the distal radius and tibia. At both sites, cortical perimeter and total bone area were similar in patients and controls. Total vBMD was lower in the AN group in the tibia (p < 0.0005) but not in the radius. In the tibia, cortical thickness was approximately 25% lower (p < 0.0005) in the AN group, whereas there was no significant difference in the radius. In terms of trabecular microarchitecture, all indices [bone volume/tissue volume (BV/TV); trabecular thickness (Tb.Th.), trabecular number (Tb.N) and trabecular spacing (Tb.Sp.)] were impaired in AN in the tibia (p values range < 0.01-0.0001). In the radius, BV/TV and Tb.N were lower (p < 0.05 and p < 0.001, respectively); Tb.Sp. was higher (p < 0.001), whereas Tb.Th. did not differ, compared to controls. Estimated failure load was lower in patients in both the radius and the tibia (p < 0.0005 and p < 0.0001, respectively), most pronounced in the tibia. In conclusion, the impairment of cortical thickness and estimated failure load were significantly more pronounced in the weight-bearing tibia, compared to the non-weight-bearing radius, implying a direct effect of low body weight on bone loss in AN. [ABSTRACT FROM AUTHOR]

Background Osteogenesis imperfecta (OI) is a hereditary connective tissue disease often due to mutations in genes coding for type 1 collagen. Collagen type 1 is important in the development of the heart and vasculature. Little is known about the risk of cardiovascular disease (CVD) in OI. Objective To investigate the risk of symptomatic CVD in OI. Design A Danish nationwide, population-based and register-based longitudinal open cohort study. Participants All patients registered with the diagnosis of OI from 1977 to 2013 and a reference population matched 5:1 to the OI cohort. Measurements Sub-hazard ratios for mitral and aortic valve regurgitation, atrial fibrillation and flutter, heart failure and vascular aneurisms and dissections comparing the OI cohort to the reference population. Results We identified 687 cases with OI (379 women) and included 3435 reference persons (1895 women). The SHR was 6.3 [95% CI: 2.5–15.5] for mitral valve regurgitation, 4.5 [95% CI: 1.4–13.9] for aortic valve regurgitation, 1.7 [95% CI: 1.1–2.8] for atrial fibrillation/flutter, and 2.3 [95% CI: 1.4–3.7] for heart failure. The SHRs were not increased arterial aneurisms or dissections. Limitation Our results were limited by lacking clinical information about phenotype and genotype of the included patients. Conclusion We confirm that patients with OI have an increased risk of CVD compared to the general population. This held true even when adjusting for factors that are known to contribute to development of these diseases. Our results suggest that the collagenopathy seen in OI may be part of the pathogenesis of CVD in OI. [ABSTRACT FROM AUTHOR]

Introduction: Polycystic ovary syndrome (PCOS) is characterized by obesity and insulin resistance. Measures of regional obesity may be used to predict insulin resistance. In the present study we compared fat distribution in patients with PCOS vs. controls and established the best measure of fat mass to predict insulin resistance in patients with PCOS.Material and Methods: The study was cross-sectional in an academic tertiary-care medical center with 167 premenopausal women with PCOS and 110 controls matched for ethnicity, BMI and age. Total and regional fat and lean body mass were assessed by whole body dual-energy X-ray absorptiometry (DXA) scans. Anthropometric measures (BMI, waist) and fasting metabolic analyses [insulin, glucose, lipids, Homeostasis model assessment (HOMA-IR), lipid accumulation product, and visceral adiposity index] were determined. Trial registration numbers: NCT00451568, NCT00145340.Results: Women with PCOS had higher central fat mass (waist, waist-hip ratio, and upper/lower fat ratio) compared with controls. In bivariate associations, the strongest associations were found between HOMA-IR and the fat mass measures trunk fat (r = 0.59), waist (r = 0.57) and BMI (r = 0.56), all p < 0.001. During multiple regression analyses, trunk fat, waist and BMI were the best predictors of HOMA-IR (R2  = 0.48, 0.49, and 0.47, respectively).Conclusions: Women with PCOS were characterized by central obesity. Trunk fat, waist and BMI were the best predictors of HOMA-IR in PCOS, but only limited information regarding insulin resistance was gained by whole body DXA scan. [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant chemotherapy has been associated with loss of bone mineral density (BMD) either as a direct effect or due to glucocorticoids used as supportive care medication. A prospective cohort study was conducted to evaluate changes in BMD from baseline to right after completion of chemotherapy, i.e., 4 months.Methods: Dual-imaging X-ray absorptiometry (DXA) was performed at baseline and after completing anthracycline- and taxane-based chemotherapy to measure BMD in the spine, hip, and forearm in early-stage breast cancer patients. High-dose prednisolone was used at three weekly intervals to reduce nausea and vomiting. Patients were advised a daily calcium/vitamin D supplement. Linear regression was used to assess mean percentage change in BMD and 95 % confidence intervals (95 % CI) according to doses of prednisolone, menopausal status, smoking, and BMI.Results: Eight patients were excluded: seven because of initiation of bisphosphonate treatment due to osteoporosis at baseline, and one had non-interpretable DXA. The final cohort included 97 patients with a mean age of 53 years (range 34-72). Mean cumulative prednisolone dose was 1308 mg (95 % CI 1255; 1362). BMD increased 1.36 % (95 % CI 0.7; 2.0, p < 0.001) in the spine and 1.27 % (95 % CI 0.9; 1.7, p < 0.001) in the hip. Forearm BMD did not change. Postmenopausal women had increases in spine BMD of 2.35 % (95 % CI 1.1; 3.6, p < 0.001) compared to premenopausal women. The spine BMD of current smokers decreased 1.67 % (95 % CI -3.3; -0.1, p = 0.04) compared to never/former smokers.Conclusions: Adjuvant chemotherapy supplemented with prednisolone was not associated with loss of BMD. Postmenopausal women gained bone mass, whereas current smokers lost bone mass. [ABSTRACT FROM AUTHOR]

Identifying persons with a high risk of osteoporotic fractures remains a challenge. DXA uptake in women with elevated risk of osteoporosis seems to be depending on distance to scanning facilities. This study aimed to investigate the ability of a small portable scanner in identifying women with reduced bone mineral density (BMD), and to define triage thresholds for pre-selection. Total hip and lumbar spine BMD was measured by dual-energy X-ray absorptiometry and phalangeal BMD by radiographic absorptiometry in 121 Danish women with intermediate or high 10-year fracture probability (aged 61-81 years). Correlation between the two methods was estimated using correlation coefficient (r) and Bland-Altman plots. A moderate correlation between phalangeal BMD versus total hip (r = 0.47) and lumbar spine (r = 0.51), and an AUC on 0.80 was found. The mean difference between phalangeal T score and total hip T score/lumbar spine T score was low, and ranged from -0.26 SD to -0.31 SD depending on site and reference database used for calculation of T scores, but, large variation was seen at an individual level. When applying a triage approach approx. one-third of all DXA scan could be avoided and only 6 % of women in the low-risk group would be false negatives. [ABSTRACT FROM AUTHOR]

Objective and design: Patients with type 2 diabetes mellitus (T2D) have an increased fracture risk despite a normal or elevated bone mineral density (BMD). The aim of this cross-sectional in vivo study was to assess parameters of peripheral bone microarchitecture, estimated bone strength and bone remodeling in T2D patients with and without diabetic microvascular disease (MVD+ and MVD- respectively) and to compare them with healthy controls. Methods: Fifty-one T2D patients (MVD+ group: n=25) were recruited from Funen Diabetic Database and matched for age, sex and height with 51 healthy subjects. High-resolution peripheral quantitative tomography (HR-pQCT) was used to assess bone structure at the non-dominant distal radius and tibia. Estimated bone strength was calculated using finite element analysis. Biochemical markers of bone turnover were measured in all participants. Results: After adjusting for BMI, MVD+ patients displayed lower cortical volumetric BMD (P=0.02) and cortical thickness (P=0.02) and higher cortical porosity at the radius (P=0.02) and a trend towards higher cortical porosity at the tibia (P=0.07) compared to controls. HR-pQCT parameters did not differ between MVD- and control subjects. Biochemical markers of bone turnover were significantly lower in MVD+ and MVD- patients compared to controls (all P<0.01). These were no significant correlations between disease duration, glycemic control (average glycated hemoglobin over the previous 3 years) and HR-pQCT parameters. Conclusion: Cortical bone deficits are not a characteristic of all T2D patients but of a subgroup characterized by the presence of microvascular complications. Whether this influences fracture rates in these patients needs further investigation. [ABSTRACT FROM AUTHOR]

Hypophosphatasia (HPP) is an autosomal recessive or dominate disease affecting bone mineralization, and adults with HPP are in risk to develop metatarsal stress fractures and femoral pseudofractures. Given to the scarce data on the bone quality and its association to the fracture risk in adults with HPP, this study aimed to evaluate bone turnover, bone strength and structure in adults with HPP. In this cross-sectional study, we included 14 adults with genetically verified HPP and 14 sex-, age-, BMI-, and menopausal status-matched reference individuals. We analyzed bone turnover markers, and measured bone material strength index (BMSi) by impact microindentation. Bone geometry, volumetric density and bone microarchitecture as well as failure load at the distal radius and tibia were evaluated using a second-generation high-resolution peripheral quantitative computed tomography system. Bone turnover markers did not differ between patients with HPP and reference individuals. BMSi did not differ between the groups (67.90 [63.75–76.00] vs 65.45 [58.43–69.55], p = 0.149). Parameters of bone geometry and volumetric density did not differ between adults with HPP and the reference group. Patients with HPP had a tendency toward higher trabecular separation (0.664 [0.613–0.724] mm vs 0.620 [0.578–0.659] mm, p = 0.054) and inhomogeneity of trabecular network (0.253 [0.235–0.283] mm vs 0.229 [0.208–0.252] mm, p = 0.056) as well as lower trabecular bone volume fraction (18.8 [16.4–22.7] % vs 22.8 [20.6–24.7] %, p = 0.054) at the distal radius. In addition, compound heterozygous adults with HPP had a significantly higher cortical porosity at the distal radius than reference individuals (1.5 [0.9–2.2] % vs 0.7 [0.6–0.7] %, p = 0.041). BMSi is not reduced in adults with HPP. Increased cortical porosity may contribute to the occurrence of femoral pseudofractures in compound heterozygous adults with HPP. However, further studies investigating larger cohorts of adults with HPP using methods of bone histomorphometry are recommended to adequately assess the bone quality in adults with HPP. • BMSi is not systematically reduced in adults with HPP. • Low BMSi does not associate with a higher number of fractures in adults with HPP. • Increased cortical porosity may contribute to fracture development in severe HPP. [ABSTRACT FROM AUTHOR]

Patients with systemic mastocytosis have an increased risk of osteoporosis, however, the risk of osteoporotic fractures among the classic chronic myeloproliferative neoplasms ( CMPN), including essential thrombocythaemia ( ET), polycythaemia vera ( PV) and chronic myeloid leukaemia ( CML), is unknown. We conducted a population-based cohort study to determine the risk of osteoporotic fractures among three cohorts of patients with newly diagnosed ET, PV, and CML. Patients were identified in medical registers including all Danish hospitals during 1980-2010 and were followed until first osteoporotic fracture. Fracture risk was compared to cohorts from the general population matched on age, sex and calendar year. We followed 7595 CMPN patients and 338 974 comparison cohort members. We found that the risk of femoral fracture after 5 years was consistently higher than the general population, being 3·01% (95% confidence interval ( CI): 2·20-4·10), 4·74% (95% CI: 4·06-5·52) and 4·64% (95% CI: 3·29-6·53) among ET, PV, and CML patients respectively. Adjusted hazard ratio for femoral fracture was increased 1·19-fold (95% CI: 0·94-1·51) for ET patients, 1·82-fold (95% CI: 1·62-2·04) for PV patients, and 2·67-fold (95% CI: 1·97-3·62) for CML patients. We conclude that CMPN patients are at higher risk of osteoporotic fractures than the general population. [ABSTRACT FROM AUTHOR]

Purpose: To compare the power of FRAX® without bone mineral density (BMD) and simpler screening tools (OST, ORAI, OSIRIS, SCORE and age alone) in predicting fractures. Methods: This study was a prospective, population-based study performed in Denmark comprising 3614 women aged 40–90years, who returned a questionnaire concerning items on risk factors for osteoporosis. Fracture risk was calculated using the different screening tools (FRAX®, OST, ORAI, OSIRIS and SCORE) for each woman. The women were followed using the Danish National Register registering new major osteoporotic fractures during 3years, counting only the first fracture per person. Area under the receiver operating characteristic curve (ROC) and statistics and Harrell's index were calculated. Agreement between the tools was calculated by kappa statistics. Results: A total of 4% of the women experienced a new major osteoporotic fracture during the follow-up period. There were no differences in the area under the curve (AUC) values between FRAX® and the simpler tools; AUC values between 0.703 and 0.722 (p=0.86). Also, Harrell's C values were very similar between the tools. Agreement between the tools was modest. Conclusion: During 3years follow-up FRAX® did not perform better in the fracture risk prediction compared with simpler tools such as OST, ORAI, OSIRIS, SCORE or age alone in a screening scenario where BMD was not measured. These findings suggest that simpler models based on fewer risk factors, which would be easier to use in clinical practice by the GP or the patient herself, could just as well as FRAX® be used to identify women with increased risk of fracture. Summary: Comparison of FRAX® and simpler screening tools (OST, ORAI, OSIRIS, SCORE) in predicting fractures indicate that FRAX® did not perform better in fracture risk prediction compared with the simpler tools or even age alone in a screening scenario without bone mineral density assessment. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The critical weight loss observed in head and neck squamous cell carcinoma (HNSCC) patients following radiotherapy is mainly due to loss of lean body mass. This is associated with decreases in muscle strength, functional performance and Quality of Life (QoL). The present study investigated the effect of progressive resistance training (PRT) on lean body mass, muscle strength and functional performance in HNSCC patients following radiotherapy. Patients and methods: Following radiotherapy HNSCC patients were randomized into two groups: Early Exercise (EE, n =20) initiated 12weeks of PRT followed by 12weeks of self-chosen physical activity. Delayed Exercise (DE, n =21) initiated 12weeks of self-chosen physical activity followed by 12weeks of PRT. Lean body mass, muscle strength, functional performance and QoL were evaluated at baseline and after week 12 and 24. Results: In the first 12weeks lean body mass increased by 4.3% in EE after PRT and in the last 12weeks by 4.2% in DE after PRT. These increases were significantly larger than the changes after self-chosen physical activity (p ⩽0.005). Regardless of PRT start-up time, the odds ratio of increasing lean body mass by more than 4% after PRT was 6.26 (p <0.05). PRT significantly increased muscle strength, whereas functional performance increased significantly more than after self-chosen physical activity only after delayed onset of PRT. Overall QoL improved significantly more in EE than DE from baseline to week 12. Conclusion: PRT effectively increased lean body mass and muscle strength in HNSCC patients following radiotherapy, irrespectively of early or delayed start-up. [Copyright &y& Elsevier]

Objective Recent studies suggested that the effect of adiponectin on insulin-stimulated glucose metabolism is mediated primarily by the high molecular weight (HMW) form of adiponectin. In the present study we evaluated total and HMW adiponectin in polycystic ovary syndrome (PCOS) patients and controls and examined possible mechanisms for increased insulin sensitivity during pioglitazone treatment. Study subjects Thirty PCOS patients randomized to pioglitazone, 30 mg/day, or placebo for 16 weeks and 14 weight-matched healthy females were studied. Design Total and HMW adiponectin levels were measured, and euglycaemic hyperinsulinaemic clamps and indirect calorimetry were performed. Δ-values denoted changes during pioglitazone treatment (16 weeks – basal). Results Pretreatment adiponectin levels were decreased in PCOS patients vs. controls ( P < 0·05), whereas no significant differences were found in HMW adiponectin levels. Following pioglitazone treatment, total and HMW adiponectin increased (all P < 0·05), whereas no significant changes were observed with placebo. Δ-total adiponectin levels correlated positively with the rate of Δ-insulin-stimulated glucose disposal ( Rd) ( r = 0·89) and Δ-oxidative glucose metabolism ( r = 0·71) and inversely with Δ-fasting free fatty acid (FFA) levels ( r =  –0·69) and Δ-lipid oxidation ( r =  –0·73) during insulin stimulation (all P < 0·01). Weaker correlations were found between Δ-HMW adiponectin levels and Δ-measures of glucose and lipid metabolism during insulin stimulation than with Δ-total adiponectin. Conclusion A close correlation between increased total adiponectin levels and increased insulin-stimulated glucose metabolism during pioglitzone treatment supports the hypothesis that the insulin-sensitizing effect of pioglitazone in PCOS is, at least in part, mediated by adiponectin. Measures of changes in HMW adiponectin did not add further information to this relationship. [ABSTRACT FROM AUTHOR]

The mechanisms leading to higher bone mineral density (BMD) in hirsute patients than in healthy controls have seldom been examined. We compared the metabolic, hormonal and bone metabolic parameters in hirsute patients and female controls and correlated BMD and bone metabolic parameters with testosterone, oestradiol and metabolic parameters.Fifty-one Caucasian, reproductive-aged, hirsute patients referred to the outpatient clinic of an academic tertiary-care medical centre and 63 healthy, female Caucasian controls matched for season, weight and age.BMD (hip, neck, lumbar and total BMD), bone metabolic parameters (osteocalcin, alkaline phosphatase, PTH, ionized calcium, phosphate and 25-hydroxyvitamin D (25OHD)) and endocrine profiles (androgen status, oestradiol and insulin) were evaluated during follicular phase. Oestradiol measurement was repeated during cycle days 8–12.Lumbar and neck BMD levels were significantly higher in hirsute patients than in controls: (mean ± SD): lumbar BMD 1·10 ± 0·12vs.1·06 ± 0·10 g/cm2 and neck BMD 0·91 ± 0·11vs.0·87 ± 0·12 g/cm2,P < 0·05. Fasting insulin and free testosterone levels were significantly higher in hirsute patients than in controls. Free testosterone correlated positively with neck and hip BMD levels in hirsute patients. During multiple regression analysis, testosterone, oestradiol and waist/hip ratio (WHR) were found to have positive effects on BMD levels independent of body mass index (BMI). 25OHD levels were significantly lower in hirsute patients[42 (13–131)] than in controls[72 (27–196)] nmol/l (geometric mean ± 2SD),P < 0·001].Hirsute patients demonstrated significantly higher bone mineral density levels than controls, which could be explained by hyperinsulinaemia and higher testosterone levels in hirsute patients compared with controls. The pathogenesis for significantly lower 25-hydroxyvitamin D levels in hirsute patients compared with controls needs to be evaluated in future studies. [ABSTRACT FROM AUTHOR]

Objective: To perform an audit on the examination of hirsute patients and to establish a rational routine examination program in an outpatient endocrine clinic. Design: Systematic, retrospective audit. Setting: Academic tertiary-care medical center. Patient(s): Three hundred forty women with hirsutism as the referral diagnosis. Intervention(s): Hormone analyses and ACTH tests during cycle days 2–8, 2 hours of oral glucose tolerance test (OGTT), and vaginal ultrasound. Main outcome measure(s): End diagnosis, fasting, 30-, 60-, and 120-minute oral glucose–stimulated levels of insulin and capillary blood glucose. Result(s): Two hundred one patients were diagnosed as having idiopathic hirsutism (IH) and 134 as having polycystic ovary syndrome (PCOS). End diagnosis: prolactinoma: n = 1, Cushing''s syndrome: n = 1, androgen-producing ovarian tumor: n = 1, late-onset 21-hydroxylase defects: n = 2. During OGTT, 4.9% (13 of 263) had previously undiagnosed diabetes; no significant difference in diabetes prevalence was found between idiopathic hirsutism and PCOS. For 50.8%, fasting insulin values were in the upper quartile for a reference population. Conclusion(s): Initial evaluation of hirsute patients with irregular menses should include serum (s)-17α-hydroxyprogesterone, s-prolactin, s-Testosterone (T), and s-sex hormone-binding globulin. Further evaluation is needed in patients with markedly elevated s-T or with clinical Cushing''s syndrome. Hirsute patients have a high risk of diabetes, although this could be due to the high number of overweight patients among this population. [Copyright &y& Elsevier]

Management of osteoporosis given reduced renal function is one of the largest challenges in the bone clinic. Identify the cut-off for renal function below which there would be no overall BMD benefit associated with bisphosphonate use. Track safety outcomes resulting in hospital encounters. Population-based, observational register-linked study of BMD trajectories in adults from the island of Funen (pop 465,000) as a function of estimated creatinine clearance (CKD-epi), treatment and adherence to oBP. One laboratory performed all the biochemical analyses for the area while all DXA scans were in a central facility. For inclusion, patients were required to have both a DXA scan and an eGFR measurement (CKD-EPI) within 1 year prior to their study index date. Medication Possession Ratio (MPR) was calculated from national data. Out of 6176 incident BP users, 1789 had eGFR and DXA measurements at appropriate timepoints for the planned analysis, while this was the case for 3908 of 29,336 non-users. Users of oBPs exhibited progressively smaller gains in BMD with decreasing renal function. However, for CKD stage 3A and better, the annual change in BMD was significantly more positive than in the non-user group at similar levels of renal function. In non-users, the average annual change in BMD was negative but largely unaffected by renal function down to stage 3B. There were no new cases of acute renal injury, glomerulonephritis or dialysis. The rate of new kidney transplantation was zero in non-users and 0.26 per 1000 PY in the BP user population. Hypocalcaemia encounters did not differ significantly from that seen in non-users. The BMD changes observed in real-world users of oBP in this population based single-clinic are consistent with those observed in the original RCTs of alendronate. We noted a gradual decrease in the absolute gains in BMD in oBP users with decreasing renal function though there was no significant interaction – largely explained by low numbers of treated patients with poor renal function - between CKD stage and adherence driven BMD change. There were no cases of acute renal injury resulting in hospital encounters. More data is needed on the efficacy and safety of bisphosphonates in CKD stage 3B to 5 and prescribers should reconsider the low use of DXA in patients with renal function impairment now that a wider range of treatment options are available. Unlabelled Image • Bisphosphonates gave smaller gains in total hip BMD with decreasing renal function. • For CKD stage 3A and better, change in BMD was significantly more positive than in non-users. • BMD loss rates in non-users was largely unaffected by renal function down to stage 3B. • There were no new cases of acute renal injury, glomerulonephritis or dialysis. • Hypocalcaemia encounters did not differ significantly from non-users. [ABSTRACT FROM AUTHOR]