Objective, design and methodsRoux-en-Y gastric bypass (RYGB) has proved successful in attaining sustained weight loss but may lead to metabolic bone disease. To assess impact on bone mass and structure, we measured a real bone mineral density at the hip and spine by dual-energy X-ray absorptiometry, and volumetric BMD (vBMD) and bone microarchitecture at the distal radius and tibia by high-resolution peripheral quantitative CT in 25 morbidly obese subjects (15 females, 10 males) at 0, 12 and 24 months after RYGB. Bone turnover markers (BTMs), calciotropic and gut hormones and adipokines were measured at the same time points.ResultsAfter a 24.1% mean weight loss from baseline to month 12 (P < 0.001), body weight plateaued from month 12 to 24 (−0.9%, P = 0.50). However, cortical and trabecular vBMD and microarchitecture deteriorated through the 24 months, such that there was a 5 and 7% reduction in estimated bone strength at the radius and tibia respectively (both P < 0.001). The declines observed in the first 12 months were matched or exceeded by declines in the 12- to 24-month period. While a significant increase in BTMs and decrease in leptin and insulin were seen at 24 months, these changes were maximal at month 12 and stabilized from month 12 to 24.ConclusionsDespite weight stabilization and maintenance of metabolic parameters, bone loss and deterioration in bone strength continued and were substantial in the second year. The clinical importance of these changes in terms of increased risk of developing osteoporosis and fragility fractures remain an important concern.

Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment of morbid obesity, with positive effects on obesity-related complications. The treatment is associated with bone loss, which in turn might increase fracture risk. The aim of this study was to evaluate changes in bone mineral density (BMD) and bone architecture assessed using dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT), 6 and 12 months after RYGB, and correlate them to changes in selected biochemical markers. A prospective cohort study included 25 morbidly obese patients (10 males, 15 females). Patients were examined with DXA of the hip and spine, HR-pQCT of radius and tibia, and blood sampling before and 6 and 12 months after RYGB. Patients lost in average 33.5 ± 12.1 kg (25.8 ± 8.5 %) in 12 months. In tibia, we found significant loss of total, cortical and trabecular volumetric BMD after 12 months (all p < 0.001). Microarchitectural changes involved lower trabecular number, increased trabecular separation, and network inhomogeneity along with thinning of the cortex. Estimated bone failure load was decreased after 12 months (p = 0.005). We found only minor changes in radius. Results demonstrate significant alterations of bone microarchitecture suggesting an accelerated endosteal resorption along with disintegration of the trabecular structure which resulted in a loss of estimated bone strength in tibia. Such changes may underlie the recently reported increased risk of fracture in bariatric patients after surgery. We only observed bone structural changes in the weight-bearing bone, which indicates that mechanical un-loading is the primary mediator.

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/m(2)) matched with healthy controls (age 25-54 years and BMI 19.5-24.8 kg/m(2)) 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.

Purpose. To evaluate the compliance and toxicity of the hypoxic radiosensitizer nimorazole in head and neck cancer patients. Methods. A retrospective study of patients with head and neck squamous cell carcinoma (HNSCC), treated in Denmark between 1990 and 2013. All patients treated with radical radiotherapy ( Ϯ chemotherapy) [66 -70 Gy; 33 -35 fractions; 2 Gy/fraction; 5 -6 fractions/week] concomitant with the hypoxic radiosensitizer nimorazole. Nimorazole was administered as oral tablets in doses of approximately 1.2 g/m 2 body surface area in connection with the fi rst of each daily radiation treatment. A second daily dose of 1 g was given in connection with the second radiotherapy fraction in the accelerated fractionation regimen. The compliance was estimated as the percentage of the initially prescribed dose, which was received by each patient. The main side effects were recorded. Results. A total of 1049 patients were investigated. The tolerance to nimorazole was fair: 58% of patients received the full prescribed total dose. Nausea and vomiting were the major complaints: among the 260 patients with dose reductions due to known side effects, (87%) were due to nausea/vomiting. All side effects ceased when treatment was interrupted, and neither severe nor long lasting side effects were observed. Female patients were signifi cantly more likely to have dose reduction (OR 2.02; 95% CI 1.50 -2.70), and nausea/vomiting. Patients aged more than 70 years were signifi cantly more likely to have dose reduction. Patients who received less than 1100 mg/m 2 were signifi cantly less likely to have dose reduction (OR 0.58; CI 0.44 -0.78), and nausea/vomiting, compared to those who received 1100 -1300 mg/m 2 . The tolerance was also less in the group of patients received accelerated chemoradiotherapy (OR 1.70; CI 1.20 -2.50) with more association with nausea/vomiting (OR 2.09; CI 1.40 -3.10). Conclusion. The compliance to nimorazole is fair, with tolerable acute, but neither persistent nor late, toxicity. It can be administered with chemotherapy and different radiotherapy fractionation schedules.

We aimed to evaluate whether macular laser still has a role in the treatment of macular oedema (MO) caused by branch retinal vein occlusion (BRVO) and provide an overview of recent studies on commonly available treatment options. A literature search was last conducted in PubMed on 26 February 2019, limited to human randomized controlled trials published in English since 2008. Seventeen articles addressing 13 trials were included in this assessment. In trials evaluating intravitreal corticosteroid and macular laser, triamcinolone was non-inferior to laser in regard to visual acuity (VA) and central retinal thickness (CRT) outcomes. Combination treatment of dexamethasone and laser resulted in better VA and lower CRT after 6 months. In trials evaluating vascular endothelial growth factor (VEGF) inhibitors versus macular laser treatment, or sham and rescue laser, better VA and CRT of VEGF inhibition treatment was consistently reported. Results of combination treatment versus VEGF inhibition monotherapy were inconsistent, with four of six studies reporting comparable outcomes and injection burden. Study comparison was affected by considerable differences in study design and inadequate reporting of laser protocol and rescue laser. Studies evaluating angiostatic treatment as monotherapy largely report the use of rescue laser, indicating that some patients would benefit from supplemental laser treatment even in the era of intravitreal therapy. Thus, we suggest further studies on optimal design of combination therapy prioritizing longer follow-up time to sufficiently evaluate the delayed effect of laser.