Laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are common and effective methods to treat severe obesity, but these procedures can adversely influence bone metabolism and areal bone mineral density (aBMD). This was a prospective 24-month single-center interventional two-arm study in 220 women and similarly aged men (median age 40.7 years) with a body mass index (BMI) >38 kg/m 2 after RYGB and SG procedures. Patients were randomized into: 1) an intervention group receiving: 28,000 IU cholecalciferol/wk for 8 weeks before bariatric surgery, 16,000 IU/wk and 1000 mg calciummonocitrate/d after surgery, daily BMI-adjusted protein supplementation and physical exercise (Nordic walking, strength perseverance, and equipment training); 2) a non-intervention group: no preoperative loading, nutritional supplementation, or obligatory physical exercise. At study endpoint, when comparing the intervention group to the non-intervention group, the relative percentage changes of serum levels of sclerostin (12.1% versus 63.8%), cross-linked C-telopeptide (CTX, 82.6% versus 158.3%), 25-OH vitamin D (13.4% versus 18.2%), phosphate (23.7% versus 32%, p < 0.001 for all), procollagen type 1 amino-terminal propeptide (P1NP, 12% versus 41.2%), intact parathyroid hormone (iPTH, -17.3% versus -7.6%), and Dickkopf-1 (-3.9% versus -8.9%, p < 0.05 for all) differed. The decline in lumbar spine, total hip and total body aBMD, changes in BMI, lean body mass (LBM), as well as changes in trabecular bone score (TBS) values (p < 0.005 for all) were less, but significantly, pronounced in the intervention group. We conclude that vitamin D loading and ongoing vitamin D, calcium, and BMI-adjusted protein supplementation in combination with physical exercise decelerates the loss of aBMD and LBM after bariatric surgery. Moreover, the well-known increases of bone turnover markers are less pronounced.

Background/Aims: Klotho deficiency results in excessive formation of 1,25(OH)₂D₃, accelerated ageing and early death. Moreover, klotho deficiency enhances eryptosis, the suicidal erythrocyte death characterized by phosphatidylserine exposure at the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i), glucose depletion, hyperosmotic shock and oxidative stress. Klotho expression is decreased and 1,25(OH)₂D₃-formation enhanced by dehydration. The present study thus explored whether dehydration influences eryptosis. Methods: Blood was drawn from hydrated or 36h dehydrated mice. Plasma osmolarity was determined by vapour pressure method, plasma 1,25(OH)₂D₃ and aldosterone concentrations using ELISA, and plasma Ca²⁺-concentration utilizing photometry. Erythrocytes were exposed to Ca²⁺-ionophore ionomycin (1 µM, 30 min), energy depletion (12 h glucose removal), hyperosmotic shock (500 mM sucrose added, 2 h) and oxidative stress (100 µM tert-butyl-hydroperoxide, 30 min) and phosphatidylserine exposure at the erythrocyte surface estimated from annexin V binding. Results: Dehydration increased plasma osmolarity and plasma 1,25(OH)₂D₃ and aldosterone concentrations. Dehydration did not significantly modify phosphatidylserine-exposure of freshly drawn erythrocytes but significantly enhanced the increase of phosphatidylserine-exposure under control conditions and following treatment with ionomycin, glucose-deprivation, hyperosmolarity or tert-butyl-hydroperoxide. Conclusions: Dehydration sensitizes the erythrocytes to spontaneous eryptosis and to the triggering of eryptosis by excessive Ca²⁺-entry, energy depletion, hyperosmotic shock and oxidative stress.

The results suggest an insufficient control of allergen-specific responses via the Treg-cell compartment under systemic immunosuppression.

No abstract