Fibroblast Growth Factor-23, Sclerostin, and Bone Microarchitecture in Patients With Osteoporotic Fractures of the Proximal Femur: A Cross-sectional Study.

This cross-sectional observational cohort study was designed to simultaneously investigate bone microarchitecture and serum markers of bone metabolism in elderly osteoporotic patients experiencing a trochanteric or femoral neck fracture. Special emphasis was put on renal function, sclerostin and fibroblast growth factor-23 (FGF-23). Eighty-two patients (median age: 84 years; 49 trochanteric fractures) scheduled for emergency surgery due to an osteoporotic fracture participated. Bone specimens for ex vivo microcomputed X-ray tomography were sampled during surgery. Blood samples for laboratory workup were collected before surgery (t0) and 1 day afterward (t1). Fifty-eight patients consented to dual-energy X-ray absorptiometry scanning of the lumbar spine and/or contralateral femoral neck after recovery during the in-patient stay. Samples were grouped according to the site of fracture. Regression coefficients were controlled for age and/or estimated glomerular filtration rate (eGFR), if appropriate. Patients experiencing a femoral neck fracture presented with better preserved renal function (eGFR) and lower C-terminal fragment of fibroblast growth factor-23 (cFGF-23) concentrations compared to those with trochanteric fractures. By contrast, serum sclerostin was similar at both time points and did not differ between groups. Age-adjusted correlation analysis revealed negative associations between eGFR and cFGF-23 determined at t1 (R=-0.34; p<0.05) as well as between eGFR and sclerostin levels at t0 (R=-0.45; p<0.05) in patients with trochanteric and femoral neck fractures, respectively. Our study provides evidence that not only an age-related decline of renal function but also the type of skeletal injury may contribute to the circulating concentrations of cFGF-23.

Postoperative development of bone mineral density and muscle strength in the lower limb after cemented and uncemented total hip replacement.

BACKGROUND: Numerous studies have shown reduction of periprosthetic bone mineral density (BMD) after hip replacement. The effect on the whole limb, however, is still unexplored. This study's objective was to analyse the postoperative development of BMD and muscle strength of the limb after total hip replacement (THR) and to determine links between these parameters. METHODS: 55 patients, who underwent THR, were included. Depending on therapeutic indication, either an uncemented stem (Group A, n=30) or a cemented stem (Group B, n=25) has been implanted. In the limbs, the measurement of BMD using DEXA and the maximum isometric muscle strength, detected by a leg press, were undertaken preoperatively and after 3, 6 and 12 months. RESULTS: A total of 12 patients (Group A: n = 6, Group B: n = 6) were excluded due to reasons which were not relevant to the study. So, the results refer to the data of 43 patients. In Group A (uncemented, n = 24), a significant decrease of BMD on the operated extremity was seen after 3, 6 and 12 months compared with preoperative values. Isometric muscle strength on the affected extremity increased significantly after 6 and 12 months. In Group B (cemented, n = 19), with a lower baseline compared to group A, an increase in BMD of the affected limb was seen postoperatively. This rise was significant after 12 months. With regard to the isometric muscle strength, a significant increase could be observed in this group after 6 and 12 months. CONCLUSION: Analogous to postoperative reduction of periprosthetic bone density, a decrease of the entire limb BMD on the operated leg occurred after implantation of uncemented hip stems. In contrast, an increase in BMD was recorded for cemented stems. Regardless of the type of anchoring, a substantial increase in muscular strength could be observed postoperatively in both groups.

Importance of endothelial nitric oxide synthase for the hypothermic protection of lungs against ischemia-reperfusion injury.

OBJECTIVES: The hypothesis that the protective effects of mild hypothermia against the pulmonary ischemia-reperfusion injury are mediated by endothelial nitric oxide synthase was tested. METHODS: Endothelial nitric oxide synthase knock-out and wild-type mice were sham operated or underwent a 1-hour occlusion of the left pulmonary hilum, followed by 5 hours of reperfusion. Temperature in the left pleural cavity during ischemia was maintained at either 36 degrees C (normothermia) or 32 degrees C (hypothermia). Inflammatory response (myeloperoxidase activity), endothelial barrier function (extravasation of Evans blue-labeled albumin), and endothelial nitric oxide synthase expression and phosphorylation were determined at the end of reperfusion. RESULTS: After normothermic ischemia both strains had a similar mortality (wild-type, 22.9%; knock-out, 15.4%), which was completely abolished by hypothermia. Endothelial barrier function was disturbed after normothermic ischemia in both wild-type and knock-out mice. Mild hypothermia significantly reduced pulmonary Evans blue extravasation in wild-type mice, but not in knock-out mice. Myeloperoxidase activity increased after normothermic ischemia to the same degree in both strains. This response was significantly attenuated by hypothermia in wild-type mice, but not in knock-out mice. In wild-type mice, endothelial nitric oxide synthase expression and phosphorylation were higher after hypothermic ischemia than after normothermic ischemia. No effect of ischemia on expression of inducible nitric oxide synthase was found in wild-type or knock-out mice. CONCLUSION: Hypothermic protection against pulmonary ischemia-reperfusion injury is dependent on endothelial nitric oxide synthase and is associated with increased expression and phosphorylation of endothelial nitric oxide synthase.