Bone mineral density testing in healthy postmenopausal women. The role of clinical risk factor assessment in determining fracture risk.

The ease of measurement and the quantitative nature of bone mineral densitometry (BMD) is clinically appealing. Despite BMD's proven capability to stratify fracture risk, data indicate that clinical risk factors provide complementary information on fracture susceptibility that is independent of BMD. Methods to quantify fracture risk using both clinical and BMD variables would have great appeal for clinical decision-making. We describe a procedure for quantifying hip fracture risk (5-yr and remaining lifetime) based on (1) the individual's age alone (base model, assuming average clinical risk factors and bone density), (2) incorporation of multiple patient-specific clinical risk factor data in the base model, and (3) incorporation of both patient-specific clinical risk factor data and BMD results.     

Preventative ibandronate treatment has the most beneficial effect on the microstructure of bone in experimental tumor osteolysis

We investigated the effect of ibandronate on three-dimensional (3-D) microstructure and bone mass in experimentally induced tumor osteolysis. Walker carcinosarcoma cells were implanted into the left femur of female rats that received 26-day ibandronate pretreatment followed by continued therapy or ibandronate posttreatment only. A tumor-only group received isotonic saline. At endpoint, excised femurs were scanned using microcomputed tomography (μCT) to assess bone volume density, bone mineral content, trabecular number/thickness, and separation for cortical plus trabecular bone or trabecular bone alone. Compared with the nonimplanted right femur, bone volume and surface density and trabecular number and thickness were reduced in the distal left femur following tumor cell implantation. μCT analysis revealed greater cortical and trabecular bone mineral content in the preventative and interventional (pre-post tumor) ibandronate group, and the interventional (post-tumor) ibandronate group, versus the tumor-only group. Bone volume density was significantly higher in pre-post and post-tumor groups compared to the tumor-only group. After preventative and interventional ibandronate, bone volume density and trabecular thickness were 13% and 60% greater, respectively, than in the post-tumor treatment group. 3-D μCT images confirmed microstructural changes. We conclude that combined interventional and preventative ibandronate preserves bone strength and integrity more than intervention alone.     

Individual and combined effects of exercise and alendronate on bone mass and strength in ovariectomized rats

Exercise and bisphosphonate therapies increase bone strength by primarily increasing bone formation and reducing resorption, respectively. Based on these different mechanisms of action, it is possible that combined introduction of exercise and bisphosphonate therapies generates greater improvements in bone mass and strength than either intervention alone. The aim of this study was to examine the individual and combined effects of exercise (treadmill running) and bisphosphonate therapy (alendronate [ALN]) on bone mass and strength in ovariectomized (OVX) rats. Seven-month-old virgin female rats were randomly assigned to either a sham-OVX group (n=13) or one of four OVX groups: vehicle-treated cage-control (VEH-CON, n=10); ALN-treated cage-control (ALN-CON, n=13); vehicle-treated plus treadmill running (VEH-RUN, n=13); and ALN-treated plus treadmill running (ALN-RUN, n=13). ALN-treated groups received twice-weekly ALN (0.015 mg/kg), and exercise groups ran on a motorized treadmill at a 5% incline for 60 min/day, 22-24 m/min, 5 days/week. In vivo measurements included dual-energy X-ray absorptiometry (DXA) of whole-body bone mineral content (BMC), and ex vivo measurements included DXA, micro-computed tomography (muCT), and mechanical testing of the femur and L4 vertebrae. After 14 weeks of intervention, exercise and ALN had additive benefits on whole body and proximal femur BMC, cross-sectional area of the L4 vertebrae, and mechanical properties of the mid-shaft femur. In comparison, for total and mid-shaft femur BMC, L4 vertebrae BMC, and mid-shaft femur cortical thickness and area, there were significant exercise and ALN interactions indicating that the two interventions worked in synergy to enhance bone properties. Supporting the contention that ALN and exercise function via distinct mechanisms of action, ALN successfully reduced medullary canal area suggesting it reduced endocortical bone resorption, whereas exercise augmented periosteal perimeter suggesting it stimulated periosteal bone formation. In summary, we found combined treadmill running and ALN to be more beneficial in preventing declines in bone mass and strength following OVX than the introduction of either intervention alone. These data suggest that a comprehensive program of bisphosphonate therapy and weight-bearing exercise may be an effective method for preventing and treating osteoporosis in post-menopausal women.     

Heat shock protein expression in cerebral vessels after subarachnoid hemorrhage

OBJECTIVE: The mechanisms of cerebral vasospasm after subarachnoid hemorrhage (SAH) remain controversial. Recent data have implicated two small heat shock proteins (HSPs), namely HSP20 and HSP27, in the regulation of vascular tone. Increases in the phosphorylation of HSP20 are associated with vasorelaxation, and increases in the phosphorylation of HSP27 are associated with impaired vasorelaxation. Therefore, we hypothesized that alterations in the expression and/or phosphorylation of these two small HSPs might play a role in cerebral vasospasm after SAH. METHODS: A rat model of endovascular perforation was used to induce SAH. Middle cerebral arteries were harvested from control animals, sham-treated animals, and animals with SAH, 48 hours after SAH induction. Dose-response curves for endothelium-independent (sodium nitroprusside, 10(-8) to 10(-4) mol/L) and endothelium-dependent (bradykinin, 10(-10) to 10(-5) mol/L) relaxing agents were recorded ex vivo. Physiological responses were correlated with the expression and phosphorylation of HSP20 and HSP27 by using one- and two-dimensional immunoblots. RESULTS: There was impaired endothelium-independent and endothelium-dependent relaxation in cerebral vessels after SAH. These changes were associated with decreased expression of both total and phosphorylated HSP20 and increases in the amount of phosphorylated HSP27. CONCLUSION: In this model, impaired relaxation of cerebral vessels after SAH was associated with increases in the amount of phosphorylated HSP27 and decreases in the expression and phosphorylation of HSP20. These data are consistent with alterations in the expression and phosphorylation of these small HSPs in other models of vasospasm.     

Potassium Bicarbonate Supplementation Lowers Bone Turnover and Calcium Excretion in Older Men and Women: A Randomized Dose‐Finding Trial

The acid load accompanying modern diets may have adverse effects on bone and muscle metabolism. Treatment with alkaline salts of potassium can neutralize the acid load, but the optimal amount of alkali is not established. Our objective was to determine the effectiveness of two doses of potassium bicarbonate (KHCO₃) compared with placebo on biochemical markers of bone turnover, and calcium and nitrogen (N) excretion. In this double‐blind, randomized, placebo‐controlled study, 244 men and women age 50 years and older were randomized to placebo or 1 mmol/kg or 1.5 mmol/kg of KHCO₃ daily for 3 months; 233 completed the study. The primary outcomes were changes in 24‐hour urinary N‐telopeptide (NTX) and N; changes in these measures were compared across the treatment groups. Exploratory outcomes included 24‐hour urinary calcium excretion, serum amino‐terminal propeptide of type I procollagen (P1NP), and muscle strength and function assessments. The median administered doses in the low‐dose and high‐dose groups were 81 mmol/day and 122 mmol/day, respectively. When compared with placebo, urinary NTX declined significantly in the low‐dose group (p = 0.012, after adjustment for baseline NTX, gender, and change in urine creatinine) and serum P1NP declined significantly in the low‐dose group (p = 0.004, adjusted for baseline P1NP and gender). Urinary calcium declined significantly in both KHCO₃ groups versus placebo (p < 0.001, adjusted for baseline urinary calcium, gender, and changes in urine creatinine and calcium intake). There was no significant effect of either dose of KHCO₃ on urinary N excretion or on the physical strength and function measures. KHCO₃ has favorable effects on bone turnover and calcium excretion and the lower dose appears to be the more effective dose. Long‐term trials to assess the effect of alkali on bone mass and fracture risk are needed. © 2015 American Society for Bone and Mineral Research.     

Factors associated with completion of patient surveys 1 year after bariatric surgery

BackgroundPatient-reported outcomes (PRO) obtained from follow-up survey data are essential to understanding the longitudinal effects of bariatric surgery. However, capturing data among patients who are well beyond the recovery period of surgery remains a challenge, and little is known about what factors may influence follow-up rates for PRO.ObjectivesTo assess the effect of hospital practices and surgical outcomes on patient survey completion rates at 1 year after bariatric surgery.SettingProspective, statewide, bariatric-specific clinical registry.MethodsPatients at hospitals participating in the Michigan Bariatric Surgery Collaborative are surveyed annually to obtain information on weight loss, medication use, satisfaction, body image, and quality of life following bariatric surgery. Hospital program coordinators were surveyed in June 2017 about their practices for ensuring survey completion among their patients. Hospitals were ranked based on 1-year patient survey completion rates between 2011 and 2015. Multivariable regression analyses were used to identify associations between hospital practices, as well as 30-day outcomes, on hospital survey completion rankings.ResultsOverall, patient survey completion rates at 1 year improved from 2011 (33.9% ± 14.5%) to 2015 (51.0% ± 13.0%), although there was wide variability between hospitals (21.1% versus 77.3% in 2015). Hospitals in the bottom quartile for survey completion rates had higher adjusted rates of 30-day severe complications (2.6% versus 1.7%, respectively; P = .0481), readmissions (5.0% versus 3.9%, respectively; P = .0157), and reoperations (1.5% versus .7%, respectively; P = .0216) than those in the top quartile. While most hospital practices did not significantly impact survey completion at 1 year, physically handing out surveys during clinic visits was independently associated with higher completion rates (odds ratio, 13.60; 95% confidence interval, 1.99?93.03; P =.0078).ConclusionsHospitals vary considerably in completion rates of patient surveys at 1 year after bariatric surgery, and lower rates were associated with hospitals that had higher complication rates. Hospitals with the highest completion rates were more likely to physically hand surveys to patients during clinic visits. Given the value of PRO on longitudinal outcomes of bariatric surgery, improving data collection across multiple hospital systems is imperative.     

Effects of hyperglycemia, hyperinsulinemia, and hyperosmolarity on neutrophil apoptosis

BACKGROUND: Hyperglycemia is an independent risk factor for increased mortality of critically ill surgical patients, but despite the recognized clinical benefits of early insulin treatment, there is a lack of understanding of the cellular and molecular mechanisms behind this phenomenon. We hypothesized that polymorphonuclear neutrophils, the first line of the innate immune defense system, suffer from altered apoptotic turnover when exposed to hyperglycemic conditions, ultimately decreasing the number of viable cells active at a site of infection. METHODS: Venous blood samples were drawn from 10 volunteers and incubated for 0.5 or 24 h in a 1:10 dilution with RPMI 1640 medium at various glucose and insulin concentrations. Mannitol was used to control for increased osmolarity. In addition, all samples were incubated either with low-dose lipopolysaccharide (LPS) (1 ng/mL) or without LPS. Neutrophils were extracted using Ficoll-Hypaque density centrifugation and stained with annexin V and propidium iodide. Fluorescence was detected by flow cytometry and analyzed using CellQuest software. RESULTS: The mean percentage of apoptotic neutrophils after 24 h of incubation at physiologic glucose concentrations (100 mg/dL) was 42.2 +/- 4.1%; exposure to low-dose LPS decreased this number to 18.4 +/- 2.5% (p < 0.01). Neither the exposure to low (10 mg/dL) nor increasingly high (200 or 400 mg/dL) glucose concentrations altered these percentages significantly. Exposing whole blood to increasing osmolarity (addition of 5.5 mM and 16.5 mM mannitol to simulate 200 and 400 mg/dL glucose) led to a mean absolute reduction of the percentage of apoptotic neutrophils to 34.6 +/- 3.6% (+5.5 mOsm; p < 0.05) and 32.3 +/- 4.5% (16.5 mOsm; p < 0.01), respectively. CONCLUSIONS: The ability of neutrophils to enter their apoptotic program in cultured whole blood withstands short-term changes in glucose and insulin concentrations. Neither hyperglycemia nor hypoglycemia led to a significant alteration of the apoptotic turnover of these cells, suggesting that the increased rate of infectious complications in short-term hyperglycemic critically ill patients may not be traced to increased apoptosis of neutrophils. However, isolated hyperosmolarity reduces neutrophil apoptosis, an observation that may warrant future investigation.     

Surgical weight loss >65 years old: is it worth the risk?

BackgroundWeight loss surgery in patients >65 years old has been underused, secondary to the morbidity and mortality concerns of healthcare providers. Comparative outcomes analyses of this patient population have been lacking. The purpose of the present report was to evaluate the safety and outcome of gastric bypass in patients >65 years of age.MethodsA prospective database was used to analyze the safety, operative morbidity, and outcome. All patients undergoing surgery since January 2005 were included.ResultsThe analysis of 1474 patients demonstrated a greater operative risk profile for patients >65 years (n = 100) compared with those <65 years old (n = 1374) related to sleep apnea (45% versus 34%), diabetes mellitus (65% versus 33%), and hypertension (81% versus 57%). The operative outcomes were similar for the 2 groups as determined by the operative time (70 versus 65 minutes), length of stay (1.97 versus 1.3 days), and 30-day readmission rate (6.0% versus 7.4%). The postoperative complication rates were low in the patients >65 years old (bleeding 1.0%, pulmonary 3.0%, cardiac 2.0%, wound 2.0%, and 30-day mortality rate 0%). The percentage of excess body weight loss in the gastric bypass patients was similar between the patients >65 years old and those <65 years old at 12 months (74.8% versus 77.8%) and 24 months (83.4% versus 78.5%).ConclusionOur experience represents one of the largest series of laparoscopic gastric bypass in elderly patients. The data have demonstrated excellent outcomes compared with a younger population.