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.     

Side-to-side nerve bridges reduce muscle atrophy after peripheral nerve injury in a rodent model

Background

Peripheral nerve injury can result in muscle atrophy and long-term disability. We hypothesize that creating a side-to-side bridge to link an injured nerve with a healthy nerve will reduce muscle atrophy and improve muscle function.

Methods

Sprague-Dawley rats were divided into four groups (n = 7 per group). Group 1: transection only—a 10-mm gap was created in the proximal tibial nerve; group 2: transected plus repaired—the transected tibial nerve was repaired; group 3: transected plus repaired plus nerve bridge—transected nerve repaired with a distal nerve bridge between the tibial and peroneal nerves via epineurial windows; and group 4: transected plus nerve bridge—transected tibial nerve left unrepaired and distal bridge added. Gait was assessed every 2 wk. At 90 d the following measures were determined: gastrocnemius mass, muscle and nerve nuclear density, and axonal infiltration into the nerve bridge.

Results

Groups 3 and 4 had greater improvements in walking track recovery than groups 1 and 2. Group 3's gastrocnemius muscles exhibited the least amount of atrophy. Groups 1, 2, and 4 exhibited greater histologic appearance of muscle breakdown compared with group 3 and control muscle. Finally, most bridges in groups 3 and 4 had neuronal sprouting via the epineurial windows.

Conclusions

Our study demonstrated reduced muscle atrophy with a side-to-side nerve bridge in the setting of peripheral nerve injury. These results support the application of novel side-to-side bridges in combination with traditional end-to-end neurorrhaphy to preserve muscle viability after peripheral nerve injuries.     

Mental and Physical Health Consequences of the September 11, 2001 (9/11) Attacks in Primary Care: A Longitudinal Study

The magnitude of the September 11, 2001 (9/11) attacks was without precedent in the United States, but long‐term longitudinal research on its health consequences for primary care patients is limited. We assessed the prevalence and exposure‐related determinants of mental disorders, functioning, general medical conditions, and service utilization, 1 and 4 years after the 9/11 attacks, in an urban primary care cohort (N = 444) in Manhattan. Although the prevalence of posttraumatic stress disorder (PTSD) and levels of functional impairment declined over time, a substantial increase in suicidal ideation and missed work was observed. Most medical outcomes and service utilization indicators demonstrated a short‐term increase after the 9/11 attacks (mean change of +20.3%), followed by a minor decrease in the subsequent year (mean change of ?3.2%). Loss of a close person was associated with the highest risk for poor mental health and functional status over time. These findings highlight the importance of longitudinal assessments of mental, functional, and medical outcomes in urban populations exposed to mass trauma and terrorism.     

A comparison of the microarchitectural bone adaptations of the concave and convex thoracic spinal facets in idiopathic scoliosis

BACKGROUND: A limited number of studies have assessed the changes in bone microarchitecture in spinal facets with use of light microscopy but not with use of electron microscopy techniques. The purpose of this study was to analyze the facets in patients with scoliosis to determine whether there are differences in the bone microarchitecture of contralateral facets at the same anatomic level. METHODS: In eight patients undergoing posterior spinal arthrodesis for the treatment of idiopathic scoliosis, biopsy specimens of facet pairs at matched anatomic levels were obtained from three locations: (1). the curve apex, (2). one level cephalad to the apex, and (3). one level caudad to the apex. The facets were analyzed for cortical bone porosity and thickness with use of scanning electron microscopy and National Institutes of Health imaging software. The concave and convex facets were compared with use of a paired t test. RESULTS: The mean porosity (and standard deviation) for the concave and convex facets was 16.5% +/- 5.8% and 24.1% +/- 6.2%, respectively. Those on the convex side were significantly more porous than those on the concave side (p 相似文献   

Osteochondritis Dissecans Knee Histology Studies Have Variable Findings and Theories of Etiology

Background

Although many etiological theories have been proposed for osteochondritis dissecans (OCD), its etiology remains unclear. Histological analysis of the articular cartilage and subchondral bone tissues of OCD lesions can provide useful information about the cellular changes and progression of OCD. Previous research is predominantly comprised of retrospective clinical studies from which limited conclusions can be drawn.

Questions/purposes

The purposes of this study were threefold: (1) Is osteonecrosis a consistent finding in OCD biopsy specimens? (2) Is normal articular cartilage a consistent finding in OCD biopsy specimens? (3) Do histological studies propose an etiology for OCD based on the tissue findings?

Methods

We searched the PubMed, Embase, and CINAHL databases for studies that conducted histological analyses of OCD lesions of the knee and identified 1560 articles. Of these, 11 met our inclusion criteria: a study of OCD lesions about the knee, published in the English language, and performed a histological analysis of subchondral bone and articular cartilage. These 11 studies were assessed for an etiology proposed in the study based on the study findings.

Results

Seven of 11 studies reported subchondral bone necrosis. Four studies reported normal articular cartilage, two studies reported degenerated or irregular articular cartilage, and five studies found a combination of normal and degenerated or irregular articular cartilage. Five studies proposed trauma or repetitive stress and two studies proposed poor blood supply as possible etiologies.

Conclusions

We found limited research on histological analysis of OCD lesions of the knee. Future studies with consistent methodology are necessary to draw major conclusions about the histology and progression of OCD lesions. Inconsistent histologic findings have resulted in a lack of consensus regarding the presence of osteonecrosis, whether the necrosis is primary or secondary, the association of cartilage degeneration, and the etiology of OCD. Such studies could use a standardized grading system to allow better comparison of findings.     

Treatment of hypertension and its effect on cardiovascular risk factors: data from the Framingham Heart Study

Analysis of the Framingham Heart Study experience between 1958 and 1970 showed a progressive increase in the rate of treatment and control of hypertension. With cross-sectional criteria to define diastolic hypertension, the treatment rate rose from 35% in 1958 through 1960 to 69% in 1968 through 1970 (p less than .001), and the treatment rate for sustained hypertension rose from 55% in 1958 through 1960 to 85% in 1968 through 1970 (p less than .001). Treated hypertensive subjects had higher pretreatment values of blood pressure but not of other cardiovascular risk factors than untreated hypertensive subjects. Treatment was more successful in controlling hypertension in later years (p less than .001), but in all years treatment reduced systolic and diastolic blood pressure without causing significant changes in mean serum cholesterol or glucose levels. In treated hypertensive subjects, the 8 year predicted risk of coronary heart disease declined by 2.3 events per 100 people compared with that in untreated hypertensive subjects (p less than .0001). The observed incidence of coronary heart disease was consistent with these predictions and suggested that treatment may be especially beneficial in subjects who have systolic blood pressures of 180 mm Hg or higher and who are treated for more than 2 successive years.     

Evidence linking glycated albumin to altered glomerular nephrin and VEGF expression, proteinuria, and diabetic nephropathy

BACKGROUND: Albumin modified by Amadori-glucose adducts has been linked to the development of diabetic nephropathy through its ability, independent of hyperglycemia, to activate protein kinase C-beta (PKC-beta), up-regulate the transforming growth factor-beta (TGF-beta) system, and stimulate expression of extracellular matrix proteins in glomerular cells, and by the demonstration that reducing the burden of glycated albumin ameliorates renal structural and functional abnormalities in the db/db mouse. METHODS: To probe whether the salutary effects consequent to lowering glycated albumin, which include reduction of albuminuria, relate to an influence of the Amadori-modified protein on nephrin, the podocyte protein critical to regulation of protein excretion, and on the angiogenic vascular endothelial growth factor (VEGF), which induces microvascular permeability, diabetic db/db mice were treated with a small molecule that inhibits the nonenzymatic glycation of albumin. RESULTS: Compared to nondiabetic db/m mice, diabetic controls exhibited increased urinary excretion of albumin and type IV collagen, elevated renal TGF-beta1 protein levels, reduced glomerular nephrin immunofluorescence and nephrin protein by immunoblotting, and increased glomerular VEGF immunostaining and renal VEGF protein content. Diabetic animals receiving test compound showed significant lowering of proteinuria, normalization of renal TGF-beta1 protein, and significant restoration of altered glomerular nephrin and VEGF expression. CONCLUSION: The findings causally implicate the increased glycated albumin associated with the diabetic state in the abnormal renal nephrin and VEGF expression found in diabetes, thereby promoting proteinuria and glomerulosclerosis.     

Race/ethnicity, poverty status, and renal transplant outcomes

BACKGROUND: There are known racial disparities in renal graft survival. Data are lacking comparing associations of race/ethnicity and socioeconomic status with graft failure and functional status after transplantation. Our goal was to test if African-American and Hispanic race/ethnicity and poverty are associated with worse outcomes following renal transplantation. METHODS: We performed a retrospective cohort study using a nationwide registry (United Network for Organ Sharing). We studied 4,471 adults who received renal transplants in 1990. Outcomes were graft failure and functional status over 10 years. RESULTS: Cumulative incidence of graft failure was higher among African-Americans and Hispanics than whites (77% vs. 64% vs. 60 %; P<0.001) and among transplant recipients living in the poorest areas (70% vs. 58% in the richest; P<0.001). African-American and Hispanic race/ethnicity were independently predictive of graft failure (RR 1.8, 95% CI 1.6-1.9; RR 1.3, 95% CI 1.2-1.6, respectively) in multivariate analyses but poverty status was not (RR 1.0, 95% CI 0.9-1.1). Days with impaired functional status were higher for African-Americans compared to whites (RR 1.6, 95% CI 1.3-1.9) but not independent of poverty. Poverty was independently associated with impaired functional status (RR 1.3, 95% CI 1.0-1.6). CONCLUSIONS: African-Americans and Hispanics had higher rates of graft failure compared to whites after adjustment for poverty and other covariates whereas poverty, but not race/ethnicity, was related to functional status following renal transplantation. National datasets should include individual-level measures of socioeconomic status in order to improve evaluation of social and environmental causes of disparities in renal transplant outcomes.     

The occurrence of hypothyroidism following radioactive iodine treatment of toxic nodular goiter is related to the TSH level

Background  Strategies to increase frequency of euthyroidism following radioactive (RAI) treatment of hyperthyroidism are required. Aims  To examine the role of TSH in development of hypothyroidism post RAI treatment in patients with Graves’ disease (N = 98) or toxic nodular goiter, TNG (N = 88). Design  This retrospective study examined thyroid status over a mean of 3.7 years post-RAI. Results  Although RAI dose was significantly higher in TNG group, hypothyroidism occurred more frequently in Graves’ disease (71.4 and 22.7%) P < 0.001. The TSH levels at the time of RAI treatment were lower in TNG patients who remained euthyroid, (0.4±0.1 vs. 1.2±0.5 mU/l, P < 0.0022). Conclusions  A higher frequency of euthyroidism occurs in patients with TNG than with Graves’ disease following RAI, particularly when suppressed TSH levels were suppressed at time of RAI-treatment.