Antiresorptive drugs (bisphosphonates), atypical fractures and rebound effect: new evidence of similitude

Background: Homeopathy is based on treatment by similitude ('like cures like') administering to sick individuals substances that cause similar symptoms in healthy individuals, employing the secondary and paradoxical action of the organism as therapeutic response. This vital or homeostatic reaction of the organism can be scientifically explained by the rebound effect of drugs, resulting in worsening of symptoms after suspension of treatment. Bisphosphonates (BPs) reduce 'typical' fractures in patients with osteoporosis, but recent studies report 'atypical' fractures of the femur after stopping the BPs, a rebound effect may be the causal mechanism. Method: Review of the literature concerning the relationship between atypical femoral fractures and antiresorptive drugs (bisphosphonates), identifying the pathogenesis of this adverse event. Results: Several studies have described multiple cases of 'atypical' low-impact subtrochanteric stress fractures or complete fractures of the femur. These fractures are often bilateral, preceded by pain in the affected thigh, may have a typical X-ray appearance, and may delayed healing. Rebound of osteoclastic activity after suspension of antiresorptive drugs is a plausible mechanism to explain this phenomenon. Conclusion: As for other classes of drugs, the rebound effect of antiresorptive drugs supports Hahnemann's similitude principle (primary action of the drugs followed by secondary and opposite action of the organism), and clarifies this 'unresolved' issue. Unfortunately, the rebound effect is little discussed among health professionals, depriving them of important knowledge ensure safe management of drugs. Homeopathy (2012) 101, 231-242.

Biomechanical Performance of Flexible Intramedullary Nails With End Caps Tested in Distal Segmental Defects of Pediatric Femur Models

Background: Unstable distal femoral fractures in children are challenging lesions with restricted surgical options for adequate stabilization. Elastic nails have become popular for treating femoral shaft fractures, yet they are still challenging for using in distal fractures. The aim of this study was to test whether end caps (CAP) inserted into the nail extremity improved the mechanical stabilization of a segmental defect at the distal femoral metaphyseal-diaphyseal junction created in an artificial pediatric bone model. Methods: Two 3.5-mm titanium elastic nails (TEN) were introduced intramedullary into pediatric femur models, and a 7.0-mm-thick segmental defect was created at the distal diaphyseal-metaphyseal junction. Nondestructive 4-point bending, axial-bending, and torsion tests were conducted. After this, the end caps were inserted into the external tips of the nails and then screwed into the bone cortex. The mechanical tests were repeated. Stiffness, displacement, and torque were analyzed using the Wilcoxon nonparametric test for paired samples. Results: In the combined axial-bending tests, the TEN + CAP combination was 8.75% stiffer than nails alone (P < 0.01); in torsion tests, the TEN + CAP was 14% stiffer than nails alone (P < 0.01). In contrast, the 4-point bending test did not show differences between the methods (P = 0.91, stiffness; P = 0.51, displacement). Thus, the end caps contributed to an increase in the construct stability for torsion and axial-bending forces but not for 4-point bending forces. Conclusions: These findings indicate that end caps fitted to elastic nails may contribute to the stabilization of fractures that our model mimics (small distal fragment, bone comminution, and distal bone fragment loss).

High frequency of osteoporosis and fractures in women with dermatomyositis/polymyositis

Bone mass was only previously studied in juvenile dermatomyositis/polymyositis (DM/PM) patients. Therefore, the objective this study was to evaluate the prevalence of osteoporosis and fractures in adult DM/PM. Forty female DM/PM and 78 age-, gender-, and BMI-matched healthy controls were studied. Medical charts and clinical interviews of all patients were evaluated for demographic and clinical data, including disease activity, cumulative doses of glucocorticoid, menarche and menopause age, and fractures. Bone mineral density (BMD) using dual X-ray absorptiometry (DXA) were measured at lumbar spine (L1-L4) and hip. A decreased BMD in lumbar spine [0.902 (0.136) vs. 0.965 (0.141) g/cm(2), P = 0.022] and femoral neck [0.729 (0.12) vs. 0.784 (0.127) g/cm(2), P = 0.027] was observed in patients compared to controls. In addition, osteoporosis was more frequent in patients than in controls in both lumbar spine (20 vs. 3.8%, P = 0.007) and the femoral neck (27.5 vs. 10.3%, P = 0.016). Moreover, a high prevalence of fractures was found in patients in comparison to healthy subjects (17.9 vs. 5.1%, P = 0.040; OR = 3.92; CI 95%: 1.07-14.33). Comparing DM/PM patients with (n = 17) and without (n = 23) osteoporosis/fractures, significant differences were observed regarding age [56.8 (11.9) vs. 48.3 (13.2) years, P = 0.042], weight [62.05 (13.56) vs. 71.51 (11.46) kg, P = 0.022] and frequency of post menopausal women (94.1 vs. 65.2%, P = 0.0002). No differences were observed concerning height, lean mass, total fat mass, disease activity, mean value of creatine kinase, cumulative glucocorticoid dose, or bisphosphonate use. Logistic regression analysis revealed a negative association between the presence of osteoporosis/fractures and weight (OR: 0.92, 95% CI: 0.85-0.98; P = 0.016). This is the first study that analyzed bone mass in adult DM/PM patients and it demonstrated that about one quarter of these patients have osteoporosis/fracture.

Changes in Complete Blood Count in Patients With Surgically Treated Facial Fractures

The purpose of this prospective study was to verify the changes in the preoperative and postoperative complete blood counts of patients with surgically treated facial fractures. Fifty consecutive patients with a mean age of 34 years who presented facial fractures and underwent surgical treatment were included. A complete blood count was performed, comprising the red and white blood cell count (cells/mu L), hemoglobin (g/dL), and hematocrit (%) levels. These data were obtained preoperatively and postoperatively during a 6-week period. Statistical analyses were performed using the Kruskal-Wallis and Mann-Whitney tests to identify the possible differences among the groups and among the periods of observation using the Friedman and Wilcoxon matched-pairs signed-ranks tests. The most common location of the fractures was the mandible (42.3%), followed by the zygomatic-orbital (36.5%) and associated locations (21.2%). Leukocytosis was associated with neutrophilia in the immediate postoperative period in all of the groups. There were no values below the reference limits of the values of hemoglobin, hematocrit, and erythrocytes, and no values above the reference limits for the remaining white blood cells, although significant differences among periods were observed in most cells, depending on the type of fracture. The primary findings were leukocytosis associated with neutrophilia, verified in the immediate postoperative period in all of the groups, and the influence of the type of fracture on the significant alterations observed among studied periods on the values of hemoglobin, hematocrit, erythrocytes, leukocytes, neutrophils, and lymphocytes.

Electromyographic Study in Patients With Surgically Treated Facial Fractures

This study, using surface electromyography, analyzed the activity of the masseter muscles of 30 patients with facial bone fractures that were surgically treated. Evaluations were made before surgery and in the 7th, 30th, and 60th days after surgery. The value of each measure and the average of 3 maximum voluntary isometric contractions lasting 5 seconds each were registered, and statistical analyses were performed. Patients had a mean age of 31 years and an average of 1.33 fractures. They were grouped according to the type of fracture as follows: mandibular (50%), zygomatic complex (33%), maxilla (10%), and associated fractures (6.7%). There was a lower masseter activity in the preoperative period, when compared with normal values in all groups of fractures. There was a sharp drop in the masseter activity in the postoperative period of 7 days, and all groups showed recovery of activity in 60 days but still below the normal value referenced in the literature. The mean values of the masseter activity, in descending order, were from the zygomatic complex, mandibular, maxillary, and associated fractures. The unilateral mandibular fractures showed higher values than the bilateral fractures in most of the evaluations. There was a highly significant difference in the comparison of the evolution of the masseter activity on both sides, for mandibular and zygomatic complex fractures, and the pairwise comparison showed significant difference between most groups. It was concluded that facial fractures and surgical procedures had negative effects in the muscle activity as observed using electromyography.

Outcomes of correction of internal hip rotation in patients with spastic cerebral palsy using proximal femoral osteotomy

Internal hip rotation (IHR) is the major cause of intoeing gait in patients with cerebral palsy (CP). Femoral derotation osteotomy (FDO) is the preferred treatment to correct excessive anteversion, however the condition may persist or recur postoperatively. Retrospective clinical and kinematic evaluation of 75 spastic diplegic CP patients was conducted for a mean duration of 22 months following proximal FDO. The patients were divided into two groups depending on the correction or persistence of IHR evident at kinematics after surgery. If corrected, mean patient follow-up was extended to 53 months. Outcomes were analyzed using Two Proportions Equality, Mann-Whitney and Wilcoxon tests. IHR persisted in 33.3% of cases at mean follow-up of 22 months and subtrochanteric femur osteotomy was more frequent in this group (p = 0.033). Thirty-five of the fifty-four patients with first-round gait correction were monitored during the extended follow-up. Those for whom IHR recurred (9.5%) had undergone FDO at a comparatively younger age. Patient gender, operations prior to or at the time of femoral osteotomy, topographic classification, GMFCS level, or the extent of preoperative clinical and kinematic abnormalities had no apparent influence on persistence or recurrence of abnormal gait. (C) 2012 Elsevier B.V. All rights reserved.

Submental Endotracheal Intubation: A Valuable Resource for the Management of Panfacial Fractures

Modern techniques for surgical treatment of midfacial and panfacial fractures in maxillofacial trauma lead to special problems for airway management. Usually, in perioperative management of panfacial fractures, the surgeon needs to control the dental occlusion and nasal pyramid assessment. For these reasons, oral and nasal endotracheal intubations are contraindicated for the management of panfacial fractures. Tracheotomy is considered by many as the preferred route for airway management in patients with severe maxillofacial fractures, but there are often perioperative and postoperative complications concerning this technique. The submental route for endotracheal intubation has been proposed as an alternative to tracheotomy in the surgical management of patients with panfacial fractures, besides it is accompanied by low morbidity. Thus, this paper aimed to describe the submental endotracheal intubation technique in a patient experiencing panfacial fracture. The subject was well treated using the submental endotracheal intubation to get good reconstruction of the fractures because the authors obtained free access of all facial fractures.

Osteoporotic hip fractures in non-elderly patients: relevance of associated co-morbidities

Osteoporotic hip fractures (OHF) are not limited to elderly; however, studies in non-elderly are scarce. Thus, the aim of this study was to evaluate co-morbidities in non-elderly patients with OHF in a Community Teaching Hospital. All hospitalizations due to OHF during a 3-year period in a Community Teaching Hospital were retrospectively evaluated for co-morbidities, and patients 18-64 years old were compared with those a parts per thousand yen65 years old. Of all hospitalizations, 232 (0.73%) were due to hip fractures, and 120/232 (51.7%) patients had OHF. The comparison of the 13 (10.8%) OHF patients < 65 years old (47.3 +/- A 9.7 years) with 107 (89.2%) a parts per thousand yen65 years old (80.4 +/- A 7.7 years) revealed a male predominance (61.5 vs. 27.1%, P = 0.022) and a distinct ethnic distribution with a lower proportion of Caucasians in the former (61.5 vs. 86.9%, P = 0.033). Moreover, non-elderly OHF patients had higher frequencies of insulin-dependent DM (38.5 vs. 3.7%, P = 0.001) and alcoholism (38.5 vs. 4.7%, P = 0.001) than aged patients. In contrast, rates of age-related co-morbidities such as stroke (7.7 vs. 18.7%, P = 0.461), heart failure (23.1 vs. 14.0%, P = 0.411), and dementia (7.7 vs. 15.9%, P = 0.689) were comparable in both groups. Logistic regression analysis demonstrated that insulin-dependent DM (OR = 25.4, 95% CI = 4.7-136.8, P < 0.001) and alcoholism (OR = 20.3, 95% CI = 3.9-103.3, P < 0.001) remained as independent risk factors for OHF in non-elderly patients. Osteoporosis is an important cause of HF in Community Hospital. Non-elderly patients with OHF have a peculiar demographic profile and associated co-morbidities. These findings reinforce the need of early osteoporosis diagnosis and rigorous fracture prevention in patients with DM and alcoholism.

Low fatness, reduced fat intake and adequate plasmatic concentrations of LDL-cholesterol are associated with high bone mineral density in women: a cross-sectional study with control group

Background: Several parameters are associated with high bone mineral density (BMD), such as overweight, black background, intense physical activity (PA), greater calcium intake and some medications. The objectives are to evaluate the prevalence and the main aspects associated with high BMD in healthy women. Methods: After reviewing the database of approximately 21,500 BMD scans performed in the metropolitan area of Sao Paulo, Brazil, from June 2005 to October 2010, high BMD (over 1400 g/cm(2) at lumbar spine and/or above 1200 g/cm2 at femoral neck) was found in 421 exams. Exclusion criteria were age below 30 or above 60 years, black ethnicity, pregnant or obese women, disease and/or medications known to interfere with bone metabolism. A total of 40 women with high BMD were included and matched with 40 healthy women with normal BMD, paired to weight, age, skin color and menopausal status. Medical history, food intake and PA were assessed through validated questionnaires. Body composition was evaluated through a GE-Lunar DPX MD + bone densitometer. Radiography of the thoracic and lumbar spine was carried out to exclude degenerative alterations or fractures. Biochemical parameters included both lipid and hormonal profiles, along with mineral and bone metabolism. Statistical analysis included parametric and nonparametric tests and linear regression models. P < 0.05 was considered significant. Results: The mean age was 50.9 (8.3) years. There was no significant difference between groups in relation to PA, smoking, intake of calcium and vitamin D, as well as laboratory tests, except serum C-telopeptide of type I collagen (s-CTX), which was lower in the high BMD group (p = 0.04). In the final model of multivariate regression, a lower fat intake and body fatness as well a better profile of LDL-cholesterol predicted almost 35% of high BMD in women. (adjusted R2 = 0.347; p < 0.001). In addition, greater amounts of lean mass and higher IGF-1 serum concentrations played a protective role, regardless age and weight. Conclusion: Our results demonstrate the potential deleterious effect of lipid metabolism-related components, including fat intake and body fatness and worse lipid profile, on bone mass and metabolism in healthy women.

Isokinetic muscle strength and knee function associated with double femoral pin fixation and fixation with interference screw in anterior cruciate ligament reconstruction

Intensive scheduling in sports requires athletes to resume physical activity shortly after injury. The purpose of this study was to investigate early isokinetic muscle strength and knee function on bone-patellar tendon-bone (BPTB) ACL reconstruction with double femoral pin fixation or interference screw technique. A prospective study was conducted from 2008 to 2009, with 48 athletes who received femoral BPTB fixation with interference screw (n = 26) or double pin (n = 22). Clinical (IKDC objective score and hop test) and isokinetic muscle strength (peak torque (PT), PT/body weight and flexion/extension rate (F/E) in 60 and 240A degrees/s) were analyzed at 6 months of follow-up. Analysis at baseline showed no differences between groups before surgery related to age, gender, associated injury, Tegner or Lysholm score; thus showing that groups were similar. During follow-up, however, there were significant differences between the two groups in some of the isokinetic muscle strength: PT/BW 60A degrees/s (Double Pin = 200% +/- A 13% vs. Interference Screw = 253% +/- A 16%*, *P = 0.01); F/E 60A degrees/s (Double Pin = 89% +/- A 29%* vs. Interference Screw = 74% +/- A 12%, *P = 0.04). No statistical differences between groups were observed on IKDC objective score, hop test and complications. The significant muscle strength outcome of the interference screw group found in this study gives initial evidence that this fixation technique is useful for athletes that may need accelerated rehabilitation. Early return to sports ability signaled by isokinetic muscle strength is of clinical relevance as it is one of the main goals for athletes' rehabilitation. III.

The protective effect of cilostazol on isolated rabbit femoral arteries under conditions of ischemia and reperfusion: the role of the nitric oxide pathway

OBJECTIVES: The clinical significance of ischemia/reperfusion of the lower extremities demands further investigation to enable the development of more effective therapeutic alternatives. This study investigated the changes in the vascular reactivity of the rabbit femoral artery and nitric oxide metabolites under partial ischemia/reperfusion conditions following cilostazol administration. METHODS: Ischemia was induced using infrarenal aortic clamping. The animals were randomly divided into seven groups: Control 90 minutes, Ischemia/Reperfusion 90/60 minutes, Control 120 minutes, Ischemia/Reperfusion 120/90 minutes, Cilostazol, Cilostazol before Ischemia/Reperfusion 120/90 minutes, and Ischemia 120 minutes/Cilostazol/Reperfusion 90 minutes. Dose-response curves for sodium nitroprusside, acetylcholine, and the calcium ionophore A23187 were obtained in isolated femoral arteries. The levels of nitrites and nitrates in the plasma and skeletal muscle were determined using chemiluminescence. RESULTS: Acetylcholine- and A23187-induced relaxation was reduced in the Ischemia/Reperfusion 120/90 group, and treatment with cilostazol partially prevented this ischemia/reperfusion-induced endothelium impairment. Only cilostazol treatment increased plasma levels of nitrites and nitrates. An elevation in the levels of nitrites and nitrates was observed in muscle tissues in the Ischemia/Reperfusion 120/90, Cilostazol/Ischemia/Reperfusion, and Ischemia/Cilostazol/Reperfusion groups. CONCLUSION: Hind limb ischemia/reperfusion yielded an impaired endothelium-dependent relaxation of the femoral artery. Furthermore, cilostazol administration prior to ischemia exerted a protective effect on endothelium-dependent vascular reactivity under ischemia/reperfusion conditions.

The impact of asymptomatic vertebral fractures on quality of life in older community-dwelling women: the Sao Paulo Ageing & Health Study

OBJECTIVES: The aim of this study was to investigate the impact of asymptomatic vertebral fractures on the quality of life in older women as part of the Sao Paulo Ageing & Health Study. METHODS: This study was a cross-sectional study with a random sample of 180 women 65 years of age or older with or without vertebral fractures. The Quality of Life Questionnaire of the European Foundation for Osteoporosis was administered to all subjects. Anthropometric data were obtained by physical examination, and the body mass index was calculated. Lateral thoracic and lumbar spine X-ray scans were obtained to identify asymptomatic vertebral fractures using a semi-quantitative method. RESULTS: Women with asymptomatic vertebral fractures had lower total scores [61.4(15.3) vs. 67.1(14.2), p = 0.03] and worse physical function domain scores [69.5(20.1) vs. 77.3(17.1), p = 0.02] for the Quality of Life Questionnaire of the European Foundation for Osteoporosis compared with women without fractures. The total score of this questionnaire was also worse in women classified as obese than in women classified as overweight or normal. High physical activity was related to a better total score for this questionnaire (p = 0.01). Likewise, lower physical function scores were observed in women with higher body mass index values (p < 0.05) and lower physical activity levels (p < 0.05). Generalized linear models with gamma distributions and logarithmic link functions, adjusted for age, showed that lower total scores and physical function domain scores for the Quality of Life Questionnaire of the European Foundation for Osteoporosis were related to a high body mass index, lower physical activity, and the presence of vertebral fractures (p < 0.05). CONCLUSION: Vertebral fractures are associated with decreased quality of life mainly physical functioning in older community-dwelling women regardless of age, body mass index, and physical activity. Therefore, the results highlight the importance of preventing and controlling asymptomatic vertebral fractures to reduce their impact on quality of life among older women.

Interaction between Advanced Glycation End Products Formation and Vascular Responses in Femoral and Coronary Arteries from Exercised Diabetic Rats

Background: The majority of studies have investigated the effect of exercise training (TR) on vascular responses in diabetic animals (DB), but none evaluated nitric oxide (NO) and advanced glycation end products (AGEs) formation associated with oxidant and antioxidant activities in femoral and coronary arteries from trained diabetic rats. Our hypothesis was that 8-week TR would alter AGEs levels in type 1 diabetic rats ameliorating vascular responsiveness. Methodology/Principal Findings: Male Wistar rats were divided into control sedentary (C/SD), sedentary diabetic (SD/DB), and trained diabetic (TR/DB). DB was induced by streptozotocin (i.p.: 60 mg/kg). TR was performed for 60 min per day, 5 days/week, during 8 weeks. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP), phenylephrine (PHE) and tromboxane analog (U46619) were obtained. The protein expressions of eNOS, receptor for AGEs (RAGE), Cu/Zn-SOD and Mn-SOD were analyzed. Tissues NO production and reactive oxygen species (ROS) generation were evaluated. Plasma nitrate/nitrite (NOx-), superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and N-epsilon-(carboxymethyl) lysine (CML, AGE biomarker). A rightward shift in the concentration-response curves to ACh was observed in femoral and coronary arteries from SD/DB that was accompanied by an increase in TBARS and CML levels. Decreased in the eNOS expression, tissues NO production and NOx- levels were associated with increased ROS generation. A positive interaction between the beneficial effect of TR on the relaxing responses to ACh and the reduction in TBARS and CML levels were observed without changing in antioxidant activities. The eNOS protein expression, tissues NO production and ROS generation were fully re-established in TR/DB, but plasma NOx- levels were partially restored. Conclusion: Shear stress induced by TR fully restores the eNOS/NO pathway in both preparations from non-treated diabetic rats, however, a massive production of AGEs still affecting relaxing responses possibly involving other endothelium-dependent vasodilator agents, mainly in coronary artery.

Necrose avascular da cabeça femoral em pacientes HIV positivos: resultados iniciais do tratamento cirúrgico por substituição articular cerâmica-cerâmica

OBJETIVOS: Avaliar os resultados funcionais iniciais e o índice de complicações precoces das artroplastias totais do quadril cerâmica-cerâmica em pacientes que convivem com o HIV e apresentam osteonecrose da cabeça femoral. MÉTODO: Doze pacientes HIV+ com diagnóstico de osteonecrose da cabeça do fêmur incongruente foram avaliados através de critérios clínicos, laboratoriais, pela escala funcional WOMAC antes e após o tratamento com substituição articular. RESULTADOS: Observamos que 83,3% dos indivíduos faziam uso de inibidores de protease, 75% apresentavam dislipidemia e 66,6% síndrome lipodistrófica, a melhora na evolução no escore WOMAC foi estatisticamente significativa para seis e 12 meses de pós-operatório em comparação com o escore pré-operatório e não observamos complicações secundárias a esse procedimento. CONCLUSÃO: A artroplastia total do quadril com implante de cerâmica-cerâmica para o tratamento da necrose avascular do quadril nessa parcela da população é opção cirúrgica adequada, apresenta melhora funcional inicial significativa e baixo índice de complicação precoce.

The impact of asymptomatic vertebral fractures on quality of life in older community-dwelling women: the São Paulo Ageing & Health Study

OBJECTIVES: The aim of this study was to investigate the impact of asymptomatic vertebral fractures on the quality of life in older women as part of the Sao Paulo Ageing & Health Study. METHODS: This study was a cross-sectional study with a random sample of 180 women 65 years of age or older with or without vertebral fractures. The Quality of Life Questionnaire of the European Foundation for Osteoporosis was administered to all subjects. Anthropometric data were obtained by physical examination, and the body mass index was calculated. Lateral thoracic and lumbar spine X-ray scans were obtained to identify asymptomatic vertebral fractures using a semi-quantitative method. RESULTS: Women with asymptomatic vertebral fractures had lower total scores [61.4(15.3) vs. 67.1(14.2), p = 0.03] and worse physical function domain scores [69.5(20.1) vs. 77.3(17.1), p = 0.02] for the Quality of Life Questionnaire of the European Foundation for Osteoporosis compared with women without fractures. The total score of this questionnaire was also worse in women classified as obese than in women classified as overweight or normal. High physical activity was related to a better total score for this questionnaire (p = 0.01). Likewise, lower physical function scores were observed in women with higher body mass index values (p<0.05) and lower physical activity levels (p,0.05). Generalized linear models with gamma distributions and logarithmic link functions, adjusted for age, showed that lower total scores and physical function domain scores for the Quality of Life Questionnaire of the European Foundation for Osteoporosis were related to a high body mass index, lower physical activity, and the presence of vertebral fractures (p<0.05). CONCLUSION: Vertebral fractures are associated with decreased quality of life mainly physical functioning in older community-dwelling women regardless of age, body mass index, and physical activity. Therefore, the results highlight the importance of preventing and controlling asymptomatic vertebral fractures to reduce their impact on quality of life among older women.