Melatonin as a treatment for mood disorders: a systematic review.

OBJECTIVE: Melatonin has been widely studied in the treatment of sleep disorders and evidence is accumulating on a possible role for melatonin influencing mood. Our aim was to determine the efficacy and acceptability of melatonin for mood disorders. METHOD: We conducted a comprehensive systematic review of randomized clinical trials on patients with mood disorders, comparing melatonin to placebo. RESULTS: Eight clinical trials were included; one study in bipolar, three in unipolar depression and four in seasonal affective disorder. We have only a small study on patients with bipolar disorder, while we have more studies testing melatonin as an augmentation strategy for depressive episodes in major depressive disorder and seasonal affective disorder. The acceptability and tolerability were good. We analyzed data from three trials on depressive episodes and found that the evidence for an effect of melatonin in improving mood symptoms is not significant (SMD = 0.37; 95% CI [-0.05, 0.37]; P = 0.09). The small sample size and the differences in methodology of the trials suggest that our results are based on data deriving from investigations occurring early in this field of study. CONCLUSION: There is no evidence for an effect of melatonin on mood disorders, but the results are not conclusive and justify further research.

Biomechanical evaluation of the less invasive stabilization system for the internal fixation of distal femur fractures.

OBJECTIVE: Comparison between a Less Invasive Stabilization System (LISS) using monocortical screws with angular stability and two conventional plate systems Condylar Buttress Plate (CBP) and Dynamic Condylar Screw (DCS) for the treatment of distal femoral fractures with respect to biomechanical properties. DESIGN: Biomechanical study using paired cadaver femurs. In Test Configuration 1 (distal test), a ten-millimeter gap at the diaphysis-metaphysis junction simulates a supracondylar femoral fracture. Test Configuration 2 (proximal test) has the same configuration, but the gap was cut in the isthmic region. Proximal and distal plate ends were fixed to corresponding cortical bone fragments in both tests. Optical displacement transducers served to quantify the system's ability to withstand a stepwise increased load. Reversible (deflection) and irreversible deformation (subsidence) of the bone-plate construct was investigated. RESULTS: In Test Configuration 1, LISS showed less irreversible deformation in 72 percent of the left-right comparisons. No correlation between bone mineral density, cross-section area of bones and the measured response of the construct under load was found between pairs. In Test Configuration 2, 83 percent of the left-right comparisons showed less permanent deformation but a higher elastic deformation for LISS. CONCLUSIONS: These results suggest an enhanced ability to withstand high loads when using the monocortical screw fixation technique with angular stability. A higher elastic deformation of LISS compared with conventional plating systems in distal femoral fractures can be explained by the lower bending stiffness caused by different design and material properties.

Prologue: discourse concerning two conventional sciences.

The form of the Discorsi of Galileo Galilei is used here to emphasize the three aspects of research objects. The point of view of the user (Simplicio), the theoretician (Salviati) and the experimenter (Sagredo). Two technical aspects of the papers which have been presented in the three Biomechanics Supplements of Injury [volumes 30(1), 31(2), and 31(3)] are discussed by these three interlocutors: i. The confidence intervals of the number of cases in the epidemiological studies, which should be high enough to reveal significant differences (i.e. a total of about 2,000 patients to show that an improvement in treatment reduces the infection rate); ii. The importance of the deformation for the quantification of the deleterious effect of stress protection, whereby it is shown that the size of the subject (small animal vs human) is non-linearly related to the effect, as was already disclosed by Galilei 367 years ago--but which is still not yet well understood by the nonmechanic.

Effect of plate position relative to bending direction on the rigidity of a plate osteosynthesis. A theoretical analysis.

Mechanical unloading of the plated bone segment is observed after plate osteosynthesis because the implant takes over a part of the physiological loading. Strain reduction in the bony tissue depends on the rigidity of the plate (cross-sectional area, geometrical form, and modulus of elasticity). The aim of the present study was to calculate theoretically the effect of plate position relative to bending direction on the overall bending stiffness of the composite system plate-bone. To calculate the rigidity, a cylindrical bone model with mechanical characteristics similar to a sheep tibia and a rectangular plate cross-section corresponding to a DC-plate with either a modulus of elasticity of steel or titanium was used. Calculations under different bending directions were performed according to the laws of the linear bending theory and the composite beam theory. The bending stiffness of a plate osteosynthesis reaches a minimum and a maximum respectively, in cases in which the bending moment acts in the direction of the main axis of the area moment of inertia of the plate. The minimum is present with the plate bent vertically, the maximum with the plate bent horizontally, e.g. on the tension side of the composite system--on the assumption that the bone structure opposite the plate is capable of withstanding compressive loading. For steel and titanium plates, factors of 2 and 2.25 respectively were calculated between the minimum and the maximum bending stiffnesses of the osteosynthesis. The bending rigidity of the plate alone has only a minimal effect on the total stiffness of the osteosynthesis. With a plate bent vertically, the difference between steel and titanium plates was 18%, with the plate bent horizontally (situated on the tension side), it was only 7%. The bending stiffness of a plate osteosynthesis depends on the cross-section, the geometrical form, and the modulus of elasticity of the plate, as well as on the plate position relative to the bending direction of the composite system. The modulus of elasticity of the plate is relatively unimportant, while with a given plate the individual plate position relative to the bending direction is of crucial importance. Thus, changing the modulus of elasticity of the plate cannot solve the problem of implant induced unloading of the bone cortex because the bending stiffness of the composite system depends much more on the plate position relative to the bending direction.

Stress protection due to plates: myth or reality? A parametric analysis made using the composite beam theory.

A generally accepted idea has been that plate fixation of fractures may result in the structural adaptation of bone (bone loss) to reduced stress (stress protection) with the subsequent danger of refracture after implant removal. This was the negative aspect of stress protection. For this reason, it was proposed that plates made from more deformable materials be used (titanium, polymers or carbon fibres). A theoretical analysis using composite beam theory, with different loading conditions (axial load and bending), demonstrates that stress protection, i.e. early temporary porosis, is a myth. Mechanics of materials shows that when an over-large plate is fixed to small bones (as in small animals, e.g. rabbits), the reduction of bone strain is exaggerated; in contrast, using plates of varying flexibility (steel, titanium or carbon fibre) on large bones leads to strain reduction with an astonishingly similar amplitude.

Force transfer between the plate and the bone: relative importance of the bending stiffness of the screws friction between plate and bone.

Stability in plate fixation of fractures relates to the motionless fastening between plate and bone. When the plate is affixed to the bone, high shear force may appear between plate and bone, particularly near the end screws, which can lead to motion under weight-bearing. Two mechanisms might be involved in the prevention of motion: the bending stiffness of the screws or the friction between the screw and the plate. Experiments performed in vivo and in vitro show that with conventional plates, motion is prevented by friction and depends upon the axial force of the screw, pressing the plate onto the bone. The torque applied to the screws is crucial. Motion appears under smooth plates under relatively low physiological loads. With newly developed internal fixators, the motion is prevented by the structural stiffness of the plate-screw system.

Strain distribution in plated and unplated sheep tibia an in vivo experiment.

After plate osteosynthesis changes in bone biology and bone mechanics are observed in the plated bone segment. Compromise of the vascular supply in the plate bed leads to a remodelling process and to a temporary porosity in the bone cortex underneath the plate. In addition, the plate takes over some of the physiological loading of the bone, which in turn alters the normal strain distribution of the cortical bone tissue. The aim of the present study is to determine the tissue deformation of the sheep tibia in vivo and the changes in tissue strain due to plating with plates of different rigidities. Measurements were performed on the intact bone at the mid diaphysis using the strain gauge technique. With different connections on the tension bridge (Wheatstone bridge), the strain was measured separately for pure axial loading, bending, and torsion before and after plating with a 4.5 mm stainless steel or titanium DCP. Under physiological load the sheep tibia is mainly deformed in torsion (62%) and bending (33%), and much less in axial loading (5%). Plating with a steel plate reduces the overall tissue strain by 18%, with a titanium plate by 13%. This reduction is mainly due to a reduction in axial tissue strain due to axial loading and bending and less to the reduction of tissue strain under torsion. In our in vivo model, plating with steel or titanium plates leads to a reduction of the physiological tissue strains. The difference between the different plates is small due to the fact that the high tissue strain under torsion is only slightly affected by plating. Thus, from the purely mechanical point of view and with regard to preserving normal tissue strains as much as possible, titanium plates offer little advantage compared with stainless steel plates. But, titanium as an implant material may offer advantages with respect to tissue compatibility and infection resistance.

Mechanical analysis of the bone to plate interface of the LC-DCP and of the PC-FIX on human femora.

The scope of this analysis was to evaluate the mechanical behaviour of newly developed plates at the junction between plate and bone (friction between plate and bone) for the limited contact dynamic compression plate (LC-DCP) and the point contact fixator (PC-Fix) under simulated physiological load and using the tension band principle on the human femur. The intact human cadaveric femora were plated on the lateral aspect according to the tension band principle (AO) and subjected to a load which simulated careful physiological load in single stance. Five strain gauges were glued around the bones, parallel to the bone axis, at five levels, whereby three of them had to be covered by a bone plate and the two others were just outside the plate location. The cross-sectional geometry had been obtained at these levels using computed tomography. One side was plated using the conventional compression plate LC-DCP and the contralateral side using the internal fixator PC-Fix. The LC-DCP was affixed using screws tightened at different torque values and the PC-Fix at a standard torque value. Motion (slippage) between the plate and the bone was indicated by a hysteresis of the strain reading during loading and unloading. Slippage was more important for the LC-DCP than for the PC-Fix, particularly at the proximal end of the plate and when the screws were insufficiently tightened on the LC-DCP. As expected, better stability was obtained with the PC-Fix.

The point of view of the clinician: a prospective study of the mechanism of accidents and the morphology of tibial and fibular shaft fractures.

In a prospective study of 210 tibial shaft fractures, the accident mechanisms and the resultant fracture morphologies were analyzed. 86 fractures occurred due to indirect impact. The fracture morphology in this group consisted of short and long spiral fractures resulting from rotational injuries complicated by anterior torsion butterfly fragments if the person fell forward, posterior torsion butterfly fragments if they fell backwards and complicated by multiple torsion butterfly fragments if it was a high velocity injury. 124 fractures occurred due to direct impact. The fracture morphology in this group consisted of transverse, oblique segmental or crush fractures, complicated by one or more butterfly fragments due to bending, the injury depending on whether it was pure, one-point, three-point, or four-point-bending and on additional axial loading and velocity. In the indirect impact group, there were a few soft tissue injuries and fibular fractures at a different level to the tibial fracture. In the direct group, a large number of soft tissue injuries and fibular fractures at the level of impact were found.

The epidemiology of diaphyseal fractures of the tibia.

AO Documentation collected reports of nearly five thousand diaphyseal tibial fractures occurring in the 1980s. The following conclusions can be drawn: i. The number of fractures affecting men is twice that affecting women. ii. These fractures occurred mainly in younger people (under 40 years of age) and no increase occurred in elderly people. iii. Most bending fractures occurred in young men (20-30 yrs) and the torsion fractures affected men and women of about 40 equally. iv. The number of simple fractures (type A) is about the same as for fractures with one fragment (type B).

The epidemiology of fractures of the proximal femur.

Between 1980 and 1989, reports on 21,145 fractures of the proximal part of the femur (15,428 women and 5,717 men) were collected by AO Documentation and are analysed in the present paper. The number of fractures increases exponentially with age for women and for men. Up to 50, the number of fractures is higher for men than for women and vice versa after 55 years. The exponential increase in the number of fractures with age appears for all the types A1 to B3 for both women and men. No special increase has been identified for women after 50 (expected age of menopause).

The epidemiology of fractures of the distal femur.

Between 1980 and 1989, reports on 2,165 fractures of the distal part of the femur (1,051 women and 1,114 men) were collected by AO Documentation and are analyzed in the present paper. The number of fractures showed a bimodal pattern with a marked variation in the number of fractures in relation to gender and age. A larger prevalence of fractures was observed either in young men (about 20 years old, traffic or sport) and in old women (about 70, fall at home, osteoporosis).

The mechanical strength of bones in torsion application to human tibiae.

How strong is a long bone in torsion? The principle of mechanical engineering of torsion on a beam is applied to the cylindrical tube model of a bone. The deformation and the strength of the tube are calculated. The calculated strength is about twice that of a real, not circular bone (human tibia) with the same cross-sectional area.

A biomechanical enigma: why are tibial fractures not more frequent in the elderly?

Epidemiology revealed that diaphyseal fractures of the tibia affect young people, particularly young men; no increase was noticed for the elderly. This indicates that osteoporosis does not lead to increased bone fragility. Obviously, this is a biomechanical enigma. Torque measurements were carried out on human cadaveric tibiae and revealed a great correlation between the polar moment of inertia of the cortical bone at the tibial isthmus and the ultimate torque at failure (r = 0.83) and a lesser correlation between the cross-sectional density at the isthmus and the torque at failure (r = 0.57). Therefore, the size is more important than the degree of osteoporosis. We can speculate that endosteal resorption due to osteoporosis is compensated for by periosteal apposition and therefore does not lead to bone weakness.

Introduction: basic concepts and definitions in mechanics.

This introduction aims to expound the basic ideas of mechanics of materials to clinicians. What happens when a bone (mechanically a beam) is submitted to standard loads: Centric axial load, bending, eccentric axial load, torque? How does the bone deform? The basic ideas of mechanical engineering are presented using an eraser under load as an illustrative object, and trying to maintain the mathematical formulae as far as possible.

Prevention of malunions in the rotation of complex fractures of the distal femur treated using the Dynamic Condylar Screw (DCS): an anatomical graphic analysis using computed tomography on cadaveric specimens.

The AO ASIF dynamic condylar screw is a popular method for the treatment of severe distal femoral fractures. Two methods of application have been presented by the AO group, one in the AO manual and the other in the teaching video tapes. The small difference in the techniques suggested that one of these methods might present a risk of rotational malunion in cases of severe comminuted fractures. The question of determining which method was less appropriate was investigated on human cadaveric specimens using a graphic analysis of computed tomograms. We found disadvantages for both methods and propose a third method combining the advantages of the two original methods.

Histology of the ligamentum flavum in patients with degenerative lumbar spinal stenosis.

The degree of calcification as well as the structural changes of the elastic fibres in the ligamentum flavum in patients with degenerative lumbar spinal stenosis were evaluated and the results were compared to those of patients without spinal stenosis. In 21 patients (13 male, 8 female) with lumbar spinal stenosis the ligamentum flavum was removed, histologically processed and stained. The calcification, the elastic/collagenous fibre ratio as well as the configuration of the fibres were evaluated with an image analyzing computer. As a control group, 20 ligaments of 10 human corpses were processed in the same way. The results were statistically analysed using the Mann-Whitney-Wilcoxon test (alpha = 0.05) and the t-test (alpha = 0.05). Nearly all the ligaments of patients with lumbar spinal stenosis were calcified (average 0.17%, maximum 3.8%) and showed relevant fibrosis with decreased elastic/collagenous fibre ratio. There was a significant correlation between age and histological changes (P<0.05). In the control group we only found minimal calcification in 3 of 20 segments (average 0.015%). No relevant fibrosis was found and the configuration of elastic fibres showed no pathologic changes. The results of this study illustrate the important role of histological changes of the ligamentum flavum for the aetiology of lumbar spinal stenosis.

Type of screw does not influence holding power in the femoral head: a cadaver study with shearing test.

We studied the holding power during cut-out tests of 4 different screw fixation devices of the femoral head, correlated to head size and bone density, on 48 paired deep frozen proximal femurs of fresh gross specimens. We found no significant effect of the device on the holding power. There was a significantly higher maximal load at failure in large and dense heads. It seems then unnecessary to advocate more sophisticated but also more expensive devices to fix femoral neck fractures.

An introduction to selected chapters in bone biomechanics.

In the introduction to this Injury supplement, an attempt is made to elaborate on important rules of biomechanical research such as were developed and used in the Davos school of biomechanics. Tribute is acknowledged to the important contributions of S.M. Perren, M. Russenberger and S.G. Steinemann. The following principles are illustrated: 1. The development of a new technique or a new implant is justified when it is the solution of a clinical problem or a clinical complication. 2. The appropriate solution in engineering is often simple and elegant. 3. The first step of a biomechanical investigation concerning fracture treatment consists in establishing to which patients this study will apply. 4. For a testing instrument, freedom is important at the junction between the bone and the loading device. 5. A selection of bones should be made prior to the experiment in regard to the clinical population involved. 6. In our biomechanical investigations, we are not interested in a "statistically significant" difference, but in a "clinically significant" difference. The communications presented in this supplement of Injury are a tribute to the 30 "Perren'sche Jahre" (Perrenic Years) of what I call the School of Biomechanics in Davos.