Glucocorticosteroid-induced spinal osteoporosis: scientific update on pathophysiology and treatment

Glucocorticosteroid-induced osteoporosis (GIOP) is the most frequent of all secondary types of osteoporosis. The understanding of the pathophysiology of glucocorticoid (GC) induced bone loss is of crucial importance for appropriate treatment and prevention of debilitating fractures that occur predominantly in the spine. GIOP results from depressed bone formation due to lower activity and higher death rate of osteoblasts on the one hand, and from increased bone resorption due to prolonged lifespan of osteoclasts on the other. In addition, calcium/phosphate metabolism may be disturbed through GC effects on gut, kidney, parathyroid glands and gonads. Therefore, therapeutic agents aim at restoring balanced bone cell activity by directly decreasing apoptosis rate of osteoblasts (e.g., cyclical parathyroid hormone) or by increasing apoptosis rate of osteoclasts (e.g., bisphosphonates). Other therapeutical efforts aim at maintaining/restoring calcium/phosphate homeostasis: improving intestinal calcium absorption (using calcium supplementation, vitamin D and derivates) and avoiding increased urinary calcium loss (using thiazides) prevent or counteract a secondary hyperparathyroidism. Bisphosphonates, particularly the aminobisphosphonates risedronate and alendronate, have been shown to protect patients on GCs from (further) bone loss and to reduce vertebral fracture risk. Calcitonin may be of interest in situations where bisphosphonates are contraindicated or not applicable and in cases where acute pain due to vertebral fracture has to be managed. The intermittent administration of 1-34-parathormone may be an appealing treatment alternative, based on its documented anabolic effects on bone resulting from the reduction of osteoblastic apoptosis. Calcium and vitamin D should be a systematic adjunctive measure to any drug treatment for GIOP. Based on currently available evidence, fluoride, androgens, estrogens (opposed or unopposed) cannot be recommended for the prevention and treatment of GIOP. However, substitution of gonadal hormones may be indicated if GC-induced hypogonadism is present and leads to clinical symptoms. Data using the SERM raloxifene to treat or prevent GIOP are lacking, as are data using the promising bone anabolic agent strontium ranelate. Kyphoplasty performed in appropriately selected osteoporotic patients with painful vertebral fractures is a promising addition to current medical treatmen

Bone Mass Distribution of the Distal Tibia in Normal, Osteopenic, and Osteoporotic Conditions: An Ex Vivo Assessment Using HR-pQCT, DXA, and Computational Modelling.

Osteoporosis leads to bone loss and structural deterioration, which increase the risk of fractures. The aim of this study was to characterize the three-dimensional (3D) bone mass distributions of the distal tibia in normal, osteopenic, and osteoporotic conditions. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the 33 % of the distal tibia and local dual-energy X-ray absorptiometry were applied to 53 intact, fresh-frozen tibiae. The HR-pQCTs were graded to assign local T-scores and merged into three equally sized average normal, osteopenic, and osteoporotic surface models. Volumetric bone mineral density (vBMD) was determined using categorized T-scores, volumetric visualization, and virtual bore probes at the dia-, meta-, and epiphyseal sites (T-DIA, T-META, and T-EPI). We observed a distinct 3D bone mass distribution that was gradually uninfluenced by T-score categories. T-DIA was characterized by the lowest bone mass located in the medullary cavity and a wide homogenous cortex containing the maximum vBMD. The T-META showed decreased cortical thickness and maximal vBMD. At the T-EPI, the relatively low vBMD of the mostly trabecular bone was similar to the maximal cortical vBMD in this sub-region. Four trabecular regions of low bone mass were identified in the recesses. The bone content gradually decreased at all sites, whereas the pattern of bone mass distribution remained essentially unchanged, with the exception of disproportionate losses at T-DIA, T-META, and T-EPI that consistently showed increased endocortical, intracortical, and trabecular bone loss. Extra information can be obtained from the specific pattern of bone mass distribution, potential disproportionate bone losses, and method used

Safety, effectiveness and predictors for early reoperation in therapeutic and prophylactic vertebroplasty: short-term results of a prospective case series of patients with osteoporotic vertebral fractures

Introduction: Vertebroplasty (VP) is a cost-efficient alternative to kyphoplasty; however, regarding safety and vertebral body (VB) height restoration, it is considered inferior. We assessed the safety and efficacy of VP in alleviating pain, improving quality of life (QoL) and restoring alignment. Methods: In a prospective monocenter case series from May 2007 until July 2008, there were 1,408 vertebroplasties performed during 319 interventions in 306 patients with traumatic, lytic and osteoporotic fractures. The 249 interventions in 233 patients performed because of osteoporotic vertebral fractures were analyzed regarding demographics, treatment and radiographic details, pain alleviation (VAS), QoL improvement (NASS and EQ-5D), complications and predictors for new fractures requiring a reoperation. Results: The osteoporotic patient sample consisted of 76.7% (179) females with a median age of 80years. A total of 54 males had a median age of 77years. On average, there were 1.8 VBs fractured and 5 VBs treated. The preoperative pain was assessed by the visual analog scale (VAS) and decreased from 54.9 to 40.4 pts after 2months and 31.2 pts after 6months. Accordingly, the QoL on the EQ-5D measure (−0.6 to 1) improved from 0.35 pts before surgery to 0.56 pts after 2 and to 0.68 pts after 6months. The preoperative Beck Index (anterior height/posterior height) improved from a mean of 0.64 preoperative to 0.76 postoperative, remained stable at 2months and slightly deteriorated to 0.72 at 6months postoperatively. There were cement leakages in 26% of the fractured VBs and in 1.4% of the prophylactically cemented VBs; there were symptoms in 4.3%, and most of them were temporary hypotension and one pulmonary cement embolism that remained asymptomatic. The univariate regression model revealed a tendency for a reduced risk for new or refractures on radiographs (OR=2.61, 95% CI 0.92-7.38, p=0.12) and reoperations (OR=2.9, 95% CI 0.94-8.949, p=0.1) when prophylactic augmentation was performed. The final multivariate regression model revealed male patients to have an about three times higher refracture risk (radiographic) (OR=2.78, p=0.02) at 6months after surgery. Patients with a lumbar index fracture had an about three to five times higher refracture/reoperation risk than patients with a thoracic (OR=0.33/0.35, p=0.009/0.01) or thoracolumbar (OR=0.32/0.22, p=0.099/0.01) index fracture. Conclusion: If routinely used, VP is a safe and efficacious treatment option for osteoporotic vertebral fractures with regard to pain relief and improvement of the QoL. Even segmental realignment can be partially achieved with proper patient positioning. Certain patient or fracture characteristics increase the risk for early radiographic refractures or new fractures, or a reoperation; a consequent prophylactic augmentation showed protective tendencies, but the study was underpowered for a final conclusio

Biologically relevant sex differences for fitness-related parameters in active octogenarians

The number of elderly people is growing in western populations, but only few maximal performance data exist for people >75years, in particular for European octogenarians. This study was performed to characterize maximal performance of 55 independently living subjects (32 women, 81.1±3.4years; 23 men, 81.7±2.9years) with a focus on sex differences. Maximal performance was determined in a ramp test to exhaustion on a bicycle ergometer with ergospirometry, electrocardiogram and blood lactate measurements. Maximal isometric extension strength of the legs (MEL) was measured on a force platform in a seated position. Body composition was quantified by X-ray absorptiometry. In >25% of the subjects, serious cardiac abnormalities were detected during the ramp test with men more frequently being affected than women. Maximal oxygen consumption and power output were 18.2±3.2 versus 25.9±5.9mlmin−1kg−1 and 66±12 versus 138±40W for women versus men, with a significant sex difference for both parameters. Men outperformed women for MEL with 19.0±3.8 versus 13.6±3.3Nkg−1. Concomitantly, we found a higher proportion of whole body fat in women (32.1±6.2%) compared to men (20.5±4.4%). Our study extends previously available maximal performance data for endurance and strength to independently living European octogenarians. As all sex-related differences were still apparent after normalization to lean body mass, it is concluded that it is essential to differentiate between female and male subjects when considering maximal performance parameters in the oldest segment of our populatio

Different response to eccentric and concentric training in older men and women

Sarcopenia is the age-related loss of muscle mass and strength and has been associated with an increased risk of falling and the development of metabolic diseases. Various training protocols, nutritional and hormonal interventions have been proposed to prevent sarcopenia. This study explores the potential of continuous eccentric exercise to retard age-related loss of muscle mass and function. Elderly men and women (80.6±3.5years) were randomized to one of three training interventions demanding a training effort of two sessions weekly for 12weeks: cognitive training (CT; n=16), conventional resistance training (RET; n=23) and eccentric ergometer training (EET; n=23). Subjects were tested for functional parameters and body composition. Biopsies were collected from M. vastus lateralis before and after the intervention for the assessment of fiber size and composition. Maximal isometric leg extension strength (MEL: +8.4±1.7%) and eccentric muscle coordination (COORD: −43±4%) were significantly improved with EET but not with RET (MEL: +2.3±2.0%; COORD: −13±3%) and CT (MEL: −2.3±2.5%; COORD: −12±5%), respectively. We observed a loss of body fat (−5.0±1.1%) and thigh fat (−6.9±1.5%) in EET subjects only. Relative thigh lean mass increased with EET (+2.5±0.6%) and RET (+2.0±0.3%) and correlated negatively with type IIX/type II muscle fiber ratios. It was concluded that both RET and EET are beneficial for the elderly with regard to muscle functional and structural improvements but differ in their spectrum of effects. A training frequency of only two sessions per week seems to be the lower limit for a training stimulus to reveal measurable benefit

Cellular Communication through Light

Information transfer is a fundamental of life. A few studies have reported that cells use photons (from an endogenous source) as information carriers. This study finds that cells can have an influence on other cells even when separated with a glass barrier, thereby disabling molecule diffusion through the cell-containing medium. As there is still very little known about the potential of photons for intercellular communication this study is designed to test for non-molecule-based triggering of two fundamental properties of life: cell division and energy uptake. The study was performed with a cellular organism, the ciliate Paramecium caudatum. Mutual exposure of cell populations occurred under conditions of darkness and separation with cuvettes (vials) allowing photon but not molecule transfer. The cell populations were separated either with glass allowing photon transmission from 340 nm to longer waves, or quartz being transmittable from 150 nm, i.e. from UV-light to longer waves. Even through glass, the cells affected cell division and energy uptake in neighboring cell populations. Depending on the cuvette material and the number of cells involved, these effects were positive or negative. Also, while paired populations with lower growth rates grew uncorrelated, growth of the better growing populations was correlated. As there were significant differences when separating the populations with glass or quartz, it is suggested that the cell populations use two (or more) frequencies for cellular information transfer, which influences at least energy uptake, cell division rate and growth correlation. Altogether the study strongly supports a cellular communication system, which is different from a molecule-receptor-based system and hints that photon-triggering is a fine tuning principle in cell chemistry

Postulates on electromagnetic activity in biological systems and cancer

A framework of postulates is formulated to define the existence, nature, and function of a coherent state far from thermodynamic equilibrium in biological systems as an essential condition for the existence of life. This state is excited and sustained by energy supply. Mitochondria producing small packets of energy in the form of adenosine and guanosine triphosphate and strong static electric field around them form boundary elements between biochemical-genetic and physical processes. The transformation mechanism of chemical energy into useful work for biological needs and the excitation of the coherent state far from thermodynamic equilibrium are fundamental problems. The exceptional electrical polarity of biological objects and long-range interactions suggest a basic role of the endogenous electromagnetic field generated by living cells. The formulated postulates encompass generation, properties and function of the electromagnetic field connected with biological activity and its pathological deviations. Excited longitudinal polar oscillations in microtubules in eukaryotic cells generate the endogenous electromagnetic field. The metabolic activity of mitochondria connected with water ordering forms conditions for excitation. The electrodynamic field plays an important role in the establishment of coherence, directional transport, organization of morphological structures, interactions, information transfer, and brain activity. An overview of experimental results and physical models supporting the postulates is included. The existence of the endogenous biological electromagnetic field, its generation by microtubules and supporting effects produced by mitochondria have a reasonable experimental foundation. Cancer transformation is a pathological reduction of the coherent energy state far from thermodynamic equilibrium. Malignancy, i.e. local invasion and metastasis, is a direct consequence of mitochondrial dysfunction, disturbed microtubule polar oscillations and the generated electromagnetic field

High-mobility 4 μm MOVPE-grown (100) β-Ga2O3 film by parasitic particles suppression

In this work, we comprehensively investigate the development of unwanted parasitic particles in the MOVPE chamber while growing μm level films. The density of the parasitic particles is found to be pronounced at film thicknesses starting from >1.5 to 2 μm. These particles seem to induce structural defects such as twin lamellae, thereby harming the electrical properties of the grown film. The origin of the parasitic particle is attributed to the parasitic reactions within the chamber triggered by the promoted gas-phase reactions during the growth process, which can be largely reduced by increasing the total gas flow and decreasing the showerhead distance to the susceptor. A film thickness of up to 4 μm has been achieved after minimizing the density of parasitic particles. Thereby, RT Hall measurements reveal carrier mobilities of 160 cm2V−1s−1 at carrier concentrations of 5.7 × 1016cm−

Suppression of particle formation by gas-phase pre-reactions in (100) MOVPE-grown β -Ga2O3films for vertical device application

This work investigated the metalorganic vapor-phase epitaxy (MOVPE) of (100) β-Ga2O3 films with the aim of meeting the requirements to act as drift layers for high-power electronic devices. A height-adjustable showerhead achieving a close distance to the susceptor (1.5 cm) was demonstrated to be a critical factor in increasing the stability of the Ga wetting layer (or Ga adlayer) on the surface and reducing parasitic particles. A film thickness of up to 3 μm has been achieved while keeping the root mean square below 0.7 nm. Record carrier mobilities of 155 cm2 V-1 s-1 (2.2 μm) and 163 cm2 V-1 s-1 (3 μm) at room temperature were measured for (100) β-Ga2O3 films with carrier concentrations of 5.7 × 1016 and 7.1 × 1016 cm-3, respectively. Analysis of temperature-dependent Hall mobility and carrier concentration data revealed a low background compensating acceptor concentration of 4 × 1015 cm-3