Effects of intervertebral disk behavior on the load distribution and fracture risk of the vertebral body

Osteoporosis is characterized by low bone mass and an increased fracture risk. Measurements of bone mass alone, however, will not provide adequate information about the fracture risk, because the trabecular architecture or spatial distribution of the bone density has an important effect on the strength. We have developed a method to estimate the tissue strength of trabecular bone directly from 3D reconstructed axial CT-scans in combination with a finite element model. The method provides the stress distribution throughout the structure which can be used as a measure for the strength and fracture risk of the bone. A matter of concern with this method are the external loading conditions placed on the vertebral body, which might be strongly affected by the behavior of the intervertebral disk. In this study we have tested the effects of various intervertebral disk models on the load distribution through the vertebral body. A 3D model of a vertebral body was developed based on serial axial CT-scans which were converted to a 3D finite element model. The model was augmented with intervertebral disks at the upper and lower endplates. The disks contained a nucleus and an annulus region. The properties of the nucleus were varied to study the effects of a healthy disk with a functional nucleus pulposus and a degenerated disk with virtually no load bearing of the nucleus pulposus. The methods introduced in this study can be used to estimate load transfer through the vertebral body directly from CT-scans and, thereby, assessing the fracture risk of the bone and thus the status of osteoporosi

Bone strength loss during long-term bed rest is related to bone loading history

Bed rest studies are an accepted model for simulating bone loss due to microgravity during space flights. In a previous 60 days bed rest study, we investigated the loss of bone mass and the microstructural degeneration at the distal radius and tibia using a high-resolution (HR) pQCT device1. In combination with micro-finite element (micro-FE) analyses, it was possible to also quantify the loss of strength during bed rest2. In that study large variations in loss of bone strength were found between subjects. For some subjects no loss of strength was found whereas for others strength was reduced by 6.5%. Although these values are small and thus may not increase the risk of fracture, it may cause premature age-related osteoporosis and understanding the fundamental nature of the skeletal response to unloading is of great interest to develop countermeasures for overcoming the adverse effects of microgravity during spaceflights. In this study we investigate if the variation in loss of bone strength between subjects as observed in the earlier bed rest study could be related to their activity level prior to the bed rest. Since we expect that subjects that were more active would be more affected by the disuse, we hypothesized that the loss of bone strength is positively correlated to the physical activity of the subjects. As the activity level of the subjects prior to the bed rest study was not known, we used a recently developed method to estimate the bone loading history based on the bone architecture and correlated that with the loss in bone strength measured in the bed rest study to test our hypothesis

Establishing reference intervals for bone turnover markers in healthy postmenopausal women in a nonfasting state.

In order to interpret bone turnover markers (BTMs), we need to establish healthy reference intervals. It is difficult to establish reference intervals for older women because they commonly suffer from diseases or take medications that affect bone turnover. The aims of this study were: (1) to identify diseases and drugs that have a substantial effect on BTMs; (2) to establish reference intervals for premenopausal and postmenopausal women; and (3) to examine the effects of other factors on BTMs in healthy postmenopausal women. We studied women aged 30-39 years (n=258) and women aged 55-79 years (n=2419) from a five-European centre population-based study. We obtained a nonfasting serum and second morning void urine samples at a single baseline visit. BTMs were measured using automated immunoassay analysers. BTMs were higher in patients with vitamin D deficiency and chronic kidney disease. Three or more BTMs were higher in women who were osteoporotic and at least two BTMs were lower in women who were oestrogen replete, taking osteoporosis treatments or having diseases known to affect bone turnover. These were used as exclusion criteria for selecting the populations for the reference intervals. The reference intervals for BTMs were higher in postmenopausal than premenopausal women. Levels of BTMs were not dependent on geographical location and increased with age

Once weekly alendronate produces a greater decrease in bone resorption than daily risedronate

peer reviewe

Bone structure and density via HR-pQCT in 60d bed-rest, 2-years recovery with and without countermeasures

We examined the effects of bed-rest, recovery and exercise countermeasures on bone density and structure at the distal tibia and radius as measured via high-resolution peripheral computed tomography. 24 subjects underwent 60-days of head-down tilt bed-rest and performed either resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8) or no exercise (n = 9; 2nd Berlin BedRest Study; BBR2-2). Measurements were performed regularly during and up to 2-years after 60d bed-rest. At the distal tibia marked reductions in cortical area, cortical thickness and bone density but increases in periosteal perimeter and trabecular area were seen (p all<0.001). Recovery of most parameters occurred within 180d after bed-rest. At the distal radius, persistent increases in cortical area, cortical thickness, cortical density and total density and decreases in trabecular area were seen (p all ≤ 0.005). A significant effect of RVE (p = 0.003), but not RE, was seen on cortical area at the distal tibia, with few effects of the countermeasures observed on the remaining parameters. The current study represents the first implementation of high-resolution peripheral computed tomography in bed-rest in male subjects and helps to understand the patterns of bone remodeling due to bed-rest and recovery

Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis: Results of a 2-year study

Summary: Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (μFEA), over 2years, in postmenopausal osteoporotic women. Introduction: Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk. Methods: Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2g/day) or alendronate (70mg/week) for 2years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers. Results: In the intention-to-treat population (n = 83, age: 64 ± 8years; lumbar T-score: −2.8 ± 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) (P < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance (P = 0.06). The estimated failure load increased with SrRan (+2.1%, P < 0.005), not with alendronate (−0.6%, NS) (between-group difference, P < 0.01). Cortical stress was lower with SrRan (P < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort (P < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (−1%) after 2years of SrRan (between-group difference at each time point for both markers, P < 0.0001). Both treatments were well tolerated. Conclusions: Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another metho

Loss and re-adaptation of lumbar intervertebral disc water signal intensity after prolonged bedrest

&copy; 2015, International Society of Musculoskeletal and Neuronal Interactions. All right reserved. The adaptation and re-adaptation process of the intervertebral disc (IVD) to prolonged bedrest is important for understanding IVD physiology and IVD herniations in astronauts. Little information is available on changes in IVD composition. In this study, 24 male subjects underwent 60-day bedrest and In/Out Phase magnetic resonance imaging sequences were performed to evaluate IVD shape and water signal intensity. Scanning was performed before bedrest (baseline), twice during bedrest, and three, six and twenty-four months after bedrest. Area, signal intensity, average height, and anteroposterior diameter of the lumbar L3/4 and L4/5 IVDs were measured. At the end of bedrest, disc height and area were significantly increased with no change in water signal intensity. After bedrest, we observed reduced IVD signal intensity three months (p=0.004 versus baseline), six months (p=0.003 versus baseline), but not twenty-four months (p=0.25 versus baseline) post-bedrest. At these same time points post-bedrest, IVD height and area remained increased. The reduced lumbar IVD water signal intensity in the first months after bedrest implies a reduction of glycosaminoglycans and/or free water in the IVD. Subsequently, at two years after bedrest, IVD hydration status returned towards pre-bedrest levels, suggesting a gradual, but slow, re-adaptation process of the IVD after prolonged bedrest

Dopaminergic systems create reward seeking despite adverse consequences

Resource-seeking behaviours are ordinarily constrained by physiological needs and threats of danger, and the loss of these controls is associated with pathological reward seeking1. Although dysfunction of the dopaminergic valuation system of the brain is known to contribute towards unconstrained reward seeking2,3, the underlying reasons for this behaviour are unclear. Here we describe dopaminergic neural mechanisms that produce reward seeking despite adverse consequences in Drosophila melanogaster. Odours paired with optogenetic activation of a defined subset of reward-encoding dopaminergic neurons become cues that starved flies seek while neglecting food and enduring electric shock punishment. Unconstrained seeking of reward is not observed after learning with sugar or synthetic engagement of other dopaminergic neuron populations. Antagonism between reward-encoding and punishment-encoding dopaminergic neurons accounts for the perseverance of reward seeking despite punishment, whereas synthetic engagement of the reward-encoding dopaminergic neurons also impairs the ordinary need-dependent dopaminergic valuation of available food. Connectome analyses reveal that the population of reward-encoding dopaminergic neurons receives highly heterogeneous input, consistent with parallel representation of diverse rewards, and recordings demonstrate state-specific gating and satiety-related signals. We propose that a similar dopaminergic valuation system dysfunction is likely to contribute to maladaptive seeking of rewards by mammals