Focal osteoporosis defects play a key role in hip fracture

$\textbf{BACKGROUND}$: Hip fractures are mainly caused by accidental falls and trips, which magnify forces in well-defined areas of the proximal femur. Unfortunately, the same areas are at risk of rapid bone loss with ageing, since they are relatively stress-shielded during walking and sitting. Focal osteoporosis in those areas may contribute to fracture, and targeted 3D measurements might enhance hip fracture prediction. In the FEMCO case-control clinical study, Cortical Bone Mapping (CBM) was applied to clinical computed tomography (CT) scans to define 3D cortical and trabecular bone defects in patients with acute hip fracture compared to controls. Direct measurements of trabecular bone volume were then made in biopsies of target regions removed at operation. $\textbf{METHODS}$: The sample consisted of CT scans from 313 female and 40 male volunteers (158 with proximal femoral fracture, 145 age-matched controls and 50 fallers without hip fracture). Detailed Cortical Bone Maps (c.5580 measurement points on the unfractured hip) were created before registering each hip to an average femur shape to facilitate statistical parametric mapping (SPM). Areas where cortical and trabecular bone differed from controls were visualised in 3D for location, magnitude and statistical significance. Measures from the novel regions created by the SPM process were then tested for their ability to classify fracture versus control by comparison with traditional CT measures of areal Bone Mineral Density (aBMD). In women we used the surgical classification of fracture location ('femoral neck' or 'trochanteric') to discover whether focal osteoporosis was specific to fracture type. To explore whether the focal areas were osteoporotic by histological criteria, we used micro CT to measure trabecular bone parameters in targeted biopsies taken from the femoral heads of 14 cases. $\textbf{RESULTS}$: Hip fracture patients had distinct patterns of focal osteoporosis that determined fracture type, and CBM measures classified fracture type better than aBMD parameters. CBM measures however improved only minimally on aBMD for predicting any hip fracture and depended on the inclusion of trabecular bone measures alongside cortical regions. Focal osteoporosis was confirmed on biopsy as reduced sub-cortical trabecular bone volume. $\textbf{CONCLUSION}$: Using 3D imaging methods and targeted bone biopsy, we discovered focal osteoporosis affecting trabecular and cortical bone of the proximal femur, among men and women with hip fracture.Arthritis Research UK (grant no. ARC17822) and Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre

Alendronate increases BMD at appendicular and axial skeletons in patients with established osteoporosis

<p>Abstract</p> <p>Background</p> <p>To identify high-risk patients and provide pharmacological treatment is one of the effective approaches in prevention of osteoporotic fractures. This study investigated the effect of 12-month Alendronate treatment on bone mineral density (BMD) and bone turnover biochemical markers in postmenopausal women with one or more non-traumatic fractures, i.e. patients with established osteoporosis.</p> <p>Methods</p> <p>A total of 118 Hong Kong postmenopausal Chinese women aged 50 to 75 with low-energy fracture at distal radius (Colles' fracture) were recruited for BMD measurement at lumbar spine and non-dominant hip using Dual-Energy X-ray Absorptiometry (DXA). 47 women with BMD T-score below -2 SD at either side were identified as patients with established osteoporosis and then randomized into Alendronate group (n = 22) and placebo control group (n = 25) for BMD measurement at spine and hip using DXA and distal radius of the non-fracture side by peripheral quantitative computed tomography (pQCT), and bone turnover markers, including bone forming alkaline phosphatase (BALP) and bone resorbing urinary Deoxypyridinoline (DPD). All measurements were repeated at 6 and 12 months.</p> <p>Results</p> <p>Alendronate treatment significantly increased BMD, more in weight-bearing skeletons (5.1% at spine and 2.5% at hip) than in non-weight bearing skeleton (0.9% at distal radius) after 12 months treatment. Spine T-score was significant improved in Alendronate group (p < 0.01) (from -2.2 to -1.9) but not in control placebo group. The Alendronate treatment effect was explained by significant suppression of bone turnover.</p> <p>Conclusion</p> <p>12 months Alendronate treatment was effective to increase BMD at both axial and appendicular skeletons in postmenopausal women with established osteoporosis.</p

Development of local strontium ranelate delivery systems and long term in vitro drug release studies in osteogenic medium

Funding Information: The authors acknowledge financial support from the Latvian Academy of Sciences though the ERANet under the frame of EuroNanoMed-II (Nanoforosteo, Project number: Z/14/1187) and the Riga Technical University and Riga Stardiņš University Cooperation Research Project No. RTU/RSU-18. Publisher Copyright: © 2018, The Author(s).It has been recognized that the operative stabilization of osteoporotic fractures should be followed up with an appropriate osteoporosis treatment in order to decrease the risk of repeated fractures. Despite the good clinical results of strontium ranelate (SrRan) towards the osteoporosis treatment, high drug doses and long treatment period cause an increased risk of serious side effects. Novel local SrRan/poly(lactic acid) (SrRan/PLA) delivery systems containing from 3.57 ± 0.28 wt% to 24.39 ± 0.91 wt% of active substance were developed. In order to resemble the naturally occurring processes, osteogenic media (OM) was used as a release medium for long term (121 days) in vitro drug release studies and UV/VIS method for the determination of SrRan content in OM was developed and validated. Biomimetic calcium phosphate precipitates were found on the surface and in the pores of prepared delivery system after microcapsule exposure to OM for 121 days as well as SrRan particles, indicating that the release of the drug have not been completed within 121 days. In vitro cell viability evaluation approved no cytotoxic effects of microcapsule suspensions and extracts.publishersversionPeer reviewe

Balancing with Vibration: A Prelude for “Drift and Act” Balance Control

Stick balancing at the fingertip is a powerful paradigm for the study of the control of human balance. Here we show that the mean stick balancing time is increased by about two-fold when a subject stands on a vibrating platform that produces vertical vibrations at the fingertip (0.001 m, 15–50 Hz). High speed motion capture measurements in three dimensions demonstrate that vibration does not shorten the neural latency for stick balancing or change the distribution of the changes in speed made by the fingertip during stick balancing, but does decrease the amplitude of the fluctuations in the relative positions of the fingertip and the tip of the stick in the horizontal plane, A(x,y). The findings are interpreted in terms of a time-delayed “drift and act” control mechanism in which controlling movements are made only when controlled variables exceed a threshold, i.e. the stick survival time measures the time to cross a threshold. The amplitude of the oscillations produced by this mechanism can be decreased by parametric excitation. It is shown that a plot of the logarithm of the vibration-induced increase in stick balancing skill, a measure of the mean first passage time, versus the standard deviation of the A(x,y) fluctuations, a measure of the distance to the threshold, is linear as expected for the times to cross a threshold in a stochastic dynamical system. These observations suggest that the balanced state represents a complex time–dependent state which is situated in a basin of attraction that is of the same order of size. The fact that vibration amplitude can benefit balance control raises the possibility of minimizing risk of falling through appropriate changes in the design of footwear and roughness of the walking surfaces

Regenerative memory in time-delayed neuromorphic photonic resonators

We investigate a photonic regenerative memory based upon a neuromorphic oscillator with a delayed self-feedback (autaptic) connection. We disclose the existence of a unique temporal response characteristic of localized structures enabling an ideal support for bits in an optical buffer memory for storage and reshaping of data information. We link our experimental implementation, based upon a nanoscale nonlinear resonant tunneling diode driving a laser, to the paradigm of neuronal activity, the FitzHugh-Nagumo model with delayed feedback. This proof-of-concept photonic regenerative memory might constitute a building block for a new class of neuron-inspired photonic memories that can handle high bit-rate optical signals

The quantitative ADAM questionnaire: a new tool in quantifying the severity of hypogonadism

Androgen deficiency is a pervasive problem in the older male population and is thought to be responsible for many symptoms once considered to be the result of normal aging. Numerous methods have been proposed to facilitate the detection of men at risk for androgen deficiency. In this article, we propose a novel screening tool, the quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire and report its successful use in quantifying the severity of androgen deficiency in a group of older men. Fifty-seven males scheduled to undergo radical prostatectomy for prostate cancer completed the qADAM as well as the Sexual Health Inventory for Men (SHIM) and the Expanded Prostate Cancer Index Composite hormonal/sexual (EPICh/EPICs) questionnaires. Thirty-four men also had serum testosterone levels measured for comparison. The qADAM showed statistically significant correlation to the SHIM (P=0.001), EPICh (P=0.016), EPICs (P=<0.001), and serum testosterone (P=0.046). The qADAM represents a viable alternative to existing questionnaires used to detect androgen deficiency and to assess response to treatment

Building the genomic nation: ‘Homo Brasilis’ and the ‘Genoma Mexicano’ in comparative cultural perspective

This article explores the relationship between genetic research, nationalism and the construction of collective social identities in Latin America. It makes a comparative analysis of two research projects – the ‘Genoma Mexicano’ and the ‘Homo Brasilis’ – both of which sought to establish national and genetic profiles. Both have reproduced and strengthened the idea of their respective nations of focus, incorporating biological elements into debates on social identities. Also, both have placed the unifying figure of the mestizo/mestiço at the heart of national identity constructions, and in so doing have displaced alternative identity categories, such as those based on race. However, having been developed in different national contexts, these projects have had distinct scientific and social trajectories: in Mexico, the genomic mestizo is mobilized mainly in relation to health, while in Brazil the key arena is that of race. We show the importance of the nation as a frame for mobilizing genetic data in public policy debates, and demonstrate how race comes in and out of focus in different Latin American national contexts of genomic research, while never completely disappearing

Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide

Summary We report the changes in biochemical markers of bone formation during the first 6 months of teriparatide therapy in postmenopausal women with osteoporosis according to previous antiresorptive treatment. Prior therapy does not adversely affect the response to teriparatide treatment. Similar bone markers levels are reached after 6 months of treatment. Introduction The response of biochemical markers of bone turnover with teriparatide therapy in subjects who have previously received osteoporosis drugs is not fully elucidated. We examined biochemical markers of bone formation in women with osteoporosis treated with teriparatide and determined: (1) whether the response is associated with prior osteoporosis therapy, (2) which marker shows the best performance for detecting a response to therapy, and (3) the correlations between early changes in bone markers and subsequent bone mineral density (BMD) changes after 24 months of teriparatide. Methods We conducted a prospective, open-label, 24-month study at 95 centers in 10 countries in 758 postmenopausal women with established osteoporosis (n = 181 treatment-naïve) who had at least one post-baseline bone marker determination. Teriparatide (20 μg/day) was administered for up to 24 months. We measured procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (b-ALP), and total alkaline phosphatase (t-ALP) at baseline, 1 and 6 months, and change in BMD at the lumbar spine, total hip and femoral neck from baseline to 24 months. Results Significant increases in formation markers occurred after 1 month of teriparatide regardless of prior osteoporosis therapy. The absolute increase at 1 month was lower in previously treated versus treatment-naïve patients, but after 6 months all groups reached similar levels. PINP showed the best signal-to-noise ratio. Baseline PINP correlated positively and significantly with BMD response at 24 months. Conclusions This study suggests that the long-term responsiveness of bone formation markers to teriparatide is not affected in subjects previously treated with antiresorptive drugs

Integrating innovations:a qualitative analysis of referral non-completion among rapid diagnostic test-positive patients in Uganda's human African trypanosomiasis elimination programme

BACKGROUND: The recent development of rapid diagnostic tests (RDTs) for human African trypanosomiasis (HAT) enables elimination programmes to decentralise serological screening services to frontline health facilities. However, patients must still undertake multiple onwards referral steps to either be confirmed or discounted as cases. Accurate surveillance thus relies not only on the performance of diagnostic technologies but also on referral support structures and patient decisions. This study explored why some RDT-positive suspects failed to complete the diagnostic referral process in West Nile, Uganda. METHODS: Between August 2013 and June 2015, 85% (295/346) people who screened RDT-positive were examined by microscopy at least once; 10 cases were detected. We interviewed 20 RDT-positive suspects who had not completed referral (16 who had not presented for their first microscopy examination, and 4 who had not returned for a second to dismiss them as cases after receiving discordant [RDT-positive, but microscopy-negative results]). Interviews were analysed thematically to examine experiences of each step of the referral process. RESULTS: Poor provider communication about HAT RDT results helped explain non-completion of referrals in our sample. Most patients were unaware they were tested for HAT until receiving results, and some did not know they had screened positive. While HAT testing and treatment is free, anticipated costs for transportation and ancillary health services fees deterred many. Most expected a positive RDT result would lead to HAT treatment. RDT results that failed to provide a definitive diagnosis without further testing led some to question the expertise of health workers. For the four individuals who missed their second examination, complying with repeat referral requests was less attractive when no alternative diagnostic advice or treatment was given. CONCLUSIONS: An RDT-based surveillance strategy that relies on referral through all levels of the health system is inevitably subject to its limitations. In Uganda, a key structural weakness was poor provider communication about the possibility of discordant HAT test results, which is the most common outcome for serological RDT suspects in a HAT elimination programme. Patient misunderstanding of referral rationale risks harming trust in the whole system and should be addressed in elimination programmes