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

Current and emerging treatment of osteoporosis

The goal of treating a patient with recent fragility fracture should not only be to treat the patient in the acute phase but also to prevent further fractures. Interventions to increase bone mass to preventing further fragility fractures can be classified as non-pharmacological and pharmacological. All European and international guidelines base the need for treatment, not on the diagnosis of osteoporosis (based on the T-score), but on the risk of fracture, which is strongly influenced by the presence of a fragility fracture, especially vertebral or femoral fractures. Before treatment, it is important to make a differential diagnosis between primary and secondary osteoporosis because anti-osteoporotic drug treatment would be useless if the primary illness causing osteoporosis is not treated too. Some studies show that anti-osteoporotic drugs are frequently interrupted within 1 month of their prescription; this happens not so much due to the occurrence of adverse events but mostly because patients have not been sufficiently informed about the importance of taking the drug and because are not receiving personalised treatment. All data confirm that, in older people, vitamin D deficiency is highly prevalent and calcium intake is often not adequate. So, osteoporosis guidelines recommend calcium and vitamin D for all patients in association with antiosteoporotic therapy. We have many drugs for the treatment of patients at high risk of fracture, but we should use drugs based on evidence of their efficacy and safety in older-age subgroups, provided by targeted studies or extrapolated data. In this chapter, we describe efficacy, route of administration, adverse events and recent technical remarks of current antiresorptive and anabolic osteoporosis therapies. Furthermore, we describe emerging therapies, such as Abaloparatide and Romosozumab

Eudor-a: a Naturalistic, European Multi-centre Clinical Study of Edor Test in Adult Patients with Primary Depression

Introduction: Previous findings suggested that electrodermal hyporeactivity has a high sensitivity (up to 97%) and high raw specificity (up to 98%) for suicide. Aim: To evaluate prevalence, sensitivity and specificity of electrodermal hyporeactivity for suicide and suicide attempt, with and without death intent and with violent method or not, in adult patients with a primary diagnosis of depression. Methods: At each study site at least 100 patients with a primary diagnosis of depression, also in remission, will be recruited. Depressive symptomatology will be evaluated through the Montgomery-Asberg Depression Scale. Previous suicide attempts will be registered and the death intent of the worst attempt will be rated according to the first eight items of the Beck Suicide Intent Scale. The risk of suicide will be assessed according to rules and traditions at the centre. The EDOR Test (ElectroDermal Orienting Reactivity) will be performed. Two fingers are put on gold electrodes. Through headphones a moderately strong tone is presented now and then during the test. Sensors located within the electrodes are able to register the electrodermal response to those tones, measuring the skin conductance (i.e. electrodermal activity from sweat gland activity). Each patient will be followed up for one year for actions of intentional self-harm that require medical care and for suicide. The death intent will also be rated. Expected results: It is expected that the EDOR test detects a previously unknown neuropsychological dysfunction that is independent of the depressive state and can predict suicidality with a high sensitivity and specificit

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia.

Introduction: The change in bone turnover markers (BTM) in response to osteoporosis therapy can be assessed by a decrease beyond the least significant change (LSC) or below the mean of the reference interval (RI). We compared the performance of these two approaches in women treated with raloxifene. Methods: Fifty postmenopausal osteopenic women, (age 51-72y) were randomised to raloxifene or no treatment for 2 years. Blood samples were collected for the measurement of BTM. The LSC for each marker was calculated from the untreated women and the RI obtained from healthy premenopausal women (age 35-40y). Bone mineral density (BMD) was measured at the spine and hip. Results: There was a decrease in BTM in response to raloxifene treatment; percentage change at 12 weeks, CTX -39% (95% CI -48 to -28) and PINP -32% (95% CI -40 to -23) P<0.001. The proportion of women classified as responding to treatment using LSC at 12 weeks was: CTX 38%, PINP 52%, at 48 weeks CTX 60%, PINP 65%. For the RI approach; at 12 weeks CTX and PINP 38%, at 48 weeks CTX 40%, PINP 45%. There was a significant difference in the change in spine BMD in the raloxifene treated group compared to the no-treatment group at week 48; difference 0.031 g/cm2, (95% CI 0.016 to 0.046, P<0.001). Conclusions: The two approaches identified women that reached the target for treatment using BTM. Both LSC and RI criteria appear useful in identifying treatment response but the two approaches do not fully overlap and may be complementary

A Multispecialty Evaluation of Thiel Cadavers for Surgical Training

Background: Changes in UK legislation allow for surgical procedures to be performed on cadavers. The aim of this study was to assess Thiel cadavers as high-fidelity simulators and to examine their suitability for surgical training. Methods: Surgeons from various specialties were invited to attend a 1 day dissection workshop using Thiel cadavers. The surgeons completed a baseline questionnaire on cadaveric simulation. At the end of the workshop, they completed a similar questionnaire based on their experience with Thiel cadavers. Comparing the answers in the pre- and post-workshop questionnaires assessed whether using Thiel cadavers had changed the surgeons’ opinions of cadaveric simulation. Results: According to the 27 participants, simulation is important for surgical training and a full-procedure model is beneficial for all levels of training. Currently, there is dissatisfaction with existing models and a need for high-fidelity alternatives. After the workshop, surgeons concluded that Thiel cadavers are suitable for surgical simulation (p = 0.015). Thiel were found to be realistic (p < 0.001) to have reduced odour (p = 0.002) and be more cost-effective (p = 0.003). Ethical constraints were considered to be small. Conclusion: Thiel cadavers are suitable for training in most surgical specialties

Electrical-thermal analytical modeling of monopolar RF thermal ablation of biological tissues: determining the circumstances under which tissue temperature reaches a steady state

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in MATHEMATICAL BIOSCIENCES doi:10.3934/mbe.2015003 AND ENGINEERING following peer review. The definitive publisher-authenticated version Mathematical Biosciences and Engineering (MBE) Pages: 281 - 301, Volume 13, Issue 2, April 2016 is available online at http://www.aimsciences.org/journals/displayArticlesnew.jsp?paperID=11998[EN] It has been suggested that during RF thermal ablation of biological tissue the thermal lesion could reach an equilibrium size after 1-2 minutes. Our objective was to determine under which circumstances of electrode geometry (needle-like vs. ball-tip), electrode type (dry vs. cooled) and blood perfusion the temperature will reach a steady state at any point in the tissue. We solved the bioheat equation analytically both in cylindrical and spherical coordinates and the resultant limit temperatures were compared. Our results demonstrate mathematically that tissue temperature reaches a steady value in all cases except for cylindrical coordinates without the blood perfusion term, both for dry and cooled electrodes, where temperature increases infinitely. This result is only true when the boundary condition far from the active electrode is considered to be at infinitum. In contrast, when a finite and sufficiently large domain is considered, temperature reaches always a steady state.This work received financial support from the Spanish "Plan Estatal de Investigacion, Desarrollo e Innovacion Orientada a los Retos de la Sociedad" under Grant TEC2014-52383-C3-R (TEC2014-52383-C3-1-R).López Molina, JA.; Rivera Ortun, MJ.; Berjano, E. (2016). Electrical-thermal analytical modeling of monopolar RF thermal ablation of biological tissues: determining the circumstances under which tissue temperature reaches a steady state. Mathematical Biosciences and Engineering. 13(2):281-301. https://doi.org/10.3934/mbe.2015003S28130113

Anabolic Therapies

The striking clinical benefits of intermittent parathyroid hormone in osteoporosis have begun a new era of skeletal anabolic agents. Recombinant human parathyroid hormone (rhPTH) (1–34) is the first US Food and Drug Administration–approved anabolic therapy. Its use has been limited by the need for subcutaneous injection. Newer delivery systems include transdermal and oral preparations. Newer anabolic therapies include monoclonal antibody to sclerostin, a potent inhibitor of osteoblastogenesis; and use of bone morphogenetic proteins and parathyroid hormone–related protein PTHrP, a calcium-regulating hormone similar to PTH