These techniques were delivered by 15 osteopathic physicians, fellows, or residents during 15-min treatment sessions at weeks 0, 1, 2, 4, 6, and 8. Treatment

fidelity methods (Bellg et al., 2004) were used to train providers Fulvestrant to perform the structural examination for biomechanical dysfunction and to deliver OMT. These methods included standardized provider training using structured practice and role playing with pilot participants and regular booster sessions to minimize drift in provider skills over time. Patients were allowed to receive their usual LBP care and other co-treatments during the study except for non-assigned manual therapies. Low back pain was measured at baseline, prior to each subsequent treatment session, and at week 12 using Rapamycin manufacturer a 100-mm visual analogue scale (VAS), which was

anchored by “no pain” at 0 mm and “worst possible pain” at 100 mm. Moderate pain improvement, defined by ≥ 30% reduction from baseline through week 12, was the minimal threshold for detecting a successful LBP response. This relative criterion, based on the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus statement recommendations (Dworkin et al., 2008), was used rather than an absolute criterion to minimize floor effects in assessing OMT efficacy. This criterion is highly sensitive and specific in predicting global impression of change in chronic pain patients (Emshoff et al., 2011) and provides readily interpretable evidence for clinical applications and recommendations (Farrar et al., 2000). Descriptive statistics were used to summarize the baseline characteristics of patients and to compare the characteristics Mannose-binding protein-associated serine protease of LBP responders

and non-responders. Complete data were available for LBP scores at baseline; however, missing pain data at subsequent visits were imputed using the last observation carried forward. Measures of biomechanical dysfunction at baseline were not recorded for 11 (5%) patients. Multiple imputation modeling was used to estimate these missing data based on the presence or absence of key somatic dysfunction within each of three anatomical regions (lumbar, sacrum/pelvis, and pelvis/innominate). The presence or absence of such findings, assessed only at baseline, was determined using the osteopathic concept of “somatic dysfunction.” The latter is defined as “impaired or altered function of related components of the somatic (body framework) system: skeletal, arthrodial, and myofascial structures, and related vascular, lymphatic, and neural elements” (American Association of Colleges of Osteopathic Medicine, 2009).

However, the technique of magic-angle spinning (MAS), first demonstrated

in the late 1950s and improved dramatically in recent years, in which solid samples are rotated very rapidly about an axis at the “magic angle” θM   = cos−1 (1/3) to the magnetic field direction using a pneumatic turbine system, approximates the effects of rotational diffusion, producing solid state NMR line widths that can approach the line widths in solution NMR spectra. Some of the most exciting applications Dasatinib in vitro of solid state NMR are possible only at very high magnetic fields. In solid state NMR of organic and biological systems, strong dipole–dipole interactions among 1H nuclei limit the achievable 1H NMR line widths, even under rapid MAS. Therefore, it is only at the highest available fields

that 1H NMR spectra of complex organic and biological systems become useful. Inorganic systems of practical and chemical interest (e.g., catalysts, glasses, battery materials) prominently contain elements whose NMR spectra are difficult or impossible to measure at low fields, because the nuclei have spin quantum numbers greater than 1/2 (e.g., 7Li, 17O, 27Al). These nuclei possess electric quadrupole interactions, which are averaged out to lowest order by MAS but make a second-order contribution to the NMR line Talazoparib ic50 widths that is inversely proportional to the magnetic field strength. For these reasons, NMR spectra of many technologically important materials are useful only if very high field equipment is used, and are increasingly informative as the field increases. In studies of biological systems, NMR is one of the two major types of Mirabegron measurements that can be used to reveal the full 3D molecular structures of macromolecules, especially proteins and nucleic acids, the other being X-ray diffraction measurements on single crystals. In addition to purely structural information, NMR measurements have the unique capability of providing detailed, site-specific information about molecular motions in macromolecules, including motions that are essential for biological function. While X-ray diffraction

measurements are largely restricted to highly structurally ordered molecules in crystalline environments, NMR methods are applicable to proteins and nucleic acids in fluid environments that more closely resemble the cytoplasmic and membrane environments of cells. Perturbations of NMR signals due to intermolecular interactions are used in the screening of molecular libraries for binding to pharmaceutically important macromolecular targets, providing an efficient approach to the identification of new lead compounds in drug development. NMR methods are also applicable to molecules that are intrinsically disordered, resistant to crystallization, and (in the case of solid state NMR) inherently non-crystalline and insoluble.

, 1977). This proof of increased consistency of laboratory experimental results prompted the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) to continue working on guideline definitions on standard operation procedures for a number of certain

enzymes. The result is, for instance, that after about 80% of laboratories in the United Kingdom National External Quality Assessment Schemes see more (UK NEQAS) had adopted the method for the measurement of creatine kinase activity according to the IFCC guidelines the inter-laboratory agreement dropped to a coefficient of variation of less than 10% (Moss, 1997). In the basic research of pathway investigation, the first approaches to the application of uniform methods were demonstrated for the experimental analysis of the enzymes involved in glycolysis in baker׳s yeast. The strategy was first to evaluate the intra-cellular conditions for cells in a determined environment and second to study the kinetics of the enzymes involved under these “physiological” conditions in comparison with commercially available enzymes (van Eunen et al., 2010; see also van Eunen and Bakker, 2014). The successful demonstration of a proof-of-principle suggests the application of this protocol to assay

all other enzymes in the yeast cytosol. In addition, the strategy demonstrated here could serve as a template for the standardization of experimental conditions in other compartments and organisms. There are some additional success stories worthy Target Selective Inhibitor Library of mention: within both the yeast systems biology network (Mustacchi et al., 2006) and the competence network of the systems

biology of liver cells (HepatoSys) (Klingmüller et al., 2006) first approaches towards the generation of comparable and reproducible quantitative data under standardized experimental conditions have been presented. However, the disadvantages of uniform standards of practice should not be concealed. Both analytical methods and laboratory techniques are subject of permanent developments and improvements. Methods and techniques, once recommended to and agreed by the community, will respond slowly the technological advances. oxyclozanide Recommended methods also can become corrupted, either inadvertently, by misinterpretation of the standards, or deliberately, to accommodate the limitations imposed by automated instrumentation. Consequently, acceptance of these recommended methods will decrease, and the procedures of experiments will not comply with a uniform practice leading to incomparable enzymology data. Last but not least, it is questionable whether standard protocols can be applied to enzymes of unknown function, identity or even cellular localization.

Expression of the proneural bHLH transcription factor Ascl2

is associated with stemness and is absolutely required for intestinal stem cell maintenance. Active Notch is required for Ascl2 expression and its loss results in precocious crypt cell differentiation [8 and 10]. The proneural protein Atoh1 acts as a master regulator of fate specification buy Epacadostat of the secretory lineage [2 and 11]. Ascl2 expression is maintained by active Notch signalling that also acts to suppress Atoh1. Expression of Atoh1 is cell-autonomously inhibited by Hes proteins and in the absence of Notch signalling, crypt stem cells precociously differentiate into secretory goblet cells [7 and 12]. The spatial organisation of cells expressing Notch ligand and receptor in the crypt evokes a classic lateral inhibition scenario for control of stem versus secretory fate (Figure 2). Stem cells towards the crypt base found preferentially adjacent to Delta-expressing Paneth cells, express Notch receptor [13• and 14], PD0332991 in vitro and are maintained in an undifferentiated state by constant Notch signalling

and suppression of Atoh1 [7, 9, 15 and 16], As migrating cells lose contact with Paneth cells and the high Notch signalling they confer, they become poised between secretory and non-secretory fate. Lineage selection may then arise by stochastic variation in Delta expression leading some cells to express higher levels than others. This initial stochastic imbalance in Delta expression becomes reinforced allowing only a subset of cells (Delta high, Atoh high) rising up the crypt to become committed to a secretory fate while the rest become absorptive enterocytes. This regulation and functional organisation readily explains a binary fate in a supra-Paneth cell poised population but fits less well with a subsequent downstream cascade of secretory lineage choices specified after a series of cell divisions each progressing unidirectionally towards a more restricted fate. Moreover, recent evidence derived from regenerating systems casts doubt both on the existence of stable populations of

progenitors and the irreversibility of lineage specification. For many years it has also been known 2-hydroxyphytanoyl-CoA lyase that intestinal regeneration following damage is not solely a function of surviving stem cells expanding to restore homeostasis (Figure 3) [17]. Following radiation induced injury the clonogenic fraction of crypt cells is elevated suggesting that these might correspond to the abundant and immature absorptive cells present within the early transit-amplifying compartment of the lower crypt. In support, specific ablation of the key Lgr5+ population using targeted diptheria toxin is not catastrophic as non-Lgr5+ cells (Bmi1+) cells are able to act as a replacement stem cell pool at least for a limited time [18].

, 2012), were classified as Type I because they presented a plateau that was almost horizontal and parallel to the pressure axis. In this study, such plateau was not reached, indicating widening of pores. Furthermore, the small amount of hysteresis observed in Fig. 1a indicates mesoporosity starting to develop, also characteristic of Type IV isotherms. Reffas et al. (2010) prepared activated carbons by H3PO4-based activation of spent coffee grounds. They observed a Type MDV3100 research buy I isotherm typical of microporous materials for adsorbents prepared with low

impregnation rate (IR = 30%). As the impregnation rate increased some hysteresis was observed, up to a point (IR ≥ 120%) where behavior changed and the isotherms assumed Type IV characteristics, associated with the presence of slit-shaped mesopores, similar to that shown in Fig. 1a. Surface and pore structure parameters derived from the nitrogen isotherms are compiled in Table 1. The produced adsorbent presents both micro and mesopores (approximately 68 and 21% of the total surface area, respectively). Both the specific surface area and total pore volume of the prepared adsorbent (CCAC) are comparable to those obtained by activation of spent coffee grounds with H3PO4 at high impregnation learn more rates (SGAC3). Evaluation of

data in Table 1 shows that SGAC3 is strictly mesoporous. The adsorbent prepared in our study, however, is mostly microporous, even though the impregnation rate was high. Such difference is attributed to differences in original porosity of the raw materials employed for production of the adsorbents (Zhang, Ghaly, & Li, 2012). The adsorbent prepared by activation of defective coffee press cake (DCAC) under the same conditions presented much lower surface area in comparison to the one herein prepared,

confirming the significant effect the precursor material have on the physical properties of the prepared adsorbent. Furthermore, the impregnation time employed in our study, 3 min, is significantly shorter than that employed Tacrolimus (FK506) by Reffas et al. (2010), 3 h, thus not being enough to increase the volume of mesopores. Nonetheless, the phenylalanine molecule is quite small (0.7 × 0.5 × 0.5 nm) and thus both the mesopores (3.6 nm average diameter) and micropores (1.3 nm average diameter) of the corn cob-based adsorbent should be accessible to the amino acid. The micro and mesoporous structure of the prepared adsorbent, as well as the presence of some slit-shaped pores can be seen in the SEM image in Fig. 1b. The functional groups at the surface of the adsorbent, characterized by the Boehm method, were predominantly acid (8.08 mmol/gsorbent), distributed as phenolic (6.66 mmol/gsorbent), carboxylic (0.46 mmol/gsorbent) and lactonic (0.95 mmol/gsorbent) groups. The amount of basic groups was 0.04 mmol/gsorbent.

(48)) to the original Carver Richards equation [6]. The explicit relations between our parameters and those in the original work are presented formally in Supplementary Section 4. In terms of present definitions, the Carver Richards equation is: equation(49) R2,effCR=R2G+R2E+kEX2-NcycTrelcosh-1(v1c)where the following identity is used to simplify the trigonometric terms [2], [42] and [43]: cosh-1(F0cosh(E0)-F2cos(|E2|))=log((F0cosh2(E0)-F2cos2(|E2|))1/2+(F0sinh2(E0)-F2sin2(|E2|))1/2)cosh-1(F0cosh(E0)-F2cos(|E2|))=log((F0cosh2(E0)-F2cos2(|E2|))1/2+(F0sinh2(E0)-F2sin2(|E2|))1/2)The

PF-02341066 price only difference between the precise form described in reference [6] and Eq. (49) is that their free precession delay τcp is effectively four times longer. Nevertheless, there are clear similarities between Eqs. (48) and (49), and so the new expression can be expressed as a linear correction to the Carver Richards result, requiring the definitions in Eq. (45): equation(50) R2,eff=R2,effCR-1Trelln1+y2+1-y2v1c2-1(v2+2pDkGE) The correction GDC-0068 factor is exactly equal to the deviations between the numerical result and the

Carver Richards equation described in Fig. 1, to double floating point precision. It is interesting to consider the region of validity of the Carver Richards result. The two results are equal when the correction is zero, which is true when: equation(51) v1c2-1≈v2+2pDkGE This occurs when kGEpD tends to zero, and so v2 = v3. The term pD is based on the product of the off diagonal elements in the CPMG propagator ( Supplementary Section 3). Setting KGEPD to zero amounts to neglecting magnetisation that starts on the ground state

ensemble and end on the excited state ensemble and vice versa. This will be a good approximation when PG ≫ PE. In practice, significant deviations from the Carver Richards equation can be incurred if PE > 1% ( Fig. 1). Incorporation of the correction term into Eq. (50), summarised in Appendix A, results in an improved description of the CPMG experiment over the Carver Ketotifen Richards equation. It is interesting to calculate the effective relaxation rate at high pulsing frequencies. As proven in Supplementary Section 6, in this limit: equation(52) R2,eff∞=R2G+R2E+kEX(1-T)2-1Trelln12T(1+e-TrelkEXT)T+tanhTrelkEXT21+ΔR2kEXwhere equation(53) T=2(PG-PE)ΔR/kEX+(ΔR/kEX)2+1 The logarithmic term in Eq. (52) accounts for the duration of the CPMG element. Intuitively, if the duration is less than the timescale of exchange, then additional contributions to the effective relaxation rate will necessarily appear, accounted for by this term. Correspondingly, in the limit TrelkEXT   ≫ 1 the logarithmic term is negligible. Going further, in the limit 1≫4PEΔR2kEX(kEX+ΔR2)-21≫4PEΔR2kEX(kEX+ΔR2)-2 (see Supplementary Section 6), true if PE is small, or if either kEX ≫ ΔR2 or ΔR2 ≫ kEX, Eq.

(2011). It is further demonstrated that PW contains other compounds that might have estrogenic effects such as napthenic

acids ( Thomas et al., 2009). On the other hand, in vivo studies showed no effect on gonad maturation or the ratio of juvenile to mature females after long-term exposure of Atlantic cod to low levels of selected PW compounds in the laboratory ( Holth et al., 2010). Risk assessment LGK-974 ic50 by Beyer et al. (2012) also concluded that the environmental exposure of fish to APs from PW is most probably too low to induce endocrine disruption to an extent that causes significant effects on the reproduction in NS fish stocks. This assessment takes into account that PW discharges offshore are rapidly diluted, which reduces the risk of population effects, and is supported by results from the monitoring of caged fish exposed to PW offshore where ERK inhibition no endocrine effects based on Vtg measurements have been detected ( Brooks et al., 2009). APs are known to

induce hydroxyl and oxygen radical generation (Fujisawa et al., 2002, Obata and Kubota, 2000 and Okai et al., 2000), but the effects on the redox status in fish are unclear. Hasselberg et al. (2004) studied the oxidative stress response to APs in Atlantic cod by measuring amounts of hepatic glutathione and hepatic activity of glutathione reductase (GR), glutathione S-transferase (GST), and glucose-6-phosphate dehydrogenase (G6PDH). The total glutathione concentration in female cod increased in response to 1-week of feeding http://www.selleck.co.jp/products/Y-27632.html with an AP-containing diet, an effect not seen after 4 weeks of feeding. Male fish had higher levels of glutathione than females. Increased GR activity was seen in both males and females after 4 weeks of exposure to a weekly dose of 0.02 mg AP kg−1 body weight. GST activity was affected only in males exposed for 1 week, and G6PDH activity increased only in females after 1 week exposure. The results provide evidence that APs may affect the redox status in Atlantic cod through increased oxidative stress and stimulated GSH dependent detoxification. When exposing rainbow trout hepatocytes to the water

soluble (by SPE) and particulate organic (by glass wool filtering) fractions of PW from 10 different NCS oil producing installations Farmen et al. (2010) recorded a concentration-dependent increase in reactive oxygen species (ROS) after 1 h exposure, and changes in levels of total glutathione and cell death after 96 h. The water soluble fraction (WSF) apparently contained most of the toxic potential, as was also seen by Tollefsen and Nilsen (2008), but in some cases the particulate fraction, containing mainly oil droplets, was equally toxic. The effects were not correlated to the total oil content in the PW. The levels of PAHs and APs varied by a factor of 10 and 60 respectively among the different PW sources tested, and the exposure concentrations were not clearly stated.

In this work the theoretical value of sea levels for a selected Baltic Sea coast was determined on the basis of the Gumbel distribution (sea level maxima) and the Pearson III type distribution (sea level minima) in the period 1960–2010 (Table 2 and Table 3). Table 2 and Table 3 show that the height of an extreme sea level with a 100-year return period (a probability of 1%, once per century) depends on the location. At Stockholm,

the 100-year annual water level is 115.3 cm for maximum sea levels above zero gauge and − 74 cm for minimum sea levels below zero gauge. This results from the fact that this gauge station is located at some distance from the open sea (Ekman, 2009 and Hammarklint, 2009). At the remaining gauge stations the theoretical selleck inhibitor 100-year extreme (maximum and minimum) sea levels

are significantly larger: Kungsholmsfort: 135 cm PD-0332991 mouse and − 91 cm, Władysławowo (Poland): 172 cm and − 87 cm, Wismar (Germany): 205 cm and − 188 cm, Kemi (Finland): 227 cm and − 128 cm, Pärnu (Estonia): 250 cm and − 126 cm. The highest of the maximum values and the lowest of the minimum values of the observed and theoretical sea level series are due to storm surges and their impact on the sea coast. The probability distributions of theoretical sea levels for two characteristic tide gauge stations in the Baltic Sea (Stockholm – an inland station, central Baltic; Kemi – the station in the northern Bay of Bothnia) are illustrated in Figure 3. This confirms the differentiation in the distribution of the probability of theoretical sea levels depending on the tide gauge’s location. Figure 4 illustrates the geographical distribution Olopatadine of the theoretical 100-year maximum and minimum water levels determined from the 50 years between 1960 and 2010, based on the maximum and minimum annual sea levels on the coasts of the Baltic Sea. The distribution of the theoretical hundred-year water levels (Figure 4) is similar to that of the real extreme water levels in the Baltic Sea (see Figure 2). This dependence is understandable since the theoretical levels

were calculated on the basis of real annual extremes. The most extreme theoretical hundred-year maximum levels (> 200 cm NAP) and theoretical minimum water levels (< − 100 cm NAP) would occur in the innermost parts of the Bay of Bothnia, Gulf of Riga, Gulf of Finland and Bay of Mecklenburg. On the other hand, the Swedish coasts of the central Baltic have the lowest theoretical hundred-year water levels (< 140 cm NAP for the maximum theoretical levels and > − 100 cm for the minimum theoretical levels). Owing to their transitory location between the North Sea and central Baltic, the Danish Straits (Skagerrak, Kattegat, Sund, the Belts) are regions with intermediate theoretical hundred-year levels, since the Danish Straits hydraulically balance the water levels between the North Sea and the Baltic Sea.

Eine fein abgestimmte selleck inhibitor Regulation der Resorption und gewebespezifischen Akkumulation von Mn ist entscheidend für die korrekte Regulation dieser Enzyme. Daher ist die Kenntnis der Regulation von Mn in der Peripherie die Voraussetzung für das Verständnis der wichtigen Funktionen und der Toxizität von Mn im Gehirn. Es wird angenommen, dass drei Hauptfaktoren den Mn-Plasmaspiegel regulieren. Erstens ist, da die Nahrung die Hauptquelle für Mn

darstellt, eine strikte Regulation der gastrointestinalen Resorption von Mn entscheidend. Zweitens ist im Anschluss an die Resorption und den gleichzeitigen Anstieg des Mn-Plasmaspiegels der Transport von Mn zu den Zielorganen wie z. B. der Leber nötig, um Mn-induzierte toxische Effekte in der Peripherie zu verhindern.

Schließlich muss das Mn, obwohl die Leber Substanzen entgiftet, durch Überführung in die Galle weiter aus dem Plasma eliminiert werden [14]. Die Resorption von Mn im Gastrointestinaltrakt ist stark abhängig von der Menge des aufgenommenen Mn und dem im Plasma netto akkumulierten Mn-Spiegel. Das Ausmaß der gastrointestinalen Resorption von Mn (1-3,5 %) wurde durch in-vivo-Experimente an Mäusen und Ratten bestimmt [29] and [30]. Während die Aufnahme von Mn in den Dickdarm durch einfache Diffusion erfolgt, wird Mn im Dünndarm durch aktiven Transport resorbiert [14]. Die Exkretion von Mn in die Galle erfolgt wahrscheinlich ebenfalls auf aktive Weise, da sie von Konzentrationsgradienten abhängt [31]. Eine Vielzahl von Plasmaproteinen oder Liganden sind als spezifische Mn-Trägerproteine R428 clinical trial vorgeschlagen worden, darunter Transglutaminase, Beta1-Globulin, Albumin und Transferrin [32] and [33]. Tatsächlich sind 80 % des Plasma-Mn an Beta1-Globulin gebunden [32]. Obwohl gezeigt wurde, dass Mn sowohl bei Kaninchen als auch beim Menschen im Plasma vorzugsweise an Albumin gebunden ist, gibt es neuere Belege dafür, dass Mn schwächer Baricitinib an Albumin bindet als Cd und Zn [34] and [35]. Intrazelluläres

Mn2+ wird im Gehirn und der Leber über den Ca2+-Uniporter in die Mitochondrien aufgenommen [36] and [37]. Die Mitochondrien sind das wichtigste Reservoir für Mn in der Zelle, jedoch wurde vorgeschlagen, dass auch der Zellkern (noch umstritten) dieses Metall bevorzugt speichern könnte [26], [38] and [39]. Der Efflux des mitochondrialen Mn2+ wird vor allem über einen aktiven, aber langsamen Na+-unabhängigen Mechanismus vermittelt; ein Na+-abhängiger Mechanismus leistet ebenfalls einen wenn auch sehr geringen Beitrag (Übersicht in Bowman et al. [10]). Dieser langsame Mn-Efflux wurde für die Nettoakkumulation von Mn in den Mitochondrien verantwortlich gemacht. Es wurde jedoch berichtet, dass der zytoplasmatische Fe2+-Exporter Ferroportin-1 Mn transportiert. Interessanterweise sind die Ferroportin-1-Oberflächenlokalisierung und -Proteinexpression nach Exposition gegenüber Mn gestört [40].

Using QCT MIAF, denosumab treatment was shown to significantly increase total hip integral vBMD from baseline and compared with placebo at months 12, 24, and 36. In the denosumab group, the mean percentage change from baseline to Selleck CHIR-99021 month 36 in total hip integral vBMD was 6.4% (p < 0.0001; Fig. 2). In the placebo group, total hip integral vBMD decreased

over the same time interval by − 1.5% (p = 0.008). The treatment difference between denosumab and placebo was significant at months 12, 24, and 36 (p < 0.01 for all). Integral volume of the total hip did not significantly change in either group (data not shown). The BMD results were similar when assessed by DXA (Fig. 2). At baseline, total hip integral vBMD and aBMD for all subjects showed a strong correlation PCI-32765 manufacturer (r = 0.83; p < 0.0001; data not shown). Changes in vBMD and aBMD during the study were moderately correlated in both the placebo group (r = 0.47; p < 0.0001) and the denosumab group (r = 0.32; p = 0.0004). The percentage gains in total hip integral vBMD in the denosumab group were accounted for by significant increases in the trabecular, subcortical, and cortical compartments at months 12, 24, and 36 (Fig. 3). Within the cortical compartment,

similar improvements were observed in the outer and inner cortical regions (data not shown). Denosumab treatment also significantly increased total hip integral BMC from baseline by month 12 (2.4%; p < 0.001), G protein-coupled receptor kinase and the improvement progressed over 36 months. Treatment with denosumab resulted in a mean percentage change from baseline

to month 36 in total hip integral BMC of 4.8% (p < 0.0001), and treatment with placebo led to a decrease of − 2.6% over the same time interval (p = 0.0004; Fig. 4). The treatment difference between denosumab and placebo was significant at months 12, 24, and 36 (p < 0.001 for all). Similar to observations with total hip integral vBMD, a strong correlation also was observed at baseline for these QCT MIAF total integral BMC measurements and DXA BMC for all subjects (r = 0.88; p < 0.0001; data not shown). Significant percentage gains in BMC from baseline and compared with placebo also were observed in the denosumab group in each bone compartment, specifically the trabecular, subcortical, and cortical compartments. In the denosumab group at month 12, BMC increased by 4.1% in the trabecular compartment, 2.3% in the subcortical compartment, and 2.2% in the cortical compartment (p < 0.001 for all). Gains also were observed in all 3 compartments at month 24 (7.2%, 3.9%, and 3.2%, respectively; p < 0.05 for all) and month 36 (8.4%, 4.9%, and 3.9%, respectively; p < 0.001 for all; Fig. 4). Outer and inner cortical regions also had significant gains from baseline and placebo (data not shown). Observed absolute changes in vBMD and BMC for integral and compartmental assessments also were significant in the denosumab group compared with the placebo group (p < 0.