Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline.

BACKGROUND: Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. OBJECTIVE: To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. METHODS: A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. RESULTS: The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D-containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. CONCLUSION: The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

Quantum Synchronization and Entanglement of Dissipative Qubits Coupled to a Resonator.

In a dissipative regime, we study the properties of several qubits coupled to a driven resonator in the framework of a Jaynes-Cummings model. The time evolution and the steady state of the system are numerically analyzed within the Lindblad master equation, with up to several million components. Two semi-analytical approaches, at weak and strong (semiclassical) dissipations, are developed to describe the steady state of this system and determine its validity by comparing it with the Lindblad equation results. We show that the synchronization of several qubits with the driving phase can be obtained due to their coupling to the resonator. We establish the existence of two different qubit synchronization regimes: In the first one, the semiclassical approach describes well the dynamics of qubits and, thus, their quantum features and entanglement are suppressed by dissipation and the synchronization is essentially classical. In the second one, the entangled steady state of a pair of qubits remains synchronized in the presence of dissipation and decoherence, corresponding to the regime non-existent in classical synchronization.

Random matrix model of Kolmogorov-Zakharov turbulence.

We introduce and study a random matrix model of Kolmogorov-Zakharov turbulence in a nonlinear purely dynamical finite-size system with many degrees of freedom. For the case of a direct cascade, the energy and norm pumping takes place at low energy scales with absorption at high energies. For a pumping strength above a certain chaos border, a global chaotic attractor appears with a stationary energy flow through a Hamiltonian inertial energy interval. In this regime, the steady-state norm distribution is described by an algebraic decay with an exponent in agreement with the Kolmogorov-Zakharov theory. Below the chaos border, the system is located in the quasi-integrable regime similar to the Kolmogorov-Arnold-Moser theory and the turbulence is suppressed. For the inverse cascade, the system rapidly enters a strongly nonlinear regime where the weak turbulence description is invalid. We argue that such a dynamical turbulence is generic, showing that it is present in other lattice models with disorder and Anderson localization. We point out that such dynamical models can be realized in multimode optical fibers.

Opinion Formation in the World Trade Network.

We extend the opinion formation approach to probe the world influence of economical organizations. Our opinion formation model mimics a battle between currencies within the international trade network. Based on the United Nations Comtrade database, we construct the world trade network for the years of the last decade from 2010 to 2020. We consider different core groups constituted by countries preferring to trade in a specific currency. We will consider principally two core groups, namely, five Anglo-Saxon countries that prefer to trade in US dollar and the 11 BRICS+ that prefer to trade in a hypothetical currency, hereafter called BRI, pegged to their economies. We determine the trade currency preference of the other countries via a Monte Carlo process depending on the direct transactions between the countries. The results obtained in the frame of this mathematical model show that starting from the year 2014, the majority of the world countries would have preferred to trade in BRI than USD. The Monte Carlo process reaches a steady state with three distinct groups: two groups of countries preferring to trade in whatever is the initial distribution of the trade currency preferences, one in BRI and the other in USD, and a third group of countries swinging as a whole between USD and BRI depending on the initial distribution of the trade currency preferences. We also analyze the battle between three currencies: on one hand, we consider USD, BRI and EUR, the latter currency being pegged by the core group of nine EU countries. We show that the countries preferring EUR are mainly the swing countries obtained in the frame of the two currencies model. On the other hand, we consider USD, CNY (Chinese yuan), OPE, the latter currency being pegged to the major OPEC+ economies for which we try to probe the effective economical influence within international trade. Finally, we present the reduced Google matrix description of the trade relations between the Anglo-Saxon countries and the BRICS+.

Graded levels of Eimeria infection linearly reduced the growth performance, altered the intestinal health, and delayed the onset of egg production of Hy-Line W-36 laying hens when infected at the prelay stage.

The aim of this experiment was to investigate how different levels of Eimeria infection affect the performance, intestinal health, oxidative status, and egg production of Hy-Line W-36 pullets and laying hens. Three hundred and sixty Hy-Line W-36 pullets, aged 15 wk, were randomly distributed into 5 treatment groups, each comprising 6 replicates and a nonchallenged control. At 15 wk, pullets were inoculated with different levels of mixed Eimeria species as high-dose, medium-high, medium-low, and low-dose treatments. The growth performance and average daily feed intake (ADFI) were measured from 0- to 18-days postinoculation (DPI), whereas hen day egg production (HDEP) was recorded from wk 19. The markers of gastrointestinal health and oxidative status were measured at 6 DPI, 14 DPI, and 23 wk of age. The findings revealed a significant linear reduction in growth performance in response to increased Eimeria challenge dosage on 6 and 14 DPI (P < 0.0001, P-L < 0.0001). An interaction between the graded level of Eimeria infection and DPI was observed for ADFI. The challenged pullets showed a reduction in ADFI starting at 4 DPI, which persisted until 14 DPI, when ADFI recovered back to normal. The most significant drop in feed intake was observed in 6 DPI in all the Eimeria-infected groups. The markers of gastrointestinal health (gastrointestinal permeability and tight junction proteins) were upregulated in challenged pullets because of infection, whereas the relative mRNA expression of key nutrient transporters was downregulated following infection on 6 and 14 DPI (P < 0.05). As a result of an infection on 6 DPI, the oxidative equilibrium was shifted toward the oxidative stress, and at the same time, upregulation of proinflammatory and inflammatory cytokines was observed (P < 0.05). An interaction between the Eimeria challenge dosage and bird age was observed for HDEP (P = 0.0427). The pullets infected with Eimeria started to lay eggs later than the Control birds. However, the HDEP of the challenged groups became similar to Control only at wk 22, 3 wk after laying eggs. In conclusion, coccidiosis reduced growth performance, altered gastrointestinal health, induced oxidative stress, and delayed egg production when infected at the prelay stage of pullets and negatively impacted the laying hens' overall performance.

Goal quest for an intelligent surfer moving in a chaotic flow.

We consider a model of an intelligent surfer moving on the Ulam network generated by a chaotic dynamics in the Chirikov standard map. This directed network is obtained by the Ulam method with a division of the phase space in cells of fixed size forming the nodes of a Markov chain. The goal quest for this surfer is to determine the network path from an initial node A to a final node B with minimal resistance given by the sum of inverse transition probabilities. We develop an algorithm for the intelligent surfer that allows us to perform the quest in a small number of transitions which grows only logarithmically with the network size. The optimal path search is done on a fractal intersection set formed by nodes with small Erdös numbers of the forward and inverted networks. The intelligent surfer exponentially outperforms a naive surfer who tries to minimize its phase space distance to target B. We argue that such an algorithm provides unique hints for motion control in chaotic flows.

Nonlinear Perturbation of Random Matrix Theory.

We consider a system of linear oscillators, or quantum states, described by random matrix theory and analyze how its time evolution is affected by a nonlinear perturbation. Our numerical results show that above a certain chaos border a weak or moderate nonlinearity leads to a dynamical thermalization of a finite number of degrees of freedom with energy equipartition over linear eigenmodes as expected from the laws of classical statistical mechanics. The system temperature is shown to change in a broad range from positive to negative values, and the dependence of system characteristics on the initial injected energy is determined. Below the chaos border the dynamics is described by the Kolmogorov-Arnold-Moser integrability. Owing to universal features of random matrix theory we argue that the obtained results describe the generic properties of its nonlinear perturbation.

Graded levels of Eimeria challenge altered the microstructural architecture and reduced the cortical bone growth of femur of Hy-Line W-36 pullets at early stage of growth (0-6 wk of age).

An experiment was carried out to evaluate the impact of mixed Eimeria challenge on skeletal health of Hy-Line W-36 pullets. A total of 540, 16-day-old pullets were randomly allocated into 5 treatment groups, including a nonchallenged control. A mixed Eimeria species solution containing 50,000 E. maxima, 50,000 E. tenella, and 250,000 E. acervulina oocysts per mL was prepared and challenged to 1 group as a high-dose treatment. The 2-fold serial dilution was done to prepare the medium-high (25,000 E. maxima; 25,000 E. tenella; 125,000 E. acervulina), the medium-low (12,500 E. maxima; 12,500 E. tenella; 62,500 E. acervulina), and the low (6,250 E. maxima; 6,250 E. tenella; 31,250 E. acervulina) dose treatments which were challenged to 3 corresponding groups, respectively. The mineral apposition rate (MAR) was measured from 0 to 14 d post inoculation (DPI) and 14 to 28 DPI using calcein injection. The microstructural architecture of the femur was analyzed using the Skyscan X-ray microtomography (microCT) on 6, 14, and 28 DPI. The results showed that the MAR decreased linearly with an increase in the challenged dose (P < 0.05) during 0 to 14 DPI. The results of microCT revealed that cortical and total BMD, BMC, bone volume (BV), and bone volume as a fraction of tissue volume (BV/TV) of femur decreased both linearly (P < 0.05). Conversely, the total number of pores increased linearly with an increase in challenge dosages on 6 and 14 DPI. Trabecular BMD, BV, BV/TV, trabecular number, and trabecular thickness decreased linearly with an increase in the challenge dosages (P < 0.05) on 6 DPI. Furthermore, Eimeria infection significantly increased the number of osteoclasts and osteoclastic activity (P = 0.001). The result of this study suggests that the mixed Eimeria challenge negatively impacts the quality of skeletal health in a linear or quadratic manner with an increase in the concentration of Eimeria oocysts. The negative impact on long bone development might be due to malabsorption, nutrient deficiency during the infection, along with oxidative stress/inflammation disrupting the balance of osteoblastic and osteoclastic cells and their functions.

Dollar-Yuan Battle in the World Trade Network.

From the Bretton Woods agreement in 1944 till the present day, the US dollar has been the dominant currency in world trade. However, the rise of the Chinese economy has recently led to the emergence of trade transactions in Chinese yuan. Here, we mathematically analyze how the structure of international trade flows would favor a country to trade whether in US dollar or in Chinese yuan. The trade currency preference of a country is modeled as a binary variable with the properties of a spin in an Ising model. The computation of this trade currency preference is based on the world trade network built from the 2010-2020 UN Comtrade data and is determined by two multiplicative factors: the relative weight of trade volume exchanged by the country with its direct trade partners and the relative weight of its trade partners in global international trade. The performed analysis, based on the convergence of the Ising spin interactions, shows that from 2010 to present a transition took place, and the majority of the world countries would now have a preference to trade in Chinese yuan if one only considers the world trade network structure.

Berezinskii-Kosterlitz-Thouless Transition in the Type-I Weyl Semimetal PtBi2.

Symmetry breaking in topological matter has become in recent years a key concept in condensed matter physics to unveil novel electronic states. In this work, we predict that broken inversion symmetry and strong spin-orbit coupling in trigonal PtBi2 lead to a type-I Weyl semimetal band structure. Transport measurements show an unusually robust low dimensional superconductivity in thin exfoliated flakes up to 126 nm in thickness (with Tc ∼ 275-400 mK), which constitutes the first report and study of unambiguous superconductivity in a type-I Weyl semimetal. Remarkably, a Berezinskii-Kosterlitz-Thouless transition with TBKT ∼ 310 mK is revealed in up to 60 nm thick flakes, which is nearly an order of magnitude thicker than the rare examples of two-dimensional superconductors exhibiting such a transition. This makes PtBi2 an ideal platform to study low dimensional and unconventional superconductivity in topological semimetals.

SNP-by-CpG Site Interactions in ABCA7 Are Associated with Cognition in Older African Americans.

SNPs in ABCA7 confer the largest genetic risk for Alzheimer's Disease (AD) in African Americans (AA) after APOE ε4. However, the relationship between ABCA7 and cognitive function has not been thoroughly examined. We investigated the effects of five known AD risk SNPs and 72 CpGs in ABCA7, as well as their interactions, on general cognitive function (cognition) in 634 older AA without dementia from Genetic Epidemiology Network of Arteriopathy (GENOA). Using linear mixed models, no SNP or CpG was associated with cognition after multiple testing correction, but five CpGs were nominally associated (p < 0.05). Four SNP-by-CpG interactions were associated with cognition (FDR q < 0.1). Contrast tests show that methylation is associated with cognition in some genotype groups (p < 0.05): a 1% increase at cg00135882 and cg22271697 is associated with a 0.68 SD decrease and 0.14 SD increase in cognition for those with the rs3764647 GG/AG (p = 0.004) and AA (p = 2 × 10-4) genotypes, respectively. In addition, a 1% increase at cg06169110 and cg17316918 is associated with a 0.37 SD decrease (p = 2 × 10-4) and 0.33 SD increase (p = 0.004), respectively, in cognition for those with the rs115550680 GG/AG genotype. While AD risk SNPs in ABCA7 were not associated with cognition in this sample, some have interactions with proximal methylation on cognition.

Effect of Dietary Supplementation of Probiotic Aspergillus niger on Performance and Cecal Microbiota in Hy-Line W-36 Laying Hens.

This study aimed to investigate the role of the probiotic Aspergillus niger on the production performance, egg quality, and cecal microbial load of Clostridium perfringens, Salmonella spp., and Escherichia coli in Hy-Line W-36 laying hens. A total of 72, 45-week-old Hy-Line W-36 laying hens were randomly allocated to one of the three dietary treatments with six replicates, and each replicate had four individually caged laying hens (n = 6 and 4 hens/replicate). The hens in each treatment group were fed a corn and soybean meal diet (Control), a diet supplemented with bacitracin methylene disalicylate (BMD) at a rate of 495 mg/kg of feed (Positive Control), or a diet supplemented with Aspergillus niger (Probioist®) at a rate of 220 mg/kg of feed (Probiotic). Supplementing probiotics in the laying hen diet significantly increased egg production at weeks 3 and 6 compared with the Positive Control. Haugh unit, a measure of egg quality, was significantly higher in laying hens fed the probiotic diet compared with the Control or Positive Control at week 10. Furthermore, the Probiotic group had numerically lower cecal microbial loads of pathogenic bacteria (Clostridium perfringens, Salmonella spp., and Escherichia coli) compared with the Control and Positive Control groups. The results suggest that Aspergillus niger could be used as a probiotic to improve laying hen performance and egg quality.

Effects of mixed Eimeria challenge on performance, body composition, intestinal health, and expression of nutrient transporter genes of Hy-Line W-36 pullets (0-6 wks of age).

A study was aimed to investigate the effects of mixed Eimeria challenge on performance, gastrointestinal health, oxidative stress, inflammation, and expression of nutrient transporter genes of Hy-Line W-36 pullets. A total of 540, 16-d old pullets were randomly allocated into 5 treatment groups with 6 replicate cages, including a nonchallenged control group. A mixed Eimeria species solution containing 50,000 E. maxima, 50,000 E. tenella, and 250,000 E. acervulina oocysts per mL was prepared and challenged to one group as a high-dose treatment (High). The 2-fold serial dilution was done to prepare the medium-high (Med-High: 25,000 E. maxima; 25,000 E. tenella; and 125,000 E. acervulina), the medium-low (Med-Low: 12,500 E. maxima; 12,500 E. tenella; and 62,500 E. acervulina), and the low (Low: 6,250 E. maxima; 6,250 E. tenella; and 31,250 E. acervulina) dose treatments, and these dosages were challenged to 3 remaining groups, respectively. Growth performance, daily feed intake (FI), and mortality were calculated from 0-14 d postinfection (DPI). Gastrointestinal permeability (GP) was measured on 3, 5, 6, 7, and 9 DPI. The result indicated significant linear responses to the Eimeria challenge dosage in average body weight and body weight gain (P < 0.0001). An interaction between treatment and DPI was observed for FI (P < 0.0001). Feed intake significantly dropped from 4 DPI and did not recover until 12 DPI in the challenged groups. The lowest FI for each of the challenged groups was observed on 5 DPI. Gastrointestinal permeability increased linearly, peaking at 5 DPI, and was recovered back to normal by 9 DPI in the challenged groups. Furthermore, gene expression of tight junction proteins was linearly upregulated by increased Eimeria dosages. The oxidative status of the pullets was lowered in the challenged groups than the nonchallenged control group, whereas the expression of inflammatory and proinflammatory cytokines was upregulated by Eimeria challenge on 6 DPI (P < 0.05). The highest mortality was observed in pullets challenged with the High, followed by the Med-High (P < 0.0001) on 5 DPI. In summary, the mixed Eimeria challenge linearly reduced the growth performance of pullets with an increase in oxidative stress and inflammation. A severe effect of Eimeria on gastrointestinal health was observed on 5 or 6 DPI as suggested by GP, tight junction genes, and mortality results. This study indicates that Eimeria infection can be a threat to gastrointestinal health related issues in pullets.

COVID-19's Impact on International Trade.

We analyze how the COVID-19 pandemic affected the trade of products between countries. With this aim, using the United Nations Comtrade database, we perform a Google matrix analysis of the multiproduct World Trade Network (WTN) for the years 2018-2020, comprising the emergence of the COVID-19 as a global pandemic. The applied algorithms-PageRank, CheiRank and the reduced Google matrix-take into account the multiplicity of the WTN links, providing new insights into international trade compared to the usual import-export analysis. These complex networks analysis algorithms establish new rankings and trade balances of countries and products considering all countries on equal grounds, independent of their wealth, and every product on the basis of its relative exchanged volumes. In comparison with the pre-COVID-19 period, significant changes in these metrics occurred for the year 2020, highlighting a major rewiring of the international trade flows induced by the COVID-19 pandemic crisis. We define a new PageRank-CheiRank product trade balance, either export or import-oriented, which is significantly perturbed by the pandemic.

Deconfinement of classical Yang-Mills color fields in a disorder potential.

We study numerically and analytically the behavior of classical Yang-Mills color fields in a random one-dimensional potential described by the Anderson model with disorder. Above a certain threshold, the nonlinear interactions of Yang-Mills fields lead to chaos and deconfinement of color wavepackets with their subdiffusive spreading in space. The algebraic exponent of the second moment growth in time is found to be in the range of 0.3-0.4. Below the threshold, color wavepackets remain confined even if a very slow spreading at very long times is not excluded due to subtle nonlinear effects and the Arnold diffusion for the case when initially color packets are located in close vicinity. In the case of large initial separation of color wavepackets, they remain well confined and localized in space. We also present the comparison with the behavior of the one-component field model of discrete Anderson nonlinear Schrödinger equation with disorder.

Some elements for a history of the dynamical systems theory.

Writing a history of a scientific theory is always difficult because it requires to focus on some key contributors and to "reconstruct" some supposed influences. In the 1970s, a new way of performing science under the name "chaos" emerged, combining the mathematics from the nonlinear dynamical systems theory and numerical simulations. To provide a direct testimony of how contributors can be influenced by other scientists or works, we here collected some writings about the early times of a few contributors to chaos theory. The purpose is to exhibit the diversity in the paths and to bring some elements-which were never published-illustrating the atmosphere of this period. Some peculiarities of chaos theory are also discussed.

Updates on Osteoporosis in Men.

Osteoporosis is less common in men than women; however, the mortality rate associated with major fragility fractures is higher in men. The diagnosis of osteoporosis is established by measurement of bone mineral density or by the presence of a fragility fracture, especially spine or hip fracture. However, many men at high risk of fracture will not meet the T-score criteria for osteoporosis, so fracture risk calculation, with a tool such as FRAX, should be performed. Bone-active agents should be prescribed for men at high risk of fracture to decrease fracture risk, and therapy must be individualized.

Fibrosis Protein-Protein Interactions from Google Matrix Analysis of MetaCore Network.

Protein-protein interactions is a longstanding challenge in cardiac remodeling processes and heart failure. Here, we use the MetaCore network and the Google matrix algorithms for prediction of protein-protein interactions dictating cardiac fibrosis, a primary cause of end-stage heart failure. The developed algorithms allow identification of interactions between key proteins and predict new actors orchestrating fibroblast activation linked to fibrosis in mouse and human tissues. These data hold great promise for uncovering new therapeutic targets to limit myocardial fibrosis.

Interdependence of Sectors of Economic Activities for World Countries from the Reduced Google Matrix Analysis of WTO Data.

We apply the recently developed reduced Google matrix algorithm for the analysis of the OECD-WTO World Network of Economic Activities. This approach allows to determine interdependencies and interactions of economy sectors of several countries, including China, Russia and the USA, properly taking into account the influence of all the other world countries and their economic activities. Within this analysis, we also obtain the sensitivity of EU countries' economies to the petroleum activity sector. We show that this approach takes into account the multiplicity of economical interactions between countries and activity sectors, thus providing a richer analysis compared to the usual export-import analysis.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS-2020 UPDATE.

Objective: The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). Methods: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. Results: The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 368 citations: 123 (33.5%) evidence level (EL) 1 (highest), 132 (36%) EL 2 (intermediate), 20 (5.5%) EL 3 (weak), and 93 (25%) EL 4 (lowest). New or updated topics in this CPG include: clarification of the diagnosis of osteoporosis, stratification of the patient according to high-risk and very-high-risk features, a new dual-action therapy option, and transitions from therapeutic options. Conclusion: This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of post-menopausal osteoporosis. Abbreviations: 25(OH)D = 25-hydroxyvitamin D; AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; AFF = atypical femoral fracture; ASBMR = American Society for Bone and Mineral Research; BEL = best evidence level; BMD = bone mineral density; BTM = bone turnover marker; CI = confidence interval; CPG = clinical practice guideline; CTX = C-terminal telopeptide type-I collagen; DXA = dual-energy X-ray absorptiometry; EL = evidence level; FDA = U.S. Food and Drug Administration; FRAX® = Fracture Risk Assessment Tool; GI = gastrointestinal; HORIZON = Health Outcomes and Reduced Incidence with Zoledronic acid ONce yearly Pivotal Fracture Trial (zoledronic acid and zoledronate are equivalent terms); ISCD = International Society for Clinical Densitometry; IU = international units; IV = intravenous; LSC = least significant change; NOF = National Osteoporosis Foundation; ONJ = osteonecrosis of the jaw; PINP = serum amino-terminal propeptide of type-I collagen; PTH = parathyroid hormone; R = recommendation; ROI = region of interest; RR = relative risk; SD = standard deviation; TBS = trabecular bone score; VFA = vertebral fracture assessment; WHO = World Health Organization.