Time course of rapid bone loss and cortical porosity formation observed by longitudinal μCT in a rat model of CKD.

Background: Rodent studies of bone in chronic kidney disease have primarily relied on end-point examinations of bone microarchitecture. This study used longitudinal in vivo microcomputed tomography (in vivo μCT) to characterize the onset and progression of bone loss, specifically cortical porosity, in the Cy/+ rat of model of CKD.

Methods: Male CKD rats and normal littermates were studied.

Loss of FKBP5 Affects Neuron Synaptic Plasticity: An Electrophysiology Insight.

FKBP5 (FKBP51) is a glucocorticoid receptor (GR) binding protein, which acts as a co-chaperone of heat shock protein 90 (HSP90) and negatively regulates GR. Its association with mental disorders has been identified, but its function in disease development is largely unknown. Long-term potentiation (LTP) is a functional measurement of neuronal connection and communication, and is considered one of the major cellular mechanisms that underlies learning and memory, and is disrupted in many mental diseases.

Skeletal vascular perfusion is altered in chronic kidney disease.

Patients with chronic kidney disease (CKD) are at an alarming risk of cardiovascular disease and fracture-associated mortality. CKD has been shown to have negative effects on vascular reactivity and organ perfusion. Although alterations in bone blood flow are linked to dysregulation of bone remodeling and mass in multiple conditions, changes to skeletal perfusion in the setting of CKD have not been explored.

Skeletal accumulation of fluorescently tagged zoledronate is higher in animals with early stage chronic kidney disease.

Unlabelled: This work examines the skeletal accumulation of fluorescently tagged zoledronate in an animal model of chronic kidney disease. The results show higher accumulation in 24-h post-dose animals with lower kidney function due to greater amounts of binding at individual surfaces.

Introduction: Chronic kidney disease (CKD) patients suffer from increased rates of skeletal-related mortality from changes driven by biochemical abnormalities.

Recent Advances in Understanding Bisphosphonate Effects on Bone Mechanical Properties.

Purpose Of The Review: Bisphosphonates have well-established effects on suppressing bone resorption and slowing bone loss, yet the effects on bone mechanical properties are less clear. We review recent data from pre-clinical and clinical experiments that assessed mechanical properties of bisphosphonate-treated specimens.

Recent Findings: Pre-clinical work has utilized new techniques to show reduced fatigue life and transfer of stress from the mineral to collagen.

Preclinical Models for Skeletal Research: How Commonly Used Species Mimic (or Don't) Aspects of Human Bone.

Preclinical studies play an indispensable role in exploring the biological regulation of the musculoskeletal system. They are required in all drug development pipelines where both small and large animal models are needed to understand efficacy and side effects. This brief review highlights 4 aspects of human bone, longitudinal bone growth, intracortical remodeling, collagen/mineral interface, and age-related changes, and discusses how various animal models recapitulate (or don't) these aspects of human skeletal physiology.

Effects of combination treatment with alendronate and raloxifene on skeletal properties in a beagle dog model.

A growing number of studies have investigated combination treatment as an approach to treat bone disease. The goal of this study was to investigate the combination of alendronate and raloxifene with a particular focus on mechanical properties. To achieve this goal we utilized a large animal model, the beagle dog, used previously by our laboratory to study both alendronate and raloxifene monotherapies.

Assessment of regional bone tissue perfusion in rats using fluorescent microspheres.

Disturbances in bone blood flow have been shown to have deleterious effects on bone properties yet there remain many unanswered questions about skeletal perfusion in health and disease, partially due to the complexity of measurement methodologies. The goal of this study was use fluorescent microspheres in rats to assess regional bone perfusion by adapting mouse-specific fluorescent microsphere protocol. Ten fifteen-week old Sprague Dawley rats were injected with fluorescent microspheres either via cardiac injection (n = 5) or via tail vein injection (n = 5).

What Animal Models Have Taught Us About the Safety and Efficacy of Bisphosphonates in Chronic Kidney Disease.

Purpose Of Review: Bisphosphonates (BPs) have long been the gold-standard anti-remodeling treatment for numerous metabolic bone diseases. Since these drugs are excreted unmetabolized through the kidney, they are not recommended for individuals with compromised kidney function due to concerns of kidney and bone toxicity. The goal of this paper is to summarize the preclinical BP work in models of kidney disease with particular focus on the bone, kidney, and vasculature.

Raloxifene Improves Bone Mechanical Properties in Mice Previously Treated with Zoledronate.

Bisphosphonates represent the gold-standard pharmaceutical agent for reducing fracture risk. Long-term treatment with bisphosphonates can result in tissue brittleness which in rare clinical cases manifests as atypical femoral fracture. Although this has led to an increasing call for bisphosphonate cessation, few studies have investigated therapeutic options for follow-up treatment.

Assessing the inter- and intra-animal variability of OsteoProbe skeletal measures in untreated dogs.

The OsteoProbe is a second-generation reference point indentation (RPI) device without a reference probe that is designed to simplify RPI testing for clinical use. Successful clinical implementation of the OsteoProbe would benefit from a better understanding of how its output, bone material strength index (BMSi), relates to the material properties of bone and under what conditions it reliably correlates with fracture risk. Large animal models have the potential to help fill this knowledge gap, as cadaveric studies are retrospective and limited by incomplete patient histories (including the potential use of bone matrix altering drugs such as bisphosphonates).

Npy deletion in an alcohol non-preferring rat model elicits differential effects on alcohol consumption and body weight.

Neuropeptide Y (NPY) is widely expressed in the central nervous system and influences many physiological processes. It is located within the rat quantitative trait locus (QTL) for alcohol preference on chromosome 4. Alcohol-nonpreferring (NP) rats consume very little alcohol, but have significantly higher NPY expression in the brain than alcohol-preferring (P) rats.

Reference point indentation is insufficient for detecting alterations in traditional mechanical properties of bone under common experimental conditions.

Reference point indentation (RPI) was developed as a novel method to assess mechanical properties of bone in vivo, yet it remains unclear what aspects of bone dictate changes/differences in RPI-based parameters. The main RPI parameter, indentation distance increase (IDI), has been proposed to be inversely related to the ability of bone to form/tolerate damage. The goal of this work was to explore the relationshipre-intervention RPI measurebetween RPI parameters and traditional mechanical properties under varying experimental conditions (drying and ashing bones to increase brittleness, demineralizing bones and soaking in raloxifene to decrease brittleness).

Raloxifene reduces skeletal fractures in an animal model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a genetic disease of Type I collagen and collagen-associated pathways that results in brittle bone behavior characterized by fracture and reduced mechanical properties. Based on previous work in our laboratory showing that raloxifene (RAL) can significantly improve bone mechanical properties through non-cellular mechanisms, we hypothesized that raloxifene would improve the mechanical properties of OI bone. In experiment 1, tibiae from female wild type (WT) and homozygous oim mice were subjected to in vitro soaking in RAL followed by mechanical tests.

True Gold or Pyrite: A Review of Reference Point Indentation for Assessing Bone Mechanical Properties In Vivo.

Although the gold standard for determining bones' mechanical integrity is the direct measure of mechanical properties, clinical evaluation has long relied on surrogates of mechanical properties for assessment of fracture risk. Nearly a decade ago, reference point indentation (RPI) emerged as an innovative way to potentially assess mechanical properties of bone in vivo. Beginning with the BioDent device, and then followed by the newer generation OsteoProbe, this RPI technology has been utilized in several publications.

Childhood Conditions and Multimorbidity Among Older Adults.

Objectives: This research tests whether childhood conditions are associated with trajectories of chronic conditions among older adults.

Methods: Using data from the Health and Retirement Study (1992-2008), a series of hierarchical linear models are used to estimate number of chronic conditions at survey midpoint and the rate of increase in chronic conditions across 18 years of data.

Results: Results suggest that lower childhood socioeconomic status (SES) and poor childhood health are associated with increased number of chronic conditions; however, childhood SES is no longer associated with chronic conditions after adjustment for adult SES and adult health.

Chaos and robustness in a single family of genetic oscillatory networks.

Genetic oscillatory networks can be mathematically modeled with delay differential equations (DDEs). Interpreting genetic networks with DDEs gives a more intuitive understanding from a biological standpoint. However, it presents a problem mathematically, for DDEs are by construction infinitely-dimensional and thus cannot be analyzed using methods common for systems of ordinary differential equations (ODEs).

The Hoosier Assurance Plan Instrument for Adults (HAPI-A): the psychometric properties of a level of functioning assessment instrument designed for use in a state managed care mental health program.

The psychometric properties of the HAPI-A were examined at intake and 90-day follow-up in consumers with mental illness (MI) or chronic addiction (CA) being served at one of 11 treatment facilities (n = 1168). A 4-factor subscale structure was confirmed and factor invariance tests indicated a single model for the CA and MI samples. Internal consistency and inter-rater reliability were good (ICCs = 0.

Social cognition and neurocognitive deficits in schizophrenia.

While research equivocally supports a relationship between social cognition and neurocognition, it is less clear whether social cognition is related to general cognitive functioning or whether specific aspects of social cognition are linked with specific forms of neurocognition. Thus, this study sought to investigate the relationships between various domains of neurocognition and two forms of social cognition, social cue recognition and social problem solving, for 40 people with schizophrenia spectrum disorders. Step-wise multiple regressions found that performance on neurocognitive tests was able to predict 47% and 38% of the variance on measures of the ability to recognize actual and suggested social cues, respectively, and 13% of participants' ability to problem solve in ambiguous social situations.