Femoral Skeletal Perfusion is Reduced in Male Mice with Type 1 Diabetes.

The bone vasculature and blood flow are critical for bone modeling, remodeling, and regeneration. Vascular complications are one of the major health concerns of people with type 1 diabetes (T1D). Moreover, people with T1D have lower bone mineral density and increased bone fragility.

Segregating the effects of ferric citrate-mediated iron utilization and FGF23 in a mouse model of CKD.

Ferric citrate (FC) is an approved therapy for chronic kidney disease (CKD) patients as a phosphate (Pi) binder for dialysis-dependent CKD, and for iron deficiency anemia (IDA) in non-dialysis CKD. Elevated Pi and IDA both lead to increased FGF23, however, the roles of iron and FGF23 during CKD remain unclear. To this end, iron and Pi metabolism were tested in a mouse model of CKD (0.

Effects of ferric citrate and intravenous iron sucrose on markers of mineral, bone, and iron homeostasis in a rat model of CKD-MBD.

Background: Anemia and chronic kidney disease-mineral and bone disorder (CKD-MBD) are common and begin early in CKD. Limited studies have concurrently compared the effects of ferric citrate (FC) versus intravenous (IV) iron on CKD-MBD and iron homeostasis in moderate CKD.

Methods: We tested the effects of 10 weeks of 2% FC versus IV iron sucrose in rats with moderate CKD (Cy/+ male rat) and untreated normal (NL) littermates.

Cortical porosity is elevated after a single dose of zoledronate in two rodent models of chronic kidney disease.

Purpose: Patients with chronic kidney disease (CKD) have high risk of fracture in part due to cortical bone deterioration. The goal of this study was to assess the impact of two different bisphosphonates and dosing regimens on cortical microstructure (porosity, thickness, area) and bone mechanical properties in animal models of CKD.

Methods: In experiment 1, Male Cy/+ (CKD) rats were treated with either a single dose or ten fractionated doses of zoledronate at 18 weeks of age.

Cortical porosity development and progression is mitigated after etelcalcetide treatment in an animal model of chronic kidney disease.

Purpose: Chronic kidney disease (CKD) leads to increased bone fragility and risk of fracture. Cortical deteriorations, including cortical porosity, are key factors in fracture susceptibility in CKD. Since secondary hyperparathyroidism is common in CKD individuals and contributes to cortical deterioration, we hypothesized that reducing parathyroid hormone (PTH) may modulate CKD-induced cortical porosity.

Iron deficiency and high-intensity running interval training do not impact femoral or tibial bone in young female rats.

In the USA, as many as 20 % of recruits sustain stress fractures during basic training. In addition, approximately one-third of female recruits develop Fe deficiency upon completion of training. Fe is a cofactor in bone collagen formation and vitamin D activation, thus we hypothesised Fe deficiency may be contributing to altered bone microarchitecture and mechanics during 12-weeks of increased mechanical loading.

The combination of aging and chronic kidney disease leads to an exacerbated cortical porosity phenotype.

Purpose: Chronic kidney disease (CKD) and aging are each independently associated with higher fracture risk. Although CKD is highly prevalent in the aging population, the interaction between these two conditions with respect to bone structure and mechanics is not well understood. The purpose of this study was to examine cortical porosity and mechanical properties in skeletally mature young and aging mice with CKD.

Blueberry Polyphenols do not Improve Bone Mineral Density or Mechanical Properties in Ovariectomized Rats.

Osteoporosis-related bone fragility fractures are a major public health concern. Given the potential for adverse side effects of pharmacological treatment, many have sought alternative treatments, including dietary changes. Based on recent evidence that polyphenol-rich foods, like blueberries, increase calcium absorption and bone mineral density (BMD), we hypothesized that blueberry polyphenols would improve bone biomechanical properties.

Adenine-induced chronic kidney disease induces a similar skeletal phenotype in male and female C57BL/6 mice with more severe deficits in cortical bone properties of male mice.

Chronic kidney disease (CKD) causes bone loss, particularly in cortical bone, through formation of cortical pores which lead to skeletal fragility. Animal models of CKD have shown variability in the skeletal response to CKD between males and females suggesting sex may play a role in this variation. Our aim was to compare the impact of adenine-induced CKD on cortical parameters in skeletally mature male and female C57Bl/6 mice.

Strain-specific alterations in the skeletal response to adenine-induced chronic kidney disease are associated with differences in parathyroid hormone levels.

Unlabelled: Chronic kidney disease (CKD) leads to loss of cortical bone through cortical thinning and the development of cortical porosity. The goal of this current study was to assess cortical bone alterations to adenine-induced chronic kidney disease (CKD) in two strains of mice with known genetic differences in cortical thickness. We hypothesized that C3H mice with thicker cortices and baseline levels of intracortical remodeling would have greater cortical porosity in response to adenine-induced CKD compared to B6 animals.

The Effect of Single Versus Group μCT on the Detection of Trabecular and Cortical Disease Phenotypes in Mouse Bones.

Micro-computed tomography is a critical assessment tool for bone-related preclinical research, especially in murine models. To expedite the scanning process, researchers often image multiple bones simultaneously; however, it is unknown if this impacts scan quality and alters the ability to detect differences between experimental groups. The purpose of this study was to assess the effect of multibone scanning on detecting disease-induced changes in bone microarchitecture and mineral density by group scanning two murine models with known skeletal defects: the model of osteogenesis imperfecta and an adenine-induced model of chronic kidney disease.

Age and sex effects on FGF23-mediated response to mild phosphate challenge.

Background: During aging, there is a normal and mild loss in kidney function that leads to abnormalities of the kidney-bone metabolic axis. In the setting of increased phosphorus intake, hyperphosphatemia can occur despite increased concentrations of the phosphaturic hormone FGF23. This is likely from decreased expression of the FGF23 co-receptor Klotho (KL) with age; however, the roles of age and sex in the homeostatic responses to mild phosphate challenges remain unclear.

Reversing cortical porosity: Cortical pore infilling in preclinical models of chronic kidney disease.

Purpose: Chronic kidney disease (CKD) patients have a high incidence of fracture due in part to cortical porosity. The goal of this study was to study cortical pore infilling utilizing two rodent models of progressive CKD.

Methods: Exp 1: Female C57Bl/6J mice (16-week-old) were given dietary adenine (0.

Erythropoietin and a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHDi) lowers FGF23 in a model of chronic kidney disease (CKD).

Iron-deficiency anemia is a potent stimulator of the phosphaturic hormone Fibroblast growth factor-23 (FGF23). Anemia, elevated FGF23, and elevated serum phosphate are significant mortality risk factors for patients with chronic kidney disease (CKD). However, the contribution of anemia to overall circulating FGF23 levels in CKD is not understood.

Carbon Monoxide and Exercise Prevents Diet-Induced Obesity and Metabolic Dysregulation Without Affecting Bone.

Objective: Carbon monoxide (CO) may counteract obesity and metabolic dysfunction in rodents consuming high-fat diets, but the skeletal effects are not understood. This study investigated whether low-dose inhaled CO (250 ppm) with or without moderate intensity aerobic exercise (3 h/wk) would limit diet-induced obesity and metabolic dysregulation and preserve bone health.

Methods: Obesity-resistant (OR) rats served as controls, and obesity-prone (OP) rats were randomized to sedentary, sedentary plus CO, exercise, or CO plus exercise.

Kidney Disease and Bone: Changing the Way We Look at Skeletal Health.

Purpose Of Review: Kidney disease imparts profound skeletal changes, and unlike many other skeletal diseases, cortical bone is predominantly impacted. Significant advances in medical imaging have led to our ability to now obtain high-resolution three-dimensional views of cortical bone. This paper overviews recent work focused on cortical bone imaging, specifically cortical porosity, in kidney disease.

Elevations in Cortical Porosity Occur Prior to Significant Rise in Serum Parathyroid Hormone in Young Female Mice with Adenine-Induced CKD.

Chronic kidney disease (CKD) leads to significant bone loss primarily through the development of cortical porosity. In both patients and animal models of CKD, sustained elevations in serum parathyroid hormone (PTH) are associated with cortical porosity. In this study, we aimed to track the progression of cortical porosity and increased PTH utilizing the adenine-induced CKD model.

Voluntary Wheel Running Has Beneficial Effects in a Rat Model of CKD-Mineral Bone Disorder (CKD-MBD).

Background: Reduced bone and muscle health in individuals with CKD contributes to their higher rates of morbidity and mortality.

Methods: We tested the hypothesis that voluntary wheel running would improve musculoskeletal health in a CKD rat model. Rats with spontaneous progressive cystic kidney disease (Cy/+ ) and normal littermates (NL) were given access to a voluntary running wheel or standard cage conditions for 10 weeks starting at 25 weeks of age when the rats with kidney disease had reached stage 2-3 of CKD.

Skeletal levels of bisphosphonate in the setting of chronic kidney disease are independent of remodeling rate and lower with fractionated dosing.

Background: Chronic kidney disease (CKD) results in a dramatic increase in skeletal fracture risk. Bisphosphates (BP) are an effective treatment for reducing fracture risk but they are not recommended in advanced CKD. We have recently shown higher acute skeletal accumulation of fluorescently-tagged zoledronate (ZOL) in the setting of CKD but how this accumulation is retained/lost over time is unclear.

Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats.

Male Cy/+ rats have shown a relatively consistent pattern of progressive kidney disease development that displays multiple key features of late stage chronic kidney disease-mineral bone disorder (CKD-MBD), specifically the development of cortical bone porosity. However, progression of disease in female Cy/+ rats, assessed in limited studies, is more heterogeneous and to date has failed to show development of the CKD-MBD phenotype, thus limiting their use as a practical model of progressive CKD-MBD. Animal and human studies suggest that estrogen may be protective against kidney disease in addition to its established protective effect on bone.

Increased FGF23 protects against detrimental cardio-renal consequences during elevated blood phosphate in CKD.

The phosphaturic hormone FGF23 is elevated in chronic kidney disease (CKD). The risk of premature death is substantially higher in the CKD patient population, with cardiovascular disease (CVD) as the leading mortality cause at all stages of CKD. Elevated FGF23 in CKD has been associated with increased odds for all-cause mortality; however, whether FGF23 is associated with positive adaptation in CKD is unknown.