• Antiepileptics
• Fracture
• Glucocorticoids
• Osteoporosis
• Proton pump inhibitors

• Humans
• Liver Transplantation/standards
• Germany
• Gastroenterology/standards
• Practice Guidelines as Topic
• Societies, Medical

• Bone density testing
• Bone disease
• Fracture
• Liver transplantation
• Serum Markers

• Humans
• Fractures, Spontaneous/diagnostic imaging
• Fractures, Spontaneous/etiology
• Bone Density
• Liver Transplantation/adverse effects
• Retrospective Studies
• Fractures, Bone/etiology
• Bone Diseases/complications
• Biomarkers

• Fracture
• Glucocorticoid
• Immunosuppressive agent
• Kidney transplantation

• Humans
• Female
• Aged
• Tacrolimus/adverse effects
• Mycophenolic Acid/adverse effects
• Kidney Transplantation/adverse effects
• Azathioprine/adverse effects
• Retrospective Studies
• MTOR Inhibitors
• Calcium
• Cohort Studies
• Immunosuppressive Agents/adverse effects
• Risk Factors
• Diabetes Mellitus
• Graft Rejection/prevention & control

• Bone metabolism
• Heart transplantation
• bone mineral density
• immunosuppressive therapy

Vitamin D belongs to the group of liposoluble steroids mainly involved in bone metabolism by modulating calcium and phosphorus absorption or reabsorption at various levels, as well as parathyroid hormone production. Recent evidence has shown the extra-bone effects of vitamin D, including glucose homeostasis, cardiovascular protection, and anti-inflammatory and antiproliferative effects. This narrative review provides an overall view of vitamin D’s role in different settings, with a special focus on chronic kidney disease and kidney transplant.

• Osteoarthritis
• Osteosarcopenia
• Rapalogues
• Rapamycin
• Rheumatoid arthritis
• mTOR

Cardiovascular disease and mineral bone disorders are major contributors to morbidity and mortality among patients with chronic kidney disease and often persist after renal transplantation. Ongoing hormonal imbalances after kidney transplant (KT) are associated with loss of graft function and poor outcomes. Fibroblast growth factor 23 (FGF-23) and its co-receptor, α-Klotho, are key factors in the underlying mechanisms that integrate accelerated atherosclerosis, vascular calcification, mineral disorders, and osteodystrophy. On the other hand, kidney donation is also associated with endocrine and metabolic adaptations that include transient increases in circulating FGF-23 and decreases in α-Klotho levels. However, the long-term impact of these alterations and their clinical relevance have not yet been determined. This manuscript aims to review and summarize current data on the role of FGF-23 and α-Klotho in the endocrine response to KT and living kidney donation, and importantly, underscore specific areas of research that may enhance diagnostics and therapeutics in the growing population of KT recipients and kidney donors.

• University of Kentucky

• Allogenic hematopoietic cell transplantation
• Bone loss
• Osteoporosis

• Graft vs Host Disease/etiology
• Graft vs Host Disease/prevention & control
• Hematologic Diseases
• Hematopoietic Stem Cell Transplantation/adverse effects
• Humans
• Transplantation Conditioning/adverse effects
• Transplantation, Homologous/adverse effects

• bone mineral density
• calcineurin inhibitors
• mammalian target of rapamycin inhibitors
• renal transplantation

Calciphylaxis is not uniquely observed in uraemic patients, as some cases have also been reported in patients with normal renal function or moderate chronic kidney disease (CKD), in association with severe vasculopathy or systemic inflammation. A particular subset worthy of studying is represented by those patients who develop calciphylaxis after kidney transplantation (KT).

Analysis of the local series of calciphylaxis after KT (n = 14) along with all the other cases reported in the literature from 1969 to 2019 (n = 31), for a total population of 45 patients, is presented. Demographic data, CKD history, risk factors, immunosuppression, clinical presentation and management have been analysed both as a whole and according to the time period (before or after the year 2000).

Calciphylaxis developed during the first year after KT in 43.2% of patients and median (interquartile range) creatinine at diagnosis was 2.4 (1.25–4.64) mg/dL. The most frequent presentation included distal purpura or ulcers in one-third of cases and 39.1% of patients were receiving vitamin K antagonists. PTH values were above 500 pg/mL and below 100 pg/mL in 50.0% and 25.0% of cases, respectively. Whole population mortality was 55.6%. As expected, clinical presentation, immunosuppression and management varied depending on the time period. Patients diagnosed after 2000 were older, with longer dialysis vintage, and treatment was usually multimodal; on the contrary, in patients diagnosed before 2000, parathyroidectomy was the treatment of choice in 61.9% of cases.

Calciphylaxis can still occur after KT, in many cases during the first year and in patients with a good renal function. Risk factors and management varied according to the time period studied.

• Drug
• Osteoporosis
• Pharmacoepidemiology
• Pharmacology
• Pharmacovigilance

• Adverse Drug Reaction Reporting Systems
• Databases, Factual
• Humans
• Marketing
• Osteoporosis/chemically induced
• Osteoporosis/drug therapy
• Osteoporosis/epidemiology
• Pharmaceutical Preparations
• Pharmacovigilance
• World Health Organization

Kidney transplantation (KT) recipients are at increased risk of low bone density (LBD) and fractures. In this retrospective study, we investigated bone mineral density (BMD), vertebral fractures, calculated risk for major osteoporotic fractures (MOF), and hip fractures in the KT recipients.

Patients who completed at least one year after KT were included in the analysis. Demographic, clinical, and laboratory data were recorded. Measurements of BMD were performed by dual-energy X-ray absorptiometry. Vertebral fractures were assessed using semi-quantitative criteria with conventional radiography. The ten-year risk for MOF and hip fracture were calculated using the FRAX@ tool with BMD.

One hundred fifty-three KT recipients were included in the study. The population included 77 women. The mean age at evaluation was 46,5±11,9 years. Seventy-eight (50.9%) patients had normal femoral neck BMD while osteoporosis and osteopenia at the femoral neck were present in 12 (7.8%) and 63 (41.1%) of the patients, respectively. Age at evaluation was the risk factor for LBD (OR 1.057; 95% CI 1.024–1.091; p = 0.001). In female KT recipients, LBD was principally affected by menopausal status whereas in males, mammalian target of rapamycin (mTOR) inhibitor use and lower BMI levels were the risk factors. The prevalent vertebral fracture was found in 43.4% of patients. In multivariate analysis, only steroid use (OR 0.121; 95% CI 0.015–0.988; p = 0.049) was found to be associated with prevalent fracture. Among all KT recipients, 1.9% had a high MOF probability (≥20% risk of fracture), and 23.5% had high hip fracture probability (≥3% risk of hip fracture) according to FRAX.

Exploring the prevalence of LBD and vertebral fracture and the risk factors would help clinicians to modify long-term follow-up strategies. Furthermore, the high hip fracture risk probability in our cohort suggested that there is a need for longitudinal studies to confirm the validity of the FRAX tool in the transplant population.

• arteriosclerosis
• cardiovascular disease
• chronic kidney disease
• renal transplantation
• vascular calcification

The ideal immunosuppressive regimen should provide for excellent immunosuppression with no side effects. Yet, current immunosuppressive therapy regimens commonly used in clinical applications fail to meet this criterion. One of the complications caused by immunosuppressive drugs is mineralization disorders in hard tissues. In this study, we evaluated the effects of three immunosuppressive therapies used after transplantation on the levels of potassium, iron, chromium, zinc, aluminum, sodium and molybdenum in the bones and teeth of female rats and their offspring. The study was conducted on 32 female Wistar rats, subjected to immunosuppressive regimens (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; and cyclosporine A, everolimus and prednisone). The hard tissues of rats were analyzed using inductively coupled plasma optical emission spectrometry (ICP-OES, ICAP 7400 Duo, Thermo Scientific) equipped with a concentric nebulizer and a cyclonic spray chamber. All the immunosuppressive regimens included in the study affected the concentrations of the studied minerals in hard tissues of female rats and their offspring. The therapy based on cyclosporine A, everolimus and prednisone led to a decline in the levels of iron in bone, zinc in teeth, and molybdenum in the bone and teeth of mothers, while in the offspring, it caused a decline of bone potassium, with a decrease in iron and increase of molybdenum in teeth. Moreover, the regimen caused an increase in aluminum and chromium in the teeth and aluminum in the bones of the offspring, and consequently, it seems to be the therapy with the most negative impact on the mineral metabolism in hard tissues.

• bone
• elements content
• immunosuppressive therapy
• pregnancy
• tooth

• autophagy
• differentiation
• osteoclast

• Autophagy/genetics
• Autophagy-Related Proteins/genetics
• Bone Resorption/genetics
• Bone Resorption/pathology
• Cell Differentiation/genetics
• Cell Survival/genetics
• Humans
• Osteoclasts/metabolism
• Osteoclasts/pathology
• Osteoporosis/genetics
• Osteoporosis/pathology

Mesenchymal stem cells (MSCs) have been widely exploited as promising candidates in clinical settings for bone repair and regeneration in view of their self-renewal capacity and multipotentiality. However, little is known about the mechanisms underlying their fate determination, which would illustrate their effectiveness in regenerative medicine. Recent evidence has shed light on a fundamental biological role of autophagy in the maintenance of the regenerative capability of MSCs and bone homeostasis. Autophagy has been implicated in provoking an immediately available cytoprotective mechanism in MSCs against stress, while dysfunction of autophagy impairs the function of MSCs, leading to imbalances of bone remodeling and a wide range of aging and degenerative bone diseases. This review aims to summarize the up-to-date knowledge about the effects of autophagy on MSC fate determination and its role as a stress adaptation response. Meanwhile, we highlight autophagy as a dynamic process and a double-edged sword to account for some discrepancies in the current research. We also discuss the contribution of autophagy to the regulation of bone cells and bone remodeling and emphasize its potential involvement in bone disease.

• Mesenchymal stem cells
• Autophagy
• Cell self-renewal
• Cell differentiation
• Cytoprotection
• Bone remodeling

• Diabetes
• drug-induced complications
• immune system
• osteoporosis
• similar etiology
• similar pathways

• Diabetes Mellitus/epidemiology
• Diabetes Mellitus/therapy
• Humans
• Incidence
• Osteoporosis/epidemiology
• Osteoporosis/therapy

• Heart transplantation
• Immunosuppressive agents
• Liver transplantation
• Lung transplantation
• Osteoporosis
• Renal transplantation

• Bone Diseases/etiology
• Calcification, Physiologic
• Europe
• Health Planning Guidelines
• Humans
• Immunosuppressive Agents/therapeutic use
• Organ Transplantation/adverse effects
• Societies, Scientific

• bone regeneration
• cell biology
• cytokine(s)
• orthodontics
• osteoclast(s)
• periodontal regeneration

• autophagosome
• autophagy
• osteoblast
• osteoclast
• osteocytes

• autophagy
• bone remodeling
• immunomodulation
• osteoimmunology
• stem cell

• CKD‐MBD
• FRACTURES
• HEMODIALYSIS
• KIDNEY TRANSPLANTATION
• PERITONEAL DIALYSIS

Airway anastomotic complications are a leading cause of mortality after lung transplantation. Among the factors that cause airway complications, preoperative steroid use has been considered to be related with postoperative airway healing. We analyzed the influence of preoperative steroid use on postoperative airway complications.

The medical records of 66 double-lung transplant recipients from January 2014 to December 2015 were reviewed. Forty patients were prescribed steroids preoperatively. The daily steroid dose was standardized using the patient’s body mass index (BMI). Patients who received preoperative steroids were sub-divided into high-dose (HD) and low-dose (LD) groups (cut-off value, 1.6 mg/BMI/day).

Thirteen patients suffered from airway complications postoperatively (bronchopulmonary fistula, 9; bronchial stenosis, 4). There was a tendency for early development of airway complications in the steroid use group compared to the non-steroid use group, but it was not significant (percentage free from airway complications in year 1: non-steroid group, 90.9% vs. steroid group, 79.2%; p=0.43). The percentage of patients in the LD and HD groups who were free from airway complications in year 1 was not significantly different (84.0% vs. 77.8%, p=0.39).

The airway complication rate did not vary significantly according to steroid use. Additionally, in patients who received preoperative steroids, the dose did not affect the rate of development of airway complications.

• Airway
• Complication
• Lung transplantation
• Preoperative steroid

• R01 DK089113 NIDDK NIH HHS

• homeostasis
• mTOR signaling
• osteoporosis bone
• therapeutic target

• Bone Diseases
• Graft Rejection
• Humans
• Immunosuppressive Agents
• Kidney Transplantation
• Steroids

• Bone Diseases
• Graft Rejection
• Immunosuppressive Agents
• Kidney Transplantation
• Steroids

• Adrenal Cortex Hormones/adverse effects
• Adult
• Aged
• Bone Density/drug effects
• Bone Diseases/epidemiology
• Bone Diseases/etiology
• Cohort Studies
• Cross-Sectional Studies
• Female
• Humans
• Immunocompromised Host
• Immunosuppressive Agents/adverse effects
• Kidney Transplantation
• Male
• Middle Aged
• Prevalence
• Retrospective Studies
• Risk Factors
• Texas

• liver transplantation
• osteoporosis
• pediatric

• Chronic kidney disease
• Dialysis
• Kidney transplantation
• Vitamin D

• Bone Diseases/drug therapy
• Dietary Supplements
• Humans
• Kidney Transplantation
• Minerals/metabolism
• Parathyroid Hormone/blood
• Practice Guidelines as Topic
• Renal Dialysis
• Renal Insufficiency, Chronic/drug therapy
• Trace Elements/metabolism
• Vascular Calcification/etiology
• Vitamin D/adverse effects
• Vitamin D/therapeutic use

• Bisphosphonates
• Calcineurin inhibitors
• Glucocorticoids
• Immunosuppression
• Osteoporosis
• Transplant

• Bone Density Conservation Agents/therapeutic use
• Calcitonin/therapeutic use
• Calcium/therapeutic use
• Denosumab/therapeutic use
• Diphosphonates/therapeutic use
• Humans
• Organ Transplantation/adverse effects
• Osteoporosis/etiology
• Osteoporosis/therapy
• Risk Factors
• Teriparatide/therapeutic use
• Vitamin D/therapeutic use

• Autophagy
• Male rats
• Osteoporosis
• Rapamycin

• Animals
• Apoptosis/drug effects
• Autophagy/drug effects
• Bone Density Conservation Agents/pharmacology
• Bone Density Conservation Agents/therapeutic use
• Drug Evaluation, Preclinical/methods
• Humans
• Lumbar Vertebrae/diagnostic imaging
• Lumbar Vertebrae/pathology
• Male
• Osteocytes/drug effects
• Osteocytes/pathology
• Osteoporosis/diagnostic imaging
• Osteoporosis/drug therapy
• Osteoporosis/pathology
• Osteoporosis/physiopathology
• Rats, Sprague-Dawley
• Sirolimus/pharmacology
• Sirolimus/therapeutic use
• Tibia/diagnostic imaging
• Tibia/pathology
• X-Ray Microtomography

The development of end stage renal failure can be seen as a catastrophic health event and patients with this condition are considered at the highest risk of cardiovascular disease among any other patient groups and risk categories. Although kidney transplantation was hailed as an optimal solution to such devastating disease, many issues related to immune-suppressive drugs soon emerged and it became evident that cardiovascular disease would remain a vexing problem. Progression of chronic kidney disease is accompanied by profound alterations of mineral and bone metabolism that are believed to have an impact on the cardiovascular health of patients with advanced degrees of renal failure. Cardiovascular risk factors remain highly prevalent after kidney transplantation, some immune-suppression drugs worsen the risk profile of graft recipients and the alterations of mineral and bone metabolism seen in end stage renal failure are not completely resolved. Whether this complex situation promotes progression of vascular calcification, a hall-mark of advanced chronic kidney disease, and whether vascular calcifications contribute to the poor cardiovascular outcome of post-transplant patients is reviewed in this article.

• morbidity
• Chronic kidney disease-mineral bone disorder
• cardiovascular disease
• chronic kidney disease
• Mortality
• Bone fractures

Improved survival following organ transplantation has brought to the forefront some long-term complications, among which osteoporosis and associated fractures are the major ones that adversely affect the quality of life in recipients. The pathogenesis of osteoporosis in transplant recipients is complex and multifactorial which may be related to increased bone resorption, decreased bone formation, or both. Studies have shown that the preexisting underlying metabolic bone disorders and the use of immunosuppressive agents are the major risk factors for osteoporosis and fractures after organ transplantation. And rapid bone loss usually occurs in the first 6–12 months with a significant increase in fracture risk. This paper will provide an updated review on the possible pathogenesis of posttransplant osteoporosis and fractures, the natural history, and the current prevention and treatment strategies concerning different types of organ transplantation.

Osteoporosis can arise in systemic lupus erythematosus (SLE) patients secondary to medication and/or chronic inflammation. To analyze if patients with SLE have phenotypically-impaired osteoclastogenesis, we differentiated ex vivo monocytes from 72 SLE patients and 15 healthy individuals into osteoclasts followed by TRAP staining and counting. We identified a subgroup of SLE patients (45%) with a significantly impaired osteoclast differentiation, relative to the other SLE patients or healthy individuals (OR 11.2; 95% CI 1.4–89.9). A review of medication indicated that patients with osteoclast counts equal to healthy donors were significantly more likely to be treated with mycophenolate mofetil (MMF) compared to patients with impaired osteoclastogenesis. We analyzed expression of RANKL and the MMF target genes IMPDH1 and IMPDH2 in osteoclasts by qPCR, but detected no difference. Since MMF might influence interferon-α (IFNα) and -γ (IFNγ) we measured serum IFNα and IFNγ levels. Patients with very low osteoclast counts also had comparably higher IFNα serum levels than patients with normal osteoclast counts. We conclude that in vitro osteoclastogenesis is impaired in a subgroup of SLE patients. This correlates inversely with MMF treatment and high IFNα serum levels. Further observational study will be required to determine whether this translates into a clinically meaningful effect.

• RANKL
• interferon alpha
• mycophenolate mofetil
• osteoclastogenesis
• systemic lupus erythematosus

• Adrenal Cortex Hormones/therapeutic use
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Blood Cell Count
• Case-Control Studies
• Cell Count
• Cell Differentiation
• Female
• Gene Expression Regulation/drug effects
• Humans
• IMP Dehydrogenase/genetics
• IMP Dehydrogenase/metabolism
• Interferon-alpha/blood
• Interferon-alpha/metabolism
• Lupus Erythematosus, Systemic/blood
• Lupus Erythematosus, Systemic/drug therapy
• Lupus Erythematosus, Systemic/genetics
• Lupus Erythematosus, Systemic/pathology
• Male
• Mycophenolic Acid/analogs & derivatives
• Mycophenolic Acid/therapeutic use
• Osteoclasts/cytology
• Osteoclasts/pathology
• Receptor Activator of Nuclear Factor-kappa B/genetics
• Receptor Activator of Nuclear Factor-kappa B/metabolism
• Treatment Outcome

• 18544 Versus Arthritis

• Bone Density/physiology
• Bone Diseases/metabolism
• Humans
• Osteoblasts/metabolism
• Osteocytes/metabolism
• Osteoporosis/metabolism
• Renal Insufficiency, Chronic/metabolism

• Bone
• CKD-MBD
• FGF23
• Mineral metabolism
• Os
• PTH
• Renal transplantation
• Transplantation rénale