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Molecular-Based Treatment Strategies for Osteoporosis: A Literature Review.

Osteoporosis is an unavoidable public health problem in an aging or aged society. Anti-resorptive agents (calcitonin, estrogen, and selective estrogen-receptor modulators, bisphosphonates, anti-receptor activator of nuclear factor κB ligand antibody along with calcium and vitamin D supplementations) and anabolic agents (parathyroid hormone and related peptide analogs, sclerostin inhibitors) have major roles in current treatment regimens and are used alone or in combination based on the pathological condition. Recent advancements in the molecular understanding of bone metabolism and in bioengin

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… Therefore, active forms of vitamin D 3 , including calcitriol, alphacalcidol (1α-hydroxyvitamin D 3 , a prodrug of calcitriol), and eldecalcitol (2β-3-hydroxypropyloxy-calcitriol, an analog of calcitriol that was developed in Japan) are mainly used in clinical trials. … The mean change in total body BMD of the calcitriol group was significantly higher than that of placebo (−1.5% vs. −2.8%). …

Reviewing the Significance of Vitamin D Substitution in Monoclonal Gammopathies.

Vitamin D is a steroid hormone that is essential for bone mineral metabolism and it has several other effects in the body, including anti-cancer actions. Vitamin D causes a reduction in cell growth by interrupting the cell cycle. Moreover, the active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, exerts various effects via its interaction with the vitamin D receptor on the innate and adaptive immune system, which could be relevant in the onset of tumors. Multiple myeloma is a treatable but incurable malignancy characterized by the growth of clonal plasma cells in protective niches in the bo

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… In a median of 29 months follow-up, relapse-free survival was significantly better in the calcitriol group (77.0%, SE = 7.0% vs. 59.0%, SE = 8.0%; p = 0.03). … . 57.5%; p = 0.001) were significantly higher with calcitriol [ 125 ]. …

Fanconi syndrome induced by adefovir dipivoxil: a case report and clinical review.

More than 150 cases of Fanconi syndrome (FS) or hypophosphatemia osteomalacia induced by low-dose adefovir dipivoxil (ADV) have been reported since 2002, when ADV was introduced for the long-term treatment of hepatitis B virus (HBV) infection. Because the life expectancy of HBV-infected individuals has increased, the adverse effects of long-term treatment with antiviral therapies are increasingly observed, and nephrotoxicity is one of the most severe adverse effects of ADV. Therefore, the number of cases may be far higher than reported. Moreover, ADV-induced FS is often misdiagnosed or diagnos

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… Phosphate, calcium, and calcitriol were also added to the treatment regimen. Meanwhile, BP and blood glucose levels remained stable, indicating protection of the liver and kidneys. … Conversely, when patients are resistant to LAM, it is recommended to cease ADV, switch to TAF, and provide supplementation with phosphate, calcium, and calcitriol. Acknowledgements We thank the patients for their involvement in this study. …

Stage-specific biomarkers in triple-negative breast cancer: Preliminary findings from bioinformatics approaches.

BackgroundIntegrated bioinformatics approaches were used to identify stage-specific candidate genes and potential drug targets in triple-negative breast cancer (TNBC).MethodsMicroarray (164 early-stage, 33 advanced-stage, and 53 normal samples) and RNA-seq (113 normal, 163 early-stage, and 30 advanced-stage TNBC samples) datasets were analyzed. Differentially expressed genes (DEGs) were identified, followed by co-expression analysis using Weighted Gene Co-expression Network Analysis (WGCNA) and protein-protein interaction analysis using the STRING database. miRNA co-regulation was evaluated us

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… Cannabidiol Leflunomide Sunitinib Valproic Acid | Anti-cancer Anti-inflammatory Anti-cancer Anti-hyperparathyroidism Anti-seizures Anti-rheumatoid arthritis Anti-cancer Anti-seizures MOCOS | JQ1 | Isotretinoin Lucanthone | Anti-seizures Radiation sensitizer NCAPD2 | Doxorubicin Palbociclib | Calcitriol … Stage | Gene | UniProt | Repurposed drug | Protein domain: docking score (Affinity (kcal/mol) Early | DNAJC6 | P60510 | Sunitinib | Clathrin Domain: −6.8 | SKP2 | Q13309 | Azathioprine | F-box Domain: −6.0 Leucine-Rich Repeat Domain: −7.6 | | | Calcitriol | F-box Domain: −6.6 Leucine-Rich Repeat …

The vitamin D receptor (VDR) gene rs11568820 variant is associated with type 2 diabetes and impaired insulin secretion in Italian adult subjects, and associates with increased cardio-metabolic risk in children.

BACKGROUND AND AIMS: 1α,25-dihydroxyvitamin-D3, the biologically active vitamin D, plays a central role in several metabolic pathways through the binding to the vitamin D receptor (VDR). VDR has been shown to be involved in cardiovascular diseases, cancer, autoimmunity and type 2 diabetes mellitus (T2DM). Several polymorphisms in the VDR gene have been described. Among these, the rs11568820 G-to-A nucleotide substitution was found to be functional, modulating the transcription of the VDR gene. Objective of this study was to perform an association study between rs11568820 polymorphism and T2DM

Vitamin D receptor gene (VDR) transcripts in bone, cartilage, muscles and blood and microarray analysis of vitamin D responsive genes expression in paravertebral muscles of juvenile and adolescent idiopathic scoliosis patients.

BACKGROUND: VDR may be considered as a candidate gene potentially related to idiopathic scoliosis susceptibility and natural history. Transcriptional profile of VDR mRNA isoforms might be changed in the structural tissues of the scoliotic spine and potentially influence the expression of VDR responsive genes. The purpose of the study was to determine differences in mRNA abundance of VDR isoforms in bone, cartilage and paravertebral muscles between tissues from curve concavity and convexity, between JIS and AIS and to identify VDR responsive genes differentiating juvenile and adolescent idiopat

Up-regulation of the alpha-secretase ADAM10 by retinoic acid receptors and acitretin.

Late-onset Alzheimer's disease is often connected with nutritional misbalance, such as enhanced cholesterol intake, deficiency in polyunsaturated fatty acids, or hypovitaminosis. The alpha-secretase ADAM10 has been found to be regulated by retinoic acid, the bioreactive metabolite of vitamin A. Here we show that retinoids induce gene expression of ADAM10 and alpha-secretase activity by nonpermissive retinoid acid receptor/retinoid X receptor (RAR/RXR) heterodimers, whereby alpha- and beta-isotypes of RAR play a major role. However, ligands of other RXR binding partners, such as the vitamin D r

[Prophylaxis and treatment of adynamic bone].

The pathogenesis of adynamic bone disease (ABD) attributes to calcium overload, active vitamin D (VD) metabolism, increase in inactive PTH (parathyroid hormone) fragments, or derangement of bone metabolism regulation factors. In particular, increased Ca overload plays a critical role in the development of ABD. Thus, alleviated Ca load by sevelamer hydrochloride and appropriate VD administration could be effective on not only prevention, and also treatment of ABD.

Human trabecular bone cells are able to express both osteoblastic and adipocytic phenotype: implications for osteopenic disorders.

The decrease in bone volume associated with osteoporosis and age-related osteopenia is accompanied by increased marrow adipose tissue formation. Reversal of this process may provide a novel therapeutic approach for osteopenic disorders. We have shown that cells cultured from human trabecular bone are not only osteogenic, but are able also to undergo adipocyte differentiation under defined culture conditions. Osteoblast differentiation was induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and adipocyte differentiation by dexamethasone (dex) plus 3-isobutyl-1-methylxanthine (IBMX) treatment. Adi

Bracing after percutaneous vertebroplasty for thoracolumbar osteoporotic vertebral compression fractures was not effective.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of bracing after percutaneous vertebroplasty (PVP) for thoracolumbar osteoporotic vertebral compression fractures (OVCF). METHODS: This is a retrospective study where we recruited 138 patients with single-level thoracolumbar OVCF who underwent PVP from January 2018 to March 2018 without bracing after PVP (Group A). The visual analog score (VAS) and vertebral body compression ratio (VCR) were recorded at preoperation, on the second day, at 2 weeks, 1 month, and 6 months after operation. Oswestry Disability Index (ODI) was

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… Anti-osteoporotic drugs (including calcium carbonate, calcitriol, and alendronate) were prescribed for at least 6 months after the operation. All patients were instructed to perform back and abdominal muscle exercises for 4 weeks after discharge. … If patients with refracture resisted conservative management or were not satisfied with pain relief after conservative treatment for 2–3 weeks, they were considered to have PVP/PKP, and at the same time, anti-osteoporotic drugs (including calcium carbonate, calcitriol, and alendronate) were prescribed …

The role of vitamin D and vitamin D deficiency in orthopaedics and traumatology-a narrative overview of the literature.

Vitamin D is considered to play an important role in musculoskeletal health. It's classical function is the regulation of calcium and phosphate homeostasis, thus ensuring a balanced bone metabolism that is characterised by an equal amount of bone resorption and bone formation. In the past decades, a plethora of pre-clinical and clinical studies reporting on potential health-beneficial properties of vitamin D have emerged. Moreover, there is an abundance of reports highlighting vitamin D deficiency and insufficiency in patients with almost innumerable diseases. Further, it is estimated that mor

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… These effects were corrected by vitamin D or calcitriol administration ( 72 , 73 ). Nonetheless, robust data on this topic are currently still missing. In summary, the impact of low serum vitamin D levels on fracture healing are not clarified satisfactory. … Enhanced Antiproliferative Effect of Combined Treatment with Calcitriol and All-Trans Retinoic Acid in Relation to Vitamin D Receptor and Retinoic Acid Receptor α Expression in Osteosarcoma Cell Lines. Int J Mol Sci 2020;21:6591. 10.3390/ijms21186591 116. …

Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

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… - CKD; Cholecalciferol - non-CKD NA NCT00585442 TERMINATED (No Reason Posted) Hypertension; Vitamin D Deficiency Calcitriol; Placebo EARLY_PHASE1 NCT00084864 TERMINATED (Study was activated prior to Roswell Park Cancer Institute (RPCI) putting a system in place to centralize data entry and data management … PI left institute and left incomplete data) Prostate Cancer DIETARY_SUPPLEMENT: calcitriol; dexamethasone; clinical observation PHASE2 NCT04197089 COMPLETED (No Results Posted) Urothelial Carcinoma Vitamin D PHASE4 NCT03415854 COMPLETED (No Results Posted) Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma …

Hypercalcemia From Trenbolone Use: A Case Report.

In this case, a patient presented to the emergency department (ED) with fatigue after CareNow noted abnormal laboratory results. The patient reported using trenbolone, an anabolic-androgenic steroid (AAS) often used for athletic performance enhancement or cosmetic purposes. In the ED, the patient was noted to have significant hypercalcemia (15 mg/dL) and acute kidney injury (AKI) (creatinine 6.02 mg/dL). The workup ruled out malignancy, hyperparathyroidism, and vitamin D toxicity. The patient was admitted and received intravenous fluids and pamidronate, which improved the patient's hypercalcem

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… In the proximal nephron, PTH increases 1α-hydroxylase transcription, which stimulates conversion of 25-hydroxyvitamin D (calcidiol) to 1,25-dihydroxyvitamin D (calcitriol) [ 12 , 13 ]. … This results in calcitriol-mediated upregulation of calcium channels and exchangers in the small intestine, increasing absorption [ 13 ]. The leading cause of hypercalcemia is malignancy [ 2 , 3 ]. …

Pamidronate-induced irreversible symptomatic hypocalcemia in a dog with hypercalcemia after glucocorticoid withdrawal: a case report.

BACKGROUND: Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog. CASE PRESENTATION: An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia.

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… Background Serum calcium concentration is controlled by regulatory hormones including parathyroid hormone (PTH), calcitriol (1,25-dihydroxyvitamin D), 24,25-dihydroxyvitamin D, and calcitonin [ 1 , 2 ]. … The cause of hypercalcemia can be diagnosed using blood tests including those for serum 25-hydroxyvitamin D, 24,25(OH)2-vitamin D, calcitriol, and PTH-related protein concentrations [ 3 ]. …

Brown Tumor From Secondary Hyperparathyroidism Mimicking Metastatic Renal Cell Carcinoma in a Patient With End-Stage Renal Disease.

Brown tumors (also known as osteitis fibrosa cystica) are rare complications of end-stage renal disease (ESRD) and secondary hyperparathyroidism (HPT), characterized by focal bone lesions that resemble neoplasms. They are often misdiagnosed as metastatic bone disease, especially in patients with a history of malignancy. We present a case of a 60-year-old man with a history of renal cell carcinoma (RCC), and ESRD on hemodialysis (HD), who developed diffuse bone lesions on imaging with osteolytic/osteoblastic appearance concerning metastases, but on further workup was found to have brown tumors.

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… A final diagnosis of severe secondary HPT with possible conversion to tertiary HPT was made, and he was started on cinacalcet 90 mg daily and calcitriol 3 mcg three times a week. Additionally, the dose of sevelamer was increased to 1600 mg three times daily for CKD-MBD. … This strategy includes vitamin D analog replacement, especially calcitriol, and calcimimetics, such as cinacalcet, to stifle the effects of PTH on peripheral bone resorption. …

Dynamics of 1α,25-dihydroxyvitamin D3-dependent chromatin accessibility of early vitamin D receptor target genes.

The signaling cascade of the transcription factor vitamin D receptor (VDR) is triggered by its specific ligand 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). In this study we demonstrate that in THP-1 human monocytic leukemia cells 87.4% of the 1034 most prominent genome-wide VDR binding sites co-localize with loci of open chromatin. At 165 of them 1α,25(OH)2D3 strongly increases chromatin accessibility and has at further 217 sites weaker effects. Interestingly, VDR binding sites in 1α,25(OH)2D3-responsive chromatin regions are far more often composed of direct repeats with 3 intervening nucleotide

Oncoprotein Cot1 represses kinase suppressors of Ras1/2 and 1,25-dihydroxyvitamin D3-induced differentiation of human acute myeloid leukemia cells.

Metabolites and derivatives of vitamin D are well-known inducers of monocytic differentiation, but the mechanistic basis for their action is not fully elucidated. Here we show that the product of protooncogene Cot1 represses the monocytic phenotype in human acute myeloid leukemia (AML) cells induced to differentiate by 1,25-dihydroxyvitamin D(3) (1,25D), even though the expression of cellular Cot1 increases early in the process of 1,25D-induced differentiation. Interestingly, the expression of the two members of the Kinase Suppressor of Ras (KSR) family of molecular scaffolds, known to be posi

Downregulation of MLL-CBP fusion gene expression is associated with differentiation of SN-1 cells with t(11;16)(q23;p13).

The translocation t(11;16)(q23;p13) has only been documented in patients with acute leukemia or myelodysplasia secondary to therapy with drugs targeting DNA topoisomerase II. We have established a myeloid cell line (SN-1) with the MLL-CBP fusion gene from an acute leukemia patient with t(11;16)(q23;p13). Although SN-1 cells were not induced to differentiate by all-trans retinoic acid (ATRA) and 1alpha,25-dihydroxyvitamin D(3) (VD3), retinoid X receptor (RXR) agonists, such as 9-cis retinoic acid and Ro48-2250, effectively induced differentiation of the cells. Downregulation of the expression o

A novel inborn error in the ligand-binding domain of the vitamin D receptor causes hereditary vitamin D-resistant rickets.

Mutations in the vitamin D receptor (VDR) cause hereditary vitamin D-resistant rickets (HVDRR), an autosomal recessive disease resulting in target organ resistance to 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. In this report, we describe the clinical case and molecular basis of HVDRR in an Asian boy exhibiting the typical clinical features of the disease including alopecia. Using cultured dermal fibroblasts from the patient, 1,25(OH)(2)D(3) resistance was demonstrated by a shift in the dose response required for 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase) mRNA induction. Western blo

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidiscip

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… Conventional therapy in XLH consists of combination therapy with phosphate and active vitamin D analogs (preferably alfacalcidol, which has a wider therapeutic range and longer half-life than calcitriol and is available in liquid form for children). … In children, initial doses of alfacalcidol of 30-50 ng/kg (or calcitriol 20-30 ng/kg bodyweight) are suggested, which can usually be given once daily (evening dosage has been suggested) ( 25 ). Other active vitamin D analogs are not available in Belgium. …