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The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (25 November 2024) | Viewed by 36457

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Dr. Daniela Merlotti

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Researcher, Department of Medicine Surgery and Neurosciences, University of Siena, Siena, Italy
Interests: metabolic bone disorders; osteoporosis; Paget’s disease of bone; rare bone diseases
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Salvatore Minisola

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Department of Clinical, Internal, Anaesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Interests: osteoporosis; bone research; bone biology; bone
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Bone formation and bone remodeling are complicated processes, regulated by systemic hormones and paracrine factors, which regulate calcium and phosphate fluxes and cellular differentiation. The various actions performed by vitamin D reinforces its importance in the processes of growth, maturation and bone aging. An understanding of these important regulators of bone metabolism is vital to understanding clinical disorders, as they are related to alterations in vitamin D metabolism and metabolic bone disease. Specific disorders of vitamin D metabolism can be related to the clinical disease states of aging, altered lifestyles, and gastrointestinal, renal and hepatic disease. Epidemiologic evidence and prospective studies have linked vitamin D deficiency with an increased risk of many chronic diseases, including autoimmune diseases, cardiovascular diseases, deadly cancers, type II diabetes and infectious diseases.

The aim of this Special Issue is to update, with new findings, the role of vitamin D in bone metabolism, with a focus not only on common bone disorders, such as osteoporosis and Paget’s disease of bone, but also in the various forms of renal osteodystrophy of chronic kidney disease—mineral and bone disorder (CKD-MBD)—and in rare bone disease.

We are soliciting original papers, review articles, as well as case reports.

Dr. Daniela Merlotti
Prof. Dr. Salvatore Minisola
Guest Editors

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Keywords

vitamin D
bone metabolism
osteoporosis
bone fragility
chronic diseases

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Published Papers (11 papers)

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Editorial

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4 pages, 194 KiB

Open AccessEditorial

The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases

by Salvatore Minisola and Daniela Merlotti

Nutrients 2023, 15(22), 4775; https://doi.org/10.3390/nu15224775 - 14 Nov 2023

Cited by 1 | Viewed by 1767

Abstract

The history of vitamin D begins more than 100 years ago, with the initial documentation of rickets in industrialized cities of England [...] Full article

(This article belongs to the Special Issue The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases)

Research

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8 pages, 574 KiB

Open AccessCommunication

Impact of Reduced Vitamin D Levels on Pain, Function, and Severity in Knee or Hip Osteoarthritis

by Cláudia Nascimento Montemor, Marcos Tadeu Parron Fernandes, Audrey Souza Marquez, Paulo Roberto Bignardi, Regina Célia Poli, Gustavo Aliano Gâmbaro, Rubens Alexandre da Silva, Suzy Ngomo and Karen Barros Parron Fernandes

Nutrients 2025, 17(3), 447; https://doi.org/10.3390/nu17030447 - 26 Jan 2025

Viewed by 1282

Abstract

Background: Vitamin D is beneficial for musculoskeletal health. Although low levels of vitamin D are linked to increased pain in knee osteoarthritis (OA), their association with functionality remains understudied. Objective: This study aimed to investigate the association between vitamin D deficiency and functional status in elderly individuals with OA and explore the potential correlation between vitamin D deficiency and plasma levels of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Methods: The study included older adults (≥60 years) from an ageing study, encompassing 105 OA patients and 152 controls. OA diagnosis was confirmed radiographically, and the WOMAC questionnaire assessed functional impairment in these patients. Blood samples were collected to measure 25(OH) vitamin D levels by chemiluminescence and TNF-α and IL-6 levels by ELISA. Results: Patients with vitamin D insufficiency/deficiency exhibited more severe cases of OA compared to those with normal vitamin D levels (p = 0.04). Vitamin D levels were inversely correlated with functional impairment in OA, according to the WOMAC Index (global: rS = −0.25, p = 0.01; pain: rS = −0.21, p = 0.03). Moreover, OA patients with vitamin D deficiency showed significantly higher levels of TNF-α and IL-6 (p < 0.05, Mann−Whitney test). Conclusions: Reduced levels of vitamin D are associated with more severe cases of hip and knee osteoarthritis, increased pain, greater functional impairment, and elevated serum levels of TNF-α and IL-6. Further research is required to elucidate the mechanisms underlying the influence of vitamin D on osteoarthritis and to evaluate the potential benefits of vitamin D supplementation for mitigating disease symptoms and progression. Full article

(This article belongs to the Special Issue The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases)

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12 pages, 1679 KiB

Open AccessArticle

Is There a Need for Vitamin D Supplements During Summer Time in Northern Germany? A Study of Hospitalised Fracture Patients

by Steffi S. I. Falk, Guido Schröder and Thomas Mittlmeier

Nutrients 2024, 16(23), 4174; https://doi.org/10.3390/nu16234174 - 30 Nov 2024

Cited by 1 | Viewed by 4144

Abstract

Background/Objectives: Vitamin D is a key factor in bone metabolism, especially in patients who have suffered fractures, a group in need of a healthy bone metabolism. In Germany, a 70-year-old person requires 20 min of sun exposure daily for sufficient endogenous production in April. While this appears to be a sufficient period on paper, it raises the question of whether sufficient synthesis is achieved, given the time and the implementation of skin cancer prevention. Furthermore, it is necessary to determine whether self-medication is a safe option. Methods: This was an analysis of vitamin D levels in patients with fractures over a one-year period. To avoid bias due to vitamin D intake, patients were divided into groups (self-medication, without, prescribed). The differences due to age, gender, fracture type and fluctuation over the year were analysed. Results: 613 patients with a mean age of 73 years (45–97) were enrolled. The mean vitamin D level across all groups was 51 nmol/L, with a mean of 40 nmol/L for patients without supplementation (n = 449). Monthly comparisons revealed significant differences between January/February and August/September. Similarly, a comparison by gender showed a significant difference (p = 0.028). However, there were no significant differences between osteoporosis-associated and non-osteoporosis-associated fractures. Conclusions: The majority of patients did not achieve sufficient vitamin D levels through endogenous synthesis and substitution did not lead to toxic levels. This suggests that substitution is reasonable and safe even during the summer months. Full article

(This article belongs to the Special Issue The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases)

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10 pages, 5752 KiB

Open AccessArticle

Protective Effects of Vitamin D on Proteoglycans of Human Articular Chondrocytes through TGF-β1 Signaling

by Jian Guan, Zhuoxin Li, Guodong Niu, Siwei Li, Weishi Li, Chunli Song and Huijie Leng

Nutrients 2024, 16(17), 2991; https://doi.org/10.3390/nu16172991 - 4 Sep 2024

Cited by 3 | Viewed by 1740

Abstract

The extracellular matrix of cartilage primarily constitutes of collagen and aggrecan. Cartilage degradation starts with aggrecan loss in osteoarthritis (OA). Vitamin D (VD) plays an essential role in several inflammation-related diseases and can protect the collagen in cartilage during OA. The present study focused on the role of VD in aggrecan turnover of human articular chondrocytes treated with tumor necrosis factor α (TNF-α) and the possible mechanism. Treatment with different doses of VD and different periods of intervention with TNF-α and TGF-β1 receptor (TGFβR1) inhibitor SB525334 were investigated. The viability of human chondrocytes and extracellular secretion of TGF-β1 were measured. The expression of intracellular TGFβR1 and VD receptor was examined. Transcriptional and translational levels of aggrecan and the related metabolic factors were analyzed. The results showed that TNF-α markedly reduced the viability, TGFβR1 expressions and aggrecan levels of human chondrocytes, and increased disintegrin and metalloproteinase with thrombospondin motifs. The alterations were partially inhibited by VD treatment. Furthermore, the effects of VD were blocked by the TGFβR1 inhibitor SB525334 in TNF-α-treated cells. VD may prevent proteoglycan loss due to TNF-α via TGF-β1 signaling in human chondrocytes. Full article

(This article belongs to the Special Issue The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases)

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17 pages, 1518 KiB

Open AccessArticle

No Impairment in Bone Turnover or Executive Functions in Well-Treated Preschoolers with Phenylketonuria—A Pilot Study

by Beatrice Hanusch, Michael Falkenstein, Stefan Volkenstein, Stefan Dazert, Thomas Lücke and Kathrin Sinningen

Nutrients 2024, 16(13), 2072; https://doi.org/10.3390/nu16132072 - 28 Jun 2024

Cited by 2 | Viewed by 1324

Abstract

Patients with phenylketonuria (PKU) present signs of impaired executive functioning and bone health in adolescence and adulthood, depending in part on the success of therapy in childhood. Therefore, nine children with well-treated PKU (4–7 years old, 22.2% ♀, seven with a full set of data, two included into partial analysis) and 18 age-, gender- and season-matched controls were analyzed for differences in executive functioning and bone parameters in plasma. Plasma was analyzed with commercially available kits. Cognitive performance in tonic alertness, visuo-spatial working memory, inhibitory control and task switching was assessed by a task battery presented on a touch screen. Regarding cognition, only the performance in incongruent conditions in inhibitory control was significantly better in children with PKU than in controls. No further differences in cognitive tests were detected. Furthermore, no significant difference in the bone turnover markers osteocalcin, undercarboxylated osteocalcin and CTX were detected between children with PKU and controls, while children with PKU had a significantly higher vitamin D concentration (69.44 ± 12.83 nmol/L vs. 41.87 ± 15.99 nmol/L, p < 0.001) and trended towards lower parathyroid hormone concentrations than controls (48.27 ± 15.16 pg/mL vs. 70.61 ± 30.53 pg/mL, p = 0.066). In this small group of well-treated preschoolers with PKU, no impairments in cognitive performance and bone turnover were observed, while vitamin D supplementation of amino acid supplements seems to be sufficient to achieve good vitamin D status. Full article

(This article belongs to the Special Issue The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases)

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9 pages, 504 KiB

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Establishing the Prevalence of Osteomalacia in Arab Adolescents Using Biochemical Markers of Bone Health

by Nasser M. Al-Daghri, Sobhy Yakout, Shaun Sabico, Kaiser Wani, Syed Danish Hussain, Naji Aljohani, Suma Uday and Wolfgang Högler

Nutrients 2022, 14(24), 5354; https://doi.org/10.3390/nu14245354 - 16 Dec 2022

Cited by 8 | Viewed by 3821

Abstract

Nutrition-acquired osteomalacia is a bone mineralization disorder associated with dietary calcium and/or solar vitamin D deficiency, risk factors considered common in the Middle Eastern region. Establishing less invasive, cheap, and widely available diagnostic markers for this underdiagnosed entity is essential, in particular for screening in high-risk groups. This study assessed the prevalence of biochemical osteomalacia in Arab adolescents. In this cross-sectional study performed between September 2019 and March 2021, adolescents aged 12–17 years from 60 different secondary and preparatory year schools in Riyadh, Saudi Arabia were included. Anthropometrics and fasting blood samples were collected. Biochemical osteomalacia was defined as any two of the following four serum markers of hypomineralization, namely low 25 hydroxyvitamin D (25OHD < 30 nmol/L), high alkaline phosphatase (ALP), low calcium (Ca), and/or inorganic phosphorous (Pi). A total of 2938 Arab adolescents [1697 girls; mean age (years) 14.8 ± 1.8; 1241 boys; mean age 15.1 ± 1.6] were recruited. Vitamin D deficiency was noted in 56.2% (n = 953) of girls and 27.1% (n = 336) of boys (p < 0.001). The overall prevalence of biochemical osteomalacia was 10.0% (n = 295/2938) and was higher in girls than boys (14.7% vs. 3.6%, p < 0.001). The prevalence of low serum Ca and/or Pi was also higher in girls than in boys (24.2% vs. 12.5%, respectively, p < 0.001), as well as elevated ALP (5.1% vs. 1.5%, p < 0.001). Overall, girls were 4.6 times (95% CI 3.3–6.4) more likely to have biochemical osteomalacia than boys. Screening of apparently healthy Arab adolescents revealed a high prevalence of deranged mineralization markers suggestive of biochemical osteomalacia, which was significantly more common in girls than boys and was likely associated with Arab traditional clothing and diet. The proposed combination of typically altered mineralization markers for the diagnosis of osteomalacia is, at best, suggestive until further comparisons with established diagnostic tools (histological analysis of bone biopsies) are conducted. Full article

(This article belongs to the Special Issue The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases)

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Review

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37 pages, 748 KiB

Open AccessReview

Vitamin D and Pancreatic Ductal Adenocarcinoma—A Review of a Complicated Relationship

by Iustina Grosu, Alexandru Constantinescu, Mihaela Daniela Balta, Ovidiu Băjenaru, Cătălina Nuța, Christopher Pavel, Vasile Sandru, Mihai Munteanu and Octavian Andronic

Nutrients 2024, 16(23), 4085; https://doi.org/10.3390/nu16234085 - 27 Nov 2024

Viewed by 1449

Abstract

Introduction: From the observation of a negative relationship between UV-B exposure and cancer rates, we hypothesized that vitamin D (VD) may play a protective role in oncogenesis. Moreover, repurposing a well-known and relatively safe drug for conditions with dismal prospects, such as pancreatic ductal adenocarcinoma (PDAC), is a tempting idea. Thus, we aimed to summarize the current knowledge regarding the role of VD in the prevention and treatment of PDAC. Methods: We conducted a systematic review of VD and PDAC using Medline-indexed studies accessed through PubMed as the primary data source. This study aimed to identify articles focusing on the role of VD as a risk and prognostic factor for PDAC, mechanistic studies evaluating the effects of VD or vitamin D analogs (VDAs) in PDAC models, and clinical trials on VDAs in PDAC. After the screening, 97 studies were included in the final manuscript. Conclusion: Even though the results from epidemiologic studies were contradictory, basic research has demonstrated that VD can act on PDAC cells either directly, inhibiting proliferation, apoptosis, EMT, migration, invasion, and stemness, or indirectly, through stromal remodeling. A better understanding of the consequences of VD-induced tumor–stroma cross-talk alterations is needed to determine whether VD/VDAs can be used to our own advantage in the treatment of PDAC. Full article

(This article belongs to the Special Issue The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases)

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14 pages, 1730 KiB

Open AccessReview

Calcifediol: Mechanisms of Action

by Simone Donati, Gaia Palmini, Cinzia Aurilia, Irene Falsetti, Francesca Marini, Francesca Giusti, Teresa Iantomasi and Maria Luisa Brandi

Nutrients 2023, 15(20), 4409; https://doi.org/10.3390/nu15204409 - 17 Oct 2023

Cited by 8 | Viewed by 3939

Abstract

Due to its essential role in calcium and phosphate homeostasis, the secosteroid hormone calcitriol has received growing attention over the last few years. Calcitriol, like other steroid hormones, may function through both genomic and non-genomic mechanisms. In the traditional function, the interaction between the biologically active form of vitamin D and the vitamin D receptor (VDR) affects the transcription of thousands of genes by binding to repeated sequences present in their promoter region, named vitamin D-responsive elements (VDREs). Non-transcriptional effects, on the other hand, occur quickly and are unaffected by inhibitors of transcription and protein synthesis. Recently, calcifediol, the immediate precursor metabolite of calcitriol, has also been shown to bind to the VDR with weaker affinity than calcitriol, thus exerting gene-regulatory properties. Moreover, calcifediol may also trigger rapid non-genomic responses through its interaction with specific membrane vitamin D receptors. Membrane-associated VDR (mVDR) and protein disulfide isomerase family A member 3 (Pdia3) are the best-studied candidates for mediating these rapid responses to vitamin D metabolites. This paper provides an overview of the calcifediol-related mechanisms of action, which may help to better understand the vitamin D endocrine system and to identify new therapeutic targets that could be important for treating diseases closely associated with vitamin D deficiency. Full article

(This article belongs to the Special Issue The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases)

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24 pages, 428 KiB

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Definition, Assessment, and Management of Vitamin D Inadequacy: Suggestions, Recommendations, and Warnings from the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS)

by Francesco Bertoldo, Luisella Cianferotti, Marco Di Monaco, Alberto Falchetti, Angelo Fassio, Davide Gatti, Luigi Gennari, Sandro Giannini, Giuseppe Girasole, Stefano Gonnelli, Nazzarena Malavolta, Salvatore Minisola, Mario Pedrazzoni, Domenico Rendina, Maurizio Rossini and Iacopo Chiodini

Nutrients 2022, 14(19), 4148; https://doi.org/10.3390/nu14194148 - 6 Oct 2022

Cited by 60 | Viewed by 10324

Abstract

In the recent years, both the prescriptions of serum 25(OH)D levels assay, and vitamin D supplementation are constantly increasing, as well as the costs to be incurred relating to these specific aspects. As in many other countries, the risk of vitamin D deficiency is particularly high in Italy, as recently confirmed by cohort studies in the general population as well as in patients with metabolic bone disorder. Results confirmed the North-South gradient of vitamin D levels described among European countries, despite the wide use of supplements. Although vitamin D supplementation is also recommended by the Italian Medicine Agency for patients at risk for fragility fracture or for initiating osteoporotic medication, the therapeutic gap for osteoporosis in Italy is very high. There is a consistent proportion of osteoporotic patients not receiving specific therapy for osteoporosis following a fragility fracture, with a poor adherence to the recommendations provided by national guidelines and position paper documents. The failure or inadequate supplementation with vitamin D in patients on antiresorptive or anabolic treatment for osteoporosis is thought to further amplify the problem and exposes patients to a high risk of re-fracture and mortality. Therefore, it is important that attention to its possible clinical consequences must be given. Thus, in light of new evidence from the literature, the SIOMMMS board felt the need to revise and update, by a GRADE/PICO system approach, its previous original recommendations about the definition, prevention, and treatment of vitamin D deficiency in adults, released in 2011. Several key points have been here addressed, such as the definition of the vitamin D status: normality values and optimal values; who are the subjects considered at risk of hypovitaminosis D; opportunity or not of performing the biochemical assessment of serum 25(OH)D levels in general population and in subjects at risk of hypovitaminosis D; the need or not to evaluate baseline serum 25(OH)D in candidate subjects for pharmacological treatment for osteoporosis; how and whether to supplement vitamin D subjects with hypovitaminosis D or candidates for pharmacological treatment with bone active agents, and the general population; how and whether to supplement vitamin D in chronic kidney disease and/or chronic liver diseases or under treatment with drugs interfering with hepatic metabolism; and finally, if vitamin D may have toxic effects in the subject in need of supplementation. Full article

(This article belongs to the Special Issue The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases)

Other

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2 pages, 181 KiB

Open AccessReply

Reply to Wimalawansa, S.J. Comment on “Bertoldo et al. Definition, Assessment, and Management of Vitamin D Inadequacy: Suggestions, Recommendations, and Warnings from the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS). Nutrients 2022, 14, 4148”

Nutrients 2023, 15(3), 499; https://doi.org/10.3390/nu15030499 - 18 Jan 2023

Cited by 1 | Viewed by 2079

Abstract

With regard to Dr. Wimalawansa’s comment [...] Full article

(This article belongs to the Special Issue The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases)

3 pages, 204 KiB

Open AccessComment

Comment on Bertoldo et al. Definition, Assessment, and Management of Vitamin D Inadequacy: Suggestions, Recommendations, and Warnings from the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS). Nutrients 2022, 14, 4148

by Sunil J. Wimalawansa

Nutrients 2023, 15(3), 498; https://doi.org/10.3390/nu15030498 - 18 Jan 2023

Cited by 2 | Viewed by 2239

Abstract

We are responding to a report by Bertoldo et al. in October 2022 in Nutrients [...] Full article

(This article belongs to the Special Issue The Effect of Vitamin D on Metabolic Bone Disease and Chronic Diseases)

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