Measurements of the Vitamin D Metabolome in the Calgary Vitamin D Study: Relationship of Vitamin D Metabolites to Bone Loss

Burt, Lauren A; Kaufmann, Martin; Rose, Michael; Jones, Glenville; Billington, Emma O; Boyd, Steven K.; Hanley, David A.

doi:10.1002/jbmr.4876

J of Bone & Mineral Res

2023

DOI: 10.1002/jbmr.4876

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Measurements of the Vitamin D Metabolome in the Calgary Vitamin D Study: Relationship of Vitamin D Metabolites to Bone Loss

Lauren A Burt

Martin Kaufmann

Michael Rose

et al.

Abstract: In a 36‐month randomized controlled trial examining the effect of high‐dose vitamin D3 on radial and tibial total bone mineral density (TtBMD), measured by high‐resolution peripheral quantitative tomography (HR‐pQCT), participants (311 healthy males and females aged 55–70 years with dual‐energy X‐ray absorptiometry T‐scores > −2.5 without vitamin D deficiency) were randomized to receive 400 IU (N = 109), 4000 IU (N = 100), or 10,000 IU (N = 102) daily. Participants had HR‐pQCT radius and tibia scans and blo… Show more

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2024

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Vitamin D: Analytical Advances, Clinical Impact, and Ongoing Debates on Health Perspectives

Cavalier,

Makris,

Heijboer

et al. 2024

Clinical Chemistry

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Background Vitamin D, acknowledged since the 1930s for its role in preventing rickets, gained additional prominence in relation to fragility fracture prevention in the late 1980s. From the early 2000s, connections between vitamin D deficiency and extra-skeletal pathologies emerged, alongside increased awareness of widespread deficits. This prompted crucial debates on optimal serum concentrations, expected to conclude when the outcomes of high-dose supplementation randomized controlled trials were available. Skepticism arose with inconclusive results from these trials. Content This review begins with an exploration of vitamin D metabolism, followed by a detailed description of the measurement of vitamin D metabolites and the crucial role of standardization. Subsequent sections focus on the association of vitamin D with bone health and explore the extra-skeletal effects. The review concludes with a comprehensive discussion on the definition of vitamin D status and its implications for supplementation. Summary Despite standardization efforts, assay variations and challenges still exist, especially in specific patient groups. Vitamin D supplementation has a significant impact on bone metabolism and optimal vitamin D status improves the efficacy of antiresorptive drugs such as bisphosphonates. The extra-skeletal effects of vitamin D remain debated, but may include potential benefits in conditions such as respiratory infections and cancer mortality, particularly in deficient individuals. The definition of vitamin D sufficiency is nuanced, especially when variations in population groups and analytical methods are taken into account. Despite ongoing debates and recent mega-trials tempering enthusiasm, vitamin D remains a complex and essential element in human health. Further research is needed to clarify its role in various health outcomes and guide supplementation strategies.

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Vitamin D: Analytical Advances, Clinical Impact, and Ongoing Debates on Health Perspectives

Cavalier,

Makris,

Heijboer

et al. 2024

Clinical Chemistry

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Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows

Giustina,

Bilezikian,

Adler

et al. 2024

Endocrine Reviews

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The 6th International Conference, “Controversies in Vitamin D,” was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.

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A global perspective on the status of clinical metabolomics in laboratory medicine – a survey by the IFCC metabolomics working group

Fux,

Lenski,

Bendt

et al. 2024

Clinical Chemistry and Laboratory Medicine (CCLM)

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Objectives Metabolomics aims for comprehensive characterization and measurement of small molecule metabolites (<1700 Da) in complex biological matrices. This study sought to assess the current understanding and usage of metabolomics in laboratory medicine globally and evaluate the perception of its promise and future implementation. Methods A survey was conducted by the IFCC metabolomics working group that queried 400 professionals from 79 countries. Participants provided insights into their experience levels, knowledge, and usage of metabolomics approaches, along with detailing the applications and methodologies employed. Results Findings revealed a varying level of experience among respondents, with varying degrees of familiarity and utilization of metabolomics techniques. Targeted approaches dominated the field, particularly liquid chromatography coupled to a triple quadrupole mass spectrometer, with untargeted methods also receiving significant usage. Applications spanned clinical research, epidemiological studies, clinical diagnostics, patient monitoring, and prognostics across various medical domains, including metabolic diseases, endocrinology, oncology, cardiometabolic risk, neurodegeneration and clinical toxicology. Conclusions Despite optimism for the future of clinical metabolomics, challenges such as technical complexity, standardization issues, and financial constraints remain significant hurdles. The study underscores the promising yet intricate landscape of metabolomics in clinical practice, emphasizing the need for continued efforts to overcome barriers and realize its full potential in patient care and precision medicine.

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Measurements of the Vitamin D Metabolome in the Calgary Vitamin D Study: Relationship of Vitamin D Metabolites to Bone Loss

Cited by 3 publications

References 37 publications

Vitamin D: Analytical Advances, Clinical Impact, and Ongoing Debates on Health Perspectives

Vitamin D: Analytical Advances, Clinical Impact, and Ongoing Debates on Health Perspectives

Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows

A global perspective on the status of clinical metabolomics in laboratory medicine – a survey by the IFCC metabolomics working group

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