Download biomedica product listUK study suggests protective effect of Vitamin D supplementation on bone metabolism
Vitamin D plays an important role in bone mineralization. It helps the body to effectively absorb calcium which is essential to good bone health. The most common way for the body to produce vitamin D is through sunlight. As we get older the natural production of vitamin D decreases. Thus, elderly people either need to take vitamin D supplements or focus on eating foods that contain vitamin D. In a recent study, UK researchers investigated the effect of vitamin D supplementation in older people for 12 months. They looked into changes in markers of bone metabolism, bone mineral density, and bone mineral content . The results suggest a protective effect of supplementation on bone metabolism. Read more: Vitamin D Supplementation for 12 Months in Older Adults Alters Regulators of Bone Metabolism but Does Not Change Wnt Signaling Pathway Markers.
Biomedica offers a wide range of high quality ELISA Kits for bone markers.
The following Wnt signaling and regulatory bone markers were measured in this study:
Sclerostin, OPG, RANKL, DKK-1, FGF23 intact, FGF23 (C-terminal)
Related publications
Vitamin D Supplementation for 12 Months in Older Adults Alters Regulators of Bone Metabolism but Does Not Change Wnt Signaling Pathway Markers.
Christodoulou M, Aspray TJ, Piec I, Washbourne C, Tang JC, Fraser WD, Schoenmakers I; VDOP Trial Group. JBMR Plus. 2022 Mar 24;6(5):e10619. doi: 10.1002/jbm4.10619. PMID: 35509637; PMCID: PMC9059470.
Abstract
Vitamin D status and supplementation regulates bone metabolism and may modulate Wnt signaling. We studied the response of hormonal regulators of bone metabolism, markers of Wnt signaling and bone turnover and bone mineral density (BMD) and bone mineral content (BMC) in a randomized vitamin D intervention trial (12,000 IU, 24,000 IU, 48,000 IU/mo for 1 year; men and women aged >70 years; n = 379; ISRCTN35648481). Associations with total and free 25(OH)D concentrations were analyzed by linear regression. Baseline vitamin D status was (mean ± SD) 25(OH)D: 40.0 ± 20.1 nmol/L. Supplementation dose-dependently increased total and free 25(OH)D concentrations and decreased plasma phosphate and parathyroid hormone (PTH) (all p < 0.05). The procollagen 1 intact N-terminal (PINP)/C-terminal telopeptide (CTX) ratio, C-terminal fibroblast growth factor-23 (cFGF23), and intact FGF23 (iFGF23) significantly increased with no between-group differences, whereas Klotho was unchanged. 1,25(OH)2D and PINP significantly increased in the 24 IU and 48,000 IU groups. Sclerostin (SOST), osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), BMD, BMC, and CTX remained unchanged. Subgroup analyses with baseline 25(OH)D <25 nmol/L (n = 94) provided similar results. Baseline total and free 25(OH)D concentrations were positively associated with 1,25(OH)2D, 24,25(OH)2D (p < 0.001), vitamin D binding protein (DBP) (p < 0.05), BMD, and BMC (p < 0.05). Associations with PTH (p <0.001), cFGF23 (p < 0.01), and BAP (p < 0.05) were negative. After supplementation, total and free 25(OH)D concentrations remained positively associated only with 24,25(OH)2D (p < 0.001) and DBP (p < 0.001) and negatively with estimated glomerular filtration rate (eGFR) (p < 0.01). PTH and SOST were significantly associated only with free 25(OH)D. There were no significant relationships with BMD and BMC after supplementation. The decrease in PTH and increase in PINP/CTX ratio suggest a protective effect of supplementation on bone metabolism, although no significant effect on BMD or pronounced changes in regulators of Wnt signaling were found. The increase in FGF23 warrants caution because of its negative association with skeletal and cardiovascular health. Associations of total and free 25(OH)D with biomarkers were similar and known positive associations between vitamin D status and BMD were confirmed. The change in associations after supplementation might suggest a threshold effect. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
The role of vitamin D in maintaining bone health in older people.
Hill TR, Aspray TJ. Ther Adv Musculoskelet Dis. 2017 Apr;9(4):89-95. doi: 10.1177/1759720X17692502. Epub 2017 Feb 14. PMID: 28382112; PMCID: PMC5367643.
Abstract
This review summarises aspects of vitamin D metabolism, the consequences of vitamin D deficiency, and the impact of vitamin D supplementation on musculoskeletal health in older age. With age, changes in vitamin D exposure, cutaneous vitamin D synthesis and behavioural factors (including physical activity, diet and sun exposure) are compounded by changes in calcium and vitamin D pathophysiology with altered calcium absorption, decreased 25-OH vitamin D [25(OH)D] hydroxylation, lower renal fractional calcium reabsorption and a rise in parathyroid hormone. Hypovitaminosis D is common and associated with a risk of osteomalacia, particularly in older adults, where rates of vitamin D deficiency range from 10-66%, depending on the threshold of circulating 25(OH)D used, population studied and season. The relationship between vitamin D status and osteoporosis is less clear. While circulating 25(OH)D has a linear relationship with bone mineral density (BMD) in some epidemiological studies, this is not consistent across all racial groups. The results of randomized controlled trials of vitamin D supplementation on BMD are also inconsistent, and some studies may be less relevant to the older population, as, for example, half of participants in the most robust meta-analysis were aged under 60 years. The impact on BMD of treating vitamin D deficiency (and osteomalacia) is also rarely considered in such intervention studies. When considering osteoporosis, fracture risk is our main concern, but vitamin D therapy has no consistent fracture-prevention effect, except in studies where calcium is coprescribed (particularly in frail populations living in care homes). As a J-shaped effect on falls and fracture risk is becoming evident with vitamin D interventions, we should target those at greatest risk who may benefit from vitamin D supplementation to decrease falls and fractures, although the optimum dose is still unclear.
The health effects of vitamin D supplementation: evidence from human studies.
Bouillon R, Manousaki D, Rosen C, Trajanoska K, Rivadeneira F, Richards JB. Nat Rev Endocrinol. 2022 Feb;18(2):96-110. doi: 10.1038/s41574-021-00593-z. Epub 2021 Nov 23. PMID: 34815552; PMCID: PMC8609267.
Abstract
Vitamin D supplementation can prevent and cure nutritional rickets in infants and children. Preclinical and observational data suggest that the vitamin D endocrine system has a wide spectrum of skeletal and extra-skeletal activities. There is consensus that severe vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) concentration <30 nmol/l) should be corrected, whereas most guidelines recommend serum 25OHD concentrations of >50 nmol/l for optimal bone health in older adults. However, the causal link between vitamin D and many extra-skeletal outcomes remains unclear. The VITAL, ViDA and D2d randomized clinical trials (combined number of participants >30,000) indicated that vitamin D supplementation of vitamin D-replete adults (baseline serum 25OHD >50 nmol/l) does not prevent cancer, cardiovascular events, falls or progression to type 2 diabetes mellitus. Post hoc analysis has suggested some extra-skeletal benefits for individuals with vitamin D deficiency. Over 60 Mendelian randomization studies, designed to minimize bias from confounding, have evaluated the consequences of lifelong genetically lowered serum 25OHD concentrations on various outcomes and most studies have found null effects. Four Mendelian randomization studies found an increased risk of multiple sclerosis in individuals with genetically lowered serum 25OHD concentrations. In conclusion, supplementation of vitamin D-replete individuals does not provide demonstrable health benefits. This conclusion does not contradict older guidelines that severe vitamin D deficiency should be prevented or corrected.
Vitamin D: Production, Metabolism and Mechanisms of Action.
Bikle DD. 2021. Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–. PMID: 25905172.
Excerpt
Vitamin D production in the skin under the influence of sunlight (UVB) is maximized at levels of sunlight exposure that do not burn the skin. Further metabolism of vitamin D to its major circulating form (25(OH)D) and hormonal form (1,25(OH)2D) takes place in the liver and kidney, respectively, but also in other tissues where the 1,25(OH)2D produced serves a paracrine/autocrine function: examples include the skin, cells of the immune system, parathyroid gland, intestinal epithelium, prostate, and breast. Parathyroid hormone, FGF23, calcium and phosphate are the major regulators of the renal 1-hydroxylase (CYP27B1, the enzyme producing 1,25(OH)2D); regulation of the extra renal 1-hydroxylase differs from that in the kidney and involves cytokines. The major enzyme that catabolizes 25(OH)D and 1,25(OH)2D is the 24-hydroxylase; like the 1-hydroxylase it is tightly controlled in the kidney in a manner opposite to that of the 1-hydroxylase, but like the 1-hydroxylase it is widespread in other tissues where its regulation is different from that of the kidney. Vitamin D and its metabolites are carried in the blood bound to vitamin D binding protein (DBP) and albumin–for most tissues it is the free (i.e., unbound) metabolite that enters the cell; however, DBP bound metabolites can enter some cells such as the kidney and parathyroid gland through a megalin/cubilin mechanism. Most but not all actions of 1,25(OH)2D are mediated by the vitamin D receptor (VDR). VDR is a transcription factor that partners with other transcription factors such as retinoid X receptor that when bound to 1,25(OH)2D regulates gene transcription either positively or negatively depending on other cofactors to which it binds or interacts. The VDR is found in most cells, not just those involved with bone and mineral homeostasis (i.e., bone, gut, kidney) resulting in wide spread actions of 1,25(OH)2D on most physiologic and pathologic processes. Animal studies indicate that vitamin D has beneficial effects on various cancers, blood pressure, heart disease, immunologic disorders, but these non-skeletal effects have been difficult to prove in humans in randomized controlled trials. Analogs of 1,25(OH)2D are being developed to achieve specificity for non-skeletal target tissues such as the parathyroid gland and cancers to avoid the hypercalcemia resulting from 1,25(OH)2D itself. The level of vitamin D intake and achieved serum levels of 25(OH)D that are optimal and safe for skeletal health and the non-skeletal actions remain controversial, but are likely between an intake of 800-2000IU vitamin D in the diet and 20-50ng/ml 25(OH)D in the blood.
Leucine-rich alpha-2-glycoprotein (LRG/LRG1) is an innovative biomarker for inflammation and angiogenesis.
Recently, researchers investigated for the first time the association between plasma LRG with cardiovascular comorbidities in hemodialysis patients with end stage renal disease:
LRG can reliably be measured by ELISA in human serum, plasma and urine samples with a fully validated assay. Only 5 µl of sample volume is required!
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Find out more: human LRG ELISA
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Related literature
Practical Guide to Immunoassay Method Validation. Andreasson U, Perret-Liaudet A, van Waalwijk van Doorn LJ, Blennow K, Chiasserini D, Engelborghs S, Fladby T, Genc S, Kruse N, Kuiperij HB, Kulic L, Lewczuk P, Mollenhauer B, Mroczko B, Parnetti L, Vanmechelen E, Verbeek MM, Winblad B, Zetterberg H, Koel-Simmelink M, Teunissen CE. AFront Neurol. 2015 Aug 19;6:179. doi: 10.3389/fneur.2015.00179. PMID: 26347708; PMCID: PMC4541289.
Abstract
Biochemical markers have a central position in the diagnosis and management of patients in clinical medicine, and also in clinical research and drug development, also for brain disorders, such as Alzheimer’s disease. The enzyme-linked immunosorbent assay (ELISA) is frequently used for measurement of low-abundance biomarkers. However, the quality of ELISA methods varies, which may introduce both systematic and random errors. This urges the need for more rigorous control of assay performance, regardless of its use in a research setting, in clinical routine, or drug development. The aim of a method validation is to present objective evidence that a method fulfills the requirements for its intended use. Although much has been published on which parameters to investigate in a method validation, less is available on a detailed level on how to perform the corresponding experiments. To remedy this, standard operating procedures (SOPs) with step-by-step instructions for a number of different validation parameters is included in the present work together with a validation report template, which allow for a well-ordered presentation of the results. Even though the SOPs were developed with the intended use for immunochemical methods and to be used for multicenter evaluations, most of them are generic and can be used for other technologies as well.
The Measurement and Interpretation of Fibroblast Growth Factor 23 (FGF23) Concentrations.Periostin functions as a ligand for integrins to support adhesion and migration of tumor cells which leads to increased cell survival, invasion, angiogenesis and metastasis in different cancer types including breast cancer (BC).
In a recent study using the Biomedica Human Periostin ELISA, Periostin levels were significantly increased in women with primary, non-metastatic breast cancer over 60 as well as in postmenopausal women. No difference was observed in patients with and without the presence of disseminated tumor cells. However, high levels of circulating Periostin were associated with a poorer BC specific survival. These results warrant further studies on the role of Periostin in cancer patients.
More information on the Biomedica Periostin assays can be found here.
Hoffman et al. High circulating levels of Periostin are associated with a poor survival in primary, non-metastatic breast cancer patients. Am Ass Cancer Res 2019; 79(4 Suppl):Abstract nr P6-09-08