Vitamin D deficiency
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2]
Synonyms and keywords: Hypovitaminosis D; Low vitamin D
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3] Associate Editor(s)-in-Chief: Ibrahim Elkhayat, M.B.B.Ch.[4] Vitamin D deficiency is a state of inadequate vitamin D supply, reflected by a low serum 25-hydroxyvitamin D [25(OH)D] concentration, that may impair calcium and phosphate homeostasis and skeletal mineralization. The biochemical threshold used to define deficiency remains disputed; thresholds differ among professional organizations and should be interpreted in the context of clinical findings and the relevant guideline. The 2024 Endocrine Society guideline does not establish a universal 25(OH)D target for generally healthy populations and addresses disease prevention rather than treatment of established deficiency.[1]
Prolonged or severe deficiency can cause rickets, defective mineralization at the growth plate before epiphyseal closure, and osteomalacia, defective mineralization of bone matrix, which may occur at any age, including in children with rickets. Nutritional deficiency should be distinguished from inherited disorders of vitamin D activation or action (vitamin D-dependent rickets). Serum 25(OH)D is typically normal in 1α-hydroxylase deficiency (type 1A) and vitamin D receptor defects (type 2), but is low in 25-hydroxylase (CYP2R1) deficiency (type 1B), which can mimic nutritional deficiency and respond poorly to standard vitamin D doses.[2]
Vitamin D is synthesized in the skin after ultraviolet B exposure or obtained from the diet as vitamin D2 or D3. It undergoes hepatic 25-hydroxylation to form 25(OH)D, followed primarily by renal 1α-hydroxylation to form the biologically active metabolite 1,25-dihydroxyvitamin D. Vitamin D supports intestinal calcium and phosphate absorption and normal skeletal mineralization. Deficiency can lead to secondary hyperparathyroidism, hypophosphatemia, rickets, and osteomalacia. Nutritional rickets may also result from inadequate calcium intake alone or in combination with vitamin D deficiency; low calcium intake increases the 25(OH)D concentration associated with a lower risk of rickets.[3][4]
Clinical significance
Vitamin D deficiency is associated with impaired skeletal mineralization and, when clinically significant, may present with bone pain, muscle weakness, deformity, fractures, or hypocalcemia. Severe hypocalcemia may cause seizures or, particularly in infants, dilated cardiomyopathy. Typical biochemical abnormalities include increased parathyroid hormone and alkaline phosphatase, low or low-normal serum calcium, and low phosphate. Radiographs may demonstrate metaphyseal cupping and fraying in rickets or pseudofractures (Looser zones) in osteomalacia. These findings are not specific and require interpretation in the clinical context.[5][3]
Risk factors include limited ultraviolet B exposure, high latitude or winter season, sun avoidance, darker skin pigmentation, institutionalization, inadequate dietary intake, malabsorption (including celiac disease, inflammatory bowel disease, cystic fibrosis, and bariatric surgery), obesity, and chronic liver or kidney disease. Medications associated with altered vitamin D metabolism or absorption include phenytoin, phenobarbital, glucocorticoids, rifampin, some antiretroviral agents, ketoconazole, cholestyramine, and orlistat.[6][7]
Population estimates depend strongly on the biochemical cutoff used. In NHANES 2011–2014, 5.0% of persons aged 1 year or older had 25(OH)D below 12 ng/mL (30 nmol/L), and 18.3% had concentrations of 12–19 ng/mL (30–49 nmol/L). More recent NHANES data describe changes in the distribution of vitamin D status through August 2021–August 2023; detailed prevalence estimates belong in Vitamin D deficiency epidemiology.[8][9]
Diagnosis and management in brief
Serum total 25(OH)D is the preferred biochemical marker of vitamin D status. Serum 1,25-dihydroxyvitamin D is not routinely used to assess vitamin D stores because its concentration may be normal or increased in nutritional deficiency. The diagnostic evaluation may include serum calcium, phosphate, alkaline phosphatase, and parathyroid hormone, with additional investigations guided by the clinical presentation. Rickets or osteomalacia with normal 25(OH)D, or a poor response to vitamin D replacement, should prompt consideration of alternative diagnoses, including hypophosphatemic (FGF23-mediated) disorders and inherited defects of vitamin D metabolism or action.[5][10]
Population screening and diagnostic testing for suspected deficiency are distinct. The 2021 United States Preventive Services Task Force (USPSTF) concluded that evidence was insufficient to assess the balance of benefits and harms of screening community-dwelling, nonpregnant adults without signs, symptoms, or conditions warranting treatment (I statement). The 2024 Endocrine Society guideline suggests against routine 25(OH)D testing in generally healthy populations, including otherwise healthy adults with obesity or dark complexion; details and exceptions are addressed in Vitamin D deficiency screening.[11][1]
Clinically significant deficiency is managed with oral vitamin D replacement (cholecalciferol is generally preferred; parenteral routes are reserved for specific situations), adequate calcium intake, and correction of contributing conditions. Replacement regimens and monitoring depend on age, severity, cause, comorbidities, and the presence of rickets or osteomalacia; see Vitamin D deficiency medical therapy. Patients with granulomatous diseases (including sarcoidosis and tuberculosis), lymphoma, or CYP24A1 loss-of-function variants require particular caution because of the risk of hypercalcemia during replacement. In primary hyperparathyroidism with coexisting vitamin D deficiency, cautious repletion is advised, with monitoring of serum and urinary calcium. Hypoparathyroidism and vitamin D-dependent rickets type 1A require active vitamin D; in adults with chronic kidney disease G3a–G5 not on dialysis, calcitriol or vitamin D analogs are not used routinely and are generally reserved for severe, progressive secondary hyperparathyroidism in G4–G5, while nutritional vitamin D deficiency is still corrected.[12][13][14]
Evidence from large randomized trials in generally vitamin D-replete populations has not established broad benefits of supplementation for prevention of cardiovascular disease, cancer, or fractures. However, an individual participant data meta-analysis of three trials in people with prediabetes found a relative reduction in progression to diabetes, which informed the conditional Endocrine Society recommendation for this population. These prevention findings should not be extrapolated to withholding treatment from patients with established deficiency, rickets, or osteomalacia.[15][16][17][18][19]
Excessive vitamin D intake can cause hypercalcemia, hypercalciuria, and nephrolithiasis. Intermittent very high-dose regimens have also been associated with increased falls and fractures in some older populations; the Endocrine Society recommends daily lower-dose rather than nondaily higher-dose supplementation in adults aged 50 years or older when supplementation or treatment is indicated.[1][20]
References
- ↑ 1.0 1.1 1.2 Demay MB, Pittas AG, Bikle DD; et al. (2024). "Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 109 (8): 1907–1947. doi:10.1210/clinem/dgae290.
- ↑ Molin A, Wiedemann A, Demers N; et al. (2017). "Vitamin D-Dependent Rickets Type 1B (25-Hydroxylase Deficiency): A Rare Condition or a Misdiagnosed Condition?". Journal of Bone and Mineral Research. 32 (9): 1893–1899. doi:10.1002/jbmr.3181.
- ↑ 3.0 3.1 Munns CF, Shaw N, Kiely M; et al. (2016). "Global Consensus Recommendations on Prevention and Management of Nutritional Rickets". The Journal of Clinical Endocrinology and Metabolism. 101 (2): 394–415. doi:10.1210/jc.2015-2175.
- ↑ Rios-Leyvraz M, Thacher TD, Dabas A; et al. (2024). "Serum 25-Hydroxyvitamin D Threshold and Risk of Rickets in Young Children: A Systematic Review and Individual Participant Data Meta-Analysis to Inform the Development of Dietary Requirements for Vitamin D". European Journal of Nutrition. 63 (3): 673–695. doi:10.1007/s00394-023-03299-2.
- ↑ 5.0 5.1 Carpenter TO, Shaw NJ, Portale AA; et al. (2017). "Rickets". Nature Reviews Disease Primers. 3: 17101. doi:10.1038/nrdp.2017.101.
- ↑ Amrein K, Scherkl M, Hoffmann M; et al. (2020). "Vitamin D Deficiency 2.0: An Update on the Current Status Worldwide". European Journal of Clinical Nutrition. 74 (11): 1498–1513. doi:10.1038/s41430-020-0558-y.
- ↑ Elder CJ, Bishop NJ (2014). "Rickets". The Lancet. 383 (9929): 1665–1676. doi:10.1016/S0140-6736(13)61650-5.
- ↑ Herrick KA, Storandt RJ, Afful J; et al. (2019). "Vitamin D Status in the United States, 2011-2014". The American Journal of Clinical Nutrition. 110 (1): 150–157. doi:10.1093/ajcn/nqz037.
- ↑ Couch CA, Williams AM, Stierman B; et al. (2026). "Trends in Vitamin D Status in the United States, 2007-2023: A Cross-Sectional Analysis of Data From the National Health and Nutrition Examination Survey". The American Journal of Clinical Nutrition. 123 (1): 101078. doi:10.1016/j.ajcnut.2025.09.046.
- ↑ Giustina A, Bilezikian JP, Adler RA; et al. (2024). "Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows". Endocrine Reviews. 45 (5): 625–654. doi:10.1210/endrev/bnae009.
- ↑ US Preventive Services Task Force, Krist AH, Davidson KW; et al. (2021). "Screening for Vitamin D Deficiency in Adults: US Preventive Services Task Force Recommendation Statement". JAMA. 325 (14): 1436–1442. doi:10.1001/jama.2021.3069.
- ↑ Wilhelm SM, Wang TS, Ruan DT; et al. (2016). "The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism". JAMA Surgery. 151 (10): 959–968. doi:10.1001/jamasurg.2016.2310.
- ↑ Song A, Zhao H, Yang Y; et al. (2021). "Safety and Efficacy of Common Vitamin D Supplementation in Primary Hyperparathyroidism and Coexistent Vitamin D Deficiency and Insufficiency: A Systematic Review and Meta-Analysis". Journal of Endocrinological Investigation. 44 (8): 1667–1677. doi:10.1007/s40618-020-01473-5.
- ↑ Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group (2017). "KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)". Kidney International Supplements. 7 (1): 1–59.
- ↑ Manson JE, Cook NR, Lee IM; et al. (2019). "Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease". The New England Journal of Medicine. 380 (1): 33–44. doi:10.1056/NEJMoa1809944.
- ↑ Scragg R, Stewart AW, Waayer D; et al. (2017). "Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study: A Randomized Clinical Trial". JAMA Cardiology. 2 (6): 608–616. doi:10.1001/jamacardio.2017.0175.
- ↑ Pittas AG, Dawson-Hughes B, Sheehan P; et al. (2019). "Vitamin D Supplementation and Prevention of Type 2 Diabetes". The New England Journal of Medicine. 381 (6): 520–530. doi:10.1056/NEJMoa1900906.
- ↑ Pittas AG, Kawahara T, Jorde R; et al. (2023). "Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes: A Systematic Review and Meta-Analysis of Individual Participant Data From 3 Randomized Clinical Trials". Annals of Internal Medicine. 176 (3): 355–363. doi:10.7326/M22-3018.
- ↑ Shah VP, Nayfeh T, Alsawaf Y; et al. (2024). "A Systematic Review Supporting the Endocrine Society Clinical Practice Guidelines on Vitamin D". The Journal of Clinical Endocrinology and Metabolism. 109 (8): 1961–1974. doi:10.1210/clinem/dgae312.
- ↑ Sanders KM, Stuart AL, Williamson EJ; et al. (2010). "Annual High-Dose Oral Vitamin D and Falls and Fractures in Older Women: A Randomized Controlled Trial". JAMA. 303 (18): 1815–1822. doi:10.1001/jama.2010.594.
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Vitamin D deficiency Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Vitamin D deficiency On the Web |
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American Roentgen Ray Society Images of Vitamin D deficiency |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [5] Associate Editor(s)-in-Chief: Ibrahim Elkhayat, M.B.B.Ch.[6]
Historical perspective
Rickets and early recognition
The first medical descriptions of rickets are variously attributed to Daniel Whistler and Francis Glisson, both practicing in England in the mid-1600s. Glisson's 1650 treatise, De Rachitide, described the clinical and post-mortem anatomical features of rickets in detail and differentiated it from infantile scurvy.[1][2]
During the Industrial Revolution, nutritional rickets became highly prevalent among children in large industrial cities in Europe and North America. By the late 19th and early 20th centuries, the disease was almost universal among young children in some large cities.[3]
In 1822, Jędrzej Śniadecki linked rickets to lack of sunlight and advocated sunlight exposure as treatment. In 1861–1862, Armand Trousseau identified lack of sunlight and poor nutrition as probable causes and recommended cod liver oil. In 1890, Theobald Palm related the geographic distribution of rickets to increasing latitude, further supporting a role for sunlight exposure.[2][1][4]
Discovery of vitamin D and the role of ultraviolet radiation
In 1916, Hess and Unger demonstrated that cod liver oil improved clinical rickets in children and subsequently showed that sunlight could also cure the disease. In 1919, Edward Mellanby produced and then cured rickets in sunlight-deprived dogs fed an oat-based diet, supporting the existence of a dietary antirachitic factor. In the same year, Huldschinsky demonstrated that ultraviolet radiation could improve rickets in children.[5][1]
In 1922, Elmer McCollum named the antirachitic factor vitamin D. He distinguished it from vitamin A by demonstrating that heating cod liver oil destroyed its antixerophthalmic activity while preserving its antirachitic activity. In 1924, Harry Steenbock and Alfred Hess independently demonstrated that ultraviolet irradiation conferred antirachitic activity on foods and oils. Subsequent work established that vitamins D2 and D3 are produced by ultraviolet irradiation of ergosterol and 7-dehydrocholesterol, respectively. Adolf Windaus and colleagues characterized the chemical structures of vitamins D2 and D3 during the 1930s.[2][5][4]
Food fortification and the control of nutritional rickets
Public health campaigns introduced vitamin D fortification of milk and other foods during the 1930s. Fortification, together with cod liver oil supplementation and increased recognition of the role of sunlight, substantially reduced nutritional rickets. By the mid-20th century, nutritional rickets had nearly disappeared in the United States.[5][3][6]
In 1938, Jeans and Stearns reported that infants receiving approximately 340–400 IU/day of vitamin D were on average 2 cm longer at 1 year than those receiving 60–135 IU/day; subsequent studies reported slower growth at intakes above approximately 1,800 IU/day. These findings contributed to the historical development of infant vitamin D intake recommendations.[1]
In Britain during the 1950s, an epidemic of idiopathic infantile hypercalcemia occurred during a period of high vitamin D supplementation of milk products, when cumulative infant intakes frequently reached approximately 4,000 IU/day. The British Ministry of Health subsequently reduced daily allowances to approximately 400 IU, after which the incidence declined, and vitamin D fortification of foods was transiently prohibited in several countries before later being reintroduced. Many cases are now attributed to genetic susceptibility, including Williams syndrome and loss-of-function variants in CYP24A1 (identified in 2011), which encodes the 24-hydroxylase that degrades vitamin D metabolites. The episode nonetheless shaped long-standing caution regarding high-dose vitamin D fortification and supplementation in infants.[7][8]
Fortification-related toxicity also occurred in the United States. Between 1985 and 1991, overfortified milk from a Massachusetts home-delivery dairy was associated with 56 cases of hypervitaminosis D and 2 deaths. Subsequent investigations also documented variability in the vitamin D content of fortified milk and infant formula.[9][10][11]
Nutritional rickets re-emerged in high-income countries from the 1980s onward. It has been reported particularly among exclusively breastfed infants, children with darker skin pigmentation, and immigrant and refugee populations. Nutritional rickets remains common in parts of Africa, the Middle East, and South Asia, where dietary calcium deficiency was also recognized as a cause of rickets independent of vitamin D status. These observations prompted calls for a global eradication program.[3][6][12][13][14]
In the United States, the American Academy of Pediatrics increased its recommended infant vitamin D intake from 200 IU/day in 2003 to 400 IU/day in 2008, primarily to prevent rickets. In 2016, a global consensus endorsed by 11 international organizations recommended 400 IU/day for all infants from birth to 12 months regardless of feeding method, and called for national rickets-prevention programs that combine supplementation and food fortification.[15][13][16]
Discovery of vitamin D metabolism and hormonal activity
Work by Hector DeLuca, Egon Kodicek, Anthony Norman, and other investigators established the metabolic activation of vitamin D. Vitamin D is hydroxylated in the liver to 25-hydroxyvitamin D [25(OH)D] and subsequently in the kidney to 1,25-dihydroxyvitamin D [1,25(OH)2D, calcitriol]. 25(OH)D was identified in 1968 and 1,25(OH)2D in 1971, independently by the groups of DeLuca, Kodicek, and Norman. Because hepatic 25-hydroxylation is not tightly regulated, circulating 25(OH)D became the accepted marker of vitamin D status. Fibroblast growth factor 23 (FGF23) was identified in 2000, and its suppression of renal 1α-hydroxylase (CYP27B1) and induction of 24-hydroxylase (CYP24A1) were characterized subsequently.[17][18][19][4]
The cloning of the vitamin D receptor in the late 1980s and the subsequent identification of vitamin D-metabolizing enzymes clarified the molecular basis of vitamin D action. Identification of PHEX in X-linked hypophosphatemia in 1995 and FGF23 in autosomal dominant hypophosphatemic rickets in 2000 further distinguished phosphopenic disorders from nutritional vitamin D deficiency.[20][18][4]
Modern controversy and reassessment of vitamin D supplementation
During the 2000s, observational studies associated lower serum 25(OH)D concentrations with numerous skeletal and extraskeletal diseases. These associations contributed to increased vitamin D testing and supplementation. Medicare Part B reimbursement volume for vitamin D testing increased more than 80-fold between 2000 and 2010, and in one analysis 25(OH)D testing rose from 0.29 to 16.1 per 1,000 person-years between 2005 and 2015.[21][22][23]
In 2011, the Institute of Medicine (IOM, now the National Academy of Medicine) concluded, on the basis of skeletal outcomes, that a serum 25(OH)D concentration of 20 ng/mL (50 nmol/L) meets the needs of at least 97.5% of the population. It set recommended dietary allowances of 600 IU/day for ages 1–70 years and 800 IU/day for ages 71 years and older, a tolerable upper intake level of 4,000 IU/day for persons aged 9 years and older, and judged the evidence for extraskeletal outcomes inconclusive. The Endocrine Society guideline published the same year recommended screening of at-risk individuals and defined deficiency as below 20 ng/mL, insufficiency as 21–29 ng/mL, and sufficiency as 30 ng/mL (75 nmol/L) or higher. These differing interpretations of the evidence contributed to ongoing controversy regarding the definition of vitamin D deficiency and the role of testing and supplementation in people without established deficiency.[24][25][26]
The U.S. Preventive Services Task Force issued an insufficient-evidence statement on screening for vitamin D deficiency in asymptomatic adults in 2014 and reaffirmed this position in 2021 for community-dwelling, nonpregnant adults.[22]
Large randomized controlled trials subsequently tested whether vitamin D supplementation prevents skeletal and extraskeletal disease. Landmark studies included VITAL, ViDA, D2d, D-Health, and DO-HEALTH. In VITAL, 2,000 IU/day of cholecalciferol for a median of 5.3 years did not reduce invasive cancer or major cardiovascular events among 25,871 U.S. adults.[27][28][29]
A VITAL ancillary study found no reduction in total, nonvertebral, or hip fractures (hazard ratio for total fractures 0.98), and DO-HEALTH (2,000 IU/day in adults aged 70 years and older) found no benefit for nonvertebral fractures or falls. Mean baseline 25(OH)D was 30.7 ng/mL in VITAL and 22.4 ng/mL in DO-HEALTH. A systematic review also suggested that high-dose intermittent dosing may increase falls compared with lower-dose daily dosing. These findings contributed to reassessment of proposed benefits derived from observational studies, particularly in populations not selected for vitamin D deficiency.[30][31][32]
The 2024 Endocrine Society guideline, subsequently revised in February 2025, addressed prevention of disease in the general population rather than evaluation and treatment of established deficiency. Its recommendations apply to generally healthy individuals without established indications for vitamin D treatment or 25(OH)D testing, and are not intended to be extrapolated to people with medical conditions known to adversely affect vitamin D physiology. It suggested against routine 25(OH)D screening in healthy children and adults, including individuals with obesity or dark complexion and during pregnancy, and no longer endorsed the 30 ng/mL target or specific thresholds defining sufficiency, insufficiency, and deficiency. It suggested empiric vitamin D supplementation (conditional recommendations) for children and adolescents aged 1–18 years, adults aged 75 years and older, pregnant individuals, and adults with high-risk prediabetes.[23][33]
Disagreement persists among experts regarding optimal vitamin D status and the interpretation of randomized trial evidence, which largely enrolled populations without established vitamin D deficiency.[34][35]
References
- ↑ 1.0 1.1 1.2 1.3 Elder CJ, Bishop NJ (2014). "Rickets". The Lancet. 383 (9929): 1665–1676. doi:10.1016/S0140-6736(13)61650-5.
- ↑ 2.0 2.1 2.2 Rajakumar K (2003). "Vitamin D, Cod-Liver Oil, Sunlight, and Rickets: A Historical Perspective". Pediatrics. 112 (2): e132–e135. doi:10.1542/peds.112.2.e132. PMID 12897318.
- ↑ 3.0 3.1 3.2 Carpenter TO, Shaw NJ, Portale AA; et al. (2017). "Rickets". Nature Reviews Disease Primers. 3: 17101. doi:10.1038/nrdp.2017.101.
- ↑ 4.0 4.1 4.2 4.3 Miller WL, Imel EA (2022). "Rickets, Vitamin D, and Ca/P Metabolism". Hormone Research in Paediatrics. 95 (6): 579–592. doi:10.1159/000527011. PMID 36446330 Check
|pmid=value (help). - ↑ 5.0 5.1 5.2 Hernigou P, Auregan JC, Dubory A (2019). "Vitamin D: Part II; Cod Liver Oil, Ultraviolet Radiation, and Eradication of Rickets". International Orthopaedics. 43 (3): 735–749. doi:10.1007/s00264-019-04288-z. PMID 30627846.
- ↑ 6.0 6.1 Rajakumar K, Thomas SB (2005). "Reemerging Nutritional Rickets: A Historical Perspective". Archives of Pediatrics & Adolescent Medicine. 159 (4): 335–341. doi:10.1001/archpedi.159.4.335.
- ↑ Schlingmann KP, Kaufmann M, Weber S; et al. (2011). "Mutations in CYP24A1 and idiopathic infantile hypercalcemia". The New England Journal of Medicine. 365 (5): 410–421. doi:10.1056/NEJMoa1103864.
- ↑ Bouillon R (2017). "Comparative analysis of nutritional guidelines for vitamin D". Nature Reviews Endocrinology. 13 (8): 466–479. doi:10.1038/nrendo.2017.31.
- ↑ Blank S, Scanlon KS, Sinks TH, Lett S, Falk H (1995). "An outbreak of hypervitaminosis D associated with the overfortification of milk from a home-delivery dairy". American Journal of Public Health. 85 (5): 656–659. doi:10.2105/AJPH.85.5.656. PMID 7733425.
- ↑ Jacobus CH, Holick MF, Shao Q; et al. (1992). "Hypervitaminosis D associated with drinking milk". The New England Journal of Medicine. 326 (18): 1173–1177. doi:10.1056/NEJM199204303261801.
- ↑ Holick MF, Shao Q, Liu WW, Chen TC (1992). "The vitamin D content of fortified milk and infant formula". The New England Journal of Medicine. 326 (18): 1178–1181. doi:10.1056/NEJM199204303261802.
- ↑ Bouillon R, Antonio L (2020). "Nutritional rickets: Historic overview and plan for worldwide eradication". Journal of Steroid Biochemistry and Molecular Biology. 198: 105563. doi:10.1016/j.jsbmb.2019.105563. PMID 31809867.
- ↑ 13.0 13.1 Munns CF, Shaw N, Kiely M; et al. (2016). "Global Consensus Recommendations on Prevention and Management of Nutritional Rickets". The Journal of Clinical Endocrinology and Metabolism. 101 (2): 394–415. doi:10.1210/jc.2015-2175.
- ↑ Chibuzor MT, Graham-Kalio D, Osaji JO; et al. (2020). "Vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.CD012581.pub2.
- ↑ Wagner CL, Greer FR (2008). "Prevention of rickets and vitamin D deficiency in infants, children, and adolescents". Pediatrics. 122 (5): 1142–1152. doi:10.1542/peds.2008-1862.
- ↑ Jullien S (2021). "Vitamin D prophylaxis in infancy". BMC Pediatrics. 21 (Suppl 1): 319. doi:10.1186/s12887-021-02776-z.
- ↑ DeLuca HF (1988). "The Vitamin D Story: A Collaborative Effort of Basic Science and Clinical Medicine". FASEB Journal. 2 (3): 224–236. doi:10.1096/fasebj.2.3.3280376. PMID 3280376.
- ↑ 18.0 18.1 The ADHR Consortium (2000). "Autosomal Dominant Hypophosphataemic Rickets Is Associated With Mutations in FGF23". Nature Genetics. 26 (3): 345–348. doi:10.1038/81664.
- ↑ Edmonston D, Wolf M (2020). "FGF23 at the crossroads of phosphate, iron economy and erythropoiesis". Nature Reviews Nephrology. 16 (1): 7–19. doi:10.1038/s41581-019-0189-5.
- ↑ The HYP Consortium (1995). "A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets". Nature Genetics. 11 (2): 130–136. doi:10.1038/ng1095-130.
- ↑ Shahangian S, Alspach TD, Astles JR, Yesupriya A, Dettwyler WK (2014). "Trends in laboratory test volumes for Medicare Part B reimbursements, 2000-2010". Archives of Pathology & Laboratory Medicine. 138 (2): 189–203. doi:10.5858/arpa.2013-0149-OA. PMID 23738761.
- ↑ 22.0 22.1 US Preventive Services Task Force; Krist AH, Davidson KW; et al. (2021). "Screening for vitamin D deficiency in adults: US Preventive Services Task Force recommendation statement". JAMA. 325 (14): 1436–1442. doi:10.1001/jama.2021.3069.
- ↑ 23.0 23.1 Demay MB, Pittas AG, Bikle DD; et al. (2024). "Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 109 (8): 1907–1947. doi:10.1210/clinem/dgae290.
- ↑ Ross AC, Manson JE, Abrams SA; et al. (2011). "The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know". The Journal of Clinical Endocrinology and Metabolism. 96 (1): 53–58. doi:10.1210/jc.2010-2704. PMID 21118827.
- ↑ Holick MF, Binkley NC, Bischoff-Ferrari HA; et al. (2011). "Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline". The Journal of Clinical Endocrinology and Metabolism. 96 (7): 1911–1930. doi:10.1210/jc.2011-0385.
- ↑ Aloia JF (2011). "Clinical Review: The 2011 Report on Dietary Reference Intake for Vitamin D: Where Do We Go From Here?". The Journal of Clinical Endocrinology and Metabolism. 96 (10): 2987–2996. doi:10.1210/jc.2011-0090.
- ↑ Manson JE, Cook NR, Lee IM; et al. (2019). "Vitamin D supplements and prevention of cancer and cardiovascular disease". The New England Journal of Medicine. 380 (1): 33–44. doi:10.1056/NEJMoa1809944.
- ↑ Bouillon R, Manousaki D, Rosen C; et al. (2022). "The health effects of vitamin D supplementation: evidence from human studies". Nature Reviews Endocrinology. 18 (2): 96–110. doi:10.1038/s41574-021-00593-z.
- ↑ Bouillon R, LeBoff MS, Neale RE (2023). "Health Effects of Vitamin D Supplementation: Lessons Learned From Randomized Controlled Trials and Mendelian Randomization Studies". Journal of Bone and Mineral Research. 38 (10): 1391–1403. doi:10.1002/jbmr.4888. PMID 37483080 Check
|pmid=value (help). - ↑ LeBoff MS, Chou SH, Ratliff KA; et al. (2022). "Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults". The New England Journal of Medicine. 387 (4): 299–309. doi:10.1056/NEJMoa2202106.
- ↑ LeBoff MS, Bischoff-Ferrari HA (2023). "The Effects of Vitamin D Supplementation on Musculoskeletal Health: The VITAL and DO-Health Trials". The Journals of Gerontology: Series A. 78 (Suppl 1): 73–78. doi:10.1093/gerona/glad073.
- ↑ Shah VP, Nayfeh T, Alsawaf Y; et al. (2024). "A Systematic Review Supporting the Endocrine Society Clinical Practice Guidelines on Vitamin D". The Journal of Clinical Endocrinology and Metabolism. 109 (8): 1961–1974. doi:10.1210/clinem/dgae312. PMID 38828942 Check
|pmid=value (help). - ↑ Liu ES, Davis AM, Burnett-Bowie SM (2025). "Vitamin D for Prevention of Disease". JAMA. 333 (20): 1824–1825. doi:10.1001/jama.2025.2278.
- ↑ Holick MF (2024). "Revisiting Vitamin D Guidelines: A Critical Appraisal of the Literature". Endocrine Practice. 30 (12): 1227–1241. doi:10.1016/j.eprac.2024.10.011.
- ↑ Giustina A, Bilezikian JP, Adler RA; et al. (2024). "Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows". Endocrine Reviews. 45 (5): 625–654. doi:10.1210/endrev/bnae009.
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