Updated perspectives on vitamin D deficiency, screening, supplementation and clinical guidance.

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Learn more: PMC Disclaimer | PMC Copyright Notice Cardiovasc Diabetol Endocrinol Rep . 2026 Jun 4;12:30. doi: 10.1186/s40842-026-00300-9 Show available content in en es Updated perspectives on vitamin D deficiency, screening, supplementation and clinical guidance Muhammad Ajmal Dina 1, ✉ , Asif Hanif 2 , Anam Arshed 3 , Asifa Karamat 4 , Muhammad Shakeel Basit 4 , Muhammad Akram Bhutta 5 , Muhammad Orangzaib Ehsan 6 Author information Article notes Copyright and License information 1 Department of Biostatistics and Epidemiology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran 2 Department of Biostatistics, Faculty of Medicine, Sakarya University, Sakarya, Türkiye 3 Rahbar Medical and Dental College, Lahore, Pakistan 4 Al Aleem Medical College, Gulab Devi Hospital, Lahore, Pakistan 5 Quaid-e-Azam Medical College, Bahawal Victoria Hospital Bahawalpur, Bahawalpur city, Pakistan 6 Health Services Academy Islamabad, Islamabad, Pakistan ✉ Corresponding author. Received 2025 Dec 12; Accepted 2026 Apr 7; Collection date 2026. © The Author(s) 2026 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ . PMC Copyright notice PMCID: PMC13235093  PMID: 42237374 Abstract Vitamin D functions like a hormone and plays a crucial role in regulating calcium levels and maintaining normal bone metabolism. A deficiency of vitamin D can lead to an increased risk of fractures, osteoporosis and osteomalacia that’s why research has linked vitamin D deficiency to various chronic diseases and certain types of cancer, thereby enhancing interest in its overall health implications. vitamin D deficiency is still prevalent among many populations. It is often found in older adults, individuals with chronic health conditions, those residing in care facilities and women who are either pregnant or nursing. There exists significant variability in clinical practices. Experts have differing opinions on who should undergo screening, what serum levels indicate sufficiency and the appropriate timing for initiating supplementation. This narrative review explores the key reservations that influence the diagnosis and management of vitamin D deficiency and current perspectives on screening, identifies high-risk populations that may benefit from testing and delineates circumstances in which empirical supplementation is a sensible and effective approach. Monitoring is beneficial and discusses how target levels correlate with bone health outcomes. A specific focus is directed towards the frequently cited 25(OH)D threshold of 30 ng/mL which is broadly linked to optimal bone health and underscores the synergistic significance of vitamin D and calcium in the management of osteoporosis and elucidates the reasons that why cholecalciferol is the favored formulation of vitamin D due to its advantageous pharmacological characteristics. Introduction Vitamin D functions as a hormone and plays a vital role in many essential processes within the body [ 1 ]. Its significance in preserving calcium balance and enhancing bone strength is well recognized but emerging research indicates that its effects reach far beyond the skeletal framework [ 2 ]. Serum 25-hydroxyvitamin D [25(OH)D] levels are commonly categorized as deficiency (< 20 ng/mL [< 50 nmol/L]), insufficiency (20–29 ng/mL [50–74 nmol/L]), and sufficiency (≥ 30 ng/mL [≥ 75 nmol/L]) [ 3 ]. Sufficient levels of vitamin D are now understood to bolster muscle function (Fig. 1 .), modulate immune responses, facilitate glucose metabolism, ensure cardiovascular health and potentially lower the risk of various chronic illnesses [ 4 ]. These extensive impacts, vitamin D deficiency (VDD) continues to pose a significant global issue and frequently remains undetected in clinical settings [ 5 ]. Vitamin D requirements may vary in special clinical conditions, including pregnancy, lactation, hyperparathyroidism, prediabetes and granulomatous diseases. These conditions require individualized assessment and tailored supplementation strategies due to altered metabolism and risk of deficiency or dysregulation. Fig. 1. Open in a new tab Vitamin D deficiency effects on wide range of populations, healthcare systems are persistently exploring straightforward, cost-effective and efficient methods for its diagnosis and management [ 6 ]. Establishing uniform guidelines has proven challenges. There is still a lack of consensus regarding the ideal serum level of 25-hydroxyvitamin D [25(OH)D] and the criteria for testing and the frequency of monitoring [ 7 ] The deficiency vitamin D is especially prevalent between individuals with limited sun exposure, older adults and those with conditions that hinder nutrient absorption, as explained in fig. 1 bellow. The review provides a clinically integrated and practice-oriented synthesis of vitamin D deficiency. It specific focus on targeted screening, cost-effectiveness, and decision-making in high-risk populations areas that remain insufficiently unified in current literature. Methodology This article was made as a structured narrative review to synthesize and critically appraise current evidence on vitamin D deficiency, screening strategies, supplementation practices and clinical guidance. Particular focus on bone health and high-risk populations. Literature Search: A comprehensive literature search was performed using the electronic databases PubMed, Scopus, Web of Science and Google Scholar. The literature search was conducted for studies published between January 2000 and December 2025. Articles were screened based on relevance to predefined objectives related to vitamin D deficiency, screening and supplementation. Study selection was performed through title, abstract and full-text review, applying predefined inclusion and exclusion criteria to ensure methodological rigor and relevance. The key search included: vitamin D deficiency, 25-hydroxyvitamin D, vitamin D screening, vitamin D supplementation, cholecalciferol, bone health, osteoporosis, fracture prevention, clinical guidelines. Eligibility Criteria: Studies were included if they met the following criteria. Peer-reviewed articles published in English Narrative reviews, systematic reviews, meta-analyses, randomized controlled trials, observational studies and international or national clinical guidelines. Exclusion criteria were: Case reports with limited clinical relevance. Editorials or opinion pieces without supporting evidence. Studies focusing exclusively on pediatric populations unless findings were relevant to general clinical practice. This structured narrative review was designed to bridge gaps between heterogeneous evidence and clinical practice by emphasizing critical appraisal, guideline discrepancies, and real-world applicability rather than purely descriptive summarization. Impact of vitamin D deficiency across organ systems Many healthcare providers advocate for empirical supplementation in individuals at high risk. This approach is practical, cost-efficient, and minimizes the necessity for regular laboratory evaluations while still addressing the primary causes of deficiency [ 8 ]. Selecting the appropriate form of vitamin D is also a critical component of treatment. Cholecalciferol (vitamin D3) is typically favored as it more effectively elevates and sustains serum 25(OH)D levels compared to other formulations [ 9 ]. Alternatives like ergocalciferol (vitamin D2), calcifediol, calcitriol and analogs such as alfacalcidol or paricalcitol are available. Patients with chronic kidney disease, severe liver disease, hypoparathyroidism, malabsorption syndromes, and disorders affecting vitamin D metabolism [ 10 ]. Where standard activation pathways are impaired. In such cases, active forms or analogs are preferred, as they bypass metabolic limitations and ensure adequate biological activity. Global prevalence, determinants and risk factors of vitamin D deficiency Vitamin D deficiency (VDD) showed significant global public health concern. Impacting individuals across all age groups and geographical locations. Although the exact threshold for deficiency remains under debate. Many definitions identify VDD as a serum 25-hydroxyvitamin D [25(OH)D] concentration below 50 ng/mL and severe deficiency typically characterized with levels falling below 30 ng/mL [ 11 ]. A comprehensive pooled analysis about nearly eight million individuals from 81 countries conducted between 2000 and 2022 revealed that 15.7% of participants had levels below 30 ng/mL, 47.9% below 50 ng/mL and 76.6% below 75 ng/mL, with minimal variation observed over the two-decade span [ 7 ]. Geographical factors significantly influence the prevalence of vitamin D deficiency (VDD) [ 12 ]. The highest prevalence rates are reported in the Middle East and South Asia [ 13 ]. Where countries indicate that over 30% of their populations have levels below 30 ng/mL [ 14 ]. On the other hand, in Africa—often considered low risk due to abundant sunshine and a younger population—approximately 18% of individuals still have vitamin D levels below ng/mL [ 15 ]. In the America, the prevalence rates showed considerable variability. North America generally reports lower deficiency rates, with 2.6% of the U.S. population having levels under 25 ng/mL and 7.4% of Canadians below 30 ng/mL [ 16 ]. In South America shows elevated rates, with 34.8% of individuals presenting with 25(OH)D levels below 20 ng/mL [ 17 ]. In Europe VDD continues to be a significant issue although ongoing public health efforts. Around 18% of the population is found to have levels below 30 nmol/L [ 18 ]. UK Biobank data indicating that 13% are severely deficient (10–25 ng/mL), a trend that is similarly observed in Spain [ 19 ]. Vitamin – D assessment: methods and clinical insights The application of laboratory tests for assessing vitamin D levels has significantly increased in recent years [ 20 ]. This flow is revealing that widespread global occurrence of vitamin D deficiency [ 21 ]. It’s a potential association with chronic diseases and mortality and the possible advantages of supplementation [ 22 ]. Research suggests that between 25% and 78% of these tests may be superfluous [ 23 ]. In affluent regions unnecessary testing can represent up to 76.5% of all vitamin D assessments [ 24 ]. Advancements in laboratory methods for vitamin D evaluation have been substantial. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is now considered the benchmark. The technique facilitates the accurate measurement of various vitamin D metabolites concurrently and can differentiate between vitamin D2 and D3 with their 3-epi-derivatives [ 7 ]. Evaluating functional deficiency the vitamin D metabolite ratio (VMR) the ratio of 24,25(OH) 2 D to 25(OH)D is of clinical significance [ 25 ]. Levels of 24,25(OH) 2 D falling below 3 ng/mL or a VMR lower than 4% are deemed indicative of vitamin D deficiency [ 26 ]. Debates and guidelines on routine, screening Routine screening for vitamin D deficiency (VDD) continues to be a subject of debate [ 27 ]. Some research shows that preventive measures can be very cost-effective and even lead to cost savings in certain demographics. Low levels of 25(OH)D may play a role in disease development rather than simply indicating poor health [ 28 ]. The primary question revolves around the necessity of population-wide screening. Supporters of universal screening contend that it can pinpoint individuals who would gain from supplementation prior to the onset of complications. Meta-analyses suggest that vitamin D supplementation in older adults with deficiencies can lower the likelihood of accidental falls [ 29 ]. At present no research has directly evaluated the effects of population-wide screening initiatives for VDD. The evidence is inadequate to warrant routine testing [ 30 ]. The United States Preventive Services Task Force (USPSTF) examined the advantages and costs of extensive screening and early intervention in community-dwelling [ 31 ]. High-risk populations and clinical considerations A growing consensus advocating for a targeted strategy regarding vitamin D. Identifying and addressing the needs of the high-risk groups. Those at elevated risk include individuals with obesity, those with limited exposure to sunlight, and people living in regions with low UV radiation [ 32 ]. Assessing vitamin D levels is particularly crucial for patients with osteoporosis. Antiresorptive medications used in osteoporosis management can induce hypocalcemia [ 33 ]. A risk that is significantly mitigated when patients maintain adequate vitamin D and calcium levels. However, implementing population-wide screening for vitamin D deficiency poses several challenges. Strict criteria may leave some deficient individuals untreated, while ambiguity in cut-off values and variability in 25(OH)D assay results can lead to diagnostic inaccuracies. Supplementation The significant prevalence of vitamin D deficiency between at risk groups has prompted the implementation of universal supplementation as a viable alternative strategy [ 34 ]. In these populations assessing 25(OH)D levels may not be economically feasible. Universal supplementation particularly for pregnant and lactating women as well as young children has demonstrated a considerable reduction in the incidence of symptomatic deficiency [ 35 ]. This approach also alleviates the pressure of extensive screening on healthcare systems, although vitamin D testing is relatively low-cost compared to many other biochemical assessments [ 36 ]. The high frequency of repeated tests can impose a substantial financial burden. In some countries the expense of testing can be as much as ten times greater than the cost of one year of supplementation. Vitamin D treatment is generally affordable and safe, except in high-dose protocols. While instances of toxicity are uncommon, the likelihood of adverse effects may increase if supplementation is indiscriminately administered across large populations. Economic considerations The rise in vitamin D testing, national regulations and ongoing discussions regarding management. The cost-effectiveness of measuring serum 25(OH)D in comparison to long-term supplementation has emerged as a significant factor [ 37 ]. Research indicates that supplementation is especially cost-effective for older adults, particularly those aged over 70 years [ 38 ]. A study conducted in Ireland assessed vitamin D3 supplementation in adults aged ≥ 50, ≥60, and ≥ 70 who were deficient (serum 25(OH)D < 30 ng/mL) [ 39 ]. For the cohort aged ≥ 70, the projected annual expenditure was €5.6 million, yielding 1,044 quality-adjusted life years (QALYs), which translates to a cost per QALY of roughly €5,400 [ 7 ]. The findings were notably sensitive to the reduction in mortality linked to supplementation [ 40 ]. Daily supplementation with cholecalciferol (800 IU) in individuals aged ≥ 65 years is associated with a modest. Its clinically meaningful reduction in the incidence of falls and hip fractures, especially among those with low baseline 25(OH)D concentrations [ 41 ]. This can help prevent associated mortality and potentially save healthcare expenditures. Clinical practice Vitamin D supplementation continues to be a viable and economical method for enhancing vitamin D levels. It can be easily implemented in most healthcare environments. Oral supplements are recommended when exposure to sunlight is limited or purposely avoided. When dietary intake is insufficient, as outlined in the guidelines set forth by the Institute of Medicine. Many expert organizations endorse this strategy for older adults as well. Recommendations from the UK government, the American Geriatrics Society, and the French Group of Geriatrics indicate that routine assessment of serum 25(OH)D is unnecessary prior to initiating supplementation in adults aged 65 and older [ 42 ]. Particularly for those with limited sun exposure like residents of care facilities. Supplementation and clinical considerations Certain populations derive clinically meaningful benefits from vitamin D supplementation, including improved musculoskeletal outcomes and reduced fracture risk; however, the magnitude of benefit depends on baseline vitamin D status, comorbidities, and the dose and formulation used (Table 1 ). These individuals can initiate supplementation and subsequent measurements of their serum 25(OH)D levels are recommended. Assessing serum 25(OH)D is essential to verify if adequate levels have been reached, irrespective of the particular threshold applied. Table 1. High-risk groups for vitamin D supplementation without prior serum testing Population Rationale Typical guidance Individuals with limited sun exposure (e.g., indoor workers, winter months) Reduced skin synthesis of vitamin D 600–1000 IU/day or per local guidelines [ 43 ] Individuals with low dietary vitamin D intake Insufficient intake from foods 600–1000 IU/day; encourage vitamin D-rich diet [ 44 ] People with darker/pigmented skin Melanin reduces cutaneous vitamin D production 800–1000 IU/day; monitor levels if risk factors present [ 45 ] Infants, children, and adolescents Critical for bone growth; prevent rickets Infants: 400 IU/day; Children/Adolescents: 600 IU/day [ 45 ] Women planning pregnancy, pregnant or breastfeeding Supports maternal and fetal bone health 600–1000 IU/day; up to 2000 IU/day in deficiency risk [ 46 ] Older adults (≥ 65 years) Reduced synthesis and fracture risk 800–2000 IU/day; combine with calcium if indicated [ 47 ] Institutionalized individuals Limited sun exposure, comorbidities 800–2000 IU/day; monitor levels periodically [ 48 ] At risk of or with osteoporosis Bone protection; prevent fractures 800–2000 IU/day; ensure adequate calcium intake [ 49 ] Obese individuals & bariatric surgery patients Reduced absorption 1000–4000 IU/day; higher doses often needed [ 50 ] Patients with malabsorption syndromes Impaired intestinal absorption 1000–5000 IU/day; may require specialized formulations [ 51 ] Patients with documented vitamin D deficiency Prevent relapse post-correction Maintenance dose individualized; 800–2000 IU/day typical [ 52 ] High-risk metabolic disorders (prediabetes, diabetes) Supports glucose homeostasis 800–2000 IU/day; individualized based on levels [ 53 ] Patients with liver disease (cirrhosis, NAFLD) Impaired 25-hydroxylation 1000–2000 IU/day; monitor serum levels [ 54 ] Open in a new tab Empirical supplementation of vitamin D may be advisable for individuals who don’t show clear deficiency but have limited sun exposure or insufficient dietary intake [ 55 ]. Dark skin tones are particularly vulnerable to deficiency due to the absorption of UVB radiation with melanin, which hinders the synthesis of vitamin D in the skin [ 56 ]. The significance of vitamin D is important during pregnancy, research indicates that supplementation can mitigate the risk of complications like preeclampsia, gestational diabetes, and preterm birth [ 57 ]. Vitamin D deficiency frequently occurs in conditions that hinder absorption, like celiac disease, cystic fibrosis, and short bowel syndrome. Obesity increases the risk because vitamin D is stored in adipose tissue, reducing its bioavailability [ 58 ]. Dosage, safety and clinical implementation Cholecalciferol is recognized as the optimal form of vitamin D for therapeutic purposes, particularly in situations where serum 25(OH)D levels are not accessible [ 9 ]. Its lipophilic characteristics contribute to a prolonged half-life of approximately 60 days, resulting in stable and sustained plasma concentrations over time. Cholecalciferol possesses a natural feedback mechanism during hepatic hydroxylation, which mitigates the risk of excessive vitamin D activity [ 9 ]. This attribute renders weekly or monthly dosing, when converted to daily equivalents, both safe and effective. To rapidly address vitamin D deficiency, a loading dose may be administered. This consists of 25,000–50,000 IU weekly for a duration of 4–6 weeks, followed by a maintenance dose [ 59 ]. Maintenance therapy is crucial to avert recurrent deficiency, irrespective of the initial treatment approach [ 60 ]. Average, an increase of 100 IU of vitamin D3 daily correlates with a rise in serum 25(OH)D of approximately 1 ng/mL [ 61 ]. Thus, a daily intake of 2000 IU can elevate levels by 20 ng/mL without inducing toxicity [ 62 ]. Vitamin D forms of and clinical monitoring Once vitamin D treatment is initiated, the necessity for monitoring is contingent upon the specific type of vitamin D utilized and the prescribed dosing regimen. The two predominant oral forms are plant-sourced vitamin D2 (ergocalciferol) and animal-sourced vitamin D3 (cholecalciferol) [ 63 ], although both are often regarded as equivalent, significant distinctions exist. Vitamin D binding protein (VDBP) exhibits a slightly weaker affinity for D2 metabolites, resulting in a shorter half-life for 25(OH)D2 approximately 10% less than that of 25(OH)D3 [ 64 ]. Research indicates that cholecalciferol is more effective in elevating circulating 25(OH)D levels compared to ergocalciferol. Furthermore, the majority of assays demonstrate greater accuracy in measuring D3 than D2. In some areas active or intermediate vitamin D metabolites like calcifediol (25(OH)D) or calcitriol (1,25(OH) 2 D), are accessible for patients experiencing impaired vitamin D metabolism [ 65 ]. The group includes individuals with severe liver disease, moderate to severe kidney disease, enzyme deficiencies, malabsorption disorders, and hypoparathyroidism [ 66 ]. The group includes individuals with severe liver disease, moderate to severe kidney disease. Defects in vitamin D–metabolizing enzymes (including 25-hydroxylase [CYP2R1] and 1α-hydroxylase [CYP27B1]), malabsorption syndromes and hypoparathyroidism in whom normal activation pathways of vitamin D are impaired [ 67 ]. Including periodic assessment of serum calcium and 25(OH)D levels to ensure safety and efficacy. In special caution is advised in high-risk conditions like renal disease, granulomatous disorders and hyperparathyroidism [ 68 ]. Where the risk of vitamin D toxicity is increased. Cholecalciferol: regimens, safety and risks Vitamin D3 (cholecalciferol) can be administered in daily, weekly, or monthly doses to rectify deficiency in adults [ 9 ]. Intermittent doses are occasionally favored for swift repletion or patient convenience. Research indicates that when the same total dose is applied, daily and intermittent regimens are comparably effective in restoring serum 25(OH)D levels over a period of 2–3 months [ 7 ]. Monthly dosing results in a quicker initial rise in 25(OH)D compared to daily dosing, which can be beneficial for rapid correction [ 69 ]. Both dosing methods are generally regarded as safe and effective but some evidence points to a slight advantage of daily dosing in specific situations. Cholecalciferol exhibits therapeutic equivalence across various dosing schedules, thereby endorsing treatment flexibility [ 70 ]. Monthly doses frequently enhance adherence and patient preference relative to daily or weekly regimens. Large bolus doses should be approached with caution. Excessive doses can elevate fibroblast growth factor 23 (FGF23), leading to a reduction in 1,25(OH) 2 D levels [ 71 ]. This can hinder calcium absorption, escalate bone turnover and increase the likelihood of fractures and falls. Extremely high single doses like 300,000–500,000 IU, have been associated with a heightened risk of falls and fractures [ 9 ]. But some studies indicate no adverse effects with monthly doses of 80,000–100,000 IU [ 72 ]. Pharmacokinetic equivalence in raising serum 25(OH)D levels does not necessarily translate into equivalent clinical outcomes. Several intervention studies have demonstrated that daily vitamin D supplementation is superior to intermittent bolus dosing with respect to physiological endpoints such as bone turnover markers, immune function and fall prevention [ 7 ]. The well-recognized “bolus is bogus” principle, supported study by the Pludowski et al. indicates that intermittent high-dose administration may paradoxically increase fall and fracture risk, possibly due to transient elevations in fibroblast growth factor 23 (FGF23) and subsequent reduction in 1,25(OH) 2 D activity. While monthly or weekly regimens offer practical adherence benefits, daily cholecalciferol administration remains the preferred regimen when clinically feasible, particularly in older adults and individuals at risk of falls or fractures [ 73 ]. Empirical vitamin D therapy Measurements of serum 25(OH)D are not consistently available and are mostly performed for individuals at elevated risk of vitamin D deficiency. Clinical guidelines suggest treatment protocols that do not require prior testing. This ensures that patients at risk continue to receive appropriate supplementation. Clinical studies indicate that regular assessment of serum 25(OH)D levels is generally unnecessary for the majority of adults, provided that supplementation remains within the advised parameters. Initial replacement can be accomplished through the administration of oral cholecalciferol (vitamin D3) at a dosage of 4000 IU daily. It can be equally effective in weekly or monthly regimens. For continued maintenance beyond a six-month period, daily intakes of up to 2000 IU are characteristically adequate to ensure sufficient vitamin D concentrations. Therapy, indications and practices Monitoring is not universally necessary for all individuals. It assumes significance in particular circumstances. In such examples, assessing levels can assist in modifying the dosage and ensuring the treatment’s efficacy. It facilitates safe decision-making, particularly when patients exhibit varied responses owing to their medical conditions, medications and other risk factors. The specific situations detailed in Table 2 illustrate when monitoring proves most beneficial for effective management. Table 2. Clinical scenarios requiring vitamin D monitoring Clinical Scenario Monitoring reason Unmonitored, Possible Risks Monitoring approach Symptomatic vitamin D deficiency To confirm response to treatment and guide dose adjustment Persistent deficiency, inadequate symptom improvement Check 25(OH)D, calcium, and phosphorus levels [ 52 ] Use of active vitamin D metabolites (calcifediol, calcitriol) These agents have a stronger effect and narrower safety margin Hypercalcemia, toxicity Frequent serum calcium, phosphorus, and renal function tests [ 6 ] High-dose supplementation beyond routine doses Higher doses increase the chance of toxicity Hypervitaminosis D, hypercalcemia Regular 25(OH)D and calcium monitoring [ 74 ] Use of medications that alter vitamin D absorption, antiepileptics, corticosteroids, etc. These drugs may reduce absorption or increase breakdown Suboptimal treatment response, persistent deficiency Periodic 25(OH)D testing and medication review [ 75 ] Use of drugs with known interactions or risks (e.g., cardiac glycosides, thiazide diuretics) Vitamin D may worsen drug-related side effects Arrhythmias, severe hypercalcemia Monitor calcium, electrolytes, and kidney function [ 76 ] Poor treatment adherence expected Ensures clinical effectiveness and safety Ongoing deficiency or inadequate improvement Repeat 25(OH)D level to confirm compliance [ 77 ] History of hypervitaminosis D, hypo/hypercalcemia, hypercalciuria, or hyperphosphatemia Higher baseline risk of metabolic imbalance Recurrence of abnormalities Check calcium, phosphate, urinary calcium, and 25(OH)D [ 78 ] Malabsorption syndromes or history of bariatric surgery Poor nutrient absorption affects vitamin D levels Persistent low levels despite supplementation More frequent 25(OH)D assessment and dose adjustment [ 79 ] Obesity (BMI > 30 kg/m²) Vitamin D is sequestered in adipose tissue Reduced therapeutic response Higher dosing needs and periodic level checks [ 80 ] Chronic liver or kidney disease Impaired vitamin D activation and metabolism Inadequate response, electrolyte imbalance Monitor 25(OH)D, calcium, PTH, and renal function [ 71 ] Metabolic bone diseases (osteoporosis, recurrent falls or fractures) Ensures treatment efficacy and bone health Fracture risk, incomplete therapeutic response Monitor bone markers, 25(OH)D, calcium, and phosphorus [ 81 ] Hyperparathyroidism or hyperthyroidism Altered calcium metabolism affects vitamin D response Increased risk of hypercalcemia Check calcium, PTH, thyroid function, and 25(OH)D [ 82 ] Vitamin D hypersensitivity disorders (24-hydroxylase deficiency, etc. Higher sensitivity to vitamin D effects Rapid onset hypercalcemia or toxicity Close monitoring of calcium, renal function, and 25(OH)D [ 83 ] Open in a new tab During vitamin D therapy, monitoring is essential and the most effective indicator for assessing status is the serum 25(OH)D level [ 53 ]. This measurement reflects the body’s response to supplementation. Furthermore, evaluating both serum and urinary calcium is crucial for identifying early signs of imbalance or toxicity [ 84 ]. Clinicians typically repeat these tests approximately three to four months after initiating vitamin D3 therapy, providing sufficient time for levels to stabilize. Challenges and guideline discrepancies The publication of more than 200 systematic reviews on vitamin D annually, the definition of vitamin D deficiency continues to be a topic of debate. Much of this ambiguity arises from the employment of non-standardized 25(OH)D assays that yield inconsistent results and complicate the correlation between vitamin D levels and essential bone health outcomes. Research regarding vitamin D supplementation and its role in fracture prevention exhibits a similar lack of consistency [ 85 ]. Many systematic reviews and meta-analyses have explored this issue, yet their findings frequently diverge. This inconsistency is reflected in international guidelines. Two recent reviews have identified more than 40 vitamin D guidelines globally, each presenting varying recommendations. Standardized vitamin D assessment That hypovitaminosis D is prevalent globally and associated with inadequate bone health and potentially other health issues establishing robust, evidence-based guidelines is imperative [ 22 ]. Thus, specialists have highlighted the necessity of reporting standardized 25(OH)D values. The utilization of standardized measurements would facilitate the accurate amalgamation of data from various studies, aiding researchers in reaching a consensus on the definition of vitamin D deficiency. Several journals have already initiated the requirement for standardized 25(OH)D results prior to the acceptance of studies for publication. Unlike prior reviews that focus on isolated aspects. This review integrates epidemiological, clinical and economic perspectives to support pragmatic, evidence-informed strategies for vitamin D assessment and supplementation. Limitations Variability in study designs, definitions of vitamin D deficiency and assay methods may affect comparability. Potential publication bias and exclusion of non-English studies are possible. Moreover, ongoing controversies in vitamin D thresholds and recommendations may limit generalizability. Conclusions Vitamin D deficiency still a major global health concern, important to skeletal and extra-skeletal implications. The current evidence supports a targeted rather than universal screening strategy, prioritizing individuals at high risk. This approach is more practical, clinically meaningful and cost-effective than population-wide testing. In settings where laboratory assessment is limited empirical supplementation with cholecalciferol within recommended doses represents a safe, feasible and economically sound public health strategy. Cholecalciferol has the preferred formulation due to its favorable pharmacokinetics and safety profile. To enhance consistency across research and clinical practice, standardized terminology and uniform reporting of serum 25-hydroxyvitamin D levels in both ng/mL and nmol/L are essential and adoption of harmonized thresholds will strengthen evidence-based decision-making and guideline alignment. Future research should order standardized vitamin D measurement. Define the population-specific optimal thresholds. Conduct high-quality trials to clarify long-term clinical outcomes and the safety of different supplementation strategies. Abbreviations 25(OH) 2 D 1,25-Dihydroxyvitamin D 24,25(OH) 2 D 24,25-Dihydroxyvitamin D 25(OH)D 25-Hydroxyvitamin D D2 Ergocalciferol D3 Cholecalciferol FGF23 Fibroblast Growth Factor 23 LC–MS/MS Liquid Chromatography–Tandem Mass Spectrometry NAFLD Non-Alcoholic Fatty Liver Disease PTH Parathyroid Hormone QALY Quality-Adjusted Life Year UVB Ultraviolet B Radiation VDD Vitamin D Deficiency Author contributions M.A.D., A.H., A.A. was involved in conceptualization, data extraction and A.K., M.S.B., M.A.B. and M.O.E. was language editing, and original manuscript writing, in methods, reviewing, analysis, and language editing. 1–7, All authors approved the final version of the manuscript. Funding No funding received for this study. Data availability No datasets were generated or analyzed during the current study. Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. 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