The official recommendation from the United States Preventive Services Task Force is that for persons that do not fall within an at-risk population and are asymptomatic, there is not enough evidence to prove that there is any benefit in screening for vitamin D deficiency.

Retinyl esters can be distinguished from retinol in serum and other tissues and quantified with the use of methods such as high-performance liquid chromatography.

Elevated amounts of retinyl ester (i.e., > 10% of total circulating vitamin A) in the fasting state have been used as markers for chronic hypervitaminosis A in humans and monkeys. This increased retinyl ester may be due to decreased hepatic uptake of vitamin A and the leaking of esters into the bloodstream from saturated hepatic stellate cells.

Infants with rickets often have bone fractures. This sometimes leads to child abuse allegations. This issue appears to be more common for solely nursing infants of black mothers, in winter in temperate climates, suffering poor nutrition and no vitamin D supplementation. People with darker skin produce less vitamin D than those with lighter skin, for the same amount of sunlight.

Rickets may be diagnosed with the help of:

- Blood tests:

- Serum calcium may show low levels of calcium, serum phosphorus may be low, and serum alkaline phosphatase may be high from bones or changes in the shape or structure of the bones. This can show enlarged limbs and joints.

- A bone density scan may be undertaken.

- Radiography typically show widening of the zones of provisional calcification of the metaphyses secondary to unmineralized osteoid. Cupping, fraying, and splaying of metaphyses typically appears with growth and continued weight bearing. These changes are seen predominantly at sites of rapid growth, including the proximal humerus, distal radius, distal femur and both the proximal and the distal tibia. Therefore, a skeletal survey for rickets can be accomplished with anteroposterior radiographs of the knees, wrists, and ankles.

The serum concentration of 25(OH)D is typically used to determine vitamin D status. Most vitamin D is converted to 25(OH)D in the serum, giving an accurate picture of vitamin D status.

The level of serum 1,25(OH)D is not usually used to determine vitamin D status because it often is regulated by other hormones in the body such as parathyroid hormone. The levels of 1,25(OH)D can remain normal even when a person may be vitamin D deficient.

Serum level of 25(OH)D is the laboratory test ordered to indicate whether or not a person has vitamin D deficiency or insufficiency.

It is also considered reasonable to treat at-risk persons with vitamin D supplementation without checking the level of 25(OH)D in the serum, as vitamin D toxicity has only been rarely reported to occur.

Levels of 25(OH)D that are consistently above 200 ng/mL (500 nmol/L) are thought to be potentially toxic, although data from humans are sparse. Vitamin D toxicity usually results from taking supplements in excess. Hypercalcemia is often the cause of symptoms, and levels of 25(OH)D above 150 ng/mL (375 nmol/L) are usually found, although in some cases 25(OH)D levels may appear to be normal. Periodic measurement of serum calcium in individuals receiving large doses of vitamin D is recommended.

Assessing vitamin A status in persons with subtoxicity or toxicity is complicated because serum retinol concentrations are not sensitive indicators in this range of liver vitamin A reserves. The range of serum retinol concentrations under normal conditions is 1–3 μmol/l and, because of homeostatic regulation, that range varies little with widely disparate vitamin A intakes

Radiological appearances include:

- Pseudofractures, also called Looser's zones.

- Protrusio acetabuli, a hip joint disorder

Biochemical features are similar to those of rickets. The major factor is an abnormally low vitamin D concentration in blood serum.Major typical biochemical findings include:

- Low serum and urinary calcium

- Low serum phosphate, except in cases of renal osteodystrophy

- Elevated serum alkaline phosphatase (due to an increase in compensatory osteoblast activity)

- Elevated parathyroid hormone (due to low calcium)

Furthermore, a technetium bone scan will show increased activity (also due to increased osteoblasts).

Begin clinical laboratory evaluation of rickets with assessment of serum calcium, phosphate, and alkaline phosphatase levels. In hypophosphatemic rickets, calcium levels may be within or slightly below the reference range; alkaline phosphatase levels will be significantly above the reference range.

Carefully evaluate serum phosphate levels in the first year of life, because the concentration reference range for infants (5.0-7.5 mg/dL) is high compared with that for adults (2.7-4.5 mg/dL).

Serum parathyroid hormone levels are within the reference range or slightly elevated, while calcitriol levels are low or within the lower reference range. Most importantly, urinary loss of phosphate is above the reference range.

The renal tubular reabsorption of phosphate (TRP) in X-linked hypophosphatemia is 60%; normal TRP exceeds 90% at the same reduced plasma phosphate concentration. The TRP is calculated with the following formula:

1 - [Phosphate Clearance (CPi) / Creatinine Clearance (C)] X 100

Vitamin D deficiency historically used to be identified through counting cases of rickets. The old theory was that if someone had enough vitamin D to prevent rickets and osteomalacia, two skeletal disorders, they were considered safe from a deficiency. Nowadays through technological advancements Vitamin D deficiencies are now identified and thus calculated through the measurement of the serum 25-OH. According to the Australian Bureau of Statistics National Health Measures Survey (NHMS), the recommend Vitamin D levels to determine deficiency are categorised as follows:

•Adequate levels: >50 nmol/L

•Mild deficiency: 30-49 nmol/L

•Moderate deficiency: 13 – 29nmol/L

•Severe deficiency: <13 nmol/L

Day to day requirements of vitamin d are set around 800-1000IU to maintain healthy levels which in most cases can be provided by sun exposure. Increased amounts are required for individuals who are previously diagnosed as deficient. For those of moderate deficiencies,oral supplementation can be implemented into the diet at levels of 3000-5000 IU per day for a 6- to 12-week period continued by an ongoing reduced dose of 1000- 2000 IU per day to maintain stores in the body.

Severe deficiency is treated through megadose therapy where patients are given doses around 100 000 IU to assist in raising stores faster to ensure physical health in restored to prevent further illness or disease.

The U.S Institute of Medicine has established a Tolerable Upper Intake Level (UL) to protect against vitamin D toxicity. These levels in microgram (mcg or µg) and International Units (IU) for male and female are:

- 0–6 months: 25 µg (1000 IU)

- 7–12 months: 38 µg (1500 IU)

- 1–3 years: 63 µg (2500 IU)

- 4–8 years:75 µg (3000 IU)

- 9+ years:100 µg (4000 IU)

- Pregnant and Lactating: 100 µg (4000 IU)

The recommended dietary allowance is 15 µg/d (600 IU per day; 800 IU for those over 70 years). Overdose has been observed at 1,925 µg/d (77,000 IU per day). Acute overdose requires between 15,000 µg/d (600,000 IU per day) and 42,000 µg/d (1,680,000 IU per day) over a period of several days to months.

Serum chemistries are identical in tumor-induced osteomalacia, X-linked hypophosphatemic rickets (XHR) and autosomal dominant hypophosphatemic rickets (ADHR). A negative family history can be useful in distinguishing tumor induced osteomalacia from XHR and ADHR. If necessary, genetic testing for PHEX (phosphate regulating gene with homologies to endopepetidase on the X-chromosome) can be used to conclusively diagnose XHR and testing for the FGF-23 gene will identify patients with ADHR.

Biochemical studies reveal hypophosphatemia (low blood phosphate), elevated alkaline phosphatase and low serum 1, 25 dihydroxyvitamin D levels. Routine laboratory tests do not include serum phosphate levels and this can result in considerable delay in diagnosis. Even when low phosphate is measured, its significance is often overlooked. The next most appropriate test is measurement of urine phosphate levels. If there is inappropriately high urine phosphate (phosphaturia) in the setting of low serum phosphate (hypophosphatemia), there should be a high suspicion for tumor-induced osteomalacia. FGF23 (see below) can be measured to confirm the diagnosis but this test is not widely available.

Once hypophosphatemia and phosphaturia have been identified, a search for the causative tumor should begin. These are small and difficult to define. Gallium-68 DOTA-Octreotate (DOTA-TATE) positron emission tomography (PET) scanning is the best way to locate these tumors. If this scan is not available, other options include Indium-111 Octreotide (Octreoscan) SPECT/CT, whole body CT or MRI imaging.

The symptom that best characterizes hypophosphatasia is low serum activity of alkaline phosphatase enzyme (ALP). In general, lower levels of enzyme activity correlate with more severe symptoms. The decrease in ALP activity leads to an increase in pyridoxal 5’-phosphate (PLP) in the blood, and correlates with disease severity. Urinary inorganic pyrophosphate (PPi) levels are elevated in most hypophosphatasia patients and, although it remains only a research technique, this increase has been reported to accurately detect carriers of the disease. In addition, most patients have an increased level of urinary phosphoethanolamine (PEA). Tests for serum ALP levels are part of the standard comprehensive metabolic panel (CMP) that is used in routine exams.

Oral phosphate, 9, calcitriol, 9; in the event of severe bowing, an osteotomy may be performed to correct the leg shape.

Possible ethnic differences in physiological pathways for ingested vitamin D, such as the Inuit, may confound across the board recommendations for vitamin D levels. Inuit compensate for lower production of vitamin D by converting more of this vitamin to its most active form.

A Toronto study of young Canadians of diverse ancestry applied a standard of serum 25(OH)D levels that was significantly higher than official recommendations. These levels were described to be 75 nmol/L as "optimal", between 75 nmol/L and 50 nmol/L as "insufficient" and < 50 nmol/L as "deficient". 22% of individuals of European ancestry had 25(OH)D levels less than the 40 nmol/L cutoff, comparable to the values observed in previous studies (40nmol/L is 15 ng/mL). 78% of individuals of East Asian ancestry and 77% of individuals of South Asian ancestry had 25(OH)D concentrations lower than 40 nmol/L. The East Asians in the Toronto sample had low 25(OH)D levels when compared to whites. In a Chinese population at particular risk for esophageal cancer and with the high serum 25(OH)D concentrations have a significantly increased risk of the precursor lesion.

Studies on the South Asians population uniformly point to low 25(OH)D levels, despite abundant sunshine. Rural men around Delhi average 44nmol/L. Healthy Indians seem have low 25(OH)D levels which are not very different from healthy South Asians living in Canada. South Indian patients with ischemic heart disease have serum 25-hydroxyvitamin D levels which are above 222.5 nmol/l and considered extremely high. Measuring melanin content to assess skin pigmentation showed an inverse relationship with serum 25(OH)D. The uniform occurrence of very low serum 25(OH)D in Indians living in India and Chinese in China does not support the hypothesis that the low levels seen in the more pigmented are due to lack of synthesis from the sun at higher latitudes.

A study of French Canadians found that a significant minority did not maximize ingested serum 25(OH)D for genetic reasons; vitamin D-binding protein polymorphisms explained as much of the variation in circulating 25(OH)D as did total ingestion of vitamin D.

Despite patient-to-patient variability and the diversity of radiographic findings, the X-ray is diagnostic in infantile hypophosphatasia. Skeletal defects are found in nearly all patients and include hypomineralization, rachitic changes, incomplete vertebrate ossification and, occasionally, lateral bony spurs on the ulnae and fibulae.

In newborns, X-rays readily distinguish hypophosphatasia from osteogenesis imperfecta and congenital dwarfism. Some stillborn skeletons show almost no mineralization; others have marked undermineralization and severe rachitic changes. Occasionally there can be peculiar complete or partial absence of ossification in one or more vertebrae. In the skull, individual membranous bones may calcify only at their centers, making it appear that areas of the unossified calvarium have cranial sutures that are widely separated when, in fact, they are functionally closed. Small protrusions (or "tongues") of radiolucency often extend from the metaphyses into the bone shaft.

In infants, radiographic features of hypophosphatasia are striking, though generally less severe than those found in perinatal hypophosphatasia. In some newly diagnosed patients, there is an abrupt transition from relatively normal-appearing diaphyses to uncalcified metaphases, suggesting an abrupt metabolic change has occurred. Serial radiography studies can reveal the persistence of impaired skeletal mineralization (i.e. rickets), instances of sclerosis, and gradual generalized demineralization.

In adults, X-rays may reveal bilateral femoral pseudofractures in the lateral diaphysis. These pseudofractures may remain for years, but they may not heal until they break completely or the patient receives intramedullary fixation. These patients may also experience recurrent metatarsal fractures.

In the United States, overdose exposure to all formulations of "vitamins" was reported by 62,562 individuals in 2004 (nearly 80% [~78%, n=48,989] of these exposures were in children under the age of 6), leading to 53 "major" life-threatening outcomes and 3 deaths (2 from vitamins D and E; 1 from polyvitaminic type formula, with iron and no fluoride). This may be compared to the 19,250 people who died of unintentional poisoning of all kinds in the U.S. in the same year (2004). In 2010, 71,000 exposures to various vitamins and multivitamin-mineral formulations were reported to poison control centers, which resulted in 15 major reactions but no deaths.

Before 1998, several deaths per year were associated with pharmaceutical iron-containing supplements, especially brightly colored, sugar-coated, high-potency iron supplements, and most deaths were children. Unit packaging restrictions on supplements with more than 30 mg of iron have since reduced deaths to 0 or 1 per year. These statistics compare with 59 confirmed deaths due to aspirin poisoning in 2003 and 147 deaths known to be associated with acetaminophen-containing products in 2003.

Hypophosphatemia is diagnosed by measuring the concentration of phosphate in the blood. Concentrations of phosphate less than 0.81 mmol/L (2.5 mg/dL) are considered diagnostic of hypophosphatemia, though additional tests may be needed to identify the underlying cause of the disorder.

The amount of biologically active calcium varies with the level of serum albumin, a protein to which calcium is bound, and therefore levels of "ionized calcium" are better measures than a "total calcium"; however, one can correct a "total calcium" if the albumin level is known.

- A normal "ionized calcium" is 1.12-1.45 mmol/L (4.54-5.61 mg/dL).

- A normal "total calcium" is 2.2-2.6 mmol/L (9-10.5 mg/dl).

- "Total calcium" of less than 8.0 mg/dL is hypocalcaemia, with levels below 1.59 mmol/L (6 mg/dL) generally fatal.

- "Total calcium" of more than 10.6 mg/dL is hypercalcaemia, with levels over 3.753 mmol/L (15.12 mg/dL) generally fatal.

Hypervitaminosis is a condition of abnormally high storage levels of vitamins, which can lead to toxic symptoms. Specific medical names of the different conditions are derived from the vitamin involved: an excess of vitamin A, for example, is called hypervitaminosis A.

Hypervitaminoses are primarily caused by fat-soluble vitamins (D, E, K and A), as these are stored by the body for longer period than the water-soluble vitamins.

Generally, toxic levels of vitamins stem from high supplement intake and not from natural food. Toxicities of fat-soluble vitamins can also be caused by a large intake of highly fortified foods, but natural food rarely deliver dangerous levels of fat-soluble vitamins. The Dietary Reference Intake recommendations from the United States Department of Agriculture define a "tolerable upper intake level" for most vitamins.

Autosomal dominant hypophosphatemic rickets (ADHR) is a rare hereditary disease in which excessive loss of phosphate in the urine leads to poorly formed bones (rickets), bone pain, and tooth abscesses. ADHR is caused by a mutation in the fibroblast growth factor 23 (FGF23). ADHR affects men and women equally; symptoms may become apparent at any point from childhood through early adulthood. Blood tests reveal low levels of phosphate (hypophosphatemia) and inappropriately normal levels of vitamin D. Occasionally, hypophosphatemia may improve over time as urine losses of phosphate partially correct.

ADHR may be lumped in with X-linked hypophosphatemia under general terms such as "hypophosphatemic rickets". Hypophospatemic rickets are associated with at least nine other genetic mutations. Clinical management of hypophospatemic rickets may differ depending on the specific mutations associated with an individual case, but treatments are aimed at raising phosphate levels to promote normal bone formation.

A vitamin deficiency can cause a disease or syndrome known as an avitaminosis or hypovitaminosis. This usually refers to a long-term deficiency of a vitamin. When caused by inadequate nutrition it can be classed as a "primary deficiency", and when due to an underlying disorder such as malabsorption it can be classed as a "secondary deficiency". An underlying disorder may be metabolic as in a defect converting tryptophan to niacin. It can also be the result of lifestyle choices including smoking and alcohol consumption.

Examples are vitamin A deficiency, folate deficiency, scurvy, vitamin D deficiency, vitamin E deficiency, and vitamin K deficiency. In the medical literature, any of these may also be called by names on the pattern of "hypovitaminosis" or "avitaminosis" + "[letter of vitamin]", for example, hypovitaminosis A, hypovitaminosis C, hypovitaminosis D.

Conversely hypervitaminosis is the syndrome of symptoms caused by over-retention of fat-soluble vitamins in the body.

- Vitamin A deficiency can cause keratomalacia.

- Thiamine (vitamin B1) deficiency causes beriberi and Wernicke–Korsakoff syndrome.

- Riboflavin (vitamin B2) deficiency causes ariboflavinosis.

- Niacin (vitamin B3) deficiency causes pellagra.

- Pantothenic acid (vitamin B5) deficiency causes chronic paresthesia.

- Vitamin B6

- Biotin (vitamin B7) deficiency negatively affects fertility and hair/skin growth. Deficiency can be caused by poor diet or genetic factors (such as mutations in the BTD gene, see multiple carboxylase deficiency).

- Folate (vitamin B9) deficiency is associated with numerous health problems. Fortification of certain foods with folate has drastically reduced the incidence of neural tube defects in countries where such fortification takes place. Deficiency can result from poor diet or genetic factors (such as mutations in the MTHFR gene that lead to compromised folate metabolism).

- Vitamin B12 (cobalamin) deficiency can lead to pernicious anemia, megaloblastic anemia, subacute combined degeneration of spinal cord, and methylmalonic acidemia among other conditions.

- Vitamin C (ascorbic acid) short-term deficiency can lead to weakness, weight loss and general aches and pains. Longer-term depletion may affect the connective tissue. Persistent vitamin C deficiency leads to scurvy.

- Vitamin D (cholecalciferol) deficiency is a known cause of rickets, and has been linked to numerous health problems.

- Vitamin E deficiency causes nerve problems due to poor conduction of electrical impulses along nerves due to changes in nerve membrane structure and function.

- Vitamin K (phylloquinone or menaquinone) deficiency causes impaired coagulation and has also been implicated in osteoporosis

To confirm the diagnosis, renal osteodystrophy must be characterized by determining bone turnover, mineralization, and volume (TMV system) (bone biopsy). All forms of renal osteodystrophy should also be distinguished from other bone diseases which may equally result in decreased bone density (related or unrelated to CKD):

- osteoporosis

- osteopenia

- osteomalacia

- brown tumor should be considered as the top-line diagnosis if a mass-forming lesion is present.