Complications
Occurs primarily because of a nutritional deficiency of vitamin D. Results in deficient mineralisation of the skeleton and reduced chondrocyte maturation and mineralisation at the growth plate of long bones, particularly at sites of rapid bone growth (distal forearm, knee, and costochondral junctions). Clinical manifestations include widening of the bones at the wrists and knees, bowing of the legs, spinal deformities, fractures, bone pain, and dental abnormalities.
Can be prevented in many cases by ensuring that children and pregnant women have sufficient vitamin D and calcium intake.
It is now recognised that vitamin D deficiency increases the risk of many chronic diseases, including cancer, autoimmune diseases, type 2 diabetes, heart disease and hypertension, neurocognitive dysfunction, and infectious diseases (including respiratory tract infections and tuberculosis).[1][2][21]
One umbrella review of observational studies, randomised controlled trials, and Mendelian randomisation studies reported consistent results demonstrating that lower concentrations of vitamin D were associated with a higher risk for all-cause mortality, Alzheimer's disease, hypertension, schizophrenia, and type 2 diabetes.[43]
The Institute of Medicine disregarded association studies as being too low evidence to support any non-skeletal beneficial claims for vitamin D.[74] Other studies have also raised questions about the value and effectiveness of vitamin supplementation for preventing cancers, cardiovascular events, and cognitive decline.[44]
The VITamin D and OmegA-3 TriaL (VITAL) study, a large randomised controlled trial evaluating vitamin D3 supplementation for the prevention of cancer and cardiovascular disease, concluded that 2000 IU of vitamin D daily did not lower the incidence of major cardiovascular events.[47] However, it found that vitamin D supplementation significantly reduced the risk of mortality associated with cancer.[48] The umbrella review showed that vitamin D supplementation was associated with a decreased risk for all-cause mortality, but not associated with the risk for Alzheimer's disease, hypertension, schizophrenia, or type 2 diabetes.[43]
One meta-analysis concluded that vitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D concentrations <10 nanograms/mL, but not in those with higher levels.[56][Evidence A]
Vitamin D deficiency causes secondary hyperparathyroidism, resulting in an increase in bone resorption, leading to a decrease in bone mineral density that can precipitate and exacerbate osteopenia or osteoporosis.[96] Diagnosis is based on bone densitometry examination of the lumbar spine, hip, and wrist. A T score of -1.0 to -2.5 indicates low bone mass (osteopenia), and a score ≤-2.5 indicates osteoporosis.
A decrease in serum parathyroid hormone in response to vitamin D treatment can be a useful indicator of decreased bone resorption. A repeat bone mineral density study 1-2 years after initiation of vitamin D therapy may also be helpful in determining whether there is improvement in osteopenia and osteoporosis.
Can occur due to a decrease in bone mineral density as a result of increased bone resorption.[96] In addition, vitamin D deficiency causes muscle weakness, thus increasing the risk of falling and fracture.[97][98][99]
The Endocrine Society in the US notes that there is consistent evidence for a beneficial effect of calcium plus vitamin D supplementation (mostly as vitamin D3), but not vitamin D alone, in reducing the risk of hip fractures and any fractures in older adults with vitamin D deficiency.[100] A Meals on Wheels programme was evaluated to determine if improvement in 25-hydroxyvitamin D concentrations would reduce falls. Clients were randomised to vitamin D3 or active placebo. After the 5-month intervention, only 1 of 34 participants randomised to vitamin D3 had 25-hydroxyvitamin D concentrations <8 nanomoles/L (<20 nanograms/mL), compared with 18 of 25 participants randomised to placebo. After adjustment for sex, race, season of year, baseline 25-hydroxyvitamin D status, and history of falls, participants randomised to vitamin D3 had a lower rate of falling than those randomised to placebo.[101] A systematic review and meta-analysis revealed a high prevalence of vitamin D deficiency in fracture patients and that vitamin D supplementation safely increased circulating 25-hydroxyvitamin D levels. One paper suggested a loading dose of vitamin D reported a trend towards improved fracture healing.[102]
For those with a hip fracture, there is only low-quality evidence that oral multinutrient supplements started before or soon after surgery prevent complications within the first 12 months after the hip fracture, with no clear effect on mortality.[103]
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Physicians are concerned about giving patients high doses of vitamin D for prolonged periods, due to the possibility of build-up of fat-soluble vitamin D in the body fat stores causing vitamin D intoxication.
Vitamin D intoxication is one of the rarest medical conditions, and is only seen when there is either inadvertent or intentional ingestion of excessively high doses of vitamin D (>10,000 IU/day).[2][104]
Vitamin D intoxication occurs when the level of serum 25-hydroxyvitamin D is >374 nanomoles/L (>150 nanograms/mL), and is associated with hypercalcaemia and hyperphosphataemia.[2] This will result in soft tissue calcification of the blood vessels and kidneys that can increase the risk for cardiovascular mortality, nephrocalcinosis, and kidney failure.[2]
Patients who have a granuloma-forming disorder or some lymphomas have a dysregulation in vitamin D metabolism increasing their risk for developing hypercalciuria and hypercalcaemia when blood levels of 25-hydroxyvitamin D are >75 nanomoles/L (>30 nanograms/mL) due to the production of 1,25-dihydroxyvitamin D by macrophages.[2]
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