Vitamin D is obtained predominantly by photosynthesis in the skin and in small amounts by dietary intake. Both skin- and bowel-derived vitamin D are biologically inert and require two hydroxylations in the liver by the vitamin D-25-hydroxylase and in the kidneys by the 25(OH)vitamin D-1α-hydroxylase to synthesize the 1,25(OH)2vitamin D, which represents the biologically active form of vitamin D.
This hormone is well known for its beneficial effects on bone health, by inducing intestinal calcium absorption and tubular calcium reabsorption, in addition to direct skeletal actions, which are not fully understood.
However, the widespread expression of both vitamin D receptors and 1,α-hydroxylase enzymes, able to locally convert calcifediol to calcitriol, could account for paracrine effects of vitamin D on many other tissues, other than those involved in skeletal health. Accordingly, many observational studies have found a significant association between hypovitaminosis D and several endocrine and metabolic diseases diseases, which recently showed an impact also on COVID-19. Conversely, randomized-controlled clinical trials, systematic reviews and meta-analysis, aimed at investigating the effects of vitamin D supplementation on extra-skeletal outcomes, have reported conflicting results.
Normal and optimal serum 25(OH)vitamin D levels as well as the operational definition of vitamin D insufficiency and deficiency are still debated. Moreover, the lack of a standardization of 25(OH)vitamin D measurement may hamper a proper diagnosis and therapy. In addition, therapeutic response to vitamin D supplementation depends on individual genetic and epigenetic factors, beyond the achievement of optimal 25(OH)vitamin D levels. However, data from meta-analyses of randomized controlled trials suggest that best benefits may be accrued at normal serum 25 OH vitamin D levels higher than 75 nmol/l for musculoskeletal and non-musculoskeletal outcomes. Accordingly, the role of vitamin D in preventing and treating bone metabolism diseases such as rickets, osteomalacia and osteoporosis is well-recognized, when the above-mentioned serum 25-OH vitamin D levels are reached and/or maintained.
Conversely, the association between hypovitaminosis D and endocrine and metabolic disorders has not been confirmed by randomized clinical intervention trials probably due to some bias. In fact, recent metanalyses support a slight favorable effect of vitamin D supplementation on the incidence of type 2 diabetes and glycemic control when considering studies both using daily Vitamin D dose ≥ 1000 UI and recruiting patients with average BMI <30 kg/m2. Moreover, recent data about a potential protective role of vitamin D against SARS-CoV2 infection and disease severity may lead to a new therapeutic scenario.
The aim of this article collection is to review the best evidence on the association of hypovitaminosis D with both skeletal and endocrine and metabolic disorders and the clinical use of vitamin D in their prevention and treatment.
- Mechanisms of skeletal effects of vitamin D
- Hypovitaminosis D and fractures
- Hypovitaminosis D and sarcopenia
- Hypovitaminosis D and hyperparathyroidism
- Hypovitaminosis D and hypoparathyroidism
- Hypovitaminosis D and diabetes mellitus
- Hypovitaminosis D and obesity
- Hypovitaminosis D and female reproductive function and pregnancy
- Hypovitaminosis D and male reproductive function
- Hypovitaminosis D and endocrine phenotype of COVID-19
Vitamin D is obtained predominantly by photosynthesis in the skin and in small amounts by dietary intake. Both skin- and bowel-derived vitamin D are biologically inert and require two hydroxylations in the liver by the vitamin D-25-hydroxylase and in the kidneys by the 25(OH)vitamin D-1α-hydroxylase to synthesize the 1,25(OH)2vitamin D, which represents the biologically active form of vitamin D.
This hormone is well known for its beneficial effects on bone health, by inducing intestinal calcium absorption and tubular calcium reabsorption, in addition to direct skeletal actions, which are not fully understood.
However, the widespread expression of both vitamin D receptors and 1,α-hydroxylase enzymes, able to locally convert calcifediol to calcitriol, could account for paracrine effects of vitamin D on many other tissues, other than those involved in skeletal health. Accordingly, many observational studies have found a significant association between hypovitaminosis D and several endocrine and metabolic diseases diseases, which recently showed an impact also on COVID-19. Conversely, randomized-controlled clinical trials, systematic reviews and meta-analysis, aimed at investigating the effects of vitamin D supplementation on extra-skeletal outcomes, have reported conflicting results.
Normal and optimal serum 25(OH)vitamin D levels as well as the operational definition of vitamin D insufficiency and deficiency are still debated. Moreover, the lack of a standardization of 25(OH)vitamin D measurement may hamper a proper diagnosis and therapy. In addition, therapeutic response to vitamin D supplementation depends on individual genetic and epigenetic factors, beyond the achievement of optimal 25(OH)vitamin D levels. However, data from meta-analyses of randomized controlled trials suggest that best benefits may be accrued at normal serum 25 OH vitamin D levels higher than 75 nmol/l for musculoskeletal and non-musculoskeletal outcomes. Accordingly, the role of vitamin D in preventing and treating bone metabolism diseases such as rickets, osteomalacia and osteoporosis is well-recognized, when the above-mentioned serum 25-OH vitamin D levels are reached and/or maintained.
Conversely, the association between hypovitaminosis D and endocrine and metabolic disorders has not been confirmed by randomized clinical intervention trials probably due to some bias. In fact, recent metanalyses support a slight favorable effect of vitamin D supplementation on the incidence of type 2 diabetes and glycemic control when considering studies both using daily Vitamin D dose ≥ 1000 UI and recruiting patients with average BMI <30 kg/m2. Moreover, recent data about a potential protective role of vitamin D against SARS-CoV2 infection and disease severity may lead to a new therapeutic scenario.
The aim of this article collection is to review the best evidence on the association of hypovitaminosis D with both skeletal and endocrine and metabolic disorders and the clinical use of vitamin D in their prevention and treatment.
- Mechanisms of skeletal effects of vitamin D
- Hypovitaminosis D and fractures
- Hypovitaminosis D and sarcopenia
- Hypovitaminosis D and hyperparathyroidism
- Hypovitaminosis D and hypoparathyroidism
- Hypovitaminosis D and diabetes mellitus
- Hypovitaminosis D and obesity
- Hypovitaminosis D and female reproductive function and pregnancy
- Hypovitaminosis D and male reproductive function
- Hypovitaminosis D and endocrine phenotype of COVID-19