Evidence suggests children and adults should have a level of serum 25-hydroxyvitamin D of >75 nanomoles/L (>30 nanograms/mL) to obtain the maximum benefit of vitamin D for overall health and wellbeing.[2]Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30.
https://academic.oup.com/jcem/article/96/7/1911/2833671
http://www.ncbi.nlm.nih.gov/pubmed/21646368?tool=bestpractice.com
The amount of vitamin D required to achieve this depends on a wide variety of factors, including age, baseline 25-hydroxyvitamin D, body mass index, sun-exposure history, and the use of medications that can affect vitamin D metabolism and intestinal absorption.
Correction of vitamin D deficiency and insufficiency in children will promote growth and deposition of calcium into the skeleton. Children with skeletal manifestations of rickets should be aggressively treated. The earlier the intervention, the more likely a favourable prognosis, with resolution of many of the associated skeletal deformities. This is especially true for deformities in the legs. Correction of vitamin D deficiency in adults improves bone mineral density and stimulates mineralisation of the collagen matrix, resulting in resolution of bone pain associated with osteomalacia.
Vitamin D replacement
The mainstay of treatment is the provision of vitamin D to correct the causative deficiency. The goal is to reach and maintain a serum 25-hydroxyvitamin D level in both children and adults of between 75-250 nanomoles/L (30-100 nanograms/mL).[1]Hossein-Nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013 Jul;88(7):720-55.
http://www.mayoclinicproceedings.org/article/S0025-6196(13)00404-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23790560?tool=bestpractice.com
[2]Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30.
https://academic.oup.com/jcem/article/96/7/1911/2833671
http://www.ncbi.nlm.nih.gov/pubmed/21646368?tool=bestpractice.com
[73]Wagner CL, Greer FR; American Academy of Pediatrics Section on Breastfeeding. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008 Nov;122(5):1142-52. [Erratum in: Pediatrics. 2009 Jan;123(1):197.]
http://pediatrics.aappublications.org/content/122/5/1142.long
http://www.ncbi.nlm.nih.gov/pubmed/18977996?tool=bestpractice.com
[88]Bischoff-Ferrari HA. Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Biol. 2014;810:500-25.
https://www.doi.org/10.1007/978-1-4939-0437-2_28
http://www.ncbi.nlm.nih.gov/pubmed/25207384?tool=bestpractice.com
A child or adult is considered vitamin D-insufficient if serum 25-hydroxyvitamin D level is between 52-72 nanomoles/L (21-29 nanograms/mL) or if history suggests lack of adequate daily vitamin D from supplements (400 IU for children <1 year of age; 600 IU for children ≥1 year of age; and 1500-2000 IU for adults), diet, and/or adequate sun exposure.[2]Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30.
https://academic.oup.com/jcem/article/96/7/1911/2833671
http://www.ncbi.nlm.nih.gov/pubmed/21646368?tool=bestpractice.com
These patients should be treated with vitamin D replacement as for those with true deficiency.
Vitamin D deficiency in adults and children is corrected by treatment with vitamin D2 (ergocalciferol) or vitamin D3 (colecalciferol) given orally for 6-8 weeks, followed by a lower maintenance dose continued throughout childhood and adulthood.[2]Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30.
https://academic.oup.com/jcem/article/96/7/1911/2833671
http://www.ncbi.nlm.nih.gov/pubmed/21646368?tool=bestpractice.com
[89]Pietras SM, Obayan BK, Cai MH, et al. Vitamin D2 treatment for vitamin D deficiency and insufficiency for up to 6 years. Arch Intern Med. 2009 Oct 26;169(19):1806-8.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/224803
http://www.ncbi.nlm.nih.gov/pubmed/19858440?tool=bestpractice.com
[90]Gordon CM, Williams AL, Feldman HA, et al. Treatment of hypovitaminosis D in infants and toddlers. J Clin Endocrinol Metab. 2008 Jul;93(7):2716-21.
https://academic.oup.com/jcem/article/93/7/2716/2598925
http://www.ncbi.nlm.nih.gov/pubmed/18413426?tool=bestpractice.com
Patients with intestinal or fat malabsorption syndromes (including liver failure and obesity), or who have a history of gastric bypass surgery, usually do not respond to small doses of vitamin D replacement. Therefore, higher daily oral doses are often required.[2]Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30.
https://academic.oup.com/jcem/article/96/7/1911/2833671
http://www.ncbi.nlm.nih.gov/pubmed/21646368?tool=bestpractice.com
Patients taking antiepileptic medications, glucocorticoids, or other drugs that activate the steroid and xenobiotic receptors (e.g., highly active antiretroviral therapy, rifampicin, St John's wort) may also require higher doses of vitamin D. Data on the optimal dose for vitamin D deficiency in pregnancy is lacking.[91]American College of Obstetricians and Gynecologists. Committee opinion no. 495: vitamin D: screening and supplementation during pregnancy. Jul 2011 [internet publication].
https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2011/07/vitamin-d-screening-and-supplementation-during-pregnancy
Seek specialist advice before starting treatment if a woman is pregnant.
Sensible sun or ultraviolet B (UV-B) radiation exposure
Adequate sensible sun exposure is an excellent source of vitamin D and should be recommended to all patients for both the treatment and prevention of vitamin D deficiency.[58]Wacker M, Holick MF. Sunlight and vitamin D: a global perspective for health. Dermatoendocrinol. 2013 Jan 1;5(1):51-108.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897598
http://www.ncbi.nlm.nih.gov/pubmed/24494042?tool=bestpractice.com
[71]National Institute for haelth and Care Excellence. Sunlight exposure: risks and benefits. Feb 2016 [internet publication].
https://www.nice.org.uk/guidance/ng34
Usually, exposure of the arms and legs (with sun protection on the face) for about 5-30 minutes (depends on degree of skin pigmentation, time of day, season, latitude, and age of patient) between 10 a.m. and 3 p.m. twice a week is sufficient to stimulate cutaneous vitamin D production. There are smartphone apps available that can provide advice about sensible sun exposure, give information about how much vitamin D is being made in the skin during current sun exposure, and alert the user when to stop the exposure to prevent sunburn.
Patients with fat malabsorption who are unable to absorb vitamin D when taken orally can benefit from exposure to UV-B radiation.[1]Hossein-Nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013 Jul;88(7):720-55.
http://www.mayoclinicproceedings.org/article/S0025-6196(13)00404-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23790560?tool=bestpractice.com
This is usually achieved by using a tanning bed for 30% to 50% of the time recommended for tanning (sunscreen should be applied to the face).[1]Hossein-Nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013 Jul;88(7):720-55.
http://www.mayoclinicproceedings.org/article/S0025-6196(13)00404-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23790560?tool=bestpractice.com
Tanning beds may also be considered in climates with limited sunlight.
Calcium and phosphate replacement
Because inadequate calcium intake may contribute to vitamin D deficiency and many patients do not meet daily calcium requirements from dietary sources alone, all patients at risk of calcium deficiency should be given calcium supplementation.[78]Uday S, Högler W. Nutritional rickets & osteomalacia: A practical approach to management. Indian J Med Res. 2020 Oct;152(4):356-37.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061584
http://www.ncbi.nlm.nih.gov/pubmed/33380700?tool=bestpractice.com
[92]Chibuzor MT, Graham-Kalio D, Osaji JO, et al. Vitamin D, calcium or a combination of vitamin D and calcium for the treatment of nutritional rickets in children. Cochrane Database Syst Rev. 2020 Apr 17;4(4):CD012581.
https://www.doi.org/10.1002/14651858.CD012581.pub2
http://www.ncbi.nlm.nih.gov/pubmed/32303107?tool=bestpractice.com
Calcium supplements, with or without vitamin D, are considered safe from a cardiovascular standpoint.[93]Kopecky SL, Bauer DC, Gulati M, et al. Lack of evidence linking calcium with or without vitamin D supplementation to cardiovascular disease in generally healthy adults: a clinical guideline from the National Osteoporosis Foundation and the American Society for Preventive Cardiology. Ann Intern Med. 2016 Dec 20;165(12):867-8.
http://www.ncbi.nlm.nih.gov/pubmed/27776362?tool=bestpractice.com
Phosphate supplementation is not usually necessary unless there is an acquired or inherited disorder causing phosphate wasting in the kidneys, such as hypophosphataemic rickets or oncogenic osteomalacia.[4]Jan de Beur SM, Minisola S, Xia WB, et al. Global guidance for the recognition, diagnosis, and management of tumor-induced osteomalacia. J Intern Med. 2023 Mar;293(3):309-28.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108006
http://www.ncbi.nlm.nih.gov/pubmed/36511653?tool=bestpractice.com
[5]Chanchlani R, Nemer P, Sinha R, et al. An overview of rickets in children. Kidney Int Rep. 2020 Jul;5(7):980-90.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335963
http://www.ncbi.nlm.nih.gov/pubmed/32647755?tool=bestpractice.com
These patients require phosphate supplementation in addition to vitamin D replacement and vitamin D metabolite. Caution should be exercised when giving phosphate supplements, because high-dose phosphate multiple times a day causes a reduction in ionised calcium, resulting in an increase in parathyroid hormone production and tertiary hyperparathyroidism. Therefore, smaller doses of phosphate should be taken more frequently throughout the day to maintain a normal serum phosphate level without causing significant hyperparathyroidism.
Disorders of vitamin D metabolism
Patients with acquired and inherited disorders of metabolism of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, or a defective recognition of 1,25-dihydroxyvitamin D, should receive vitamin D along with either 1,25-dihydroxyvitamin D3 (calcitriol) or one of its active analogues (e.g., paricalcitol or doxercalciferol), depending on the cause of the abnormality.[1]Hossein-Nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013 Jul;88(7):720-55.
http://www.mayoclinicproceedings.org/article/S0025-6196(13)00404-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23790560?tool=bestpractice.com
Patients with chronic kidney disease have high-normal or elevated serum phosphate levels and a decreased capacity to produce 1,25-dihydroxyvitamin D, which causes secondary hyperparathyroidism. Therefore, they need to maintain a serum 25-hydroxyvitamin D of between 75-250 nanomoles/L (30-100 nanograms/mL) and control their serum phosphate level by using a phosphate binder (e.g., calcium carbonate). In addition, if the estimated GFR is <50% of normal, they may also require 1,25-dihydroxyvitamin D3 or one of its active analogues (to treat and prevent secondary hyperparathyroidism).[1]Hossein-Nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013 Jul;88(7):720-55.
http://www.mayoclinicproceedings.org/article/S0025-6196(13)00404-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23790560?tool=bestpractice.com
[10]Kidney Disease: Improving Global Outcomes (KDIGO). KDIGO 2017 clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl. 2017 July;7(1):1-59.
http://kdigo.org/wp-content/uploads/2017/02/2017-KDIGO-CKD-MBD-GL-Update.pdf