Vitamin D deficiency
- Overview
- Theory
- Diagnosis
- Management
- Follow up
- Resources
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
insufficiency
vitamin D
The optimal serum concentration of 25-hydroxyvitamin D remains debated.[1]Giustina A, Adler RA, Binkley N, et al. Controversies in vitamin D: summary statement from an international conference. J Clin Endocrinol Metab. 2019 Feb 1;104(2):234-40. https://academic.oup.com/jcem/article/104/2/234/5148139 http://www.ncbi.nlm.nih.gov/pubmed/30383226?tool=bestpractice.com A child or adult may be considered vitamin D-insufficient if serum 25-hydroxyvitamin D level is between 52 and 72 nanomoles/L (21-29 nanograms/mL) or if history suggests lack of adequate daily vitamin D (400 IU/day for children aged <1 year; 600 IU/day for those aged ≥1 year; and 600-800 IU/day for adults depending on age, but possibly up to 1500-2000 IU/day) from supplements, diet, and/or adequate sun exposure.[79]Institute of Medicine. Dietary reference intakes for calcium and vitamin D. 2011 [internet publication]. https://www.nap.edu/catalog/13050/dietary-reference-intakes-for-calcium-and-vitamin-d [85]Heaney RP, Armas LA, French C. All-source basal vitamin D inputs are greater than previously thought and cutaneous inputs are smaller. J Nutr. 2013 May;143(5):571-5. https://www.sciencedirect.com/science/article/pii/S0022316622011683?via%3Dihub http://www.ncbi.nlm.nih.gov/pubmed/23514768?tool=bestpractice.com [86]Hamid Z, Riggs A, Spencer T, et al. Vitamin D deficiency in residents of academic long-term care facilities despite having been prescribed vitamin D. J Am Med Dir Assoc. 2007 Feb;8(2):71-5. http://www.ncbi.nlm.nih.gov/pubmed/17289534?tool=bestpractice.com
These patients may be treated with vitamin D replacement following shared decision-making. Vitamin D2 (ergocalciferol) and D3 (colecalciferol) are equally effective in maintaining circulating concentrations of 25-hydroxyvitamin D.[136]Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. 2008 Mar;93(3):677-81. https://academic.oup.com/jcem/article/93/3/677/2598025 http://www.ncbi.nlm.nih.gov/pubmed/18089691?tool=bestpractice.com [137]Thacher TD, Fischer PR, Obadofin MO, et al. Comparison of metabolism of vitamins D2 and D3 in children with nutritional rickets. J Bone Miner Res. 2010 Sep;25(9):1988-95. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153403 http://www.ncbi.nlm.nih.gov/pubmed/20499377?tool=bestpractice.com
For older adults, daily low-dose regimens are often preferred over infrequent large bolus doses. Daily low-dose regimens help reduce the risk of falls in older individuals, whereas infrequent large bolus doses may increase this risk.[67]Giustina A, Bouillon R, Dawson-Hughes B, et al. Vitamin D in the older population: a consensus statement. Endocrine. 2023 Jan;79(1):31-44. https://pmc.ncbi.nlm.nih.gov/articles/PMC9607753 http://www.ncbi.nlm.nih.gov/pubmed/36287374?tool=bestpractice.com
Data on the optimal dose for vitamin D insufficiency in pregnancy is lacking.[115]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 If deficiency of vitamin D is identified during pregnancy, supplementation with 1000-2000 IU/day of vitamin D is generally considered to be safe, according to the American College of Obstetricians and Gynecologists (ACOG).[115]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 Doses above 2000 IU/day of vitamin D are sometimes required, and may be recommended by the patient’s obstetrician, but are typically only used under specialist medical supervision, with appropriate monitoring for potential risks such as hypercalcaemia and toxicity.[128]Dawodu A, Saadi HF, Bekdache G, et al. Randomized controlled trial (RCT) of vitamin D supplementation in pregnancy in a population with endemic vitamin D deficiency. J Clin Endocrinol Metab. 2013 Jun;98(6):2337-46. http://www.ncbi.nlm.nih.gov/pubmed/23559082?tool=bestpractice.com Seek specialist advice before starting treatment if a woman is pregnant.
Treatment course is typically 6-8 weeks, followed by a lower maintenance dose continued throughout childhood and adulthood.
Primary options
ergocalciferol: children: 2000 IU orally once daily or 50,000 IU orally once weekly for 6-8 weeks, followed by 400-1000 IU/day (children <1 year of age) or 600-1000 IU/day (children ≥1 year of age) as maintenance; non-pregnant adults: 6000 IU orally once daily or 50,000 IU orally once weekly for 8 weeks, followed by 1500-2000 IU/day as maintenance; pregnant adults: 1000-2000 IU orally once daily
More ergocalciferolDose regimens for vitamin D vary and you should consult your local guidelines or drug information source for more information.
OR
colecalciferol: children: 2000 IU orally once daily or 50,000 IU orally once weekly for 6-8 weeks, followed by 400-1000 IU/day (children <1 year of age) or 600-1000 IU/day (children ≥1 year of age) as maintenance; non-pregnant adults: 6000 IU orally once daily or 50,000 IU orally once weekly for 8 weeks, followed by 1500-2000 IU/day as maintenance; pregnant adults: 1000-2000 IU orally once daily
More colecalciferolDose regimens for vitamin D vary and you should consult your local guidelines or drug information source for more information.
calcium
Additional treatment recommended for SOME patients in selected patient group
Because inadequate calcium intake may contribute to vitamin D deficiency or insufficiency 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.[88]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 [130]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
There is consensus that vitamin D given in conjunction with calcium reduces fracture risk in the older population, and is recommended in this group.[67]Giustina A, Bouillon R, Dawson-Hughes B, et al. Vitamin D in the older population: a consensus statement. Endocrine. 2023 Jan;79(1):31-44. https://pmc.ncbi.nlm.nih.gov/articles/PMC9607753 http://www.ncbi.nlm.nih.gov/pubmed/36287374?tool=bestpractice.com
Calcium supplementation should continue indefinitely or until adequate intake is achieved through dietary sources.
While some studies suggest no significant cardiovascular risk associated with calcium supplements, other research indicates potential concerns, particularly at higher doses.[131]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 [132]Huo X, Clarke R, Halsey J, et al. Calcium supplements and risk of CVD: a meta-analysis of randomized trials. Curr Dev Nutr. 2023 Mar;7(3):100046. https://pmc.ncbi.nlm.nih.gov/articles/PMC10111600 http://www.ncbi.nlm.nih.gov/pubmed/37181938?tool=bestpractice.com [133]Qiu Z, Lu Q, Wan Z, et al. Associations of habitual calcium supplementation with risk of cardiovascular disease and mortality in individuals wth and without diabetes. Diabetes Care. 2024 Feb 1;47(2):199-207. https://diabetesjournals.org/care/article/47/2/199/151370/Associations-of-Habitual-Calcium-Supplementation http://www.ncbi.nlm.nih.gov/pubmed/37506393?tool=bestpractice.com [134]Myung SK, Kim HB, Lee YJ, et al. Calcium supplements and risk of cardiovascular disease: a meta-analysis of clinical trials. Nutrients. 2021 Jan 26;13(2):368. https://pmc.ncbi.nlm.nih.gov/articles/PMC7910980 http://www.ncbi.nlm.nih.gov/pubmed/33530332?tool=bestpractice.com
Primary options
calcium carbonate: children: 45-65 mg/kg/day orally given in 4 divided doses; adolescents/adults: 1-2 g/day orally given in 3-4 divided doses
More calcium carbonateDose expressed as elemental calcium.
deficiency
vitamin D
The optimal serum concentration of 25-hydroxyvitamin D remains debated.[1]Giustina A, Adler RA, Binkley N, et al. Controversies in vitamin D: summary statement from an international conference. J Clin Endocrinol Metab. 2019 Feb 1;104(2):234-40. https://academic.oup.com/jcem/article/104/2/234/5148139 http://www.ncbi.nlm.nih.gov/pubmed/30383226?tool=bestpractice.com Some experts recommend a goal serum 25-hydroxyvitamin D concentration >75 nanomoles/L (>30 nanograms/mL), particularly in older adults, in order to maximise vitamin D effects on the skeleton and on calcium and phosphate metabolism.[117]Vieth R. What is the optimal vitamin D status for health? Prog Biophys Mol Biol. 2006 Sep;92(1):26-32. https://www.sciencedirect.com/science/article/pii/S0079610706000216?via%3Dihub http://www.ncbi.nlm.nih.gov/pubmed/16766239?tool=bestpractice.com [118]Dawson-Hughes B, Mithal A, Bonjour JP, et al. IOF position statement: vitamin D recommendations for older adults. Osteoporos Int. 2010 Jul;21(7):1151-4. http://www.ncbi.nlm.nih.gov/pubmed/20422154?tool=bestpractice.com [83]American Geriatrics Society Workgroup on Vitamin D Supplementation for Older Adults. Recommendations abstracted from the American Geriatrics Society consensus statement on vitamin D for prevention of falls and their consequences. J Am Geriatr Soc. 2014 Jan;62(1):147-52. https://agsjournals.onlinelibrary.wiley.com/doi/epdf/10.1111/jgs.12631 http://www.ncbi.nlm.nih.gov/pubmed/24350602?tool=bestpractice.com [84]LeBoff MS, Greenspan SL, Insogna KL, et al. The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 2022 Oct;33(10):2049-102. https://pmc.ncbi.nlm.nih.gov/articles/PMC9546973 http://www.ncbi.nlm.nih.gov/pubmed/35478046?tool=bestpractice.com [3]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 [119]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
Vitamin D2 (ergocalciferol) and D3 (colecalciferol) are equally effective in maintaining circulating concentrations of 25-hydroxyvitamin D.[136]Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. 2008 Mar;93(3):677-81. https://academic.oup.com/jcem/article/93/3/677/2598025 http://www.ncbi.nlm.nih.gov/pubmed/18089691?tool=bestpractice.com [137]Thacher TD, Fischer PR, Obadofin MO, et al. Comparison of metabolism of vitamins D2 and D3 in children with nutritional rickets. J Bone Miner Res. 2010 Sep;25(9):1988-95. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153403 http://www.ncbi.nlm.nih.gov/pubmed/20499377?tool=bestpractice.com
Some patients, for example those with intestinal or fat malabsorption syndromes (including liver failure), or who have a history of gastric bypass surgery, often require higher doses of vitamin D under specialist supervision. Patients taking anticonvulsants, glucocorticoids, or other drugs that activate the steroid and xenobiotic receptors (e.g., antiretroviral therapy [ART], rifampicin, St. John's wort) may also require higher doses of vitamin D.
The threshold at which vitamin D becomes toxic is not well defined. The National Academy of Medicine sets the tolerable upper intake level (UL) for vitamin D at 4000 IU/day for healthy adults and children aged 9-18 years.[79]Institute of Medicine. Dietary reference intakes for calcium and vitamin D. 2011 [internet publication]. https://www.nap.edu/catalog/13050/dietary-reference-intakes-for-calcium-and-vitamin-d The UL is lower for infants and children up to 9 years, varying by age. In some cases, patients may need doses exceeding the National Academy of Medicine's UL to correct deficiency, requiring specialist (endocrinology) oversight and close monitoring to avoid toxicity (e.g., people with malabsorption syndromes).
For older adults, daily low-dose regimens are often preferred over infrequent large bolus doses. Daily low-dose regimens help reduce the risk of falls in older individuals, whereas infrequent large bolus doses may increase this risk.[67]Giustina A, Bouillon R, Dawson-Hughes B, et al. Vitamin D in the older population: a consensus statement. Endocrine. 2023 Jan;79(1):31-44. https://pmc.ncbi.nlm.nih.gov/articles/PMC9607753 http://www.ncbi.nlm.nih.gov/pubmed/36287374?tool=bestpractice.com
Data on the optimal dose for vitamin D deficiency in pregnancy is lacking.[115]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 If deficiency of vitamin D is identified during pregnancy, supplementation with 1000-2000 IU/day of vitamin D is generally considered to be safe, according to the American College of Obstetricians and Gynecologists (ACOG).[115]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 Doses above 2000 IU/day of vitamin D are sometimes required, and may be recommended by the patient’s obstetrician, but are typically only used under specialist medical supervision, with appropriate monitoring for potential risks such as hypercalcaemia and toxicity.[128]Dawodu A, Saadi HF, Bekdache G, et al. Randomized controlled trial (RCT) of vitamin D supplementation in pregnancy in a population with endemic vitamin D deficiency. J Clin Endocrinol Metab. 2013 Jun;98(6):2337-46. http://www.ncbi.nlm.nih.gov/pubmed/23559082?tool=bestpractice.com Seek specialist advice before starting treatment if a woman is pregnant.
Dosing regimens have been recommended.[3]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 Treatment course is typically 6-8 weeks, followed by a lower maintenance dose continued throughout childhood and adulthood.
Primary options
ergocalciferol: children: 2000 IU orally once daily or 50,000 IU orally once weekly for 6-8 weeks, followed by 400-1000 IU/day (children <1 year of age) or 600-1000 IU/day (children ≥1 year of age) as maintenance; non-pregnant adults: 6000 IU orally once daily or 50,000 IU orally once weekly for 8 weeks, followed by 1500-2000 IU/day as maintenance; pregnant adults: 1000-2000 IU orally once daily
More ergocalciferolDose regimens for vitamin D vary and you should consult your local guidelines or drug information source for more information.
OR
colecalciferol: children: 2000 IU orally once daily or 50,000 IU orally once weekly for 6-8 weeks, followed by 400-1000 IU/day (children <1 year of age) or 600-1000 IU/day (children ≥1 year of age) as maintenance; non-pregnant adults: 6000 IU orally once daily or 50,000 IU orally once weekly for 8 weeks, followed by 1500-2000 IU/day as maintenance; pregnant adults: 1000-2000 IU orally once daily
More colecalciferolDose regimens for vitamin D vary and you should consult your local guidelines or drug information source for more information.
calcium
Additional treatment recommended for SOME patients in selected patient group
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.[88]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
There is consensus that vitamin D given in conjunction with calcium reduces fracture risk in the older population, and is recommended in this group.[67]Giustina A, Bouillon R, Dawson-Hughes B, et al. Vitamin D in the older population: a consensus statement. Endocrine. 2023 Jan;79(1):31-44. https://pmc.ncbi.nlm.nih.gov/articles/PMC9607753 http://www.ncbi.nlm.nih.gov/pubmed/36287374?tool=bestpractice.com
Calcium supplementation should continue indefinitely or until adequate intake is achieved through dietary sources.
While some studies suggest no significant cardiovascular risk associated with calcium supplements, other research indicates potential concerns, particularly at higher doses.[131]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 [132]Huo X, Clarke R, Halsey J, et al. Calcium supplements and risk of CVD: a meta-analysis of randomized trials. Curr Dev Nutr. 2023 Mar;7(3):100046. https://pmc.ncbi.nlm.nih.gov/articles/PMC10111600 http://www.ncbi.nlm.nih.gov/pubmed/37181938?tool=bestpractice.com [133]Qiu Z, Lu Q, Wan Z, et al. Associations of habitual calcium supplementation with risk of cardiovascular disease and mortality in individuals wth and without diabetes. Diabetes Care. 2024 Feb 1;47(2):199-207. https://diabetesjournals.org/care/article/47/2/199/151370/Associations-of-Habitual-Calcium-Supplementation http://www.ncbi.nlm.nih.gov/pubmed/37506393?tool=bestpractice.com [134]Myung SK, Kim HB, Lee YJ, et al. Calcium supplements and risk of cardiovascular disease: a meta-analysis of clinical trials. Nutrients. 2021 Jan 26;13(2):368. https://pmc.ncbi.nlm.nih.gov/articles/PMC7910980 http://www.ncbi.nlm.nih.gov/pubmed/33530332?tool=bestpractice.com
Primary options
calcium carbonate: children: 45-65 mg/kg/day orally given in 4 divided doses; adolescents/adults: 1-2 g/day orally given in 3-4 divided doses
More calcium carbonateDose expressed as elemental calcium.
vitamin D
The optimal serum concentration levels of 25-hydroxyvitamin D remains debated.[1]Giustina A, Adler RA, Binkley N, et al. Controversies in vitamin D: summary statement from an international conference. J Clin Endocrinol Metab. 2019 Feb 1;104(2):234-40. https://academic.oup.com/jcem/article/104/2/234/5148139 http://www.ncbi.nlm.nih.gov/pubmed/30383226?tool=bestpractice.com Some experts recommend a goal serum 25-hydroxyvitamin D concentration >75 nanomoles/L (>30 nanograms/mL), particularly in older adults, in order to maximise vitamin D effects on the skeleton and on calcium and phosphate metabolism.[117]Vieth R. What is the optimal vitamin D status for health? Prog Biophys Mol Biol. 2006 Sep;92(1):26-32. https://www.sciencedirect.com/science/article/pii/S0079610706000216?via%3Dihub http://www.ncbi.nlm.nih.gov/pubmed/16766239?tool=bestpractice.com [118]Dawson-Hughes B, Mithal A, Bonjour JP, et al. IOF position statement: vitamin D recommendations for older adults. Osteoporos Int. 2010 Jul;21(7):1151-4. http://www.ncbi.nlm.nih.gov/pubmed/20422154?tool=bestpractice.com [83]American Geriatrics Society Workgroup on Vitamin D Supplementation for Older Adults. Recommendations abstracted from the American Geriatrics Society consensus statement on vitamin D for prevention of falls and their consequences. J Am Geriatr Soc. 2014 Jan;62(1):147-52. https://agsjournals.onlinelibrary.wiley.com/doi/epdf/10.1111/jgs.12631 http://www.ncbi.nlm.nih.gov/pubmed/24350602?tool=bestpractice.com [84]LeBoff MS, Greenspan SL, Insogna KL, et al. The clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 2022 Oct;33(10):2049-102. https://pmc.ncbi.nlm.nih.gov/articles/PMC9546973 http://www.ncbi.nlm.nih.gov/pubmed/35478046?tool=bestpractice.com [3]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 [119]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
Vitamin D2 (ergocalciferol) and D3 (colecalciferol) are equally effective in maintaining circulating concentrations of 25-hydroxyvitamin D.[136]Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D. J Clin Endocrinol Metab. 2008 Mar;93(3):677-81. https://academic.oup.com/jcem/article/93/3/677/2598025 http://www.ncbi.nlm.nih.gov/pubmed/18089691?tool=bestpractice.com
For older adults, daily low-dose regimens are often preferred over infrequent large bolus doses. Daily low-dose regimens help reduce the risk of falls in older individuals, whereas infrequent large bolus doses may increase this risk.[67]Giustina A, Bouillon R, Dawson-Hughes B, et al. Vitamin D in the older population: a consensus statement. Endocrine. 2023 Jan;79(1):31-44. https://pmc.ncbi.nlm.nih.gov/articles/PMC9607753 http://www.ncbi.nlm.nih.gov/pubmed/36287374?tool=bestpractice.com
Data on the optimal dose for vitamin D deficiency in pregnancy is lacking.[115]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 If deficiency of vitamin D is identified during pregnancy, supplementation with 1000-2000 IU/day of vitamin D is generally considered to be safe, according to the American College of Obstetricians and Gynecologists (ACOG).[115]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 Doses above 2000 IU/day of vitamin D are sometimes required, and may be recommended by the patient’s obstetrician, but are typically only used under specialist medical supervision, with appropriate monitoring for potential risks such as hypercalcaemia and toxicity.[128]Dawodu A, Saadi HF, Bekdache G, et al. Randomized controlled trial (RCT) of vitamin D supplementation in pregnancy in a population with endemic vitamin D deficiency. J Clin Endocrinol Metab. 2013 Jun;98(6):2337-46. http://www.ncbi.nlm.nih.gov/pubmed/23559082?tool=bestpractice.com Seek specialist advice before starting treatment if a woman is pregnant.
Treatment course is typically 6-8 weeks, followed by a lower maintenance dose continued throughout childhood and adulthood.
Primary options
ergocalciferol: children: 2000 IU orally once daily or 50,000 IU orally once weekly for 6-8 weeks, followed by 400-1000 IU/day (children <1 year of age) or 600-1000 IU/day (children ≥1 year of age) as maintenance; non-pregnant adults: 6000 IU orally once daily or 50,000 IU orally once weekly for 8 weeks, followed by 1500-2000 IU/day as maintenance; pregnant adults: 1000-2000 IU orally once daily
More ergocalciferolDose regimens for vitamin D vary and you should consult your local guidelines or drug information source for more information.
OR
colecalciferol: children: 2000 IU orally once daily or 50,000 IU orally once weekly for 6-8 weeks, followed by 400-1000 IU/day (children <1 year of age) or 600-1000 IU/day (children ≥1 year of age) as maintenance; non-pregnant adults: 6000 IU orally once daily or 50,000 IU orally once weekly for 8 weeks, followed by 1500-2000 IU/day as maintenance; pregnant adults: 1000-2000 IU orally once daily
More colecalciferolDose regimens for vitamin D vary and you should consult your local guidelines or drug information source for more information.
1,25-dihydroxyvitamin D3 or active analogue
Treatment recommended for ALL patients in selected patient group
Given that acquired or inherited conditions of vitamin D metabolism adversely affect the metabolism of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, or the recognition of 1,25-dihydroxyvitamin D, vitamin D replacement alone is not usually sufficient but should be given together with 1,25-dihydroxyvitamin D3 (calcitriol) or one of its active analogues (e.g., paricalcitol, doxercalciferol).
Patients with chronic kidney disease who have a GFR of <50% of normal usually require 1,25-dihydroxyvitamin D3 or one of its active analogues in conjunction with vitamin D to treat and prevent secondary hyperparathyroidism. This is due to a decreased capacity to produce 1,25-dihydroxyvitamin D, which causes secondary hyperparathyroidism.
Primary options
calcitriol: children and adults: consult specialist for guidance on dose
OR
paricalcitol: children and adults: consult specialist for guidance on dose
OR
doxercalciferol: children and adults: consult specialist for guidance on dose
calcium
Additional treatment recommended for SOME patients in selected patient group
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.[88]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
There is consensus that vitamin D given in conjunction with calcium reduces fracture risk in the older population, and is recommended in this group.[67]Giustina A, Bouillon R, Dawson-Hughes B, et al. Vitamin D in the older population: a consensus statement. Endocrine. 2023 Jan;79(1):31-44. https://pmc.ncbi.nlm.nih.gov/articles/PMC9607753 http://www.ncbi.nlm.nih.gov/pubmed/36287374?tool=bestpractice.com
Furthermore, 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), which can independently reduce parathyroid hormone levels, and control their serum phosphorus level by using a phosphate binder such as calcium carbonate.[14]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 [138]Ennis JL, Worcester EM, Coe FL, et al. Current recommended 25-hydroxyvitamin D targets for chronic kidney disease management may be too low. J Nephrol. 2016 Feb;29(1):63-70. http://www.ncbi.nlm.nih.gov/pubmed/25736620?tool=bestpractice.com
Calcium supplementation should continue indefinitely or until adequate intake is achieved through dietary sources.
While some studies suggest no significant cardiovascular risk associated with calcium supplements, other research indicates potential concerns, particularly at higher doses.[131]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 [132]Huo X, Clarke R, Halsey J, et al. Calcium supplements and risk of CVD: a meta-analysis of randomized trials. Curr Dev Nutr. 2023 Mar;7(3):100046. https://pmc.ncbi.nlm.nih.gov/articles/PMC10111600 http://www.ncbi.nlm.nih.gov/pubmed/37181938?tool=bestpractice.com [133]Qiu Z, Lu Q, Wan Z, et al. Associations of habitual calcium supplementation with risk of cardiovascular disease and mortality in individuals wth and without diabetes. Diabetes Care. 2024 Feb 1;47(2):199-207. https://diabetesjournals.org/care/article/47/2/199/151370/Associations-of-Habitual-Calcium-Supplementation http://www.ncbi.nlm.nih.gov/pubmed/37506393?tool=bestpractice.com [134]Myung SK, Kim HB, Lee YJ, et al. Calcium supplements and risk of cardiovascular disease: a meta-analysis of clinical trials. Nutrients. 2021 Jan 26;13(2):368. https://pmc.ncbi.nlm.nih.gov/articles/PMC7910980 http://www.ncbi.nlm.nih.gov/pubmed/33530332?tool=bestpractice.com
Primary options
calcium carbonate: children: 45-65 mg/kg/day orally given in 4 divided doses; adolescents/adults: 1-2 g/day orally given in 3-4 divided doses
More calcium carbonateDose expressed as elemental calcium.
phosphate
Additional treatment recommended for SOME patients in selected patient group
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.[8]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 [9]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 1,25-dihydroxyvitamin D3 or one of its active analogues.
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.
Phosphate supplementation should be avoided in patients with chronic kidney disease, due to their already high-normal or elevated serum phosphate levels.
Primary options
sodium phosphate/potassium phosphate: children and adults: consult specialist for guidance on dose
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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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