Highlights
- •Bone health is decreased in individuals with HIV infection.
- •Vitamin D intake may have beneficial effects on skeletal outcomes in HIV patients.
- •Vitamin D supplementation can improve serum 25 (OH) vitamin D in HIV patients.
Abstract
Purpose
There is growing evidence that bone health is decreased in individuals with HIV infection.
Vitamin D deficiency is also highly prevalent among HIV-infected patients. The literature
was systematically reviewed to determine whether bone health and bone-related parameters
may improve with vitamin D supplementation in HIV-infected individuals.
Methods
Four databases were systematically searched for randomized clinical trials of vitamin
D supplementation in HIV infection, published from January 1990 to September 2021.
No language or publication restrictions were applied. Standardized mean differences
(SMD) with 95% CIs are reported. A random-effects model was used to perform meta-analysis.
Findings
Ten studies met the inclusion criteria (N = 733 participants at study completion).
The mean ages of the patients in the included trials ranged from 10 to 49 years. The
meta-analysis indicated that with vitamin D supplementation, serum 25-hydroxy vitamin
D (25[OH]D) level was significantly increased (SMD, 1.86; 95% CI, 1.02 to 2.70; I2 = 94.4%), but there were no significant effects on levels of serum 1,25-dihydroxy
vitamin D (1,25-[OH]2D) (SMD, 0.29; 95% CI, –0.07 to 0.64; I2 = 67.4%), total bone mineral density (SMD, 0.07; 95% CI, –0.23 to 0.37; I2 = 00.0%), spine bone mineral density (SMD, 0.15; 95% CI, –0.19 to 0.49; I2 = 17.3%), and parathyroid hormone level (SMD, –0.18; 95% CI, –0.37 to 0.02; I2 = 1.2%) in HIV-infected patients.
Implications
This study showed that vitamin D supplementation can improve serum 25(OH)D in HIV-infected
patients. The effects of vitamin D supplementation on other bone health–related parameters
such as bone mineral density and parathyroid hormone in HIV-infected patients need
to be further investigated in larger-scale, well-designed randomized, controlled trials.
Graphical abstract
Graphical Abstract
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical TherapeuticsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global mortality and morbidity of HIV/AIDS.in: Holmes KK Bertozzi S Bloom BR Jha P Major Infectious Diseases. 2017 (Washington, DC)
- Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study.J Acquir Immune Defic Syndr. 2006; 43: 27-34
- Bone health and HIV in resource-limited settings: a scoping review.Curr Opin HIV AIDS. 2016; 11: 306-325
- Osteoarticular manifestations associated with HIV infection.Joint Bone Spine. 2017; 84: 29-33
- People living with HIV and fracture risk.Osteoporos Int. 2020; 31: 1633-1644
- Deficits in bone strength, density and microarchitecture in women living with HIV: a cross-sectional HR-pQCT study.Bone. 2020; 138115509
- Vitamin D deficiency and altered bone mineral metabolism in HIV-infected individuals.Curr HIV/AIDS Rep. 2014; 11: 263-270
- Dietary carbohydrate intake and risk of bone fracture: a systematic review and meta-analysis of observational studies.Public Health. 2020; 181: 102-109
- Vitamin D deficiency.N Engl J Med. 2007; 357: 266-281
- Vitamin D deficiency: a worldwide problem with health consequences.Am J Clin Nutr. 2008; 87: 1080S-1086S
- Vitamin D and chronic diseases.Aging Dis. 2017; 8: 346
- Vitamin D and chronic diseases: the current state of the art.Arch Toxicol. 2017; 91: 97-107
- Vitamin D deficiency in HIV infection: not only a bone disorder.BioMed Res Int. 2015; 2015735615
- Effects of vitamin D deficiency and combination antiretroviral therapy on bone in HIV-positive patients.AIDS. 2012; 26: 253-262
- Continued interest and controversy: vitamin D in HIV.Curr HIV/AIDS Rep. 2018; 15: 199-211
- Low bone mineral density in HIV-positive young Italians and migrants.PLoS One. 2020; 15e0237984
- Reduced bone mineral density in human immunodeficiency virus-infected patients and its association with increased central adiposity and postload hyperglycemia.J Clin Endocr Metab. 2004; 89: 1200-1206
- Effect of high-dose cholecalciferol (vitamin D3) on bone and body composition in children and young adults with HIV infection: a randomized, double-blind, placebo-controlled trial.Osteoporosis Int. 2017; 28: 201-209
- Effect of low dose oral vitamin D on bone mineral density changes in HIV patients.Infect Disord Drug Targets. 2019; 20: 651-658
- Vitamin D and calcium attenuate bone loss with antiretroviral therapy initiation: a randomized trial.Ann Intern Med. 2015; 162: 815-824
- Effects of vitamin D supplementation on bone mineral density and bone markers in HIV-infected youth.J Acquir Immune Defic Syndr. (1999). 2017; 76: 539
- Long-term impact of calcium and vitamin D supplementation on bone density in HIV+ patients with documented deficiencies.AIDS Res Human Retroviruses. 2020; 36: 58-64
- A randomized placebo-controlled trial of low versus moderate dose vitamin D3 supplementation on bone mineral density in postmenopausal women with HIV.J Acquir Immune Defic Syndr (1999). 2019; 80: 342
- Effects of sunlight exposure and vitamin D supplementation on HIV patients.J Steroid Biochem Mol Biol. 2020; 105664
- Association of low vitamin D with complications of HIV and AIDS: a literature review.Infect Disord Drug Targets. 2020; 20: 122-142
- Use of bisphosphonates, calcium and vitamin D for bone demineralization in patients with human immunodeficiency virus/acquired immune deficiency syndrome: a systematic review and meta-analysis of clinical trials.J Bone Metab. 2020; 27: 175
- The impact of vitamin D supplementation on musculoskeletal health outcomes in children, adolescents, and young adults living with HIV: a systematic review.PLoS One. 2018; 13e0207022
- Effect of vitamin D supplementation with anti-viral therapy on CD4 levels in HIV-infected patients: systematic review and meta-analysis.Int J Med Investig. 2018; 7: 1-10
- Micronutrient supplementation in adults with HIV infection.Cochrane Database Syst Rev. 2017; CD003650
- Interventions for the treatment of decreased bone mineral density associated with HIV infection.Cochrane Database Syst Rev. 2007; CD005645
- Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.PLoS Med. 2009; 6e1000097
- Cochrane Handbook for Systematic Reviews of Interventions.John Wiley & Sons, 2019
- Vitamin D: deficiency, sufficiency and toxicity.Nutrients. 2013; 5: 3605-3616
- Effect of supplementation with cholecalciferol and calcium on 2-y bone mass accrual in HIV-infected children and adolescents: a randomized clinical trial.Am J Clin Nutr. 2012; 95: 678-685
- Correlation of increases in 1,25-dihydroxyvitamin D during vitamin D therapy with activation of CD4+ T lymphocytes in HIV-1-infected males.HIV Clin Trials. 2012; 13: 162-170
- Vitamin D and calcium supplement attenuate bone loss among HIV-infected patients receiving tenofovir disoproxil fumarate/emtricitabine/efavirenz: an open-label, randomized controlled trial.Curr HIV Res. 2020; 18: 52-62
- Vitamin D3 decreases parathyroid hormone in HIV-infected youth being treated with tenofovir: a randomized, placebo-controlled trial.Clin Infect Dis. 2012; 54: 1013-1025
- Vitamin D supplementation and CD4 count in children infected with human immunodeficiency virus.J Pediatr. 2011; 159: 951-957
- Vitamin D supplementation and endothelial function in vitamin D deficient HIV-infected patients: a randomized placebo-controlled trial.Antiviral Ther. 2012; 17: 613-621
- Vitamin D and phenylbutyrate supplementation does not modulate gut derived immune activation in HIV-1.Nutrients. 2019; 11: 1675
- Comprehensive safety monitoring of 12-month daily 7000-IU vitamin D-3 supplementation in human immunodeficiency virus-infected children and young adults.J Parenteral Enteral Nutr. 2016; 40: 1057-1063
- High-dose vitamin D-3 supplementation in children and young adults with HIV: a randomized, placebo-controlled trial.Pediatr Infect Dis J. 2015; 34: E32-E40
- Alendronate/Vitamin D for attenuating bone mineral density loss during antiretroviral initiation: a pilot randomized controlled trial.HIV Res Clin Pract. 2019; 20: 140-150
- Vitamin D and bone loss in HIV.Curr Opin HIV AIDS. 2016; 11: 277-284
- Vitamin D in human immunodeficiency virus infection: influence on immunity and disease.Front Immunol. 2018; 9: 458
- Effects of vitamin D supplementation on circulatory YKL-40 and MCP-1 biomarkers associated with vascular diabetic complications: a randomized, placebo-controlled, double-blind clinical trial.Diabetes & Metabolic Syndrome: Clin Res Rev. 2019; 13: 2873-2877
- Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.J Clin Endocrinol Metab. 2011; 96: 1911-1930
- Vitamin D deficiency: is the pandemic for real?.Indian J Community Med. 2015; 40: 215-217
- Factors associated with bone microstructural alterations assessed by HR-pQCT in long-term HIV-infected individuals.Bone. 2020; 133115210
- Antiretroviral therapy and bone mineral measurements in HIV-infected youths.Bone. 2010; 46: 1633-1638
- Clinical review: The role of the parent compound vitamin D with respect to metabolism and function: why clinical dose intervals can affect clinical outcomes.J Clin Endocrinol Metab. 2013; 98: 4619-4628
- Impact of vitamin D supplementation on falls and fractures-A critical appraisal of the quality of the evidence and an overview of the available guidelines.Bone. 2020; 131115112
- Immune modulatory effects of vitamin D on Viral Infections.Nutrients. 2020; 12: 2879
- RANKL as a key figure in bridging between the bone and immune system: Its physiological functions and potential as a pharmacological target.Pharmacol Ther. 2020; 107682
Article info
Publication history
Published online: March 05, 2022
Accepted:
December 19,
2021
Identification
Copyright
© 2022 Elsevier Inc.
