Abstract
ObjectiveHIV-positive children, adolescents, and young adults are at increased risk poor musculoskeletal outcomes. Increased incidence of vitamin D deficiency in youth living with HIV may further adversely affect musculoskeletal health. We investigated the impact of vitamin D supplementation on a range of musculoskeletal outcomes among individuals aged 0–25 years living with HIV.MethodsA systematic review was conducted using databases: PubMed/Medline, CINAHL, Web of Knowledge, and EMBASE. Interventional randomised control trials, quasi-experimental trials, and previous systematic reviews/meta-analyses were included. Outcomes included: BMD, BMC, fracture incidence, muscle strength, linear growth (height-for-age Z-score [HAZ]), and biochemical/endocrine biomarkers including bone turnover markers.ResultsOf 497 records, 20 studies met inclusion criteria. Thirteen studies were conducted in North America, one in Asia, two in Europe, and four in Sub-Saharan Africa. High-dose vitamin D supplementation regimens (1,000–7,000 IU/day) were successful in achieving serum 25-hydroxyvitamin-D (25OHD) concentrations above study-defined thresholds. No improvements were observed in BMD, BMC, or in muscle power, force and strength; however, improvements in neuromuscular motor skills were demonstrated. HAZ was unaffected by low-dose (200–400 IU/day) supplementation. A single study found positive effects on HAZ with high-dose supplementation (7,000 vs 4,000IU/day).ConclusionsMeasured bone outcomes were unaffected by high-dose vitamin D supplementation, even when target 25OHD measurements were achieved. This may be due to: insufficient sample size, follow-up, intermittent dosing, non-standardised definitions of vitamin D deficiency, or heterogeneity of enrolment criteria pertaining to baseline vitamin D concentration. High-dose vitamin D may improve HAZ and neuromuscular motor skills. Adequately powered trials are needed in settings where HIV burden is greatest.PROSPERO Number: CRD42016042938.
Highlights
The global scale-up of antiretroviral therapy (ART) has dramatically improved survival of those living with HIV and converted what was once a life-threatening infection into a chronic, treatable condition
No improvements were observed in bone mineral density (BMD), BMC, or in muscle power, force and strength; improvements in neuromuscular motor skills were demonstrated
Measured bone outcomes were unaffected by high-dose vitamin D supplementation, even when target 25OHD measurements were achieved
Summary
The global scale-up of antiretroviral therapy (ART) has dramatically improved survival of those living with HIV and converted what was once a life-threatening infection into a chronic, treatable condition. HIV management includes treatment of HIV infection, as well as associated chronic comorbidities, for example increased risk of low bone mineral density (BMD) [1,2,3,4]. Multiple observational studies, in both high- and low-middle-income countries (LMIC), have demonstrated vitamin D insufficiency in HIV-positive children, adolescents, and young adults [6,7,8,9], with a single study demonstrating increased rates compared to HIV-negative age-matched controls [10]. ‘Low bone mass’, defined as a dual energy X-ray absorptiometry (DXA) measured BMD Z-score -2 has been associated with low 25OHD and altered vitamin D metabolism in HIV-positive youths [15,16]. Direct and indirect effects of HIV on musculoskeletal health are multifactorial and are potentially exacerbated by inadequate vitamin D
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