Running head: EFFICACY OF VITAMIN D + CALCIUM

Efficacy of Vitamin D + Calcium as Treatment for Bone Fragility in Children with HIV Infection
Nicole S. Mize
California Polytechnic State University, San Luis Obispo

THE EFFECTS OF CALCIUM SUPPLEMETNATION

The introduction of combination antiretroviral therapy (cARV) for the treatment of

human immunodeficiency virus (HIV) has considerably increased the life expectancy of HIVinfected adults and children. Simultaneously, noninfectious complications of HIV infection and
its corresponding treatments have become apparent. Low bone mineral density (BMD) leading to
bone fragility and osteoporosis is the most common bone pathology noted among ARV therapy
(Cotter & Powderly, 2011). When compared with population norms, Children with HIV had
lower than expected bone mass for their age and gender which may delay growth and increase
bone disease severity (Jacobson et al., 2005). Research is required to understand this process and
determine effective management, especially in children, to prevent progression of bone wasting.
The purpose of this paper is to examine the efficacy of vitamin D and calcium supplementation
as treatment for bone fragility in children with HIV infection.
Worldwide, the current estimates for people living with HIV lies at 42 million as of 2012
with 3.5 million children under 15 years of age infected (Puthanakit & Siberry, 2013). Treatment
has effectively increased the lifespan of those infected with HIV, yet this has led to an increase in
morbidity and mortality due to secondary issues such as HIV bone disease. HIV infected
pediatric populations have a greater incidence in reduction of BMD compared to controls
(Panayiotopoulos, Bhat, & Bhangoo, 2013). Several factors influence the total amount of peak
bone mass attained through childhood and adolescence, including gender, ethnicity, genetics,
nutrition, and level of weight-bearing physical activity (Panayiotopoulos, 2013). It is important
to target these risks, as bone mass is a predictor of the future risk of osteoporosis and fractures in
adulthood (Panayiotopoulos, 2013). Many factors that predict suboptimal levels of peak bone
mass are common in HIV-infected children, including insufficient intake of calcium and vitamin
D (Panayiotopoulos, 2013). Vitamin D levels have strong correlation with bone disease in HIV-

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infected youth and are not only dependent on HIV management but interaction of pharmacologic
management and inflammatory process (Panayiotopoulos, 2013). It is estimated that 90% of HIV
infected individuals may have sub optimal serum vitamin D levels (serum 25(OH)D)
(Panayiotopoulos, 2013). Therefore, understanding the mechanisms of HIV and treatment drugs
interacting with vitamin D in the body is important when determining effective treatment.
Vitamin D is a vital hormone involved in calcium and bone metabolism. Insufficient
levels of serum vitamin D (serum 25(OH)D<30 ng/ml) are involved with osteomalacia
(Panayiotopoulos, 2013). This is due to high bone turnover and increased bone resorption that
occurs in conjunction with secretion of parathyroid hormone (Panayiotopoulos, 2013). One study
found when low vitamin D levels are present in addition to cART and HIV itself, there was an
increase in proinflamatory cytokines, creating an inflamatory cascade that can possible induce
bone demineralization and osteroblast (bone-mineralizing cell) turnover (Panayiotopoulos,
2013). During these conditions, vitamin D becomes less effective due to its inability to become
hydroxylated to the active form (1,25(OH)2 D) (Panayiotopoulos, 2013).
When these conditions arise, bone mineralization slows or ceases, possibly leading to
bone fragility, which can have prolonged negative effects in children and adolescents. Bone
fragility is classified based on BMD, according to the T-score (number of standard deviations
(SDs) below the mean BMD) and adjusted for sex and ethnicity (Stone, Dockrell, Bowman, &
McCloskey, 2010). A z- score less than or equal to 2.0 is classified as abnormal in individuals
younger than 30 years (Stone, 2010).
Over the past decade, vitamin D and calcium as treatment for bone fragility in children
with HIV has been more closely studied. A 2013 review found that vitamin D deficiency in HIV
infected children can be corrected with Vitamin D2 (ergocalciferol) Vitamin D3 (cholecalciferol)

THE EFFECTS OF CALCIUM SUPPLEMETNATION

(Panayiotopoulos, 2013). Vitamin D2 can be replaced either in high weekly doses of 50,000 IU
for 12 weeks and then monthly or D3 can be given in daily doses of 2,000 IU for 12 weeks and
then continued at a lower dose of 1,000 IU(Panayiotopoulos, 2013). However, another trial
found that very high annual loading doses (500,000 IU each year) may be associated with higher
risk of fractures (Bunders, Frinking, Scherpbier, van Arnhem, van Eck-Smit, et al. 2013). That
same trial found optimal calcium to range between 1-2 grams per day, along with 1-2 grams of
phosphorous supplements to re-mineralze bone with patients who already had signs of bone
fragility (Bunders, 2013).
One specific study cited in the above 2013 review studied 13 HIV-infected children with
a mean age of 7 years to determine differences in dosage for vitamin D and calcium compared to
uninfected children (Zamboni, Antoniazzi, Bertoldo, Lauriola, Antozzi,, et al.(2003). Results
showed a positive correlation between appropriate vitamin D and calcium intakes and normal
BMD (Zamboni, 2003). However, there was little addition improvement in BMD when dosage is
above the RDA for healthy children.
The recent literature on children with HIV and bone fragility suggests vitamin D and
calcium treatments are effective in slowing the onset of bone fragility. However, sources
disagree on the absolute effective dosage and whether or not BMD levels can be maintained at
normal levels with ongoing HIV treatment. Children with HIV infection have two forces
working against their ability to build strong bones the infection itself and treatment drugs, but
fortunately, data does suggest their effects can be diminished with supplementation of vitamin D
and calcium. Yet, there is still not a consensus as to whether or not higher-than-normal doses are
necessary or if low BMD can be reversed once its effects are severe.

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