1.1 Nutrition

The primary sources of vitamin D are from cutaneous production and healthy diet. Adolescents with AIS have poor nutritional status compared with healthy controls, and generally lean body figure is an acknowledged feature of AIS. Those with AIS were found to have a lower BMD and lean mass compared with those without.⁶

Leptin is a small polypeptide mainly secreted by adipose tissues. It regulates food intake and energy metabolism and plays multiple important roles in bone growth and bone metabolism. The decreased BMI and adipose tissues of AIS patients have been associated with decreased leptin secretion, increased leptin utilization, and abnormal downstream signaling in leptin pathways.⁷ Additionally, A strong positive association among decreased plasma leptin, elevated PTH, and inadequate vitamin D levels have been reported.⁸

There are some other chronic conditions that increase the need of vitamin D in these patients when malnutrition already exists. Periodic pulmonary infection increases the risk of hospitalization and antibiotic use. Mood disorders may lead to alcohol consumption and subsequent nutritional VDD.⁹ The extremely low BMI found in some AIS patients may suggest a possible link between AIS and anorexia nervosa which is quite common in this age group.¹⁰

Chronic functional gastrointestinal disorders including abdominal pain, dyspepsia, irritable bowel syndrome, and diarrhea are prevalent among AIS patients.¹¹ These conditions predispose patients to VDD through decreased absorption of vitamin D and minerals due to in-appetite, inflamed intestinal epithelium, reduced surface area, and disrupted enterohepatic circulation.

1.2 Female gender

Majority of the AIS patients are girls at their puberty with increased need of vitamin D and other supplements, while dietary intake is generally inadequate during this growth period. Actually, The prevalence of adolescent undernutrition and underweight is estimated about 20.7 and 27.5 %, respectively in the developing countries.¹² The rates doubles for adolescent girls.¹³

Adolescence is the period of rapid growth and development with significant physical and psychological milestones. Adolescent girls experience more physical changes through phases of thelarche and menarche. Generally, menstrual cycles are irregular and could be heavy during adolescence. This puts the patients in risk of iron deficiency anemia, protein and other micronutrients deficiencies. On the other hand, menarche is delayed in AIS patients with fluctuations in estrogen, melatonin and leptin hormones.¹⁴

Eating disorders are common among adolescent girls. Anorexia nervosa and bulimia nervosa are the most common eating disorders with potential medical complications associated with malnutrition. Any chronic disease or trauma including AIS during this period of vulnerability could greatly complicate these eating disorders, leading to excessive and potentially permanent physical and psychological consequences.

Inappropriate dietary habits including poor appetite, skipping meals, and a dominant desire for sweet foods are common fashion among adolescent girls. Adolescent girls usually follow culture of overdieting and unhealthy weight loss, less likely to choose healthy diet, and more likely to be influenced by their peers. Depression and other mood disorders are also prevalent during this period. Both situations are linked with micronutrient deficiencies and malnutrition.

Girls are usually less sun-exposed and physically active compared to their peer boys. The socioeconomic conditions, gender barriers, and social and cultural norms put girls in risk of VDD through lower skin-mediated synthesis of vitamin D.

The other factors including early pregnancy, poor access to healthcare, and lower education and knowledge could also potentially lead to malnutrition among adolescent girls.

1.3 Physical activity

Globally, 81 % of adolescents are physically inactive, leading to psychological distress including anxiety, stress, and depression. Adolescents with AIS have lower physical activity compared to their peers due to lower level of energy, lower psychosocial motivation, low back pain, decreased cardiopulmonary function, and general body image. Moreover, adolescents with AIS have abnormalities related to their posture, proprioception, and equilibrium control leading to decreased physical activity.¹⁵

Adolescents with AIS may feel less confident conducting physical activities and fear of injury could negatively impact their desire of participation. Bracing itself could decrease their physical activity.¹⁶

Physical inactivity had been associated with VDD. On the other hand, exercise could significantly increase serum vitamin D levels possibly through increased fat metabolism and releasing stored vitamin D in adipose tissues.¹⁷ Additionally, exercise might act as a trigger to up-regulate 1-α-hydroxylase enzyme gene to increase synthesis of vitamin D in muscles.¹⁸

1.4 Dressing habits

Although body image dissatisfaction is a common feature among adolescents, its prevalence is higher among patients with AIS. One adaptation of the adolescents with AIS is an attempt to cover their body imbalance by dressing. However, as 90 % of vitamin D production is determined by cutaneous production under ultraviolet radiation, dressing could dramatically induce VDD.

The use of sunscreen or sun avoidance is a common fashion among adolescent girls which could restrict UVB exposition. Additionally, exposition time by indoor activities is reduced which is more prevalent among adolescent girls compared to boys.

Cultural factors, dressing codes, and social restrictions are other items which limit the exposition time especially among adolescent girls.

Bracing for curve correction or progression restriction could potentially cause over-dressing and outdoor activity avoidance either due to its weight or visual appearance. Adolescents who wear braces have reported wearing additional outerwear or loose-fit clothing styles to maintain a positive body image and minimize the unpleasant feelings caused by the brace.¹⁹ This dressing habit could result in decreased sun exposure and vitamin D synthesis.

1.5 Psychological discomfort

Adolescents with AIS experience different aspects of psychological discomfort in the forms of anxiety, stress, distortion of the body image, reduced self-esteem, negative emotions, and communication problems.²⁰ These psychological discomforts could potentially cause eating problems, physical inactivity, outdoor avoidance, and treatment uncooperativeness including the mineral supplement discontinuation.

Drugs used for these psychological discomforts have additional effects on the vitamin D absorption, synthesis, and metabolism. Mood stabilizers and antiepileptic medications could cause gastrointestinal upset, decreased appetite, constipation, and increased clearance of vitamin D metabolites.²¹

1.6 Cardiopulmonary function

Scoliosis and thoracic curvature could potentially affect the respiratory function through reduction of chest wall compliance, impaired lung growth and impaired respiratory muscle strength.²² Additionally, thoracic-dominant scoliosis has an impact on cardiac function, altering pulmonary artery resistance causing mitral valve prolapse.²³ Cardiopulmonary impairment could result in limitation on aerobic exercises, anorexia, intestinal congestion, malabsorption, and reduced health-related quality of life.^24,25

Beside malabsorption which reduces intestinal absorption of vitamin D, cardiopulmonary impairment could cause anemia and reduce cutaneous microcirculation, leading to decreased vitamin D synthesis. Additionally, hepatic and renal congestion induced by low cardiac function could impair vitamin D hydroxylation.²⁶

1.7 Bone turnover

Bone turnover is increased in patients with AIS and the risk of curve progression is associated with higher serum markers of bone turnover including P1NP and CTX.²⁷ This high bone resorption could be a possible cause of low bone mineral density in patients with AIS, a direct risk factor of VDD.

To restore the normal bone density and restrict curve progression, osteoblasts have an important role. Mesenchymal stem cells should differentiate into osteoblasts and then osteoblasts should proliferate to mineralize bone matrix into normal mineral density. The osteogenic differentiation, osteoblast proliferation, and bone mineralization is stimulated by vitamin D. Vitamin D has even a direct receptor on osteoblasts to regulate gene expression.²⁸ This process increases the need of vitamin D in patients with AIS.

1.8 Vitamin D receptor

Vitamin D receptor has both critical genomic and non-genomic actions in cells. The genomic actions of the receptor include regulation of energy metabolism, control of cell immunity, cell growth, and calcium hemostasis. The non-genomic actions of the receptor are a series of downstream effects resulting in opening of ion channels of calcium and phosphate, insulin secretion, and induction of second messengers.²⁹

As the familial aggregation phenomenon and an autosomal-dominant mode of inheritance have been recently noted among AIS patients, genetic factors have been acknowledged to be associated with the occurrence and development of AIS. Vitamin D receptor gene polymorphism has recently been introduced to be associated with AIS.³⁰ A significant association between the receptor polymorphism and low bone mineral density has been reported in AIS patients.³¹ Additionally, receptor polymorphism may predict poor response to brace treatment.³² Receptor malfunction may present VDD outcomes despite appropriate vitamin D levels.

1.9 Conclusion

Here we have reviewed some possible common risk factors of VDD in AIS patients. Although the list is widespread, the significant risk factors for developing VDD in AIS patients are female gender, poor dietary intake, dressing habits, low cardiopulmonary condition, high bone turnover, and polymorphism of vitamin D receptor. It should be remembered that items introduced here have bidirectional link with vitamin D, as some are influenced by VDD themselves. By identifying patients with low vitamin D preoperatively, patients may be treated with supplementation to potentially minimize complications. Future studies are needed to identify more definite risk factors and to consider targeted intervention protocols.