**3. Pathophysiology**

*Vitamin D Deficiency*

or have clinically meaningful effects on bone mineral density, and suggested 'little justification to use vitamin D supplements to maintain or improve musculoskeletal health'). A recent umbrella review did conclude that most RCTs have been carried out in populations that are not vitamin D deficient and, because of this, possible beneficial effects from vitamin D supplementation cannot be excluded [7]. Further, complementary medicine supplementation receives less stringent regulation for approval to the general public. For example, in Australia, vitamin D or other supplements which claim that it 'may' improve bone health and general well-being are approved on the Therapeutic Goods Administration as an ARTG [8]

*In many countries, there is an abundance of sunlight throughout the entire year. Ironically, the sun-protective messages for the primary prevention of skin cancers become stronger than those of the moderate benefits of* 

Given the urgent need for the general population, clinicians and consumers will benefit from the latest evidence for vitamin D supplementation (through diet, extraneous supplementation and sunlight therapy), including its efficacy and

Vitamin D deficiency is a major global public health problem in all aged groups, particularly in the Middle East. There is striking lack of data in infants, children and adolescents worldwide and in most countries of South America and Africa [9].

compared with vitamin D as a medication.

potential harm (**Figure 1**).

**2. Epidemiology**

**Figure 1.**

*sunlight.*

**96**

Vitamin D is crucial in calcium and vitamin D metabolism, as its absence around 15% of dietary calcium and 60% of phosphorus is absorbed. 1,25-Dihydroxyvitamin D interacts with the vitamin D receptor which increases

**Figure 2.** *Vitamin D Metabolism (From Horlick [10]).*

the intestinal calcium absorption to 40% and phosphorus to 80% (**Figure 2**, [10]). Vitamin D is transformed for activation through two hydroxylations in the body. Among the metabolic products or modified versions of vitamin include calcitriol (1,25-dihydroxyvitamin D3); the active form of vitamin D, with a 15-hour half-life; and calcifediol (25-hydroxyvitamin D3) with a 15-day half-life [10]. Vitamin D is bounded to specific receptors located throughout the body. Whilst serum 25(OH) D levels do not indicate the amount of vitamin D stored in body tissues, it is the best indicator of vitamin D status.

When the level was 30 ng/mL or less, there was a significant decrease in intestinal calcium absorption that was associated with increased parathyroid hormone [10]. Further, there is strong support from reports that maternal vitamin D deficiency leads to overt bone disease (congenital rickets) from before birth to post-natal life [11]. Throughout the world, there has been widespread debate as to the serum 25(OH)D concentrations associated with deficiency (e.g. rickets), for optimal bone health and optimal overall health, and most cut points have not been developed by an agreed mutual scientific process. The US Institute of Medicine concluded that individuals are at risk of vitamin D deficiency at serum 25(OH)D concentrations <30 nmol/L (<12 ng/mL). However, some individuals are potentially at risk for inadequacy even at levels ranging from 30 to 50 nmol/L (12–20 ng/mL). The committee agreed with sufficient levels at ≥50 nmol/L (≥20 ng/mL) and that 50 nmol/L is the serum 25(OH)D level that covers the majority of needs of the population (97.5%) [12].

Further, hypovitaminosis D in its mild but especially in severe forms can exacerbate symptomatic hypocalcaemia following intravenous bisphosphonate (zoledronic acid) [13]. Even though this is rare, associated hypocalcaemia may be life-threatening and require immediate resuscitation and evaluation, often requiring hospitalisation to prevent additional morbidity and mortality risk from tetany, refractory hypotension, seizures or arrhythmias. Therefore it makes good sense to optimise vitamin D levels prior to administration of these agents [14].

Vitamin D toxicity can occur when blood 25(OH)D levels are 88 ng/mL or greater [15]. Symptoms may include sleepiness, vomiting, weakness, headache, nausea and constipation, and acute toxicity may cause hypercalcaemia and hypercalciuria.
