**2.1 Vitamin D deficiency**

Vitamin D is inevitable for retaining the rate of metabolism in bone. The major function of vitamin D is to boost calcium and phosphorus intestinal absorption by its active metabolite 1,25dihydroxyvitamin D3 along with fostering the continuance of neuromuscular function as well as bone remodeling. Disorders in which this active metabolite is deficient can pose a greater risk of the incidence of bone disorders [6]. Low levels of vitamin D results in decreased absorption of intestinal calcium and phosphorus, with a drop in the level of calcium in serum with an increased synthesis of PTH. A rise in the level of PTH in plasma preserves the level of normal serum calcium by enhancing 1,25-(OH)2D renal development, growing bone yield, and escalating loss in mass of bone. Lack of sufficient intake or a maternal lack of vitamin D is the most leading cause of deficiency of vitamin D. Renal failure or the incidences of hepatic disease, receptor defects, or synthesis of congenital vitamin D are the other instances that cause a vitamin D deficiency. Additionally, two other rare genetic diseases, including vitamin D-dependent rickets type 1 or pseudovitamin D deficiency rickets, are caused due to the mutation in the gene encoding 1α-hydroxylase enzyme (CYP27B1 gene), which is a rate-limiting enzyme involved in the bioactivation of vitamin D.

A recent report has evaluated vitamin D status and its relationship with skeletal health in 40 healthy adult Nigerians (aged between 21 and 50 years) [7]. An array of physiological parameters were evaluated, which predominantly included markers of bone health, thyroid function and renal function, levels of parathyroid hormone, calcium excretion rates, and serum 25-hydroxyvitamin-D levels. The observed results indicated the fact that approximately 70% of the reported cases had an incidence of vitamin D insufficiency with 25% of the subjects indicated osteopenia, while none of the subjects presented with osteoporosis. The bone mineral density (BMD) T-score for osteopenic subjects was significantly lower than for non-osteopenic subjects. It was also observed that osteocalcin levels in serum were considerably higher in osteopenic subjects versus non-osteopenic subjects; however, a 24-hour calcium excretion was comparable between the two groups. Mean serum 25-hydroxyvitamin-D was lower in subjects with osteopenia compared to nonosteopenic subjects, while parameters for thyroid, renal, and calcium-phosphorus were not significantly different in the observed group [7].

#### **2.2 Disorders related to homeostasis of calcium and phosphorus**

Disorders related to homeostasis of calcium and phosphorus results in ultimate clinical consequences for neonates. A fine positive balance between calcium and phosphorus is indispensable for sufficient bone growth and maturation. Neonates with persistent malabsorption are at high prospects of poor absorption of calcium, phosphorus, magnesium, or vitamin D, either due to medical or surgical interventions [8].

### **2.3 Drug-related factors**

Some drugs that are frequently used in premature births also support the incidence of MBD. Some of the prominent classes of such drugs are loop diuretics such as furosemides, corticosteroids, methylxanthines, antifungals, and certain antiepileptics. The most probable reason may be activation of osteoclasts and reduction of osteoblast proliferation and decreased absorption, thereby the ultimate elimination of calcium by the kidneys [9].

#### **2.4 Parent related nutrition**

The concentration of minerals such as calcium and phosphorus in premature breast milk is inadequate in regard to the estimated requirement, presuming that they ingest approximately one third that is essential in fetal life [9]. In addition, milk products are high in concentration of the stated minerals but have a lower bioavailability; hence, consumption of mineral fortified milk is essential for preventing and treating MBD.

#### **2.5 Biomechanical factors**

Biomechanical factors that impact the alteration of bone structure is accountable for the reduction of bone mass caused by reduced activity level. The majority of bone-loading process occurs during the third trimester. Nevertheless, in the absence of bone loading, bone formation stops and further osteoclasts are activated leading to a reduction in bone strength [10]. Neonatal demineralization of the skeleton may result from immobilization due to the prevalence of other disease conditions or neurological implications.

#### **2.6 Endocrinology-related factors**

Thyroid hormones are prerequisite for the development of the skeleton and are prime regulators of bone maintenance. Hypothyroidism induces delayed development of the skeleton and growth retardation with delayed bone development owing to inadequate endochondral ossification. Hyperparathyroidism also impacts bone metabolism, which causes significant conditions such as hypercalcemia, demineralization of the bone, and delay in growth and development. Due to these abovementioned-stated issues, a decline in the normal function of kidneys eventually leads to mineral and bone metabolism disturbances culminating in serious skeletal deformities [11].

### **3. Diagnosis**

Since there are no ultimate diagnosis and therapy indications for MBD, and the related sign and symptoms also appear very late, it is, therefore, appropriate to monitor the subjects at risk for the development of the related disorder.

#### **3.1 Serum markers**

Levels of alkaline phosphatase (ALP) rise physiologically at about 6–12 weeks of age over the first 3 weeks of life. Regardless of the lack of signs and symptoms, ALP levels > 500 IU/L suggest impaired bone homeostasis and values >700 IU/L is associated with bone demineralisation [12].

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*Calcium and Metabolic Bone Disorders DOI: http://dx.doi.org/10.5772/intechopen.92977*

of 24.7–33.0 weeks [13].

**3.3 Radiological markers**

bone transmission time [15].

**4. Prevention of MBD**

**4.1 Physical activity**

**4.2 Adequate calcium and vitamin D intake**

issued [16].

monitored [18].

**3.2 Urinary markers**

Serum phosphate levels <5.6 mg/dl are strongly linked with the prevalence of the radiologically apparent disorder in preterm infants with an average gestational age

Hypophosphatemia is the most prevalent physiological modification coupled with premature MBD, which causes a reduced release of PTH and thereby increases the reabsorption of phosphate from the renal tubular. Infants born <28 weeks of gestation have a reduced baseline value for phosphate, resulting in increased excretion of phosphate in urine, even in the mere existence of lower levels of phosphate

Dual-energy X-ray absorptiometry (DEXA) is the conventional method used for BMD assessments. DEXA employs the use of low ionizing radiation and measures

Quantitative ultrasound is another technique that is relatively inexpensive and measures the mineral content of bone as well as the organic matrix. The parameters that are evaluated by the abovementioned technique are the speed of sound and

There are certain non-pharmacological approaches that need to be inculcated in

Individuals with MBD should be educated about the potential advantages of physical activity and motivated to be active within their ability and in keeping their values and goals as realistically possible. They should be given training on how to self-monitor for signs and symptoms that should be brought to their healthcare team's attention and the emergency contact information for this team should be

The Institute of Medicine (IOM) prescribes that dietary calcium consumption should be limited to 1000 mg daily for men aged 50–70 years, and 1200 mg daily for women aged 51 years and over [17]. Presently, the impact of calcium supplementation on stone formation is unclear. Large doses of supplemental calcium are likely to lead to stone formation, especially if given separately from a meal. If appropriate, patients with stones should be advised to take a meal with calcium supplements, and further, the disease condition needs to be closely

Vitamin D is a vital component of calcium absorption, which helps in the maintenance of bone health. The IOM recommends 600 IU and 800 IU per day for men and women who are aged 51–70 years and over 70 years, respectively [17]. Earlier reports indicate the fact that combined vitamin D and calcium intake demonstrated a reduction in the risk of fracture in older adults, but the effects varied according to

.

that appear as a significant marker for MBD incidence [14].

the calcium content in bone in terms of grams of hydroxyapatite/cm2

daily life for the prevention of MBD. Some of them are discussed below:

Serum phosphate levels <5.6 mg/dl are strongly linked with the prevalence of the radiologically apparent disorder in preterm infants with an average gestational age of 24.7–33.0 weeks [13].
