Calcium and Vitamin D | Medical Science Optional Notes for UPSC PDF Download

Mineralization of Bone and Osteoblastic Activity

• Bone Formation: Osteoblastic activity involves collagen synthesis and the creation of the mineralized bone matrix.
• Role of Osteoblasts: Osteoblasts are key players in bone formation, responsible for synthesizing and releasing collagen.

**2. Formation of Osteoid

• Post-Resorption Process: Osteoblasts release collagen into the cavity formed after bone resorption.
• Osteoid Formation: Collagen fibers organize into regular units, forming the organic matrix known as osteoid.

3. Mineralization Process

• Deposition of Minerals: Mineralization is the deposition of minerals onto the bone matrix.
• Required Elements: Adequate calcium and phosphate in the extracellular fluid (ECF) are essential for mineralization.

4. Key Mineralization Steps

• Initiation Timing: Begins approximately 10 to 12 days after osteoid formation.
• Primary Deposition: Initial large quantities of calcium phosphate are deposited.
• Crystalline Formation: Hydroxide and bicarbonate ions are gradually added, leading to the formation of hydroxyapatite crystals.

5. Role of Alkaline Phosphatase

• Acceleration of Mineralization: Alkaline phosphatase, an enzyme secreted by osteoblasts, accelerates the mineralization process.

6. Transformation of Osteoblasts

• Surrounding Mineralized Bone: Completely mineralized bone surrounds the osteoblast.
• Synthetic Activity Reduction: Osteoblast synthetic activity diminishes, and the cell undergoes transformation into osteocytes.

Factors regulating bone remodeling

Vitamin D

• Vitamin D is a fat-soluble vitamin that shares structural similarities with sterols and functions akin to a hormone. Strictly speaking, it is categorized as a hormone. 
• The body produces vitamin D through synthesis following exposure to sunlight, and subsequent activation occurs in the liver and kidneys. Once activated, it assumes a hormonal role, primarily regulating calcium metabolism.

Unlike other vitamins such as A and C, vitamin D undergoes a unique activation process before becoming usable by the body. D3 serves as the prohormone, 25(OH)D represents the primary circulating form, and 1.25(OH)2D functions as the hormonally active form.

Biosynthesis of Vitamin D

The process of endogenous Vitamin D synthesis involves several sequential steps:

• Provitamin D₃ (7-dehydrocholesterol) is synthesized from cholesterol in both the liver and the skin.
• Provitamin D₃ undergoes a conversion in the skin facilitated by UV radiation, resulting in the formation of Vitamin D₃.
• In the liver, Vitamin D₃ is hydroxylated to produce calcidiol (25-hydroxycholecalciferol) through the action of the enzyme 25-hydroxylase.
• The final hydroxylation occurs in the kidneys, where Vitamin D₃ is converted to its biologically active form, calcitriol (1,25-dihydroxyvitamin D₃), through the activity of the enzyme 1-alpha-hydroxylase. This active form plays a crucial role in various physiological processes.

Vitamin D deficiency

Causes

• Lack of sun exposure
• Malnutrition (common in alcohol use disorder) 
• Malabsorption disorders (e.g., fat malabsorption, chronic Gl disease) 
• Chronic kidney or liver disease: due to the impaired hydroxylation of active vitamin D precursors
• Breastfeeding without supplementation of vitamin D

Symptoms 

• In adults: Osteomalacia
• In children: Rickets (bone deformities such as genu varum or "bow legs") 
• Clinical features of hypocalcemia (e.g., tetany)

Vitamin D deficiency: Manifestations due to hypocalcemia

• Increased neuromuscular excitability → tetany
• Paresthesias (typically acral and/or perioral tingling or "pins and needles" sensation)
• Muscle spasms, such as carpopedal spasm (possible in any muscle) and cramps
• Additional tests for tetany in physical exam
• Chvostek’s sign = contraction of the facial muscles elicited by tapping the facial nerve in the area of the cheek (approx. 2 cm ventral to the ear lobe) 
• Trousseau's sign = ipsilateral carpopedal spasm occurring several minutes after inflation of a blood pressure cuff to pressures above the systolic blood pressure
• Seizures 
• Cardiac arrhythmias
• Abdominal cramping and diarrhea

Role of Calcium in the body

1. It helps in development of bones and teeth
2. Interaction of calcium with troponin C trigger muscle contraction
3. Blood clotting process is calcium dependent
4. Helps in transmission of nerve impulse
5. It helps in maintaining cell membrane integrity and permeability
6. Helps in activation of enzymes such as lipase, ATPase and succinate dehydrogenase
7. Calcium-calmodulin complex activates certain enzymes (adenylate cyclase)
8. It is an intracellular messenger for hormonal action (epinephrine, ADH)
9. Release of hormones from endocrine glands is facilitated by Calcium
10. It helps in cell to cell communication
11. Prolongs systole by acting on myocardium

Renal Rickets (Renal Osteodystrophy) 

Calcium metabolism-Repeats 

Q1: Describe the mechanism of mineralization of bone. Enumerate the clinical features of deficiency of the factor responsible for mineralization (2007).
Q2: Chronic renal failure leads to Osteodystrophy. Outline the chain of events. (2010)
Q3: Write the various roles of calcium in the body. How blood calcium is level regulated? (2014)
Q4:  Justify the statement 'Vitamin D is a hormone'. Describe the synthesis, mechanism of action and physiological functions of vitamin D. (2017)
Q5: Give an account of characteristics of a hormone. Describe the hormonal regulation of » calcium level in the blood. (2018)