Bone Growth and Height Factors

Nonhormonal Factors for Bone Growth

• Genes significantly affect bone size, density, and overall growth, leading to individual variations
• Sufficient protein and calcium intake is essential for healthy bone development
• Vitamin C aids in collagen synthesis, which is vital for bone and connective tissue
• Vitamin D (technically a hormone), regulates calcium absorption for bone health
• Chronic stress and elevated cortisol interfere with bone formation and calcium absorption

Human Height and Genetics

• Height is a polygenic phenotype, influenced by multiple genes interacting

Distribution of Height

• Human height follows a bell-shaped curve, clustering around an average
• Genetic and environmental factors play a complex role in height variation

GH-IGF-1 Pathway

• Growth hormone (GH), or somatotropin, prompts the liver to produce Insulin-like Growth Factor 1 (IGF-1)
• IGF-1 encourages bone and tissue lengthening

Origins of Hormones

• GH is secreted by the anterior pituitary gland
• IGF-1 is primarily produced in the liver
• Both GH and IGF-1 are proteins and organic molecules

Thyroid Hormone’s Role

• Thyroid hormones such as T3 and T4 (derived from iodine and tyrosine) are vital for skeletal development
• They enhance the effects of GH

Testosterone vs. Estrogen in Growth

• Both testosterone and estrogen stimulate growth during puberty but have different effects
• Estrogen accelerates growth plate closure, resulting in shorter height in females
• Testosterone prolongs the growth phase, contributing to greater height in males

Commonalities (Testosterone, Estrogen, Cortisol)

• All three are derived from cholesterol
• Testosterone and estrogen stimulate skeletal growth while cortisol inhibits it

Height Differences in Siblings

• Hormonal differences, particularly testosterone and GH levels, and slower growth plate closure contribute to male height advantage

Hormones Regulating Calcium Homeostasis

• Parathyroid Hormone (PTH), also known as parathormone, raises blood calcium levels
• PTH stimulates osteoclasts to break down bone, releasing calcium into the bloodstream
• PTH increases calcium reabsorption in the kidneys, reducing urinary calcium excretion
• PTH promotes activation of vitamin D (calcitriol) which enhances intestinal calcium absorption
• PTH's effects are considered hypercalcemic
• PTH is a peptide hormone composed of amino acids

Calcitonin

• Calcitonin, or thyrocalcitonin, lowers blood calcium levels, counteracting PTH
• It inhibits osteoclasts, reducing calcium release from bone
• It encourages calcium excretion by the kidneys
• The effects are hypocalcemic
• Calcitonin is a peptide hormone composed of amino acids

Vitamin D/Calcitriol

• Vitamin D/Calcitriol, or 1,25-dihydroxycholecalciferol, enhances calcium absorption from the intestines
• It helps maintain calcium homeostasis and bone mineralization
• It complements PTH to increase blood calcium levels, making it hypercalcemic
• Vitamin D/Calcitriol is a steroid hormone derived from cholesterol

Precursors Leading to Activation

• Vitamin D3 (Cholecalciferol) is synthesized in the skin with UV exposure or obtained from the diet
• It undergoes hydroxylation in the liver to form 25-hydroxyvitamin D (calcidiol)
• Calcidiol is then hydroxylated in the kidneys to produce the active form, calcitriol

Precursors, Organs, and Conditions for Vitamin D Production

• Precursors include:
  • Cholecalciferol (Vitamin D3) synthesized in the skin upon UVB exposure
  • Ergocalciferol (Vitamin D2) derived from plants and dietary sources
• Organs involved are:
  • Skin produces cholecalciferol under sunlight exposure
  • Liver hydroxylates cholecalciferol into calcidiol
  • Kidneys hydroxylate calcidiol into the active form, calcitriol
• Low calcium levels stimulate PTH secretion, triggering calcitriol activation in the kidneys

Hormonal Control of Vitamin D Activation

• PTH is the key hormone controlling the second hydroxylation step in the kidneys, converting calcidiol into calcitriol

Role of Hydroxylation in Active Vitamin D Production

• Hydroxylation Steps:
  • First Hydroxylation (Liver): Cholecalciferol is converted to Calcidiol
  • Second Hydroxylation (Kidneys): Calcidiol is converted to Calcitriol
• Importance:
  • Converts inactive precursors into calcitriol, the biologically active form that enhances calcium absorption in the intestines

Cholecalciferol and Calcidiol as Pre-hormones

• Cholecalciferol and calcidiol are pre-hormones as they must undergo hydroxylation to become the active hormone calcitriol

Effects of Calcium Imbalances on Neuromuscular Physiology

• Low Calcium (Hypocalcemia):
  • Symptoms include muscle cramps, spasms, and tetany (involuntary muscle contraction)
  • Mechanism: Calcium is essential for stabilizing voltage-gated ion channels in neurons and muscle cells
• High Calcium (Hypercalcemia):
  • Symptoms include weakness, slowed reflexes, and confusion
  • Mechanism: Excessive calcium dampens excitatory signals, reducing neuronal and muscular activity

Hypercalcemic Hormones and Their Mechanisms

• PTH:
  • Stimulates calcium release from bones (osteoclast activity)
  • Enhances calcium reabsorption in the kidneys
  • Activates calcitriol, increasing calcium absorption in the intestines
• Calcitriol:
  • Boosts calcium absorption in the intestines
  • Promotes calcium reabsorption in the kidneys
  • Supports bone mineralization

Interaction Between Hypercalcemic Hormones

• PTH’s hypercalcemic effect is indirectly enhanced by calcitriol, which stimulates its activation in the kidneys

Hypocalcemic Hormone and Mechanism

• Calcitonin:
  • Reduces osteoclast activity, limiting calcium release from bones
  • Encourages calcium excretion in the kidneys

Relative Importance of Hypocalcemic vs Hypercalcemic Hormones

• PTH and calcitriol are more critical for calcium homeostasis than calcitonin because they prevent dangerously low calcium levels

Negative Feedback Regulation

• Components:
  • Variable: Blood calcium levels
  • Signal: Detected by calcium-sensing receptors in parathyroid cells
  • Controller: Parathyroid gland (secretes PTH in response to low calcium)
  • Effectors: Bones, kidneys, intestines
• How It Works:
  • Low calcium stimulates PTH secretion
  • High calcium inhibits PTH and may stimulate calcitonin

Medical Conditions Linked to High Calcium

• Hypercalcemia Causes:
  • Overactive parathyroid glands (hyperparathyroidism)
  • Malignancies producing PTH-related protein
• Treatments:
  • Address underlying causes (e.g., surgery for hyperparathyroidism)
  • Use calcitonin or bisphosphonates to lower calcium levels

Parathyroid Surgery and Temporary Gland Dysfunction

• Surgery on the thyroid or parathyroid can impair parathyroid function, leading to hypocalcemia
• Management:
  • Calcium supplements
  • Vitamin D therapy to enhance intestinal calcium absorption