Bone Mineral Homeostasis, Hormonal Regulation, and Fracture Repair

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The relationship between calcium in the blood and reserves in bone is dynamic, reflecting constant exchange to maintain physiological balance.

Bone contains 99% of the body's calcium, making it the most abundant mineral in the human body (2.2 – 4.4 lbs in body).
Calcium regulation is controlled via mechanisms in the intestine, bone, and kidneys.
Calcium is essential for muscle contraction, nerve impulse generation, and blood coagulation.
Significant fluctuations in blood calcium (>30–35%) can be lethal; daily flux as high as 10% is unusual.
Bone also stores other minerals: magnesium, sodium, potassium, and carbonate.

Blood calcium levels are tightly regulated by three main hormones: parathyroid hormone (PTH), calcitonin, and calcitriol.

Parathyroid hormone (PTH): Increases blood calcium levels.
Calcitonin: Decreases blood calcium levels.
Calcitriol: Active form of vitamin D, enhances calcium absorption in the intestines.

When blood calcium levels fall below 8.5 mg/dL, the body initiates mechanisms to restore balance.

Parathyroid glands secrete PTH in response to low calcium.
PTH stimulates:
- Release of factors causing immature osteoclasts to mature, accelerating erosion of bone matrix and releasing calcium.
- Enhanced calcium-absorbing effects of calcitriol on intestines, increasing Ca2+ absorption.
- Increased production of calcitriol by the kidneys.
- Stimulates reabsorption of calcium by kidneys, reducing urinary loss.

If blood calcium levels rise above 11 mg/dL, the body acts to lower them.

C cells in the thyroid gland secrete calcitonin.
Calcitonin effects:
- Inhibits osteoclasts (reducing bone resorption), but not osteoblasts.
- Decreases PTH or calcitriol levels, reducing intestinal absorption of calcium.
- Suppresses calcium reabsorption in kidneys, increasing urinary excretion.

Hormone	Source	Main Effect	Target Organs
Parathyroid Hormone (PTH)	Parathyroid glands	Increases blood Ca2+	Bone, kidneys, intestines
Calcitonin	Thyroid gland (C cells)	Decreases blood Ca2+	Bone, kidneys, intestines
Calcitriol	Kidneys (from vitamin D)	Increases Ca2+ absorption	Intestines

Fractures are classified based on their cause and whether the skin is broken.

Traumatic fracture: Caused by injury.
Pathological (spontaneous) fracture: Occurs due to disease (e.g., osteoporosis, cancer).
Compound (open) fracture: Bone punctures the skin, increasing risk of infection.
Closed fracture: No break in the skin.

Bone repair is a complex process involving several stages to restore bone integrity.

Hematoma Formation: Blood vessels break, periosteum tears, and blood fills the damaged area, forming a hematoma (clot).
Cellular Invasion: Within days to weeks, osteoblasts from the periosteum invade the area.
- Osteoblasts divide near blood vessels, producing spongy bone.
- Fibroblasts produce fibrocartilage further from blood vessels, forming a cartilage callus.
- Phagocytes and osteoclasts clean up debris.
Callus Replacement: The cartilage callus is replaced by bony callus through a process similar to endochondral ossification.
Remodeling: The bony callus is remodeled to resemble the original bone structure.

Day 1: Hematoma forms.
Days 2–7: Osteoblasts and fibroblasts invade, forming spongy bone and cartilage callus.
Weeks 2–6: Cartilage callus replaced by bony callus.
Months: Remodeling restores original bone shape.