Calcium and phosphate metabolism

Question 1

Explain the actions of PTH, vit D and FGF23 in maintaining plasma calcium and phosphate

Answer 1

1) Parathyroid Hormone (PTH):

• Secreted by the parathyroid glands, PTH plays a key role in regulating calcium levels in the body
• When blood calcium levels drop, PTH is released. It has three main actions:

1. On the bones, it promotes the release of calcium (and phosphate) into the bloodstream
2. In the kidneys, it enhances calcium reabsorption, reduces phosphate reabsorption, and stimulates the conversion of vitamin D to its active form (calcitriol)
3. Through the activated Vitamin D, it indirectly increases calcium absorption from the diet in the intestines

2) Vitamin D:

• The active form of Vitamin D (calcitriol) promotes calcium and phosphate absorption in the gut
• It also works synergistically with PTH to mobilise calcium from the bone and reabsorb calcium in the kidneys
• Additionally, Vitamin D can inhibit PTH secretion to form a negative feedback loop

Fibroblast Growth Factor 23 (FGF23):

• Primarily produced by osteocytes in the bone, FGF23 plays a critical role in phosphate homeostasis
• It decreases the reabsorption of phosphate in the kidneys, leading to increased excretion of phosphate in urine
• FGF23 also reduces the production of calcitriol, thereby reducing intestinal phosphate absorption

Question 2

Describe causes of hypercalcaemia and hypocalcaemia

Answer 2

Hypercalcemia:

Primary Hyperparathyroidism:

• It happens when one or more of the parathyroid glands produce too much parathyroid hormone (PTH), leading to increased calcium reabsorption in the kidneys, increased bone resorption, and increased intestinal absorption of calcium

Malignancy:

• Certain cancers can cause hypercalcemia through bone metastasis (causing bone breakdown and release of calcium) or production of a protein (PTH-related protein) that acts like PTH

Medications:

• Certain drugs, like thiazide diuretics, can cause hypercalcemia by increasing renal calcium reabsorption

Vitamin D Toxicity:

• Overconsumption of Vitamin D leads to increased intestinal absorption of calcium, which can result in hypercalcemia

Granulomatous Diseases:

• Diseases such as sarcoidosis or tuberculosis can cause hypercalcemia due to the increased production of Vitamin D in granulomas

Hypocalcemia:

Hypoparathyroidism:

• Low levels of PTH (due to damage or surgical removal of the parathyroid glands, for example) can lead to decreased calcium levels because of reduced bone resorption, reduced intestinal absorption, and increased renal excretion of calcium

Vitamin D Deficiency:

• Lack of vitamin D reduces calcium absorption from the gut, leading to hypocalcemia

Magnesium Deficiency:

• Magnesium is needed for PTH secretion. Therefore, low levels of magnesium can indirectly cause hypocalcemia

Increased Phosphate Levels:

• High levels of phosphate can bind to calcium and precipitate out of the blood, thereby reducing free calcium levels

Question 3

Distinguish osteomalacia and osteoporosis

Answer 3

Osteomalacia:

• This condition is characterised by a softening of the bones, typically as a result of a deficiency or impaired metabolism of vitamin D. In children, this condition is known as rickets
• In osteomalacia, the mineralisation of new bone tissue during remodelling is deficient
• This results in an increased amount of osteoid, which is the organic matrix of bone before it mineralises
• Symptoms of osteomalacia might include bone pain and tenderness, muscle weakness, and difficulty walking
• The treatment usually involves replenishing low levels of vitamin D and calcium and treating the underlying disorder that caused the condition

Osteoporosis:

• This condition is characterised by a decrease in bone mass and density, which can lead to an increased risk of fracture
• In osteoporosis, both the bone mineral (hard part of the bone) and the matrix (structures that hold the bone mineral together) are lost
• The leading cause of osteoporosis is a drop in estrogen in women at the time of menopause and a decrease in testosterone in men
• It can also be caused by hormonal disorders, dietary factors, medications, and other medical conditions
• Treatment often includes medication, a healthy diet, and weight-bearing exercise to help prevent bone loss or strengthen already weak bones

In sum, while both conditions involve a weakening of the bones, osteomalacia results from a defect in the bone-building process, while osteoporosis signifies a weakening of previously constructed bone tissue

Question 4

Describe the diagnosis and treatment of osteoporosis

Answer 4

Diagnosis of Osteoporosis:

1) Bone Mineral Density test:

• It’s a form of X-ray technology that measures bone density in the spine and hip. The results are scored in relation to two norms: “T-score” compares the patient’s bone density to that of a healthy young adult of the same sex
• A T-score of -2.5 or lower indicates osteoporosis.
• The “Z-score” compares the patient’s bone density to what is normally expected in someone of their age, sex, weight, and ethnic or racial origin

2) Blood tests:

• These tests check for levels of Vitamin D, calcium, and phosphate, and can also rule out other diseases

3) Fracture risk assessment:

• This tool uses information about the patient, such as age, sex, weight, height, and medical history, to estimate the risk of bone fracture in the next ten years

Question 5

Explain how disorders of calcium and phosphate metabolism in renal failure may impact bone health