Calcium and Phosphate Metabolism

Question 1

Importance of bone turnover and what does it work in conjugation with?

Answer 1

Serves homeostasis of serum calcium and phosphate in conjugation with: PTH, Calcitriol, Calcitonin, FGF-23

Question 2

Clinical features of hypercalcemia

Answer 2

• Depression, Fatigue, Anorexia, Nausea and Vomiting
• Abdominal pain and Constipation
• Renal calcification which forms kidney stones
• Painful bones, renal stones, abdominal groans and psychic moans
• In severe cases, cardiac arrhythmias and cardiac arrest can also occur.

Question 3

Causes of hypercalcemia

Answer 3

• Hyperparathyroidism: most common cause - benign tumor; this is in ambulatory patients
• Malignancy: in hospitalised patients
• Less common causes include: hyperthyroidism and excessive intake of vitamin D

Question 4

Serum biochemistry in hypercalcemia

Answer 4

• Serum calcium: modest to marked increase
• Serum phosphate: low or normal
• Serum alkaline phosphatase: Raised in 20% of cases
• Serum creatinine: can be elevated in longstanding disease such as kidney damage
• Serum PTH concentration: should be interpreted in relation to calcium

Question 5

How does malignancy cause hypercalcemia?

Answer 5

• Humoural = via fluid circulation such as lung carcinoma secreting PTHrP. This is a peptide related to the PTH so it can bind to the PTH receptors and cause hyperparathyroidism
• Metastatic = the bone tumour grows and secretes cytokines which promote osteoclasts differentiation. This leads to bone reabsorption which leads to hypercalcaemia
• Haematological = A tumour originating from the haematopoietic stem cells such as myeloma.

Question 6

Causes of hypocalcemia

Answer 6

• Vitamin D deficiency
• Renal failure
• Less common cause: Hypoparathyroidism

Question 7

Rickets

Answer 7

Bone disease associated with Vitamin D deficiency

Rickets in children causes failure of bone mineralization and disordered cartilage formation.

Question 8

Osteomalacia

Answer 8

In adults, it causes impaired bone mineralization. Loss of bone mineralisation

Question 9

Features of osteomalacia

Answer 9

Diffuse bone pain, waddling gait, muscle weakness

On X ray, there may be stress fractures

Question 10

Serum biochemistry in osteomalacia

Answer 10

• Low to normal calcium
• Hypophosphataemia
• Raised alkaline phosphatase which is a sign of increased bone turnover
• Secondary hyperparathyroidism, due to low calcium leading to negative feedback

Question 11

Osteoporosis

Answer 11

Loss of bone mass which can be due to a number of things including endocrine, malignancy, drug-induced, renal disease, nutritional and age

Question 12

Difference between osteoporosis and osteomalacia

Answer 12

Osteomalacia is a loss of bone mineralisation whereas osteoporosis is a loss of bone mass. This is why osteoporosis is asymptomatic meaning there is no sign for it, and therefore the first sign must be a fracture. Whereas with osteomalacia, the first sign will be a pain.

Question 13

Diagnosis of osteoporosis

Answer 13

• Measurement of bone mineral density (BMD)
• Dual-energy X-ray absorptiometry (DEXA or DXA scan)
• Then look at the T score and the Z score

Question 14

T score

Answer 14

Number of standard deviations below average for a young adult at peak bone density
Normal: T-score of -1 or above
Osteopenia: T-score lower than -1 and greater than -2.5
Osteoporosis: T-score of -2.5 or lower
Severe osteoporosis: T-score of -2.5 or lower, and presence of at least one fragility fracture

Question 15

Z score

Answer 15

Matched to age and/or group

Question 16

Endocrine causes of osteoporosis

Answer 16

• Hypogonadism = leads to oestrogen deficiency
• Excess glucocorticoids whether that’s endogenous or exogenous
• Hyperparathyroidism - most common
• Hyperthyroidism

Question 17

Bone density in women at different ages

Answer 17

• Oestrogen production in women terminated at menopause. The remaining oestrogen production will be due to the conversion of androgens to oestrogen via aromatase.
• In a typically healthy female, there will be peak bone density at around 27 years of age which starts to decline after that. Menopause accelerates the decline.
• The curve for a male would be almost the same, but the highest point would be bigger and there would be no acceleration due to no menopause

Question 18

Treatments for osteoporosis

Answer 18

• Postmenopausal: hormone replacement therapy, effects well established but the safety of long-term treatment has been questioned.
• Bisphosphonates: Risedronate and Alendronate; inhibit the function of osteoclasts and therefore no more bone resorption.
• PTH analogues: Low levels of PTH, favour remodelling, whereas high levels favour resorption.
• Denosumab: antibody against RANK-ligand; Therefore, stops osteoclast differentiation
• Romosozumab: Antibody against sclerostin protein; This stops the inhibition of osteoblast formation.
• Ensure adequate calcium and Vit D intake, appropriate exercise. Exercise promotes bone remodelling