Calcium and phosphate metabolism

Question 1

What is osteoporosis and what can cause it?

Answer 1

Osteoporosis:
Loss of bone mass (mineral and organic matrix)

Causes can include:
→ Endocrine
→ Malignancy
→ Drug-induced
→ Renal disease
→ Nutritional
→ Age

Question 2

How is osteoporosis diagnosed?

Answer 2

Osteoporosis can be diagnosed by
1. Taking a measurement of bone mineral density (BMD)
2. Using Dual-energy X-ray absorptiometry (DEXA or DXA scan) (uses 2 x ray beams essentially)

→ T score
Number of Standard Deviations (SDs) below average for young adult at peak bone density

→ Z score
Matched to age and/or group

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 3

What do endocrine causes of osteoporosis include?

Answer 3

1. Hypogonadism – notably any cause of oestrogen deficiency
2. Excess glucocorticoids – endogenous or exogenous (eg Cushing’s syndrome left untreated)
3. Hyperparathyroidism lead to excess bone reabsorption over bone formation
4. Hyperthyroidism

Question 4

What do treatments of osteoporosis include?

Answer 4

1. Ensure adequate calcium and vit D intake, appropriate exercise

Postmenopausal:
Hormone Replacement therapy – effects well established but safety of long term treatment was questioned in early 2000s

Bisphosphonates – inhibit function of osteoclasts: risedronate, alendronate usually first line in therapy
PTH analogues

Denosumab – human monoclonal antibody against RANK ligand

Romosozumab – human monoclonal antibody against sclerostin (very recent)

Question 5

What is osteomalacia? What are some signs and symptoms?

Answer 5

Loss of bone mineralization (termed rickets in children)

Signs and symptoms:
→ Permanent deformities in bone growth (rickets)
→ Diffuse aches and pains
→ Chronic fatigue
→ Weak bones
→ Low Ca, Pi
→ Elevated alkaline phosphatase
→ PTH may be elevated

Question 6

What can cause osteomalacia?

Answer 6

1. Vitamin D deficiency (most common)
2. Mutations leading to errors in vitamin D metabolism (rare)
3. Hypophosphataemia

→ Treatment most commonly involves ensuring adequate Vit D and Ca

Question 7

What can Vitamin D (calcitriol) be increased and decreased by?

Answer 7

Increased by
1. PTH
2. Low Ca
3. Low Pi

Decreased by
1. FGF-23
2. High Ca
3. High Pi

Question 8

What is FGF-23?

Answer 8

FGF-23- a hormone secreted by osteocytes

Phosphate balance: increases renal excretion

Disorders:
1. Oncogenic osteomalacia (tumour secreting FGF-23)
2. X-linked hypophophataemic rickets
3. Autosomal dominant hypopho-phataemic rickets (gain of function mutation)

Question 9

What can an imbalance of calcium and phosphate lead to?

Answer 9

Renal disease - calcium low, phosphate high