Calcium and phosphate metabolism

Question 1

Bone turnover serves homeostasis of serum calcium and phosphate, in conjunction with

Answer 1

Bone turnover serves homeostasis of serum calcium and phosphate, in conjunction with

Parathyroid hormone (PTH)
Vitamin D (1,25-dihydroxy D3)
Calcitonin
FGF-23

Question 2

Clinical features of hypercalcemia

Answer 2

Depression, fatigue, anorexia, nausea, vomiting,
Abdominal pain, constipation
Renal calcification (kidney stones)
Bone pain
“painful bones, renal stones, abdominal groans, and psychic moans,”

Severe: cardiac arrhythmias, cardiac arrest

Question 3

Causes of hypercalcaemia

Answer 3

Most common causes:
In ambulatory patients: primary hyperparathyroidism
In hospitalized patients: malignancy

Less common causes include:
Hyperthyroidism
Excessive intake of vitamin D

Question 4

Serum biochemistry - hypercalcaemia

Answer 4

Serum calcium - modest to marked increase
Serum phosphate - low or low normal
Serum alkaline phosphatase raised in ~ 20% of cases
Serum creatinine may be elevated in long standing disease (kidney damage)
Serum PTH concentration should be interpreted in relation to calcium

Question 5

Most common cause of hypercalcaemia in hospitalized patients

Answer 5

Most common cause of hypercalcaemia in hospitalized patients
Humoral, e.g., lung carcinoma secreting PTHrP
Metastatic

Question 6

Causes of hypocalcaemia

Answer 6

Most common causes:
Vitamin D deficiency
Renal failure 
Less common causes include:
Hypoparathyroidism

Question 7

Rickets and osteomalacia - define both

Answer 7

Bone disease associated with vitamin D deficiency

Rickets - in children, failure of bone mineralisation and disordered cartilage formation

Osteomalacia - in adults, impaired bone mineralisation

Question 8

Features of osteomalacia

Answer 8

Diffuse bone pain
Waddling gait, muscle weakness
On X-ray, stress fractures

Question 9

Serum biochemistry - osteomalacia

Answer 9

Serum biochemistry:
Low/normal calcium
Hypophosphataemia
Raised alkaline phosphatase
Secondary hyperparathyroidism

Question 10

Osteoporosis - define

Answer 10

Osteoporosis: loss of bone mass
Endocrine 
Malignancy 
Drug-induced
Renal disease
Nutritional

Question 11

Diagnosis of osteoporosis

Answer 11

Measurement of bone mineral density (BMD)

Dual-energy X-ray absorptiometry (DEXA or DXA scan)

T score
Number of SDs below average for young adult at peak bone density

Z score
Matched to age and/or group

Question 12

Endocrine causes of osteoporosis

Answer 12

Hypogonadism – notably any cause of oestrogen deficiency
Excess glucocorticoids – endogenous or exogenous
Hyperparathyroidism
Hyperthyroidism

Question 13

Source of oestrogen

Answer 13

Growing follicles are the source of oestrogen. No more follicles, no more oestrogens.

Question 14

Treatments for osteoporosis

Answer 14

Postmenopausal: HRT – effects well established but safety of long term treatment has been questioned
Bisphosphonates – inhibit function of osteoclasts: risedronate, alendronate
PTH analogues
Denosumab – antibody against RANK ligand
Ensure adequate calcium and vit D intake, appropriate exercise

Question 15

Guidelines for HRT

Answer 15

Short-term therapy (3-5 years) for treating vasomotor symptoms
Lowest effective dose to be used
Long term use not recommended

Question 16

Osteoporosis - characteristics

Answer 16

Loss of bone density
Increased fracture risk
Increase in bone resorption over formation

Question 17

Induction of osteoclast differentiation by RANK ligand

Answer 17

RANK (receptor activator of nuclear factor kappa-B): surface receptor on pre-osteoclasts, stimulates osteoclast differentiation

RANK-ligand: produced by pre-osteoblasts, osteoblasts and osteocytes; binds to RANK and stimulates osteoclast differentiation

OPG (osteoprotogerin): decoy receptor produced by osteocytes; binds to RANK-L, preventing activation of RANK

Question 18

Wnt pathway function

Answer 18

In adult animals wnt is involved in growth, differentiation and maintenance of many tissues, including bone. Wnt signalling is under negative control by various proteins.