Calcium And Phosphate Metabolism

Question 1

What is osteoporosis?

Answer 1

• Loss of bone mass - specifically mineral and organic matrix
• Can lead to fragility fractures

Question 2

State 6 general possible causes of osteoporosis?

Answer 2

• Endocrine
• Malignancy
• Drug-induced
• Renal disease
• Nutritional
• Age

Question 3

State 4 endocrine causes of osteoporosis?

Answer 3

• Hypogonadism - notably any cause of ostrogen deficiency (e.g. postmenopause)
• Excess glucocorticoids - endogenous or exogenous
• Hyperparathyroidism
• Hyperthyroidism

Question 4

What is used to diagnosis osteoporosis?

Answer 4

• Measurement of bone mineral density (BMD)
• Uses dual-energy X-ray absorptiometry (DEXA or DXA scan)

Question 5

State the two types of scores in BMD

Question 6

State the 4 status of bone density with their ranges?

Answer 6

• Normal: T-score of -1 or above
• Osteopenia: T-score lower than -1 and greater than -2.5 (Intermediate condition between normal + Osteoporosis
• Osteoporosis: T-score of -2.5 or lower
• Severe osteoporosis: T-score of -2.5 or lower, and presence of at least one fragile bone

Question 7

State 5 possible treatments for osteoporosis with drug names?

Answer 7

• Ensure adequate calcium and vit D intake, appropriate exercise
• Bisphosphonates: inhibit function of osteoclasts: risedronate, alendronate
• PTH analogues
• Denosumab: Human monoclonal antibody against RANK ligand
• Romosozumab: Human monoclonal antibody against sclerostin
• Sclerostin = Inhibitior of Wt signalling which stimulates osteoblast formation

Question 8

What is meant by menopause and post menopause?

Answer 8

Postmenopause = Menopause is a natural stage in a woman’s life. It occurs in middle age when your body stops ovulating, which causes you to stop having monthly menstrual cycles. This shift occurs because of the change of hormones in your body.

Question 9

State a possible treatment of osteoporosis as a result of postmenopausal?

Answer 9

• Osteoporosis occurs due to drop in estrogen levels
• Possible treatment = Hormone replacement therapy (HRT) - effects well established but safety of long term treatment was questioned in early 2000s

Question 10

What is oestomalacia?

Answer 10

• Loss of bone mineralisation = softening of bone
• Called rickets in children

Question 11

State 7 key symptoms of osteomalacia?

Answer 11

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

Question 12

State the 3 major causes and what is commonly used for treatment of osteomalacia?

Answer 12

• Vitamin D deficiency (most common)
• Mutations leading to errors in vitamin D metabolism (rare)
• Hypophosphataemia
• Treatment most commonly involves ensuring adequate Vit D and Ca

Question 13

Rare causes of osteomalacia: Hypocalcaemia
State 4 disorders characterised by hypocalcaiemia that lead to osteomalacia?

Answer 13

• Vit. D deficiency
• Renal disease
• 1 alpha hydroxylase mutation -> Vitamin D dependent rickets type 1
• (Point above) a. Enzyme involved in vitamin D conversion (calcitriol), so vitamin D is not formed or at v. low levels
• Vit.d D receptor mutation - Vitamin D dependent rickets type 2

Question 14

Complete the table

Answer 14

VD

Question 15

What 3 factors increase Vitamin D (calcitriol) and also descrease it? VD

Answer 15

• Increases by: PTH, Low Ca, Low Pi
• Decreased by: FGF-23, High Ca, High Pi

Question 16

Hypophostaemia
State the major hormone and 3 disorders characterised by hypophosphataemia that lead to osteomalacia?

Answer 16

• Primarily due to FGF-23 (hormone secreted by osteocytes)
• FGF-23 -> increases renal excretion + inhibition of vit. D - J Pi for balance
  1. X-linked hypophophataemic rickets
  2. Autosomal dominant hypophophataemic rickets
  a. Gain of function mutation which leads to excess FF activity
  3. Oncogeneic osteomalacia
  a. Tumour secreting FGF-23

Question 17

Complete the table

Answer 17

VD

Question 18

Renal osteodystrophy
What is renal osteodystrophy?

Answer 18

Spectrum of conditions associated with bone lesions in renal failure

Question 19

State how Renal osteodystrophy occurs with the key findings?

Answer 19

• Impaired Pi excretion due to renal failure
• High plasma Pi
• Impaired Vit D activation
• Low plasma Ca
• PTH rises
• Excess bone resorption
• Ultimately leads to bone erosion
• May be augmented by acidosis - increasing acidity within blood and body
• Due to impaired renal H+ excretion