Calcium and Phosphate Metabolism

Question 1

What is osteoporosis

Answer 1

Loss of bone mass (mineral and organic matrix)

Question 2

What are the causes of osteoporosis

Answer 2

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

Question 3

How is osteoporosis diagnosed

Answer 3

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 4

What T-values are classified as normal and osteoporosis

Answer 4

Normal: -1 or above
Osteopenia: Lowe than -1 and greater than -2.5
Osteoporosis: -2.5 or lower
Severe osteoporosis: -2.5 or lower and presence of at least one fragility fracture

Question 5

What are the endocrine causes of osteoporosis

Answer 5

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

Question 6

What are the risk factors for osteoporosis

Answer 6

• Low peak bone mass
• Early menopause
• Faster post-menopausal decline

Question 7

What are the treatments for osteoporosis

Answer 7

• Ensure adequate calcium and Vit D intake, appropriate exercise
• Postmenopausal: HRT – effects well established but safety of long term treatment was questioned in early 2000s
• Bisphosphonates – inhibit function of osteoclasts: risedronate, alendronate
• PTH analogues
• Denosumab – human monoclonal antibody against RANK ligand
• Romosozumab – human monoclonal antibody against sclerostin (very recent)

Question 8

What is osteomalacia

Answer 8

Loss of bone mineralisation (termed rickets in children)

Soft and pliable like cartilage

Question 9

What are the signs and symptoms of osteomalacia?

Answer 9

• 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 10

What are the causes of osteomalacia

Answer 10

• Vitamin D deficiency (most common) - Lack of sunlight, lack of Vitamin D supplementation
• Mutations leading to errors in vitamin D metabolism (rare)
• Hypophosphataemia

Treatment most commonly involves ensuring adequate Vit D and Ca

Question 11

Describe 1a hydroxyls mutation

Answer 11

• The enzyme converts Vit D into calcitriol, here that doesn’t occur due to enzyme mutation
• Cause of Vit D dependant rickets type 1
• Excess Vit D but low calcitriol concentration
• High PTH

Question 12

Describe Vit D receptor mutation

Answer 12

• Low Ca and Pi stimulate calcitriol production but the excess calcitriol has no effect as its receptor doesn’t work
• Cause of Vit D dependant rickets type 2
• High PTH

Question 13

Describe how vitamin D is regulated

Answer 13

Increased by:
- PTH
- Low Ca
- Low Pi

Decreased:

• FGF-23 - Osteocytes secrete in response to rise in PO3
• High Ca
• High Pi

Question 14

What is Autosomal dominant hypopho-phataemic rickets

Answer 14

Mutation leading to excess FGF-23 activity

Question 15

What is Oncogenic osteomalacia

Answer 15

Ectopic FGF secretion (benign tumour)

Question 16

What is FGF-23

Answer 16

• A hormone secreted by osteocytes
• Increases renal excretion

Question 17

what are the disorders involved with FGF-23

Answer 17

• Oncogenic osteomalacia (tumour
  secreting FGF-23)
• X-linked hypophophataemic rickets
• Autosomal dominant hypopho- phataemic rickets (gain of function mutation)

Question 18

What is renal osteodystrophy

Answer 18

Spectrum of conditions associated with bone lesions in renal failure

Question 19

What are the characteristics of renal osteodystrophy

Answer 19

• Impaired Pi excretion
• High plasma Pi
• Impaired Vit D activation
• Low plasma Ca
• PTH rises
• Excess bone resorption
• May be augmented by acidosis (impaired renal H+ excretion)