Endocrine and metabolic bone disorders

Question 1

RANKL is expressed on

Answer 1

surface of osteoblasts

Question 2

RANKL binds to

Answer 2

RANK receptors on osteoclast precursors stimulating their formation and activity

Question 3

Osteoprotegrin is

Answer 3

a decoy receptor and inhibits osteoclast differentiation

Question 4

Renal bone disease involves a decrease in

Answer 4

GFR

Question 5

A decrease in GFR results in

Answer 5

less phosphate excreted in urine (so increase in serum phosphate)

reduced calcitriol formation due to less alpha hydroxylation of 25[OH]D3 (formation is also inhibited by a high serum phosphate)

Question 6

In renal bone disease…. develops due to….

Answer 6

hypocalcaemia
precipitation of calcium with phosphate (high phosphate) in tissues
Impaired intestinal absorption of calcium due to reduced calcitriol

Question 7

What develops in response to hypocalcaemia in renal bone disease

Answer 7

Secondary hyperparathyroidism

Question 8

Persistent Secondary hyperparathyroidism can lead to …which contributes to…

Answer 8

bone resorption

Osteitis fibrosis cystic

Question 9

Management of renal bone disease

Answer 9

decrease dietary phosphate and use phosphate binders (reduce intestinal absorption of phosphate)

Use of active vitamin D metabolite eg Alfacalcidol to aim to suppress PTH.

Parathyroidectomy

Question 10

Define osteoporosis

Answer 10

Reduced bone mass and distortion of the bone microarchitecture which predisposes to fracture after minimal trauma.

Question 11

osteoporosis RF

Answer 11

• Post-menopausal oestrogen deficiency
• Age related (increase in PTH, osteoblast senescence)
• Hypogonadism in young people
• Increased glucocorticoid levels (stimulates osteoclasts) e.g. Cushing’s
• Hyperprolactinaemia
• Hypothyroidism, primary hyperparathyroidism
• DM
• Acromegaly

Question 12

Management of osteoporosis

Answer 12

Adequate intake of calcium and Vit D

Lifestyle review e.g. avoid glucocorticoids

Treat underling endocrine condition e.g. give oestrogen to post-meno

Question 13

Treatment options

Answer 13

OESTROGEN (HRT)
Anti-resorptive and prevent bone loss.
Women with intact uterus need progestogen to prevent endometrial hyperplasia/cancer.
Use limited due increased risk of breast cancer and venous thromboembolism.
SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS)
Eg Raloxifene – inhibits bone resorption (ER agonist in bone), reduces risk of breast cancer (antagonises ER in breast). Risk of venous thromboembolic events and stroke.
BISPHOSPHONATES
eg. Alendronate (oral), Zolendronic acid (intravenous)
Bind to hydroxyapatite (crystalline form of calcium and phosphate in bone) and are ingested by osteoclasts, inhibiting bone resorption.

Question 14

Define Paget’s disease

Answer 14

very active, localised but disorganised bone metabolism; usually slowly progressive (abnormal, large osteoclasts)

Question 15

Paget’s disease Causes

Answer 15

Significant genetic component

Evidence for viral origin (e.g. measles virus)

Question 16

Paget’s disease Symptoms

Answer 16

• Increased vascularity (warmth over affected bone)
• Increased osteoclast/osteoblast activity; initially osteoclast activity (increased deformity and fracture risk), followed by increased osteoblast activity (thickening of deformed bone)
• Pelvis, femur, thoracolumbar spine, skull and tibia most commonly affected
• Fractures
• Pain (nerve entrapment, joint involvement)

Question 17

Paget’s disease Diagnosis

Answer 17

Plasma [Ca2+] usually normal
Plasma [alkaline phosphatase] usually increased
Radiology (plain x rays)
Lytic lesions (early)
Thickened, enlarged deformed bones (later)

Question 18

Paget’s disease treatment

Answer 18

Bisphosphonates - reduce pain and disease activity

Simple analgesia