Metabolic Bone Disease

Question 1

What factors stimulate bone remodelling?

Answer 1

• Systemic hormones include PTH, vitamin D, thyroid hormone, growth hormone and parathyroid hormone-related protein
• Local factors include IL-1, TNF, IGF, IL-6, RANK-L, prostaglandins and M-CSF

Question 2

What factors inhibit bone remodelling?

Answer 2

• Systemic hormones include oestrogens, androgens, progesterone and calcitonin
• Local factors include OPG, mechanical loading, IFG, IL-4, IL-10, IL-13, IL-18 and transforming growth factor beta

Question 3

What is osteoporosis?

Answer 3

• Disorder characterised by compromised bone strength predisposing a person to increased risk of fracture

Question 4

What is RANK-L and what does it do?

Answer 4

• RANK Ligand is an essential mediator for osteoclast formation, function, and survival in both cortical and trabecular bone throughout the skeleton.
• RANK Ligand is expressed (both in a transmembrane and soluble form) from the osteoblast lineage cells.
• RANK Ligand subsequently binds to its receptor, RANK, on immature and mature osteoclasts, which leads to maturation of prefusion osteoclasts to multinucleated osteoclasts, and finally to activated osteoclasts.

Question 5

What are the WHO criteria for the diagnosis of osteoporosis? (T-score from DEXA scan)

Answer 5

• Normal ≥-1
• Osteopenia -1 to -2.5
• Osteoporosis ≤-2.5
• ‘Established’ osteoporosis ≤-2.5 + presence of one or more fractures

Question 6

How do bisphosphonates work?

Answer 6

• Bisphosphonates are analogs of pyrophosphate, which is characterised by phosphoric acid groups bound to a central oxygen molecule
• Bisphosphonate-based drugs’ specificity comes from the two phosphonate groups (and possibly a hydroxyl at R1) that work together to coordinate calcium ions. Bisphosphonate molecules preferentially “stick” to calcium and bind to it. The largest store of calcium in the human body is in bones, so bisphosphonates accumulate to a high concentration only in bones.
• Bisphosphonates, when attached to bone tissue, are “ingested” by osteoclasts, the bone cells that break down bone tissue, leading to their apoptosis and death.