Drugs used to treat disorders of bone Flashcards
Which cells are present in bone?
Osteoblasts
Osteoclasts
Osteocytes
What makes up the matrix of bone?
Osteoid (e.g. collagen)
Minerals (calcium, phosphate)
Briefly describe how new bone is formed?
Osteoblasts secrete new bone matrix (osteoid)
Osteoid is mineralised (hydroxyapatite)
How much bone is remodelled per year in adults?
25% trabecular bone
3% cortical bone
Which bones have the highest desnity of trabecular bone?
What is the consequence of this?
Femoral neck and vertebral bodies
Most affected by processes that alter bone remodelling (e.g. osteoporosis)
Describe the factors which affect bone remodelling?
Ageing
Physical factors (e.g. exercise, loading)
Hormones (oestrogen)
Drugs (crorticosteroids)
Describe how osteoblasts regulate osteoclast activity?
Calcitriol and PTH stimulate osteoblasts to express RANKL > RANKL interacts with RANK on osteoclasts > osteoclast maturation
How does PTH affect bone remodelling?
Increased osteoblast and osteoclast activity
How does oestrogen affect bone remodelling?
Decreased osteoclast activity
How do glucocortcoids affect bone remodelling?
Increased osteoclast activity
Decreased osteoblast activity (apoptosis induced)
How do embedded cytokines affect bone remodelling?
Increase osteoblast activity
How does calcitonin affect bone remodelling?
Decreased osteoclast activity
Which two factors regulate bone mineralisation?
1) Vitamin D
2) PTH and calcitonin
Define osteoporosis?
Reduction in bone mass more than 2.5 SD below mean for healthy 30 yo woman
Define osteopaenia?
Reduction in bone mass 1-2.5 SD below norm for healthy 30 yo woman
Describe how bone density changes over the life span?
Increases until peak at 30
Declines afetr menopause
Describe the changes that occur in bone in osteoporosis?
Loss of cells and matrix
Loss of trabeculae and thinning
Los of trabecular connectivity
Describe the pathophysiology of osteoporosis?
What are the two categories of drugs used in bone disorders?
Antiresorptive agents
Bone anabolic agents
List three types of antiresorptive agents?
Bisphosphonates
Selective oestrogen receptor modulators
RANKL inhibitors
List four types of bone anabolic agents?
PTH
Oral calcium
Oral Vitamin D analogues
Calcitonin
What are bisphosphonates?
Antiresorptive agents
Analogues of pyrophosphate
Describe the action of bisphosphonates?
Incorporated into bone matrix > ingested by osteoclasts > toxic
Inhibit recrutimnet of osteoclasts
Promote apoptosis of osteoclasts
Describe the administration of bisphosphonates?
Administered weekly (due to accumulation)
Don;t lie down for for hours after administration (due to reflux)
Describe the risks and benefits of bisphosphonates?
BENEFITS
Reduced fracture risk
RISKS
Oesophageal cancer?
Atypical fractures?
Osteonecrosis of jaw?
What is Raloxifene?
Selective oestrogen receptor modulator
Describe the actions of Raloxifene?
Agonist at oestrogen receptors in bone and cardiovascualr tissue
Antagonist at oestrogen receptors in mammary tissue and uterus
What is Denosumab?
RANKL inhibitor
Human monoclonal antibody
Describe the actions of Denosumab?
Binds RANKL > inhibits RANKL activity > reduces osteoclast activity
Why is Denosumab not commonly used?
New and expensive
Describe the paradoxical behaviour of PTH?
Acutely promotes osteoblast development and activity
Continuous or high exposure promotes osteoclast activity
Describe the use of oral calcium in bone disorders?
Used as an adjunctive therapy in osteoporosis
Describe the side effects of oral calcium?
GI disturbances
What is strontium?
Oral calcium
Describe the use of Vitamin D in treatment of bone disorders?
Used in deficiency states (e.g. Rickets and osteomalacia)
Used in endocrine dysfunction (e.g. hypoparathyroidism)
Used in chronic renal disease
Describe the effects of calcitonin?
Decsreases mobilisation of calcium from bone
Describe the types of calcitonin available for use?
Natural: porcine
Synthetic: Salcatonin
Describe the suggested treatment options for women with osteoporosis?
