Endocrine and metabolic bone disorders Flashcards
What are the two components of bone?
Organic components, (osteoid – unmineralised bone)
(35% bone mass), Type 1 collagen fibres (95%)
Inorganic mineral component (65% bone mass), Calcium hydroxyapatite crystals fill the space between collagen fibrils
Describe the two types of cell related to bone formation and resorption?
Osteoblasts- synthesise osteoid and participate in mineralisation/calcification of osteoid
Osteoclasts-release lysosomal enzymes which break down bone
Describe how osteoclasts are activated?
Osteoblasts express RANK-L on their surface and this binds to RANK-R on osteoclasts to activate them.
Describe 2 types of bones?
You have cortical bone which is hard bone found on the outside and trabecular bone which is spongy bone found on the inside. They both have lamellar patterns where collagen fibrils are laid down in and organised alternating orientation.
Describe difference between rickets and osteomalisia.
Rickets is in children and affects cartilage of epiphysial growth plates and bone. Osteomalasia is in adults and arises after epiphyseal closure and affects bone.
Describe symptoms of vitamin D deficiency state?
Rickets- skeletal abnormalities and pain, growth retardation, increased fracture risk.
Osteomalsia- skeletal pain, increased fracture risk, proximal myopathy
Looser zones are common to both- normal stresses on abnormal bone cause insufficiency fractures
Describe the pathophysiology of the 3 types of hyperparathyroidism?
Primary due to parathyroid tumour driving PTH secretion, secondary due to low calcium levels prompting PTH secretion, tertiary when PTH levels have been elevated for so long due to low calcium when calcium is corrected PTH level remain autonomously high.
Describe pathophysiology of osteitis fibrosa cystica?
Otherwise called hyperparathyroid disease…you get excess osteoclastic bone resorption 2o to high PTH.
Identified on X rays by translucent lesions called brown tumours.
Describe treatment of OFC?
Low phosphate diet
Phosphate binders – reduce GI phosphate absorption
Alphacalcidol – ie calcitriol analogues
Parathyroidectomy in 3o hyperparathyroidism
How is osteoporosis diagnosed?
Bone mineral density (BMD) > 2.5 standard deviations below the average value for young healthy adults (usually referred to as a T-score of -2.5 or lower).
You do a DEXA scan which measures the mineral content of the neck and femoral spine.
What are the differences between osteoporosis and osteomalcia?
OSTEOMALACIA
Vitamin D deficiency (adults) causing inadequately mineralised bone
Serum biochemistry abnormal (low 25(OH) vit D, low/low N Ca2+, high PTH (2o hyperparathyroidism)
OSTEOPOROSIS
Bone reabsorption exceeds formation
Decreased bone MASS
Serum biochemistry normal
What are pre-disposing factors that put you at risk of developing osteoporosis?
Postmenopausal oestrogen deficiency Age-related deficiency in bone homeostasis (men and women) eg osteoblast senescence Hypogonadism in young women and in men Cushing’s syndrome Hyperthyroidism Primary hyperparathyroidism Prolonged use of glucocorticoids Heparin
Name 4 drugs used to treat osteoporosis?
Oestrogen
Bisphosphonates
Denosumab
Teriparatide
Why is oestrogen used?
Treatment of post-menopausal women with pharmacological doses of oestrogen
- Anti-resorptive effects on the skeleton
- Prevents bone loss
What are risk factors of using oestrogen?
- Increased risk of breast cancer
- Venous thromboembolism
- Endometrial hyperplasia-women put on progesterone to lessen this risk alongside.
Describe bisphosphonates method of action?
Bind avidly to hydroxyapatite and ingested by osteoclasts – impair ability of osteoclasts to reabsorb bone
Decrease osteoclast progenitor development and recruitment
Promote osteoclast apoptosis (programmed cell death)
Net result = reduced bone turnover.
Describe pharmacokinetics of bisphosphonates?
Orally active but poorly absorbed; take on an empty stomach (food, especially milk, reduces drug absorption generally)
Accumulates at site of bone mineralisation and remains part of bone until it is resorbed - months, years
Describe side effects of bisphosphonates?
Osteophagitis, osteonecrosis of the jaw, atypical fractures due to suppression of remodelling in prolonged use.
Describe the method of action of Denosumab?
Human monoclonal antibody
Binds RANKL, inhibiting osteoclast formation and activity
Hence inhibits osteoclast-mediated bone resorption
SC injection 6/12ly
2nd line to bisphosphonates
Describe method of action of Teriparatide?
Recombinant PTH fragment - amino-terminal 34 amino acids of native PTH
Increases bone formation and bone resorption, but formation outweighs resorption
3rd line treatment for osteoporosis
Daily s.c. injection
Describe pathophysiology of Paget’s disease?
Accelerated, localised but disorganised bone remodelling
Excessive bone resorption (osteoclastic overactivity) followed by a compensatory increase in bone formation (osteoblasts)
New bone formed = WOVEN bone
structurally disorganised
mechanically weaker than normal adult lamellar bone
Describe epidemiology of Paget’s disease?
Often positive family history
Evidence for viral origin (e.g. measles virus)
Highest in UK, N America, Australia and NZ
Lowest in Asian and Scandinavia
Men and women affected equally
Disease usually not apparent under age 50y
Most patients are asymptomatic
Describe clinical features of Paget’s disease?
Arthritis Fracture Pain Bone deformity Increased vascularity (warmth over affected bone) Deafness – cochlear involvement Radiculopathy – due to nerve compression
Describe diagnosis of Paget’s disease?
Plasma [Ca2+] normal
Plasma [alkaline phosphatase] usually increased
Plain x rays = you get Lytic lesion (thickened deformed bone)
Describe treatment of Paget’s disease?
Bisphosphonates – very helpful for reducing bony pain and disease activity
Simple analgesia
