Osteoporosis Flashcards
What is osteoporosis?
slow progressive bone disease characterised by low BMD - leads to increased bone fragility and increased risk of bone fracture
How is BMD measured?
Using dual energy x-ray absorptiometry (DXA) - beams of different energy measures the absorption of each bone, giving information on BMD.
Generally lumbar spine, femoral neck, and total hip are measured (total hip - most precise) for BMD but forearm can also be measured.
Repeat measurements should be done on the same machine as BMD measurements are not standardised across different machines.
What is T-score?
obtained from BMD - number of standard deviations a patient’s BMD differs from that of a healthy patient in the same gender and ethnicity.
> -1 = normal
-2.5 < x < -1 = osteopenia (weaker than normal but not as weak as those with osteoporosis)
< - 2.5 = osteoporosis
What is Z-score? and is this different from T scores.
Compares BMD to an average person of the same age, sex, and body size. This is different to T scores as T scores is generally used to diagnose whether a person has osteoporosis or not whereas z-scores evaluate where a person bone density is typical within their age group.
What are the risk factors for osteoporosis?
- female gender (esp menopausal women, premature menopause, women with a hysterectomy before 45)
- elderly
- family history
- low BMI
- low physical activity
- low vit D and calcium intake
- smoking and high alcohol intake
Briefly explain the process of bone haemostasis.
Bone resorption: osteoclasts break down bone tissue.
Bone formation: osteoblasts help form new bones.
This continuous process is important to maintain bone strength and and overall mineral balance in the body.
Osteocytes keep bone remodelling in balance → preserves bone microstructure to keep osteoclast & osteoblast activity in equilibrium (bone homeostasis).
Bone homeostasis also regulated by sex hormones & parathyroid hormone-activated vitamin D.
An imbalance in homeostasis can lead to osteoporosis.
What two drugs cause osteoporosis due to increased bone turnover?
Aromatase inhibitors: anastrozole, letrozole, and exemestane
By lowering oestrogen levels through the inhibition of aromatase, these drugs help control the growth of oestrogen-dependent cancer cells. Oestrogen has an inhibitory effect on osteoclasts. Hence lowering oestrogen leads to increased osteoclast activity.
Gonadotropin-releasing hormone (GnRH) agonists: Goserelin, nafarelin
GnRH agonists initially bind to the GnRH receptors on the pituitary gland. This binding stimulates the release of gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH) causing an increase in oestrogen and testosterone. Continuous administration of GnRH agonists leads to desensitisation of GnRH receptors → decrease FSH and LH levels → decrease oestrogen and testosterone levels.
How does glucocorticoids induce osteoporosis?
Direct effects:
Affects osteoblast differentiation → leads to decreased bone formation.
Stimulates osteoclast activity → leads to excessive bone resorption.
Indirect effects:
Decrease intestinal calcium absorption
Suppression of growth hormones
Alters sex hormone levels
Changes secretion of parathyroid hormone → affects vitamin D activation.
How does antiepileptic drugs induce osteoporosis?
Antiepileptic Drugs
All antiepileptic drugs are associated with accelerated bone loss & increased risk of fractures. Thought to be due to inactivation of vitamin D and direct inhibitory effects on osteoblasts.
Valproate and carbamazepine may affect sex hormones.
How do PPIs induce osteoporosis?
Suppression of gastric acid secretion thought to lead to decreased intestinal calcium absorption & therefore increased bone resorption.
Short-term use is unlikely to be associated with increased risk of fractures.
Use for longer than one year is associated with increased risk of hip and vertebral fractures.
How do SSRIs induce osteoporosis?
Serotonin receptors and transporters are known to be present in osteoblasts and osteoclasts – can reduce activity of osteoblasts and increase activity of osteoclasts.
Can also affect hormones such as calcium homeostasis and affect levels of PTH.
How can pioglitazone induce osteoporosis?
Agonist of PPARγ which regulates genes involved in lipid and glucose metabolism → increases sensitivity of peripheral tissues to insulin & decreases hepatic glucose output. Activation of PPAR-γ shifts the balance from osteogenesis (bone formation) to adipogenesis (fat formation) in the bone marrow. Also can inhibit the differentiation of osteoblasts and increase differentiation of osteoclasts.
When should you start treatment for osteoporosis?
- low BMD (< - 2.5 or < - 1.5 if on LT corticosteroids)
- presence or history of osteoporotic fracture
What are some lifestyle changes for osteoporosis?
- weight bearing exercises to improve muscle strength, muscle mass, etc.
- stop smoking and reduce alcohol
- VitD and Ca intake
- maintain normal BMI (between 20-25 kg/m²)
What are the recommended intake guidelines for calcium and vitamin D?
calcium: daily is 1300 mg for osteo patients or women > 50 and men > 70.
Reduce to 1000 mg for women < 50 and men < 70 y.o.
Prioritise calcium for dairy sources. Otherwise supplement with calcium carbonate or citrate ( absorbed better than calcium carbonate in elderly or people taking PPIs, does not require gastric acidity for absorption and reduced risk of renal calculi in hypercalciuria).
Vitamin D: Maintain a serum 25-hydroxyvitamin D concentration of 75 nmol/L or higher.
Promotes absorption of calcium and phosphate from the gut & assists bone mineralisation by interacting with parathyroid hormone.
Calcitriol is the active form of VitD
