Osteoporosis Flashcards
What are the types of bones
Flat bones and long bones
Cortical and trabecular bone
What are osteoclasts
largely nucleated cells responsible for bone resorption
Under the influence of RANKL, interleukins, PTH, cytokines etc. which initiate bone resorption
How is mineralised bone formed
After osteoclastic resorption and apoptosis, proliferation of osteoblasts occurs
What are osteoblasts
single nucleated mesenchymal stem cells involved in bone formation. Function as a group of connected cells called an osteon. Hydroxyapatite is produced.
What are markers of bone resorption
urine, hydroxyproline, C telopeptide of type 1 colalgen, N telopeptide of type 1 collagen serum, NTX, CTX
What are markers of bone formation
bone specific alkaline phosphatase, osteocalcin, P1CP. P1NP
What is DEXA
a bone density scan using densitometry X-ray measures how much mineral is in the area being measured. Results are given as standard deviation, the number of units above or below average
What is osteoporosis
Systemic skeletal disorder characterised by low bone mass and microarchitecture deterioration of bone tissue and an increased risk of fracture. Bone mineral density or BMD below 2.5 SD is described as osteoporosis.
Why are women at greater risk of osteoporosis
decrease in oestrogen production at menopause, which accelerates bone loss
2% at 50 to 50% at 80
What are the modifiable determinants of low bone structure
low body mass (BMI under 18.5), alcohol intake over 14 units per week, smoking, current or frequent use of glucocorticoid, vitamin D and calcium homeostasis
What are the non-modifiable determinants of low bone structure
age, gender (women accumulate less peak bone mass and lose more following menopause), ethnicity (Caucasians and Asians are at higher risk), previous fragility fractures, family history of hip fractures
How does diabetes contribute to osteoporosis
low bone turnover, reduced anabolic effect if insulin and IGF1. Poor vision, neuropathy increase fracture potential
How does chronic kidney disease contribute to osteoporosis
renal osteodystrophy is complex, osteitis fibrosa cystic due to secondary hyperparathyroidism or low bone turnover disease (osteomalacia, adynamic bone disease)
How does inflam rheumatic disease contribute to osteoporosis
increased expression of RANKL, interleukins, steroids
GI diseases: inflammation, intestinal malabsorption, bowel surgery and steroid
What is FRAX
calculates 10 yr absolute risk of major osteoporotic fractures and hip fracture
What investigations need to be undertaken for osteoporosis
Bone profile - corrected CA, PO4, Mg, alkaline phosphatase (marker of bone turnover) Pth 25 OH vitamin D Renal functions and LFTs Serum electrophoresis Coeliac screen TFTs Gonadotrophins DEXA X-rays MRI Many elderly are on proton pump inhibitors to reduce the effects of aspirin
What do bisphosphonates do
prevent vertebral, non-vertebral and hip fractures in men and women
Available as weekly, monthly tablets and year infusion
Treat for a period of 3-5 years unless on steroids, over 75 or previous history
Long term risk of osteonecrosis of the jaw and atypical fractures
How to treat younger post menopausal women
HRT (Selective oestrogen receptor modulators
Testosterone replacement in some hypogonadal men )
What is denosumab
Human monoclonal antibody that targets and binds with high affinity and specificity to RANKL, preventing activation of RANKL on the surface of osteoclast precursors an osteoclasts
Prevention of the RANKL/RANK interaction inhibits osteoclast formation, function and survival
In postmenopausal women, it significantly reduces the risk of vertebral, non vertebral and hip fractures
What is hypophosphatasia
heritable rickets, sub-normal BALP (bone alkaline phosphatase) activity
What is homocysteinurea
autosomal recessive disorder, cystathionine beta-deficiency, Marfnoid habitus, thromboembolism and osteoporosis
What is mucopolysaccharidosis
diminished activity of lysosomal enzymes that degrade glycosaminoglycans and accumulation of complex CHO within the bone marrow
What is Paget’s disease of the bone
Localised disorder of bone remodelling
Disorganised mosaic of new bone formation resulting in less compact, more vascular and bone susceptible to deformity and fracture
Driven by genetic and environmental factors
Rare in people less than 55 years of age
Men are more commonly affected
Presents with bone pain, deformities, fractures or isolated increase in BALP
Bisphosphonates are the mainstay of treatment
What is Teriparatie
rhPTH(1-34) produced using recombinant DNA technology
Identical to the 34 N-terminal amino acid sequence of endogenous human PTH
Anabolic agent
What is the relation between cancer and bone disease
Bone metastasis occur in 80% of patients with advanced breast or prostate cancer and 15-30% of thyroid, lung or renal cancer
Metastatic cancer cells flourish within the bone microenvironment
Present as severe pain, pathological fractures or abnormalities in calcium
What is the role of vitamin D
essential for musculoskeletal health. Promotes calcium absorption from the bowel, enables mineralisation of newly formed osteoid tissue in bone and plays an important role in muscle function.
What is the recommended serum 25OHD level
> 50nmol/L
What is the treatment for vit D deficiency
Oral vitamin D3/cholecalciferol
Describe vitamin D absorption pathway
D3 goes to liver, converted to 25(OH)D3.
25(OH)D3 converted to 1,25(OH)2D3 in kidneys. This is responsible for calcium homeostasis, muscle health, bone health, immunomodulation, blood pressure regulation, cardiovascular health
25(OH)D3 converted to 1,25 (OH)2D3 in prostate gland, breast, colon and lungs. This is for regulation of cell growth
