metabolic bone disease Flashcards
What controls the bone turnover
Osteoblasts
How do osteoblasts stimulate osteoclasts
Release RANK ligand which binds to the osteoclasts causing the intake of nuclei into the osteoclast and then the osteoclast divide which allows for more bone resorption
What stimulates osteoblasts
vitamin D
Where do we get vitamin D from
Sun
Oily fish and egg yolks
Describe the production of Vitamin D
UVB change 7DHC on the skin into the preform of vitamin D
the liver then changes this into 25(OH) vit D - which is the storage form
The kidney then changes the storage form into 1,25(OH)Vit D which is the active form for use
What Vitamin D is checked when doing tests
the storage vitamin D - 25(OH)vit D
What is the function of Vitamin D
Maintaining extracellular fluid calcium levels
What is Paget’s disease of bone
Increased bone resorption followed by increased bone formation which leads to a disorganised bone
What are the features of a bone after Paget’s disease
Bigger, less compact, more vascular and more susceptible to deformity and fracture
What genes are correlated with Paget’s disease
Loci of SQSTM1
What environmental triggers are thought to cause pagets disease
Chronic viral infection within osteoclasts
What are the symptoms of Paget’s disease
Over 40 years old patient presents with bone pain
Occasional deformity
Heat over the Pagetic bone due to the increased vascularity
Neurological complications - nerve deafness
What age is paget’s commonly in
Has to be over 40 at least but commonly around 60
What is the main way of diagnosing Paget’s disease
Bone scan
What is the common presentation of Paget’s -including bloods
Increased ALP
Bone pain and local heat
bone deformity or fracture
hearing loss
rare development of osteosarcoma in the affected bone
What is the treatment of Paget’s disease
IV bisphosphonate therapy - one off - first line - IV zoledronic acid
Should you treat someone with asymptomatic Paget’s disease
No unless the Paget’s is in their skull which would cause them nerve deafness
What causes rickets and osteomalacia
severe vit D or calcium deficiency
What is the difference between rickets and osteomalacia
Rickets occurs in children before the epiphyseal plates fuse while osteomalacia occurs in adults after the epiphyseal plate fuses
How do rickets and osteomalacia look on blood tests
Low calcium
raised alp
Raised PTH
very low vitamin D
How does rickets present
The fontanelles haven’t closed
Large forehead
odd shaped ribs and breast bone
odd curve to spine
Their epiphysis widen so there are more prominent parts on the bone
What is the treatment for Rickets and osteomalacia
Calcium and vitamin D supplements
On Xray what is a common finding in osteomalacia
Micro - fractures
What is osteogenesis imperfecta
Genetic disorder of connective tissue that is characterised by fragile bones which can fracture from mild trauma and normal daily acts
What causes osteogenesis imperfecta
Defects in type one collagen
What are the signs and symptoms of osteogenesis imperfecta
growth deficiency
defective tooth formation
hearing loss
blue sclera
scoliosis
barrel chest
ligamentous laxity
easily bruised
What scoring system measures hypermobility
The beighton score
What is the management of osteogenesis imperfecta
Surgical - to treat fractures
IV bisphosphonates to prevent the fractures
What is osteoporosis
Metabolic bone disease characterised by low bone mass and micro-architectural deterioration of bone tissue which leads to bone fragility and increase in fracture risk
What is the definition of osteoporosis on a bone density scan (DXA bone scan)
If you are more than 2.5 standard deviations below the young adult mean
Why is osteoporosis in women over 50 common
There is an accelerated loss of bone when menopause begins
Which gender most commonly gets osteoporosis
women but it is common in men
Which age group is osteoporosis more common in
Older age
How common is it to break fracture in men and women over 50
50% of women over 50
20% of men over 50
What are endocrine causes of osteoporosis
Thyrotoxicosis - hyper thyroidism
hyper and hypoparathyroidism
cushings
hyperprolactinaemia
hypopituitarism
early menopause
What are the rheumatic causes of osteoporosis
Inflammatory conditions:
Rheumatoid arthritis
ankylosing spondylitis
polymyalgia rheumatica
What are GI causes of osteoporosis
UC and crohns
Liver disease - Primary biliary cirrhosis, chronic alcoholic hepatitis, alcoholic cirrhosis and viral cirrhosis (HEP C)
Malabsorption - chronic pancreatitis , coeliac disease, whipples, short gut and ischaemic bowel
What medications cause osteoporosis
Steroids
PPI
Enzyme inducing anti epileptic medications
Aromatase
GnRH inhibitors
Warfarin
What is the management of osteoporosis
Minimise risk factors of fractures
Ensure good intake of calcium and vitamin D
medications
What medications are given in osteoporosis
Bisphosphonates are first line
Antiresorptive therapy - prevent breakdown of bone - HRT - hormone replacement therapy , SERMs - selective oestrogen receptor modulators , Biphosphonates and denosumab
Anabolic therapies - teriparatide - PTH analogue and romosuzumab - antiscerostin agent
What are the side effects of HRT
Increased risk of blood clots
Increased risk of breast cancer if used into late 50s
Increased risk of heart disease and stroke if used after long time after menopause (more than 3 years usually)
What are the negative effects of SERMs - selective oestrogen receptor modulators
Hot flushes if taken too close to menopause
Increased clotting risk
Lack of protection at the hip
What is required for biphosphonates to be prescribed
adequate renal function and intake of calcium and vitamin D
What are the side effects of biphosphonates
Oral bisphosphonates can cause heart burn and indigestion
Iritis /Uveitis
osteonecrosis of the jaw
atypical femoral shaft fractures
Drug holidays are given in between long spells of bisphosphonate treatments
What is denosumab
Monoclonal antibody against RANK ligand which reduces osteoclastic bone resorption
How often is denosumab given
injection every 6 months
What is used in patients with significant renal impairment as treatment for osteoporosis
denosumab - safer than biphosphonates in patients with renal impairment
What are the side effects of denosumab
Allergy/rash
symptomatic hypoglycaemia if given to someone who has low Vitamin D
Osteonecrosis of the jaw
Atypical femoral shaft fractures
What is teriparatide
Anabolic therapy which is a PTH analogue - reduces refracture rates
What are the side effects of teriparatide
Injection site irritation
Hypercalcaemia - rare
Allergy
Very expensive
What is romosozumab
Monoclonal antibody which inhibits sclerotin
It increases bone formation and decreases resorption
How often is romosozumab given
Monthly injections
What are the side effects of romosozumab
High risk of allergy - difficulty breathing, swelling, burning eyes, red/purple rash
Severe symptoms - heart attack, stroke, chest pain and shortness of breath
