Metabolic Bone Disease Flashcards
What are the 2 main cells of bone remodelling?
- Osteoblasts
- Osteoclasts
What type of cell do osteoblasts develop from?
Mesenchymal progenitor cell
What type of cell do osteoclasts develop from?
Myeloid progenitor cell
What is the role of osteoclasts?
Bone resorption
What is the role of osteoblasts?
Bone formation
How do osteoblasts control osteoclasts?
- When stimulated they produce RANKL
- RANKL binds to pre-osteoclasts
- Activation of osteoclasts
What produces vitamin D?
UVB
Where is vitamin D stored?
Liver, fat and muscle
Where is vitamin D activated?
Kidney
In what form is vitamin D found in the skin?
7DHC
In what form is vitamin D found in the liver?
25(OH)vit D
In what form is vitamin D stored in the kidney?
1,25(OH)2 vit D
What happens to PTH when extracellular calcium is reduced?
Increases
What is Paget’s disease?
- Localised disorder of bone turnover
- Increased bone resorption followed by increased bone formation
What does Paget’s disease lead to?
Disorganised bone: bigger, less compact, more vascular and mores susceptible to deformity and fracture
What is the aetiology of Paget’s disease?
- Strong genetic component
- 15-30% are familial
- Loci of SQSTMI
- Restricted geographic distribution: those of Anglo-Saxon origins
- Environmental trigger: Possibility of chronic viral infection within Osteoclast
How does Paget’s disease present?
- Patient>40 years
- Bone pain
- Bony deformity (occasional)
- Excessive heat over Pagetic bone
- Neurological complications (such as nerve deafness)
How is Paget’s investigated?
X-ray
- Marked expansion of the bone
- Dense and lucid areas
Bone scan
-Most useful definitive test
Isolated elevation of serum alkaline phosphotase
What can rarely develop from Paget’s?
Osteosarcoma in the affected bone
How is Paget’s disease treated?
- No evidence to treat asymptomatic Paget’s unless in skull or in area requiring surgical intervention.
- Do not treat based on a raised alkaline phosphatase alone
- Intravenous Bisphosphonate therapy-One off zoledronic acid infusion
What is the difference between rickets and osteomalacia?
- Rickets occurs in children before the epiphyseal plates fuse
- Osteomalacia occurs in adults after the epiphyseal plates fuse
What causes rickets/osteomalacia?
Severe nutritional vitamin D or Calcium deficiency causes insufficient mineralisation and thus Rickets in a growing child and Osteomalacia in the adult when the epiphyseal lines are closed
What does vitamin D do?
Stimulates the absorption of calcium and phosphate from the gut and calcium and phosphate then become available for bone mineralisation
What effect doe low vitamin D have on muscle function?
Impaired function
How does Rickets present in infants?
- Stunted growth
- Bandy legs (once they start walking)
- Splayed epiphyses
- Large head (due to failure of fontanelles to close)
- Nodules on sides of ribs
- Failure to thrive
- Fragile
What are the symptoms of osteomalacia?
- Bone pain
- Muscle weakness
- Increased falls risk
What develops in osteomalacia?
Microfractures
What is osteogenesis imperfecta?
- Genetic disorder of connective tissue characterised by fragile bones from mild trauma and even acts of daily life
- Other non bone clinical features
- Broad clinical spectrum
What is the cause of OI?
Defects in type I collagent (There are 8 types of OI in total with 1 to 4 being the most common)
Describe types 1-4 of OI.
- Type I: Milder form-when child starts to walk and can present in adults
- Type II: Lethal by age 1
- Type III: Progressive deforming with severe bone dysplasia and poor growth
- Type IV : Similar to type 1 but more severe
What non-skeletal features can OI present with?
- Growth deficiency
- Defective tooth formation (dentigenesis imperfecta)
- Hearing loss
- Blue sclera
- Scoliosis / Barrel Chest
- Ligamentous laxity
- Easy bruising
What scoring chart is used for hypermobility in OI?
Beighton score
How is OI managed?
- Surgical: to treat fractures
- Medical: IV bisphosphonates to prevent fractures
- Social: education and social adaptions
- Genetic: genetic counselling for parents and next generation
How do we define osteoporosis?
A metabolic bone disease characterised by low bone mass and micro architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk
How is osteoporosis defined by DXA scan?
A result on DXA bone scanning <2.5 SDs below the young adult mean in a post-menopausal women (T score)
What is fracture in osteoporosis related to?
- Age
- BMD
- Falls
- Bone turnover
How can we assess risk of osteoporotic fracture?
Q fracture score
What is Q fracture?
-Fracture risk score
-Applicable to those aged 30-85 (men and women)
-Contains multiple variables including CV risks, falls and TCAs
-Cannot add BMD
Some of the variable risks can not be altered by osteoporotic medications
What does a DXA scan of the spine look at?
- L2-L4
- Thickening means secondary degenerative change has occurred
What does a DXA T score compare you to?
Young adult
What does a DXA Z score compare you o?
Peer of the same age
What should happen if someone’s fracture risk from osteoporosis is deemed significant?
If the risk is consider significant ( normally defined as a >10% risk of osteoporotic fracture over 10 years) the individual should be referred for a DXA scan ( Dual energy X-ray Absorptiometry)
What should happen if someone is on oral steroids or has a low trauma fracture?
Should be referred for a DXA bone scan regardless of their fracture risk percentage
How common is osteoporosis?
- I in 2 women over 50 will have an osteoporotic fracture before they die
- I in 5 men over 50 will suffer and osteoporotic fracture
- A 50 year old woman has a lifetime risk of 17% of a hip fracture
- If you suffer 1 vertebral fracture you are 5 times more likely to have another and twice as likely to have hip fracture than if you had no vertebral fractures.
What endocrine causes of osteoporosis are there?
- Thyrotoxicosis
- Hyper and Hypoparathyroidim
- Cushings
- Hyperprolactinaemia
- Hypopituitarism
- Low sex hormone levels
What rheumatic causes of osteoporosis are there?
- Rheumatoid arthritis
- Ankylosing Spondylitis
- Polymyalgia Rheumatica
What GI causes of osteoporosis are there?
- Inflammatory diseases: UC and crohns
- Liver diseases: PBC, CAH, Alcoholic cirrhosis, Viral cirrhosis (Hep C)
- Malabsorption: Cystic Fibrosis, chronic pancreatitis, coeliac disease, whipples disease, short gut syndromes and ischaemic bowel
What medications can cause osteoporosis?
- Steroids
- PPI
- Enzyme inducting antiepileptic medications
- Aromatase inhibitors (anti-oestrogens used in breast cancer)
- GnRH inhibitors
- Warfarin
How does our bone mass change with time?
- 0-20: increasing bone size
- About 25: peak bone mass
- Gradual decrease in bone mass
- Accelerated bone loss when menopause begins
- Gradual bone loss in the elderly
How do we prevent osteoporotic fractures?
- Minimise risk factors
- Ensure good calcium and vitamin D status
- Falls prevention strategies
- Medications
What medication helps to prevent osteoporotic fractures?
- HRT: Oestrogen and testosterone
- Selective oestrogen receptor modulator (raloxifene) SERM
- Bisphosphonates
What are the side effects of HRT?
- Increased risks of blood clots
- Increased risk of breast cancer with extended use into late 50s/early 60s
- Increased risk of Heart disease and stroke if used after large gap from menopause (more than 3 year gap)
What are the negative effects of SERM?
- Hot flushes if taken close to menopause
- Increased clotting risks
- Lack of protection at hip site
What is the first line pharmacotherapy for fracture prevention in osteoporosis?
Oral bisphosphonates
What must be ensured before commencing oral bisphosphonates?
- Adequate renal function
- Adequate calcium and vitamin D status
- Good dental health and hygiene advised
What are the possible side effects of bisphosphonates?
- Oesophagitis
- Iritis/uveitis
- Not safe when eGFR<30 mls/min
- Osteonecrosis of the jaw
- Atypical femoral shaft fractures
Drug holiday of 1-2 years after 10 years of use
What is Denosumab?
A monoclonal antibody against RANKL
How is denosumab used?
- SC injection every 6 months
- Safer in patients with significant renal impairment then bisphosphonates
What does denosumab do?
Reduces osteoclatic bone resportion
What are the possible side effects of denosumab?
- Allergy/rash
- Symptomatic hypocalcaemia if given when vitamin D deplete
- ?ONJ
- ? Atypical femoral shaft fractures
What is teriparatide?
Part of PTH that purely stimulates osteoblasts
What are the side effects/disadvantages of teriparatide?
- Injection site irritation
- Rarely hypercalcaemia
- Allergy
- COST
