Metabolic Bone Disease Flashcards
Which factors stimulate osteoblast expression of RANK ligand?
- TNF-alpha
- PTHrP
- IL-1 and IL-11
- Vitamin D
- Glucocorticoids
- PTH
- PGE-2
What is Paget’s bone disease and what does it cause?
- Increased bone resorption followed by increased bone formation
- Leads to bigger, less compact, disorganised bone which is more vascular and more susceptible to deformity and fracture
Describe the aetiology of Paget’s disease
- Genetics: large proportion are familial
- Distribution restricted to those of anglo-saxon origins
- Environmental: chronic viral infection within osteoclasts
What are the symptoms of Paget’s disease?
- Patients > 40
- Bone pain
- Occasionally bone deformity
- Excessive heat over Pagetic bone
- Neurological complications e.g. nerve deafness
How does Paget’s disease present?
- Isolated elevation of serum alkaline phosphatase
- Bone pain and local heat
- Bone deformity or fracture
- Hearing loss
- Rarely: osteosarcoma in affected bone
How can Paget’s disease be treated?
- Only treat asymptomatic if in skull or other areas requiring surgical intervention
- Not to be done on raised alkPhosphatase alone
- IV bisphosphonate therapy - one off IV zoledronic acid
Which bone diseases are caused by severe nutritional vitamin D or calcium deficiency which causes insufficient mineralisation?
- Rickets in children
- Osteomalacia in adults (whose epiphyseal lines are closed)
What are the clinical features of rickets?
- Stunted growth
- Large forehead
- Odd curve to spine or back
- Odd shaped ribs or breast bones
- Large abdomen
- Odd shaped legs
- Wide joints at elbow and wrist
- Wide ankles and wide bones in the leg
What is osteogenesis imperfecta?
A genetic disorder of connective tissue characterised by fragile bones from mild trauma and even acts of daily life
List the four most common types of osteogenesis imperfecta and how they present
- Type I: mild (when child starts to walk/can present in adults)
- Type II: lethal by age 1
- Type III: severe bone dysplasia and poor growth
- Type IV: similar to type I but more severe
What are the signs and symptoms of osteogenesis imperfecta?
- Growth deficiency
- Defective tooth formation
- Hearing loss
- Blue sclera
- Scoliosis
- Barrel chest
- Ligamentous laxity
- Easy bruising
How can osteogenesis imperfecta be managed?
- Surgically: to treat fractures
- Medically: IV bisphosphonates (to prevent fractures)
- Socially: educational and social adaptations
- Genetic counselling
What is the definition of 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
When would a DXA bone scan be diagnostic of osteoporosis (T score)?
A result of < -2.5 SDs below the young adult mean in a post menopausal woman
What is the risk of fracture related to in osteoporosis?
- Age
- Bone mass density
- Falls
- Bone turnover
Which tool is used to assess fracture risk?
FRAX - WHO fracture risk assessment tool
What does the Q fracture score use to calculate risk and what are the drawbacks?
- Aged 30-85, men/women
- CVS risks, falls and TCA
- No ability to add BMD and some of the variables/risks can’t be altered by osteoporotic medications
List the endocrine causes of osteoporosis
- Thyrotoxicosis
- Hyper and hypoparathyroidism
- Cushings
- Hyperprolactinaemia
- Hypopituitarism
- Early menopause
List the rheumatic causes of osteoporosis
- Rheumatoid arthritis
- Ankylosing spondylitis
- Polymyalgia rheumatica
List the GI causes of osteoporosis
- Inflamm diseases: UC and Crohns
- Liver: PBC, CAH, alcoholic cirrhosis and hep C
- Malabsorption: chronic pancreatitis, coeliac disease, whipples disease, short gut syndromes and ischaemic bowel
List the medications which can cause osteoporosis
- Steroids
- PPIs
- Enzyme inducting anti-epileptics
- Aromatase inhibitors
- GnRH inhibitors
- Warfarin
How can osteoporotic fractures be prevented?
- Minimise risk factors
- Ensure good calcium and vitamin D status
- Falls prevention strategies
- Medications
When should osteoporosis be treated?
- T score below -2.5
- Osteopenia: T score -1 to -2.5 with previous fracture
- 20% 10 year risk at any site over the next 10 years
When should a patient be referred for a DXA scan?
FRAX or QFracture score of > 10% fracture risk at any site over the next 10 years
Which medications can be used to treat osteoporosis?
- HRT
- Selective Oestrogen Receptor Modulator (SERMS)
- Bisphosphonates (main treatment option)
What are the potential side effects of HRT?
- Increased risks of blood clots
- Increased risk of breast cancer with extended use
- Increased risk of heat disease and stroke if used after large gap from menopause
What are the negative effects of SERMS?
- Hot flushes if taken close to the menopause
- Increased clotting risks
- Lack of protection at hip site
Give two examples of biphosphonates
- Alendronate
- Risedronate
Give an example of a SERMS
Raloxifene
What are the potential side effects of bisphosphonates?
- Oesophagitis
- Iritis/uveitis
- ONJ?
- Atypical femoral shaft fractures?
- Need a drug holiday after ten years
What is denosumab and how is it used?
- Monoclonal antibody against RANKL
- Reduces osteoclastic bone resorption
- SC injection every 6 months
- Safer in patients with significant renal impairment
What are the potential side effects of denosumab?
- Allergy/rash
- Symptomatic hypocalcaemia ( if given when vitD deplete)
- ?ONJ
- ? Atypical femoral shaft fractures
What is teripatide?
A synthetic version of the parathyroid hormone which regulates calcium metabolism
What are the potential side effects of teriparatide?
- Injection site irritation
- Rarely hypercalcaemia
- Allergy
- (Cost)
