Metabolic Bone Disease Flashcards
1
Q
Pre-osteoclasts are formed from what type of progenitor cell?
A
Myeloid progenitor cell
2
Q
Pre-osteoblasts are formed from what type of progenitor cell?
A
Mesenchymal progenitor cell
3
Q
Many Factors Stimulate Osteoblast Expression of RANK Ligand, name 3.
A
- Osteoblasts appear to be controlling cell of bone turnover
- Vitamin D
- Glucocorticoids
- IL-1, IL-11
- RANK ligand required for activated osteoclast
4
Q
Where does vitamin D come from?
A
- Sunshine
* Diet - oily fish, egg yolk
5
Q
What reaction occurs when UV rays hit the skin?
A
7DHC (hydrocholesterol) is transformed into a precursor of Vit D which circulates protein bound
6
Q
What stage of Vit D pathway occurs at the liver?
A
Conversion of the Vit D precursor to 25(OH)vit D - MAIN STORAGE FORM OF VITAMIN D
7
Q
What stage of Vit D pathway occurs at the kidney?
A
Conversion of 25(OH)vit D to 1,25(OH)2 vit D - ACTIVE FORM OF VITAMIN D
8
Q
What is the main function of vit D?
A
•Absorption of calcium from the gut
9
Q
What is another role of vit D?
A
•Works with parathyroid to move calcium in and out of tissues
10
Q
What test is used to measure vit D status?
A
25-hydroxy vit D
11
Q
What can caused vit D deficiency?
A
- Kidney and liver disease
- Darker skin - melanocytes competing for the UV radiation and prevent first reaction
- Older people have less 7DHC in skin
12
Q
Why is regulation of calcium metabolism so important?
A
To maintain Ca2+ levels in the ECF (at expense of bon calcium)
13
Q
What does parathyroid hormone do?
A
Regulates calcium levels (stimulates active vit d production etc.)
14
Q
What is Paget’s disease?
A
- LOCALISED disorder of bone turnover
* Increased bone resorption followed by increased bone formation
15
Q
What are the bone features of Paget’s?
A
- Disorganised bone
- Bigger
- Less compact
- More vascular
- More susceptible to deformity and fracture
16
Q
What is the aetiology of Paget’s?
A
- Relatively common
- 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 (in youth)
17
Q
What are the symptoms of Paget’s?
A
- > 40s
- Bone pain
- Occasionally presents with bone deformity
- excessive heat over affected (Pagetic) bone
- Neurological complications such as deafness
18
Q
What are the clinical signs of Paget’s?
A
- Isolated elevation of serum alkaline phosphatase - do not treat on this alone (incidental finding)
- Occasionally the development of osteosarcoma in the affected bone
- Do x-ray then isotope bone scan (for metabolic activity)
19
Q
What is the treatment of Paget’s?
A
- No evidence to treat if asymptomatic unless in skull or an areas requiring surgical intervention
- Intravenous bisphosphonate therapy - one-off zoledronic acid infusion, oral option is also available
ZOLEDRONIC ACID
20
Q
What are rickets and osteomalacia?
A
- Severe nutritional vit D or calcium deficiency causing insufficient mineralisation
- Vitamin D stimulates the absorption of calcium and phosphate from the gut and calcium and phosphate then become available for bone mineralisation
- Muscle function is also impaired in low vitamin D states
- Rickets - in growing child
- Osteomalacia - in adult when the epiphyseal lines are closed
21
Q
How does rickets present?
A
- Stunted growth
- Large forehead
- Odd-shaped legs
- Odd-shaped ribs and breast bones
- Wide joint at elbow, wrist and ankle
- Odd curve to spine or back
- Wide bones
22
Q
How does osteomalacia present?
A
- Particularly in elderly - housebound/institutionalised
- Bone pain
- Muscle weakness
- Increased falls risk
- More common in POC
- May see micro-fractures on x-rays
23
Q
How are rickets and osteomalacia treated?
A
•Vit D and calcium supplementation
24
Q
What is osteogenesis imperfecta?
A
- Genetic disorder of connective tissue characterised by fragile bones from mild trauma and even acts of daily life
- Defect in type 1 collagen
25
Which of the 28 types of type 1 collagen defect are most common?
1-4
26
How is type 1 characterised?
Milder form-when child starts to walk and can present in adults
27
How is type 2 characterised?
Lethal by age 1
28
How is type 3 characterised?
Progressive deforming with severe bone dysplasia and poor growth
29
How is type 4 characterised?
Similar to type 1 but more severe
30
What are other clinical features of osteogenesis imperfecta?
* Growth deficiency
* Defective tooth formation (dentigenesis imperfecta)
* Hearing loss
* BLUE SCLERA
* Scoliosis/Barrel Chest
* Ligamentous laxity - HYPERMOBILTIY (Beighton score)
* Easy bruising
31
How if OI treated?
* Surgical - treat fractures
* Medical - IV bisphophonates (to prevent fracture)
* Social - educational and social adaptations
* Genetic - genetic counselling for parent and next generation
32
What is 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
* A result on DXA bone scanning
33
What are risk factors for fractures in osteoporosis?
* Age
* BMD - bone mineral density
* Falls
* Bone turnover
34
What is FRAX?
WHO fracture risk assessment tool
35
Q fracture is another risk assessment tool for fracture risk which was developed in the UK. What variables does it take into account?
* CV risk
* Falls
* TCA (tricyclic antidepressants)
* Does not have the ability to add BMD
36
When should a patient be referred for a DXA scan?
* When risk assessment score is greater than 10%
* When they are on oral steroids
* When they have had a previous scan
37
What does a DXA scan measure?
* BMD
* T-score - compares patient to young adult (only age is not the same)
* Z-score - compares patient to absolute peer group
38
Who is at risk of 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
39
What are the endocrine causes of osteoporosis (7)?
* Thyrotoxicosis - hyperthyroidism
* Hyper and Hypoparathyroidim
* Cushings (hypercortisolism)
* Hyperprolactinaemia
* Hypopituitarism
* Low sex hormone levels
40
What are the rheumatic causes of osteoporosis (3)?
* Rheumatoid arthritis
* Ankylosing Spondylitis
* Polymyalgia Rheumatica
41
What are the gastroenterological causes of osteoporosis (3)?
* 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
42
Which medications cause osteoporosis?
* Steroids
* PPI
* Enzyme inducting antiepileptic medications
* Aromatase inhibitors - post-menopausal women
* GnRH inhibitors
* Warfarin
43
How does our bone mass change with time?
* Increases to ~30y
* Decreases >40y
* Accelerated loss after menopause
44
How do we prevent osteoporotic fractures?
* Minimise risk factors
* Ensure good calcium and Vitamin D status
* Falls prevention strategies
* Medications - HRT
45
What are the side effects of HRT?
* Increased risk 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, would not start if 2-3 years have passed
* Increased risk of prostate cancer in men
* No HRT after 60 years
46
What are SERMs?
* Selective oEstrogen Receptor Modulators
* Raloxifene - reduce vertebral fracture rate but no effect on other bones
* Reduce breast cancer risk
RALOXIFENE
47
Negative effects of SERMs?
* Hot flushes if taken close to menopause
* Increased clotting risks
* Lack of protection at hip site
48
What is the main osteoporosis treatment?
* Bisphosphonates
* Oral Bisphosphonates generally the first line of treatment
* Adequate Renal function required
* Adequate Calcium and Vitamin D status
* Good Dental Health and Hygiene advised - Notify dentist on Bisphosphonates, Encourage regular check ups/well fitting dentures
49
How do bisphophonates work?
* Bisphosphonate binds to bone mineral
* When the osteoclast breaks down the bone, it takes the bisphosphonate too
* The bisphosphonate poisons the osteoclast
* The osteoclast becomes aware it is damaged at carries out apoptosis
* The bisphophonate and the bone it was secured to are both regurgitated by the osteoclast back onto the bone surface
50
What are the side effects of bisphosphonates?
* Oesophagitis
* Iritis/uveitis
* Not safe when eGFR<30 mls/min
Extremely rare:
•ONJ - osteonecrosis of the jaw
•Atypical femoral shaft fractures
51
When is a drug holiday taken from bisphosphonates?
* Drug Holiday for 1-2 years
* Usually after 10 years Oral Bisphosphonates
* 5 year course very safe
52
What is denosumab?
* Monoclonal antibody against RANKL
* Prevents any osteoclastic stimulation
* Reduces osteoclastic bone resorption
53
How is denosumab administered?
* Subcutaneous injection every 6 months
| * Allows bone to break down
54
Why is denosumab beneficial?
* Safer in patients with significant renal impairment then bisphosphonates
* Reduce risk of hip fracture
* Use in older individual
55
What are the side effects of denosumab?
* Allergy/rash
* Symptomatic hypocalcaemia if given when vitamin D depleted
* Rebound fracture risk when treatment stopped
* ?ONJ
* ? Atypical femoral shaft fractures
56
What is teriparatide?
* Intermittent human parathyroid hormone (IHPT)
| * Used in people having vertebral fractures despite other therapies
57
How is teriparatide administered?
•Daily injection
58
What are the side effects of teriparatide?
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•Injection site irritation
•Rarely hypercalcaemia
•Allergy
•Limited to one course due to osteosarcoma risk - seen in rats
COST
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