Metabolic bone conditions Flashcards
How do serum results for Ca, PO4, ALP, PTH and 1,25(OH)D2 present for Pagets disease? [5]
Explain your answer [1]
Ca: normal
PO4: normal
ALP: raised
PTH normal
Vit D: normal
ALP raised due to characterised by high burn turnover
How do serum results for Ca, PO4, ALP, PTH and 1,25(OH)D2 present for renal failure [5]
Explain your answer [1]
failure leads to vitamin D deficiency, as 1,25(OH)2 D3 is made in the kidney.
This results in high PO4, low calcium and normal/high alkaline phosphatase
Why do women suffer from osteoporosis than men? [2]
Women start with less bone and have an accelerated decline around 45-60 years (during menopause)
Osteoporosis
What is T and Z score on a DEXA scan? [2]
Which is more commonly used? [1]
T-score = number of standard deviations from the mean young (30 yr) same gender and ethnicity. More commonly used
Z-score = number of standard deviations from same age, gender and ethnicity. Used for younger populations
Which 3 locations do you measure a T score from in the body? [3]
Why do you measure these areas? [1]
Neck of femur, lumbar vert or distal radius
Have high areaa trabecular bone here [1]
After 50, women have a lifetime risk of 1:3 in [] osteoporosis [1]
Which bone?
After 50, women have a lifetime risk of 1:3 in vertebral osteoporosis [1]
What T score is a clinical cut off that suggests osteoporosis? [1]
What T score is a clinical cut off that suggests osteopenia?
Osteoporosis: T-score lower than -2.5. [1]
Osteopenia: T-score between –1.0 and –2.5 standard deviations below normal.
How would a patient present with osteoporosis? [1]
Have a fracture due to low force injury
Name two bones that are more likely to suffer from osteoporosis [2]
Vertebral bodies
Femoral neck
Describe pathophysiology of osteoporosis [3]
- Bone formation is normal
- Just relative increase in bone resorption not matched by formation
- Trabecular bone more at risk
Trabecular bone almost dissapeared on R (L is normal)
Describe the clinical presentation of osteoporosis [3]
- Fracture is the only cause of symptoms in osteoporosis
- Sudden onset of severe pain in the spine, often radiating to the front
- Thoracic vertebral fractures may lead to kyphosis - ‘widows stoop’
Regardless of age, which supplements are provided as part of treatment for osteoporosis? [2]
What treatment is commonly given to peri-menopausal women? [1]
Ca & Vit. D [2]
HRT: replaces the oestrogen lost in the menopause
What is first line treatment for osteoporosis? [1]
Describe MoA [3]
Bisphosphonates:
- inhibits osteoclast activity
- promotes osteoclast apoptosis
- Decreases RANKL expression (so osteoblasts don’t turn into osteoclasts [?])
What is important to note about bisphosphinate treatment for osteoporosis? [1]
Bisphosphonates reduce fracture risk by approximately 50%, yet it’s important to note they don’t increase bone mass but prevent further loss. You will still be osteoporotic with bisphosphonates; they just prevent the osteoporosis from progressing and becoming worse.
Describe complications of bisphosphonates
Kills off osteoclasts: don’t remove old bone: thickened bone
Get giant osteoclasts: poisoned osteoclasts
Osteonecrosis occurs
Where does osteonecrosis commonly occur as a complication of bisphosphinate treatment? [1]
jaw
To avoid complications of bisphosphonates, how long should give a holiday for:
- mild T score [1]
- Moderate T score [1]
- Hight T scorep1[
Mild T score 3-5 years
Moderate T score 5-10 years holiday 2-3 years before restart
High T score 10 years 1-2 years holiday
Osteoporosis treatment
Describe the MoA of Teriparatide [2]
Teriparatide is a recombinant PTH:
- PTH upregulates RANKL - signals osteoblast to differentiate when have low Ca2+: work indirectly on osteoclasts to boost bone making potential
- Intermittent exposure to PTH activates osteoblasts more than osteoclasts
Osteoporosis treatment
Describe the MoA of Denosumab [2]
PTH normally inhibits OPG.
Denosumab is a an osteoprotegrin artificial antibody & acts as a monoclonal antibody to RANK:
Denosumab: human monoclonal antibody that inhibits RANKL and helps regulate turnover in healthy bone. Denosumab binds with high specificity and affinity to the cytokine RANKL, inhibiting its action; as a result, osteoclast recruitment, maturation and action are inhibited, and bone resorption slows
Rickets aka? [1]
Osteomalacia
How does osteomalacia present:
In children [1]
In adults [1]
Children:
* the epiphyseal growth plate is still open, meaning Osteomalacia is more deforming and can cause the legs to bend outwards
Adults:
* epiphyseal growth plate is closed, meaning Osteomalacia is less deforming
What would lab results of a patient with osteomalacia show:
- Ca2+ levels [1]
- PO4- levels [1]
- ALP levels [1]
- Vitamin D levels [1]
- Reduced serum calcium and phosphorous
- High alkaline phosphatase (as this is a product of osteoblasts, so there is increase compensatory osteoblastic activity)
- Low vitamin D levels
Explain pathophysiology of osteomalacia
Describe the pathophysiology of osteomalacia [2]
Osteomalacia is a condition that is the result of insufficient calcium and phosphate to mineralise new bone osteoid.
This results in bones becoming softer and more liable to bend or fracture
. It is usually result of vitamin D deficiency either in diet or production, and has different clinical presentation in adults and kids:
Explain three treatments for osteomalacia [3]
- Vitamin D supplements – may need to be taken for the rest of the individuals life
- Dietary changes – increase calcium (milk, bread, beans and pulses, dried fruit, leafy green vegetables) and also vitamin D (mushrooms, salmon, mackerel)
- Sun or UV exposure: 15 minutes of sun of hands and face 2-3 times a week in spring and summer is sufficient
How would you diagnose osteomalacia from a bone biopsy? [1]
Normal bone:
- approx. 20% unmineralized bone osteoid
Osteomalacia:
- wide seams of unmineralized osteoid. In severe cases, up to 100% of the bone is covered by unmineralised osteoid.
Which drug would allow you to determine the level of bone mineralisation [1]
Tetracycline chelates: less labelling would be seen
Descibe pathophysiology of Pagets disease [2]
Describe the three phases of Pagets disease [3]
(Theory) osteoclasts: may be infected with a virus that alters them AND genetics
Phases:
1. increased rate of bone resorption:
* large number of giant osteoclasts
2. Compensatory phase / proliferative:
* increased bone formation & accelerated depostion in disorganised manner
3. Burnt out phase: sclerotic:
* Hyper-vascular bone marrow; Bone hypercellularity may diminish leaving dense “Pagetic bone”
Which bones are commonly affected in Pagets? [4]
Pelvis, femur, vertebrae, skull, tibia
What phase of Pagets Disease is depicted? [1]
Explain your answer [1]
Burnt-out sclerotic phase of Paget disease (Phase 3):
Woven bone appears as bony shelves divided by cement lines into irregular regions.
What are the arrows pointng to in this slide from a Pagets disease patient? [1]
Cement lines
After 50, women have a lifetime risk of 1:3 in [] osteoporosis [1]
Which bone?
After 50, women have a lifetime risk of 1:3 in vertebral osteoporosis [1]
Name a rare complication of Paget’s disease that occurs in 1% of cases [1]
Osteosarcoma
How would you confirm Osteosarcoma from a biopsy? [1
Giant cells confirm the diagnosis of an osteosarcoma arising out of Paget’s disease.
Which pathology is depicted in this X-ray
Osteoporosis
Osteomalacia
Pagets Disease
Osteoarthiritis
Osteosarcoma
Which pathology is depicted in this X-ray
Osteoporosis
Osteomalacia
Pagets Disease
Osteoarthiritis
Osteosarcoma
Osteosarcoma arises as a complication from:
Osteoporosis
Osteomalacia
Pagets Disease
Osteoarthiritis
Osteosarcoma arises as a complication from:
Osteoporosis
Osteomalacia
Pagets Disease
Osteoarthiritis
How do you treat Pagets disease? [5]
- Bisphosphonates work directly on osteoclasts to slow bone resorption. Can be given orally for 2-6 months, or IV single infusion-3 infusions. Bisphosphonates can almost cure Paget’s disease if you catch it early, and stop the osteoclast hyperactivity, as this will prevent sclerotic bone from forming.
- Calcium and vitamin D supplements
- Pain management
- Surgery
- Calcitonin used to be used more often, but now less than bisphosphonates
What is sclerostosis caused by? [1]
How do patients with sclerotosis present? [2] Explain your answer [1]
Absence, abnormal or reduced produced of sclerostin
Sclerostin produced by healthy osteocytes and inhibtis osteoblasts to prevent XS bone formation
Condition results in resistance to fractures and XS height
How do serum results for Ca, PO4, ALP, PTH and 1,25(OH)D2 present for osteoporosis? [1]
Normal
How do serum results for Ca, PO4, ALP, PTH and 1,25(OH)D2 present for osteomalacia? [1]
Explain each result
Low Ca
Low PO4
ALP high
PTH high
Vit D low
- Main cause of osteomalacia: low vitamin d
- Low PO4 and Ca due to phosphate being excreted in order to keep any calcium possible via renal regulation).
- ALP high because produced in osteoblasts
- PTH high due to low Ca2+
