Metabolic bone conditions

Question 1

How do serum results for Ca, PO4, ALP, PTH and 1,25(OH)D2 present for Pagets disease? [5]

Explain your answer [1]

Answer 1

Ca: normal
PO4: normal
ALP: raised
PTH normal
Vit D: normal

ALP raised due to characterised by high burn turnover

Question 2

How do serum results for Ca, PO4, ALP, PTH and 1,25(OH)D2 present for renal failure [5]

Explain your answer [1]

Answer 2

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

Question 3

Why do women suffer from osteoporosis than men? [2]

Answer 3

Women start with less bone and have an accelerated decline around 45-60 years (during menopause)

Question 4

Osteoporosis

What is T and Z score on a DEXA scan? [2]

Which is more commonly used? [1]

Answer 4

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

Question 5

Which 3 locations do you measure a T score from in the body? [3]

Why do you measure these areas? [1]

Answer 5

Neck of femur, lumbar vert or distal radius

Have high areaa trabecular bone here [1]

Question 6

After 50, women have a lifetime risk of 1:3 in [] osteoporosis [1]

Which bone?

Answer 6

After 50, women have a lifetime risk of 1:3 in vertebral osteoporosis [1]

Question 7

What T score is a clinical cut off that suggests osteoporosis? [1]

What T score is a clinical cut off that suggests osteopenia?

Answer 7

Osteoporosis: T-score lower than -2.5. [1]

Osteopenia: T-score between –1.0 and –2.5 standard deviations below normal.

Question 8

How would a patient present with osteoporosis? [1]

Answer 8

Have a fracture due to low force injury

Question 9

Name two bones that are more likely to suffer from osteoporosis [2]

Answer 9

Vertebral bodies
Femoral neck

Question 10

Describe pathophysiology of osteoporosis [3]

Answer 10

• 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)

Question 11

Describe the clinical presentation of osteoporosis [3]

Answer 11

• 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’

Question 12

Regardless of age, which supplements are provided as part of treatment for osteoporosis? [2]

What treatment is commonly given to peri-menopausal women? [1]

Answer 12

Ca & Vit. D [2]

HRT: replaces the oestrogen lost in the menopause

Question 13

What is first line treatment for osteoporosis? [1]
Describe MoA [3]

Answer 13

Bisphosphonates:

• inhibits osteoclast activity
• promotes osteoclast apoptosis
• Decreases RANKL expression (so osteoblasts don’t turn into osteoclasts [?])

Question 14

What is important to note about bisphosphinate treatment for osteoporosis? [1]

Answer 14

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.

Question 16

Describe complications of bisphosphonates

Answer 16

Kills off osteoclasts: don’t remove old bone: thickened bone

Get giant osteoclasts: poisoned osteoclasts

Osteonecrosis occurs

Question 17

Where does osteonecrosis commonly occur as a complication of bisphosphinate treatment? [1]

Answer 17

jaw

Question 18

To avoid complications of bisphosphonates, how long should give a holiday for:

• mild T score [1]
• Moderate T score [1]
• Hight T scorep1[

Answer 18

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

Question 19

Osteoporosis treatment

Describe the MoA of Teriparatide [2]

Answer 19

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

Question 20

Osteoporosis treatment

Describe the MoA of Denosumab [2]

Answer 20

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

Question 21

Rickets aka? [1]

Answer 21

Osteomalacia

Question 22

How does osteomalacia present:

In children [1]
In adults [1]

Answer 22

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

Question 23

What would lab results of a patient with osteomalacia show:

• Ca2+ levels [1]
• PO4- levels [1]
• ALP levels [1]
• Vitamin D levels [1]

Answer 23

• 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

Question 24

Explain pathophysiology of osteomalacia

Question 25

Describe the pathophysiology of osteomalacia [2]

Answer 25

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:

Question 26

Explain three treatments for osteomalacia [3]

Answer 26

1. Vitamin D supplements – may need to be taken for the rest of the individuals life
2. Dietary changes – increase calcium (milk, bread, beans and pulses, dried fruit, leafy green vegetables) and also vitamin D (mushrooms, salmon, mackerel)
3. Sun or UV exposure: 15 minutes of sun of hands and face 2-3 times a week in spring and summer is sufficient

Question 27

How would you diagnose osteomalacia from a bone biopsy? [1]

Answer 27

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.

Question 28

Which drug would allow you to determine the level of bone mineralisation [1]

Answer 28

Tetracycline chelates: less labelling would be seen

Question 29

Descibe pathophysiology of Pagets disease [2]

Describe the three phases of Pagets disease [3]

Answer 29

(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”

Question 30

Which bones are commonly affected in Pagets? [4]

Answer 30

Pelvis, femur, vertebrae, skull, tibia

Question 31

What phase of Pagets Disease is depicted? [1]

Explain your answer [1]

Answer 31

Burnt-out sclerotic phase of Paget disease (Phase 3):

Woven bone appears as bony shelves divided by cement lines into irregular regions.

Question 32

What are the arrows pointng to in this slide from a Pagets disease patient? [1]

Answer 32

Cement lines

Question 33

After 50, women have a lifetime risk of 1:3 in [] osteoporosis [1]

Which bone?

Answer 33

After 50, women have a lifetime risk of 1:3 in vertebral osteoporosis [1]

Question 34

Name a rare complication of Paget’s disease that occurs in 1% of cases [1]

Answer 34

Osteosarcoma

Question 35

How would you confirm Osteosarcoma from a biopsy? [1

Answer 35

Giant cells confirm the diagnosis of an osteosarcoma arising out of Paget’s disease.

Question 36

Which pathology is depicted in this X-ray

Osteoporosis
Osteomalacia
Pagets Disease
Osteoarthiritis
Osteosarcoma

Answer 36

Which pathology is depicted in this X-ray

Osteoporosis
Osteomalacia
Pagets Disease
Osteoarthiritis
Osteosarcoma

Question 37

Osteosarcoma arises as a complication from:

Osteoporosis
Osteomalacia
Pagets Disease
Osteoarthiritis

Answer 37

Osteosarcoma arises as a complication from:

Osteoporosis
Osteomalacia
Pagets Disease
Osteoarthiritis

Question 38

How do you treat Pagets disease? [5]

Answer 38

• 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

Question 39

What is sclerostosis caused by? [1]

How do patients with sclerotosis present? [2] Explain your answer [1]

Answer 39

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

Question 40

How do serum results for Ca, PO4, ALP, PTH and 1,25(OH)D2 present for osteoporosis? [1]

Answer 40

Normal

Question 41

How do serum results for Ca, PO4, ALP, PTH and 1,25(OH)D2 present for osteomalacia? [1]

Explain each result

Answer 41

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+