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 i**nsufficient 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+**