MSPA: OSTEOMALACIA, RICKETS, Paget's disease , and renal dystrophy Flashcards

1
Q

What are the disease of impaired bone mineralization ?

A

Rickets and Osteomalacia

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2
Q

What are the etiologies of osteomalacia and Rickets ?

A
  • Vitamin D deficiency due to poor direct, low sun exposure or malabsorption due to Coeliac or Crohn’s disease.
  • Liver disease- Impaired conversion of Cholecalciferol to Calcidiol.
  • Kidney disease- Which impairs conversion of Calcidiol to Calcitriol.
  • Iatrogenic – Phenytoin
  • Tumour-induced osteomalacia – tumour production of FGF23 which
    inhibits conversion from Calcidiol to Calcitriol.
  • Vitamin D Resistance – inherited disorder
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3
Q

What is the presentation of osteomalacia and Rickets ?

A

They presents with
* Diffuse bone and joint pain
* Proximal muscle weakness
* Bone fragility
* Fractures from minor trauma
* Muscle spasms/cramps

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4
Q

What are the signs seen in Rickets ?

A
  • Craniotabes
  • Delayed closure of fontanelles
  • Genu varum
  • Prominent frontal bone
  • Protruding abdomen
  • Rachitic Rosary
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5
Q

What are the laboratory findings in Rickets and Osteomalacia ?

A
  • Low serum Vitamin D levels
  • Low Calcium
  • Elevated Alkaline Phosphatase
  • High Parathyroid Hormone (PTH)
    due to Low serum Phosphate
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6
Q

What are the radiological finding in osteomalacia and Rickets ?

A

Looser Zones which are cortical infarctions and Milkman’s lines which are Psuedo fractures.

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7
Q

What are the characteristic radiological findings in Rickets ?

A

Metaphysial widening of long bones and frayed metaphisial edges due to poor mineralization of the growth plates.

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8
Q

What is the Tx for Osteomalacia and Rickets ?

A

Treat underlying cause, if it is Vitamin D deficiency
Oral Vitamin D
▪ Daily replacement of vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol)
▪ High dose (1000 – 6000 IU per day depending on age) for three months
▪ Maintenance dosing thereafter (400 – 600 IU per day depending on age)
Calcium supplementation
▪ 30-50 mg/kg body weight per day (diet or supplements)
* Resolution of biochemical and radiologic abnormalities should occur within 3 months of therapy

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9
Q

What is the aetiology of Paget’s disease?

A

The exact aetiology is unknown genetic and viral aetiologies are suspected.

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10
Q

What are the three phases of Paget’s disease ?

A
  • I – Lytic Phase: Abnormal osteoclasts demonstrate aggressive
    demineralization of bone, creating lytic lesions in bone
  • II – Mixed Phase: Mixed between lytic and blastic phases; abnormal
    number of osteoblasts begin to lay down bone rapidly in a disorganized
    manner
  • III – Sclerotic Phase: Bone formation exceeds bone resorption creating
    structurally disorganized and weak bones
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11
Q

What is the dormant state of Paget’s disease ?

A

It is a state in which osteoblast and osteoclast activity is slowed or
halted.

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12
Q

What are the risk factors for Paget’s disease ?

A
  • Genetics / family history of disease
  • Age > 40 years old
  • Western European descent
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13
Q

What is the Tx of Paget’s disease ?

A
  • Pain can be managed with NSAIDS
  • Bone lysis can be managed with bisphosphonates, Vitamin D and Calcium.
  • Surgical correction of nerve impingements may be needed.
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14
Q

What is the laboratory indicator of Paget’s disease Tx success ?

A

ALP level normalisation.

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15
Q

What is the pathophysiology of renal osteodystrophy ?

A

It is a disorder of the bone mineral homeostasis occurs secondary to CKD. CKD causes hyperphosphatenemia, which is initially off-set by increasing serum calcium from bone resorption resulting in bone weakness. The CKD also causes impaired conversion of calcidiol into calcitriol leading to impaired absorption of dietary calcium and hypocalcemia. Hypocalcemia occurs later in the disease. Declining kidney function, declining calcitriol production and
hypocalcemia lead to higher releases of PTH which leads to increased bone resorption and
weakened bones in order to release calcium into the blood resulting in renal osteodystrophy.

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16
Q

What are the risk factors for renal osteodystrophy ?

A
  • Stage II CKD (GFR 60-89 mL/min) – begin to see issues with
    serum phosphate, calcium and PTH
  • ESRD (GFR < 15 mL/min) - 90% will have evidence of renal
    osteodystrophy or CKD-MBD
17
Q

What is the clinical presentation of renal osteodystrophy ?

A

Patients with CKD or ESRD presents with bone pain, proximal muscle pain and weakness. They may also present with pathological fractures and signs of hypocalcemia such as parasthesias, muscle spasms and cramps, Tetany, perioral numbness and seizures.

18
Q

What are the laboratory findings in renal osteodystrophy ?

A
  • Hyperphosphatemia
  • Hypocalcemia
  • increased Parathyroid hormone
19
Q

What are the radiological findings in renal osteodystrophy ?

A

Looser Zones, Milkman’s pseudo fractures, and Brown tumor.

20
Q
A
21
Q

What is the Tx of Renal osteodystrophy ?

A

*Avoid foods high in phosphate such as milk, chocolate, beer etc.
* Vitamin D supplementation and phosphate binders.
* Cinacalcet to reduce PTH production
* Parathyroidectomy is an option.

22
Q

Calcium is stored in the bones as ?

A

Hydroxyapatite

23
Q

What are the three forms in which calcium in blood?

A

45% free ionized form, 45% albumin bound, 10% complexed with anions.

24
Q

What type of calcium is measured in routine blood test?

A

Total calcium

25
Q

What is the formula for calculating calcium dosage in hypoalbuminemia?

A

Measured calcium+ (0.8(4-albumin))

26
Q

The vast majority of phosphate is stored in the body as ?

A

Hydroxyapatite

27
Q

What is the ratio of inorganic phosphates at the body pH 7.4?

A

Hydrogen phosphate (4): Dihydrogen phosphate (1)

28
Q

What is the structure and function of PTH?

A

It is a 86 amino acid polypeptide chain responsible for increasing serum calcium and decreasing serum serum phosphate

29
Q

What is the role of calcitriole, the active form of vitamin D?

A

Increase serum calcium and increase serum phosphate

30
Q

PTH is produced by the?

A

Chief cells of parathyroid gland.

31
Q

What is the regulation dynamics of PTH?

A

The increase in serum calcium decreases PTH and vice versa. Similarly a small decrease in magnesium causes an increase in PTH and vice versa. However significant hypomagnesemia causes decrease in PTH and unresponsiveness to PTH leading to hypocalcemia.

32
Q

What is the role of renal enzyme Vitamin D1 alpha hydroxylase?

A

It converts calcidiol (25(OH) cholecalciferol) to the active form of vitamin D also known as calcitriole ( 1,25(OH) cholecalciferol).

33
Q

What are the factors that upregulate the activity of Vitamin D-1- alpha hydroxylase?

A

Increase in PTH and decrease in serum phosphate

34
Q

What are the factors that inhibit vitamin D 1 alpha hydroxylase?

A

Increase in serum phosphate and FGF23 released by the osteoclasts and osteoblasts in response to elevated PTH and Hyper phosphatemia also inhibits Vitamin D-1-alpha hydroxylase.

35
Q

What is the function of active D or calcitriole?

A

It facilitates the GI absorption of calcium and phosphate and their deposition on the osteoid bone matrix generated by the osteoblasts. In addition, Calcitriole along with PTH also regulates bone formation and resorption cycle.

36
Q

What is the role of calcitonin?

A

Calcitonin is released by the para follicular cells or C cells of the thyroid gland which is a weak inhibitor of bone resorption. It is used a treatment for severe hypercalcemia

37
Q

What is the difference in the action of PTH and calcitriole in renal reabsorption of calcium and phosphate?

A

Calcitriole promotes reabsorption of both calcium and phosphate.whereas PTH only promotes reabsorption of calcium only.

38
Q

What is the role of FGF23 in the renal tubules?

A

To inhibit reabsorption of phosphate in the renal tubules.