Metabolic Bone Disease

Question 1

What cells are osteoblasts derived from?

Answer 1

Pluripotent mesenchymal cells

Question 2

Which bone cells do PTH and Vit D bind to? What are their effects?

Answer 2

Stimulate RANKL production

Decrease OPG production

Question 3

What osteoporosis fracture is most common?

Answer 3

Vertebral fracture

Question 4

5 causes of secondary osteoporosis

Answer 4

Excess glucocorticoids
Low testosterone
Hyperthyroid
Hyperparathyroid
Malignancies

Question 5

Effects of excess glucocorticoids on bone

Answer 5

• Decreased gut Ca absorption
• Increased RANKL
• Suppressed maturation / increased apoptosis of osteoblasts
• Increased renal Ca / phosphate losses.
• Suppressed LH / FSH and thus gonadal hormone production
• Suppressed ACTH and thus adrenal androgen production

Question 6

T score

Population

Answer 6

# of standard deviations px’s BMD is from mean of population of sex-matched, young healthy controls
Most useful in post-menopausal women, but also used for men over age 50.

Question 7

Z score

Population

Answer 7

• Same as T score but using population of sex-matched and AGE-matched controls.
• Most useful in premenopausal women and young men.

Question 8

Sxs of osteomalacia (3)

Cause of sxs

Answer 8

• Osteomalacia may involve bone pain / tenderness, muscle weakness, and increased risk of fracture
• Undermineralized bone attracts water → swelling → pain

Question 9

Pseudo Vit D deficiency Rickets

Treatment

Answer 9

Homozygous inactivating mutation of 1-alpha-hydroxylase.

Tx w/ calcitriol.

Question 10

Hereditary Vit D resistant Rickets

Treatment

Answer 10

Homozygous defect in Vit D receptor.

Tx w/ high doses of Ca and phosphate.

Question 11

X-linked / Autosomal dominant hypophosphatemic rickets

Treatment

Answer 11

Due to mutation that produces excess FGF-23 → renal phosphate loss + impaired 1-alpha-hydroxylase.
Tx w/ high dose phosphate.

Question 12

Tumor-induced osteomalacia

Treatment

Answer 12

Tumor makes excess FGF-23 → renal phosphate loss + impaired 1-alpha-hydroxylase.
Tx w/ tumor removal.

Question 13

Paget's Disease of Bone
Cause
2 characteristics
Population
Sxs (3)
Treatment

Answer 13

• Focal lesions of uncontrolled resorption. Osteoclasts are hyperactive → chaotic osteoblastic activity.
• Does NOT spread. Look for elevated Alk Phos.
• More common in older adults.
• Sxs – Warmth, pain, fracture at lesions. May be asymptomatic.
• Treatment – suppress bone resorption w/ bisphosphonates

Question 14

Fibrous Dysplasia of Bone
Characteristic
Cause
Associated syndrome

Answer 14

• Expanding bone lesions.
• Caused by somatic mosaicism for gain-of-function mutation in Gs-alpha receptor for PTH (opposite as pseudohypoparathyroidism)
• McCune-Albright Syndrome

Question 15

McCune-Albright Syndrome
3 characteristics
4 other glands that may be involved

Answer 15

• FD, peripheral precocious puberty, and café-au-lait spots.

* May also cause constitutive activation of hormone receptors in thyroid, parathyroid, pituitary, and adrenals.