Msi Week 2: Metabolic Bone Disease

Front 1

Is most of the bone matrix made up of organic or inorganic components?

Back 1

Inorganic.

60% Inorganic (calcium hydroxyapatite)
40% organic (osteoid)

Front 2

List 4 general components that make up the organic material in bone matrix.

Back 2

1. Type I collagen (tensile strength)
2. Proteoglycans (compressive strength)
3. Osteocalcin/osteonectin
4. Growth factors/ cytokines/ osteoid

Front 3

What organic component provides tensile strength to the bone matrix?

Back 3

Type I collagen

Front 4

What organic component provides compressive strength to the bone matrix?

Back 4

Proteoglycans

Front 5

Name the inorganic component that contributes to bone matrix.

Back 5

Calcium hydroxyapatite

Front 6

Name 3 bone cells.

Back 6

1. Osteoblasts
2. Osteocytes
3. Osteoclasts

Front 7

What are the channels called that provide communication between osteocytes and osteoblasts?

Back 7

Canaliculi

Front 8

List the 4 stages of bone remodeling.

Back 8

1. Activation
2. Resorption
3. Reversal
4. Formation

Front 9

What type of stem cells are osteoclasts derived from?

What type of stem cells are osteoblasts derived from?

Back 9

Osteoclasts from Hematopoietic stem cells

Osteoblasts from Mesenchymal stem cells

Front 10

Which cells secrete osteoid

Back 10

Osteoblasts

Front 11

Name the cytokine that is found on osteoblasts and that serves to activate osteoclasts?

Back 11

RANKL

*Key factor for osteoclast differentiation and activation

Front 12

Name the factor that is secreted by osteoblasts and serves to inhibit the activity of osteoclasts?

Back 12

OPG (osteoprotegerin)

*This is a decoy receptor for RANKL, so it acts as an inherent RANKL blocker, preventing the activation/differentiation of osteoclasts

Front 13

List 2 types of bone structures (primary/ secondary)

Back 13

1. Woven (primary)
2. Lamellar (secondary)

Front 14

What type of bone structure is cortical or compact and trabecular or cancellous?

Back 14

Lamellar (secondary; mature)

Front 15

What type of bone structure is immature, and is only seen in adult bone under pathological conditions or if the bone is healing?

Back 15

Woven

Front 16

What type of lamellar bone structure makes up 80% of total bone mass?

Back 16

Cortical or compact bone
(long bones)

*Very dense and provides much of the tensile strength for weight bearing

Front 17

Which type of lamellar bone structure has a slow turnorver (relatively metabolically inactive)?

Back 17

Cortical or compact bone

Front 18

What type of lamellar bone makes up 20% of total bone mass?

Where is this type of bone tissue found?

Back 18

Trabecular or cancellous bone

Found in vertebral bodies, ends of long bones

Front 19

Which type of lamellar bone structure has a very rapid turnover (relatively metabolically active)

Back 19

Trabecular or cancellous bone

Front 20

Which type of lamellar bone is more affected in post-menopausal women?

Back 20

Trabecular or cancellous bone

Front 21

What type of lamellar bone tissue is more prominent near joints to resist compression forces?

Back 21

Trabecular or cancellous bone

Front 22

At what age to men and women typically reach their high peak bone mass?

Back 22

Age 30

Front 23

Name the major peptide regulator of calcium levels.

Back 23

Parathyroid hormone (PTH)

Front 24

What type of cells produce and secrete PTH?

Back 24

Chief cells of the parathyroid gland

Front 25

How is PTH regulated indirectly?

Back 25

By changes in phosphate levels

Front 26

The release of parathyroid hormone requires __________.

Back 26

Magnesium

Front 27

What can inhibit the release of PTH in a negative feedback system?

Back 27

Calcitriol (1,25- dihydroxy Vitamin D)

Front 28

What is the effect of high levels of Vitamin D on PTH?

Back 28

Decrease PTH levels

(1,25 (OH)2 Vitamin D inhibits the release of PTH)

Front 29

Which organs are involved in the control of calcium levels?

Back 29

1. Bone
2. Kidneys
3. Gut

*Respond to PTH

Front 30

What effect does PTH have on bone?

Back 30

Increases Ca/PO4 release--> increases bone resorption

Front 31

What effects does PTH have on the kidneys, in regard to Ca/PO4 levels?

Back 31

Causes:
1. Increased reabsorption of Ca
2. Increased excretion of PO4

Front 32

What effect does PTH have on the gut in regards to calcium?

Back 32

Causes indirect increase in calcium reabsorption by stimulating activation of Vitamin D metabolism

Front 33

How is calcitonin release stimulated?

Back 33

Stimulated by increases in plasma calcium
(released by parafollicular cells)

*Also stimulated by GI hormones (pentagastrin)

Front 34

What is the net effect of calcitonin?

Back 34

To promote calcium deposition in bone
(directly antagonistic against PTH)

Front 35

What are the target organs of Calcitonin?

Back 35

1. Bone (suppresses Ca2+ resorption)
2. Kidney (increases Ca2+ excretion)

Front 36

What is the major storage form of Vitamin D that is measured clinically?

Is this form active or inactive?

Back 36

25(OH)-Vitamin D

*Inactive form

Front 37

Which form of Vitamin D is active?

Back 37

1,25 (OH)2- Vitamin D

Front 38

Vitamin D produced in the skin or obtained from food first travels to which organ to get hydroxylated?

Back 38

LIVER

Becomes 25(OH)-Vitamin D

Front 39

25(OH)-Vitamin D from the liver travels to which organ to get transformed into its active form?

Back 39

KIDNEY

(Gets hydroxylated to 1,25 (OH)2- Vitamin D)

Front 40

Which form of Vitamin D is necessary to absorb adequate amounts of Ca2+ in the GI tract?

Back 40

1,25 (OH)2- Vitamin D

(active form)

Front 41

In what circumstances would a patient need to take 1,25 (OH)2- Vitamin D?

Back 41

If the patient has renal failure

(this form of Vitamin D is made in the kidneys, so patients w/ renal failure will be unable to make it, and therefore they will not be able to absorb adequate amounts of Ca2+ in the GI tract)

Front 42

How does PTH indirectly affect the absorption of Ca2+ in the GI tract?

Back 42

PTH stimulates the enzyme that converts 25(OH)-Vit D to 1,25(OH)2- Vit D, which is necessary for Ca2+ absorption in the GI tract.

Front 43

List 4 hormones that increase bone resorption (stimulate osteoclasts).

Back 43

1. PTH (high levels)
2. Glucocorticoids
3. Thyroid hormone
4. Vitamin D metabolites in HIGH doses

Front 44

List 2 hormones that decrease bone resorption (protect against bone loss)

Back 44

1. Calcitonin
2. Gonadal steroids (estrogen)

Front 45

List 3 hormones that increase bone formation.

Back 45

1. Growth hormone
2. Vitamin D metabolites
3. Gonadal steroids

Front 46

Which hormone stimulates osteoclasts AND inhibits osteeoblasts?

Back 46

Glucocorticoids
(increases bone resorption and decreases bone formation)

Front 47

What is a biochemical marker for osteoblast activity?

Back 47

Bone-specific alkaline phosphatase

Front 48

What is a biochemical marker for osteoclast activity?

Back 48

Hydroxyproline metabolites in blood or urine

Front 49

What is the purpose of using tetracycline and demeclocycline labels to check rates of mineralization in bone tissue?

Back 49

To find out how metabolically active the bone tissue is.
*More metabolically active bone will be more responsive to drug therapies

Front 50

When interpreting BMD measurement reports, which score describes bone mass compared with the mean peak bone mass of healthy, young adult women in terms of standard deviation?

Back 50

T-score

*Can help confirm the diagnosis of low bone mass or osteoporosis

Front 51

What does a T-score of -1 mean?

Back 51

One standard deviation below the young adult normal.

*For every 1 SD below, the risk of fracture DOUBLES

Front 52

When interpreting BMD measurement reports, which score is most clinically relevant?

Back 52

T-score
(bone mass compared to mean peak of young adult women)

Front 53

When interpreting BMD measurement reports, which score describes a patient's bone mass compared with the age-matched and sex-matched mean in terms of standard deviation?

Back 53

Z-score

Front 54

Should Z-scores be used in the diagnosis of osteoporosis?

Back 54

NO.
A patient may have values that compare favorably with age-matched controls, but still be at increased risk for fracture

*This score is just useful to determine how aggressive you need to be with therapy.

Front 55

What is the T-score of an individual with "normal" bone mass?

Back 55

T is above or equal to -1

Front 56

What is the T-score of an individual with osteopenia (low bone mass)?

Back 56

T is between -1 and -2.5

Front 57

What is the T-score of an individual with osteoporosis?

Back 57

T is -2.5 or lower

Front 58

Term for incomplete mineralization of osteoid in adult bone tissue.

Back 58

Osteomalacia

(softening of bones)

Front 59

What is osteomalacia known as in kids?

Back 59

Rickets
(growth plates affected)

Front 60

What are the 2 types of osteomalacia and which is most common?

Back 60

1. Vitamin D deficiency (Most common)
2. Vitamin D resistant

Front 61

How might renal failure or liver disease result in osteomalacia?

Back 61

Decreased synthesis of Vitamin D

Front 62

What happens to growth plates in children with Rickets?

As a result, what sort of characteristic shape do the leg bones take on?

Back 62

Growth plate becomes thick, wide and irregular
(the newly formed bone within the growth plate fails to mineralize)

*Bowing of legs occurs

Front 63

What sort of Ca/PO4 levels are observed in osteomalacia? (increased or decreased)

Back 63

Decreased levels

Front 64

List 4 possible causes of Osteomalacia.

Back 64

1. Decreased intake of Vitamin D
2. Decreased synthesis of Vitamin D (by liver or kidney)
3. Increased excretion (kidney)
4. Congenital

Front 65

Is alkaline phosphatase activity increased or decreased in osteomalacia?

Back 65

Increased

Front 66

Based on the following results, what would be your diagnosis?
1. Ca/PO4 decreased
2. Alkaline phosphatase increased
3. Urinary Ca excretion decreased
4. Ca x PO4 product is less than 2.4

Back 66

Osteomalacia
(a bone biopsy would confirm the diagnosis)

Front 67

Pseudofractures are classic pathognomonic for what bone condition?

Back 67

Osteomalacia

Front 68

Parathyroid gland disease which secretes the hormone without proper regulation

Back 68

Primary hyperparathyroidism

Front 69

Disease outside the parathyroid gland that leads to excessive secretion of PTH (i.e kidney disease, inadequate nutrition).

Back 69

Secondary hyperparathyroidism

Front 70

Secondary hyperparathyroidism which becomes autonomous.

Back 70

Tertiary hyperparathyroidism
(almost always due to renal failure)

Front 71

In cases of excess PTH secretion, what abnormality is typically present?

Back 71

Typically result of parathyroid adenoma or hyperplasia
(primary hyperparathyroidism)

Front 72

Is hyperparathyroidism usually related to high or low Ca2+ levels?

Back 72

HIGH
(PTH stimulates osteoclasts/bone resorption and therefore increases Ca2+ plasma levels)

Front 73

List some signs and symptoms seen in hyperparathyroidism.

Back 73

1. Mental confusion
2. Depression
3. Headaches
4. Polyuria
5. Polydispia
6. Corneal calcifications (due to excess Ca2+ deposition)
7. Renal stones
8. Pancreatitis
9. Bone loss

Front 74

Of the following terms, which would you expect to see in lab results from a patient with hyperparathyroidism?
1. Hypercalcemia or hypocalcemia
2. Hyperphosphatemia or hypophosphatemia
3. Hypercalciuria or hypocalciuria

Back 74

1. Hypercalcemia (elevated Ca2+ in blood due to high levels PTH which stimulates bone resporption)
2. Hypophosphatemia (low phosphate levels in blood)
3. Hypercalciuria (increased Ca2+ in urine)

Front 75

What are the treatment options for hyperparathyroidism?

Back 75

Severe cases = surgical resection of overactive parathyroid tissue

Mild cases = promote diuresis to facilitate urinary calcium loss

Front 76

What is the most common cause of primary hyperparathyroidism?

Back 76

Parathyroid adenoma
(more common than hyperplasia)

Front 77

Hypoparathyroidism is most often seen in what kind of patients?

Back 77

Those who have undergone neck surgery

Front 78

In hypoparathyroidism, would you expect to see hypercalcemia or hypocalcemia?

Back 78

Hypocalcemia

Front 79

List some symptoms of hypoparathyroidism.

Back 79

1. Convulsions
2. Obtundation--(comatose)
3. Tetany
4. Laryngiospasm
5. Cataracts

Front 80

In a patient with hypoparathyroidism, what kind of PTH and Vitamin D levels would you expect to find?

Back 80

1. Low PTH levels
2. Low Vitamin D levels
(you will also find low plasma Ca2+ levels-- hypocalcemia)

Front 81

List 2 treatments for hypoparathyroidism.

Back 81

1. Calcitriol
2. Calcium

Front 82

Name of the condition associated with a combination of osteomalacia and a secondary PTH increase caused by renal disease.

Back 82

renal osteodystrophy

*Inactive kidney causes Vitamin D deficiency

Front 83

What is osteitis fibrosis cystica?

Back 83

Brown tumors from fibrous bone replacement seen in primary and tertiary hyperparathryoidism (renal osteodystrophy)

Front 84

What disease results in bone enlargement and thickening due to increased osteoclast/osteoblast activity?

Back 84

Paget's Disease

Front 85

Name 2 treatments for Paget's disease.

Back 85

1. Bisphosphonates
2. Calcitonin

*Treatment aimed to inhibit osteoclast activity

Front 86

Paget's disease puts patient at risk for...?

Back 86

Osteosarcoma

Front 87

A technetium 99m-bisphosphonate bone scan revealing multiple dark areas would be indicative of what disease?

Back 87

Paget's disease

(dark areas = sites of increased bone metabolism)

Front 88

What type of bone tissue do you expect to find in a bone biopsy of a patient w/ Paget's disease?

Back 88

Woven bone
(mosaic pattern of bone matrix)

Front 89

In what circumstances should you use drug treatment for Paget's disease?

Back 89

1. If patient is experiencing pain
2. If disease is in vertebral body or base of skull-- want to avoid nerve damage

Front 90

What type of individuals are most at risk for developing osteoporosis?

Back 90

Post-menopausal caucasian women

Front 91

Name 3 groups of drugs that can result in secondary osteoporosis.

Back 91

1. Glucocorticoids
2. Anticonvulsants
3. Immune suppressive drugs

*All interfere with vitamin D metabolism

Front 92

What T-score necessitates therapy for osteoporosis?

Back 92

-2.0 or less = definitely begin treatment
(therapy should still be considered, though, with a score of -1.5 or less)

Front 93

Name 5 pharmacologic treatments for post-menopausal osteoporosis.

Back 93

1. Estrogen replacement therapy (ERT)
2. Selective estrogen receptor modulators (SERMs): raloxifene
3. Calcitonin
4. Bisphosphonates
5. Denosumab (RANKL inactivating Ab)

Front 94

Explain the difference in the effects of low doses versus high doses of PTH.

Back 94

High doses PTH = stimulates osteoclast activity

Low doses PTH = stimulates osteoblast activity

*So low doses of PTH can actually be used to increase bone formation, maintain bone mass, and reduce fracture risk

Front 95

List 2 calcium supplements that can be taken to reduce risk of osteoporosis?

Back 95

1. Calcium carbonate (cheaper but less bioavailable)
2. Calcium citrate phosphate (better absorbed, but more expensive)

Front 96

To avoid osteoporosis, how much calcium and vitamin D should be taken daily?

Back 96

Calcium intake of 1000-1500 mg/day
Vitamin D -- 400 I.U./day

*Also avoid smoking/ excess alcohol