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Musculoskeletal and Skin Pathology > Osteoporosis > Flashcards

Osteoporosis Flashcards

1
Q

Osteoblasts can modify osteoclast differentiation in two ways… what are they?

A

RANK ligand can bind RANK receptor on osteoclasts, encouraging their survival and differentiation.

Osteoprotegenin is an analog for RANK that blocks the RANK receptor, promoting osteoclast apoptosis and preventing their differentiation (present on osteocytes and osteoblasts)

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2
Q

Calcium requirements for 4-8 and 19-70 year olds?

A

1000 mg/day

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3
Q

Calcium requirements for post-menopausal women?

A

1200 mg/day

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4
Q

Calcium requirements for 9-18 and pregnant or lactating women?

A

1300 mg/day

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5
Q

What is the maximum amount of absorbable calcium in one sitting?

A

500 mg

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6
Q

What’s the maximum tolerated daily calcium intake?

A

2000-2500 mg

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7
Q

Four major factors that impact calcium homeostasis?

A
  1. Vitamin D
  2. Parathyroid Hormone
  3. Calcitonin
  4. Estrogen and Androgen
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8
Q

What is animal Vitamin D?

A

Cholecalciferol (D3)

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9
Q

What is plant vitamin D, and what’s the difference?

A

Ergocalciferol (D2)…. contains a double bond and extra methyl group

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10
Q

Natural Vitamin D sources are..

A

Fish and eggs

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11
Q

Vitamin D is synthesized de novo how?

A

7-dehydrocholesterol is converted to pre-Vitamin D3 from UV light activation, which undergoes further modifcation to Vitamin D3.

This is then hydroxylated by Vitamin D 25-Hydroxylase in the liver. A p450 enzyme. This is then sent to the kidney and hydroxylated by Kidney 25-OH-Vitamin D 1-alpha-Hydroxylase… This is a step that is regulated.

This generates calcitrol, the activate form of vitamin D3 (1,25-OH-VitD)

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12
Q

Regulation of 25-OH-VitD 1-alpha-Hydroxylase

A

PTH stimulates its activity. Drop in calcium stimulates its activity. Drop in phosphate stimulates its activity. Estrogen and prolactin stimulate its activity.

BUT… declining PTH, rise in Ca, Rise in Phosphate all inhibit its activity

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13
Q

What happens in adults with vitamin D deficiency?

A

Severe: Osteomalcia (softening of the bone)

Mild: Osteoporosis (loss in bone density/mass)

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14
Q

How is PTH regulated

A

IONIZED calcium binds calcium-sensing receptors in parathyroid chief cells… this blocks PTH release.

When not enough calcium is present, PTH is released, which encourages bone resorption, kidney activation of 25(OH)VitD 1alpha hydroxylase… which increases calcium directly, but also encourages more calcium absorption from the gut via Vit D increase. Also, Kidney itself will retain more calcium in the presence of PTH

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15
Q

Calcitonin regulation

A

High calcium stimulates calcitonin release… this blocks reabsorption of calcium by the kidney and osteoclast-mediated bone resorption

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16
Q

Estrogens on calcium

A

Estrogen acts on osteocytes, osteoblasts and osteoclasts.

Estrogen prevents osteoblasts and osteocytes from apoptosing, but encourages apoptosis of osteoclasts

Also reduces inflammation, T cell activity, and oxidative stress

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17
Q

What is an osteocyte?

A

Only found in mature bone…. Basically do everything osteoblasts. A differentiated product of an osteoblast

18
Q

Phosphate goes where?

A

Phosphate will follow calcium out and in, since it is the ionic partner

19
Q

What is osteoporosis?

A

Los of bone tissue by excessive degradation of bone by osteoclasts relative to deposition of bone

Reduce strength, higher fracture risk

20
Q

Diagnosing osteoporosis with what test?

A

Dual Energy X-ray Absorptiometry (DEXA)

21
Q

What’s a T score?

A

For young, healthy patients. Matched for race and gender

22
Q

What’s a Z score?

A

An age-matched control for same race and gender for post-menopausal women

23
Q

WHO criteria for osteoperosis

A

2.5 or more SD below peak bone mass density, based on a T score -2.5

24
Q

WHO criteria for ostepenia

A

BMD -1 to -2.5 below peak

25
Q

Normal bone density based on WHO

A

Within one standard deviation

26
Q

Who does WHO criteria for osteoporosis apply to?

A

White, postmenopausal women. NOT men or younger people or minorities

27
Q

Do irregular weight bearing activities help or harm bone strength?

A

They help it. Weight bearing activities are recommended to encourage bone turnover in postmenopausal women

28
Q

Female athlete triad

A
  1. Starts with inadequate nutrition to meet the demands of the female body.
  2. This leads to a calorie deficit.
  3. This calorie deficit can suppress GnRH and ultimately LH such that ovaries and estrogen are suppressed and periods are lost.
  4. Without estrogen being produced by the understimulated ovaries, bone resorption is favored as osteoclasts are no longer in check.
29
Q

Z scores for young women

A

Z scores -2.0 without risk factors for children or premenopausal women compared to the age appropriate bone density. This is osteoporosis.

A Z score of -1 to -1.9 is low BMD

If you see a young girl with frequent fracture, or patients with improper (inadequate) diet, or people on steroids are all people to look for a Z score in.

30
Q

What is the general recommendations of calcium and vitamin D for women over 50

A

800-1000 IU Vitamin D

1200 mg calcium

31
Q

At what age is BMD testing routine?

A

Women over 65 and men over 70. If an adult has already suffered a fracture after 50, then recommendations are to continue surveillance of bone density

32
Q

CAuses of secondary osteoporosis should also be accounted for by what types of labs…

A

TSH levels, 25(OH)D levels, PTH levels, chemistry levels of calcium, renal function, liver function tests, etc.

33
Q

In >50, when does treatment begin (both sexes)?

A

T scores -2.5 or worse femoral neck, hip, or lumbar spine by DXA

If T score is between -1 or -2.5 at these locations, you may initiate treatment if they have 10 year hip fracture probability >3% or a 10 year major osteoporosis related fracture probability >20%

34
Q

What is FRAX and when should it be used?

A

Fracture Risk Assessment Tool a digital risk factor application. Used when pharmacological treatment is unclear, or for people with moderate bone density loss (t -1. to -2.5) who aren’t currently treated and with no history of osteoporosis related events or fracture

35
Q

What is the long term goals of pharmacologic treatment for osteoporosis

A

No pharmacologic therapy should be considered indefinite in duration!!! 3-5 year treatment period, and then reassessment should be performed.

36
Q

Bisphosphonates

A

Pyrophosphate analogs that directly incorporate into the bone matrix.

Released as bone is resorbed by osteoclasts, exposing them to high concentrations.

First generation promoted osteoclast apoptosis

Second generation (most current meds) inhibit osteoclast attachment and anchoring by inhibiting their farnesyl synthase to make cholesterol… they cannot adhere to the ruffled border.

Accumulate in the bone and remain their for months or years

Renally excreted unchanged

Side Effects: GI disturbance, esophagitis, gastritis, osteonecrosis of the jaw if given IV.

For oral types, take first thing in the morning on an empty stomach sitting upright

Some patients can get atypical femur fractures, unknown why

37
Q

Calcitonin (as a drug)

A

Prepared from synthetic salmon or synthetic human calcitonin

Given SubQ or IM… for salmon, can also be intranasal

4-12 minute half life, but the action lasts for several hours

Nausea (injected), rhinitis (nasal)

Treats osteoporosis; patients become refractory after a few days due to downregulation of the receptor

38
Q

Teriparatide

A

A synthetic PTH.

Although PTH triggers bone resorption, SPIKES of PTH triggers osteoblast differentiation and is anabolic to the bone.

Osteoporosis in men and women

Osteosarcoma in rat studies; carries a black box warning

Transient hypercalcemia or nausea

39
Q

Estrogens (as a drug)

A

Limited in use for osteoporosis only to women with other estrogen indications (such as ongoing vasomotor symptoms) who are NOT at an increased event for CV for thromoembolism risk

40
Q

Raloxifene

A

Selective estrodiol receptor modulator (SERM)

Non-steroidal estrogen agonist in bone
Antiestrogen in breast

Stimulates osteoblasts, inhibits osteoclasts

Treats osteoporosis in postmenopausal women

Risk: Thromboembolism, hot flashes

Do not use in pregnant women or women with CV/thromboembolic risks

41
Q

Denosumab

A

Human monoclonal antibody that binds RANKL

Blocks RANK/RANKL interaction on osteoclasts, preventing their formation/differentiation and activation

SubQ for men and postmenopausal women at high risk for fracture

Fatigue, weakness, headache, N/V

42
Q

What happens if you give a patient placebo for osteoporosis?

A

It continues to get worse!

Musculoskeletal and Skin Pathology (10 decks)

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