Acquired Metabolic Diseases of Bone

Question 1

Bone: Actively Metabolizing Tissue

• Need intact ____ supply
• Responds (poorly) to interruption of blood supply
• – Necrosis
• – New bone deposition

Answer 1

blood

Question 2

Bone Healing is Unique

• Active metabolizing tissue-needs ____ blood supply
• Interruption of blood supply
– Continuous→ ____
– Transient→ new ____ deposition

• New bone - from tissue regeneration
• (Unlike tissue repair and ____ formation)
• Cell proliferation
• Collagen synthesis

Answer 2

intact
necrosis
bone
scar

Question 3

Bone Homeostasis

• Bone development
– Endochondral ossification
– Intramembranous ossification
– Modeling (\_\_\_\_ and \_\_\_\_ decades)
– Remodeling-\_\_\_\_ through life

• Modeling and Remodeling
– During growth-establish skeletal ____ bone strength
– In adulthood-____ strength and remove ____ areas

• Role of remodeling
– ____ mobilization (Ca2+-PO43- homeostasis)
– ____ adaptation

Answer 3

1st
2nd
continuous

peak
maintain
damaged

calcium
mechanical

Question 4

Cells Involved in Bone Homeostasis

• Bone remodeling: Continuous throughout life (____ till death)
• ____ = group of cells collaboratively and sequentially involved in bone remodeling
– Osteoclasts-resorb bone
– Osteoblasts-form bone
– ____-maintain bone
– ____-cover bone surface

Answer 4

utero
bone remodeling unit (BRU)
osteocytes
lining cells

Question 5

Bone remodeling

Bone homeostasis is the balance between bone ____ and bone ____

Entire ____ is renewed throughout our lifetime

Answer 5

formation
resorption

skeleton

Question 6

Metabolic Bone Diseases

• Disorders of Bone:
– ____
– Proteins
– ____ Constituents

• Dysregulation of Major Functions:
– ____ (Support, Muscular attachment)
– ____ (Vital organs and bone marrow)
– ____ (Ion reserve, serum homeostasis)

Answer 6

minerals
cellular

mechanical
protective
metabolic

Question 7

Some Examples of Acquired and Genetic Metabolic Bone Diseases

Disorders of Bone Minerals:

• ____
• Osteomalacia
• Renal ____
• Paget’s disease
• ____ calcification

Disorders of Bone Proteins/Enzymes:

• ____
• Hypophosphatasia

Disorders of Bone Cells:

• ____
• Skeletal metastasis

Drug-Induced:
- ____

Answer 7

osteoporosis
osteodystrophy
ectopic

osteogenesis imperfecta

fibrous dysplasia

antiresorptive induced-jaw osteonecrosis

Question 8

Osteoporosis in the USA

• Osteoporosis: affects 10 million individuals
• Osteopenia (low bone mass): ____ million (increased risk)
• Osteoporosis can strike at any ____

Osteoporosis-related fractures
• ____ million annually
• At age >= 50 years: ____% women and 25% men
• Hip fractures: 80,000 men annually (____ die within a year)
• Annual healthcare cost = $14 billion
Major challenge: ____ population
By 2020: 52 million Americans ≥ 65 years.
By 2040: 68 million people worldwide ≥ 65 years.

Answer 8

34
age

1.5
50
1/3

Aging

Question 9

Osteoporosis

• Osteoporosis = “Porous bone”; “Bone with holes”
• Characterized by too ____ bone formation or ____ bone loss or a combination of both.
• Osteoporosis is defined as: ____ bone strength leading to an ____ risk of fractures.
• Loss of bone tissue is associated with deterioration in skeletal ____

Answer 9

little
excessive

decreased
increase

microarchitecture

Question 10

Symptoms of Osteoporosis

• Asymptomatic bone loss (“____”)
• Bone fracture – ____ impact trauma (strain, bump and fall)
• Collapsed ____
• Severe back pain
• Loss of ____
• Spinal deformities
  (e. g. ____)

Answer 10

silent disease
low
vertebrae
height
kypohsis

Question 11

Osteoporosis

____ ____ disease

• Low bone mass (bone ____)

• Micro-architectural deterioration of bone
tissue (bone ____)

• Increased bone ____
• Consequent increase in fracture risks (hip, spine, wrist – from accidental falls).
• ____ and ____

Answer 11

progressive
systemic
quanity
quality
fragility
preventable
treatable

Question 12

Osteoporosis: Loss of Bone Strength

Loss of bone strength

• Fewer bone ____
____ Bone density

• Thin and ____ bone trabeculae
• ____ in fatty infiltration
____ Bone quality.

Increased risks for fractures

Answer 12

trabeculae
decreased

disjointed
increase
decrease

Question 13

Mechanism of Cancellous Bone Loss in Osteoporosis

This balance is controlled by hormones. especially in females, it is controlled by ____ and as the female gets old and ____ kicks in there would be a problem in estrogen levels and causing problem with the bone remodeling. This explains why there is more ____ with osteoporosis problem.

Answer 13

estrogen
menopause
females

Question 14

While balanced, bone cell activity is not always equal

at birth there is a increased ____ activity, increased bone formation the balance is tilted toward the ____. the imbalance is due to the fact that the osteoclast activity can not catch up with the bone formation.

As the ____ starts tipping off the balance start tilting toward the ____. this results in decreased bone formation and increased risked for osteoporosis. from birth to early 20s we have a increased ____. but there is difference in the amount of bone formation that male and female accrue up to their 20s. males have ____ formation of bone.

Answer 14

osteoblast
osteoblast

hormones
osteoclast
bone formation
higher

Question 15

Age-Related Osteoporosis

Effects of age and gender: life-time changes in bone mass

up to early 20: gain of ____ (females are at a ____)

bt early 20’s to 50’s: balance the remodeling - ____ (depositing money in the bank; females put less and it’s much lower)

age 50: females lose ____ bone than males (begin to curve)

Answer 15

bone
disadvantage

consolidating

more

Question 16

Model: Pathophysiology of Osteoporosis

____/ ____changes/ medication can decrease the bone ____ and bone ____ eventually leading to osteoporosis and eventually leading to low impact trauma and ____

Answer 16

post menopausal
hormonal
mass
quality
fracture

Question 17

• ____
– Predictor of osteoporotic fracture risk.
– Measured by Dual-Energy X-ray Absorptiometry (DEXA)

• A decrease of ____ SD in bone mass at the Spine DEXA scan spine, hip or wrist is associated with a
____ of fracture risk.

•Women with a BMD < ____ SDs below the mean for a young adult are classified as osteoporotic.

Answer 17

bone mineral density (BMD)

1
doubling

-2.5

Question 18

BMD scales

Normal = ____
Low bone mass (osteopneia) = ____
Osteoporosis = ____

The T-score compares an individual’s BMD with the mean value for young normal individuals and expresses the difference as a standard deviation score.

Answer 18

> = -1
-2.5 and < -1
=< -2.5

Question 19

MicroCT Assessment of Trabecular Bone Microstructure

____ bone biopsy by high resolution quantitative CT

Answer 19

non-invasive

Question 20

Dental Implications: Osteoporosis and Periodontal Disease Share Common Etiological Factors

Age effects on periodontal health

age and gender also affects periodontitis. the picture below show excess bone loss around the teeth. As the bone is lost around the teeth the attachment is lost with it as well.
attachment is lost with ____ in age

the periodontal bone loss with age which translates to tooth lost with age. ____ and ____ cooperates to act upon the periodontal status

Answer 20

increase
osteoporosis
age

Question 21

Dental Implications: Osteoporosis and Periodontal Disease Share Common Etiological Factors

Age and gender effects on tooth loss

here it show how age/ gender/ osteoporosis all affects the periodontal status

average of ____ have lost their teeth for male and average ____ of female have lost their teeth for females. the trends coincide with ____.

**remember that osteoporosis and periodontal diseases share common ____ factors. These factors would lead to advanced periodontal disease and eventually leading to tooth lost.

Answer 21

17
19
osteoporosis
etiological

Question 22

Renal Osteodystrophy

— Kidney damage
– ____ damage
– ____

Renal Osteodystrophy has to do with calcium ____. The parathyroid releases parathyrodial hormone that acts upon the kidneys and the bone that changes the dynamics of the serum calcium phophate. in the kidney, it makes sure that it does not lose the calcium(tries to preserve the calcium). also the kidney converts the vitamin D to be active and act upon the kidney to increase absorption of the calcium. that way you have a balance of calcium. as you have a high level of calcium in the bone the feedback mechanism would go the pituitary and then parathyroid to reduce the release parathyroid hormones. if there is a damage in the kidney there would be a disruption in the ____. Any kind of tubular damage would prevent the formation of the ____

Answer 22

tubular
dialysis

homeostasis
balance
vitamin D

Question 23

Renal Osteodystrophy

• Renal tubular dysfunction – Renal failure
– Dialysis

• ____ 25-(OH)Vit D conversion to 1,25 (OH)-Vit D
• ____ serum Ca2+
• ____ serum PO43-
• Dysregulated bone ____
• Dysregulated mineral ____

Answer 23

decrease
decrease
increase
turnover
homeostasis

Question 24

Renal Osteodystrophy

the disrupted bone remodeling can lead to little lesion the ____ that are pushed up part is done by disrupted bone reomodeling.

you may not know this until the ____.

Answer 24

roots

serum chemistry

Question 25

Rickets/Osteomalacia

• Abnormalities of ____-cartilage/bone
• ____ deficiency
• Enzyme deficiency ( ____ ALKPse- hypophosphatasia)
• Inhibitors of mineralization e.g. ____
• Rickets (____: before skeletal maturity)
  • ____ of epiphyseal growth plates

Osteomalacia - ____
• ____ of epiphyseal growth plates

Answer 25

mineralization
vitamin D
decrease
aluminum
children
pre-closure
adults
post-closure

Question 26

Osteomalacia is restored post ____ therapy

In adults with osteomalacia, you will not see bowing but moreso ____

Answer 26

vitamin D

fractures

Question 27

Oncogenic Osteomalacia

Acquired \_\_\_\_ syndrome
– Disorder of bone \_\_\_\_
– \_\_\_\_
– Vitamin D-\_\_\_\_ osteomalacia
– Induced by a bone/soft tissue \_\_\_\_
– Metabolic abnormality completely reversed with \_\_\_\_

Answer 27

paraneoplastic
mineral
osteopenia
resistant
tumor
tumor removal

Question 28

Oncogenic Osteomalacia

The tumor is ultimately impairing ____ metabolism

• Pathophysiology: (____ Effect)
– Renal ____ wasting
– Impaired synthesis of ____

This all leads to:

Poor bone ____, pain, ____

Answer 28

vitamin D

dual
phosphate
1,25(OH)2D3

mineralization
fractures

Question 29

Oncogenic Osteomalacia

Patients may lose their ____

Answer 29

metacarpals

Question 30

Pathophysiology-Mechanism

phosphotericmesenchmal mixed connective tissue variant is the tumor cell that should be identified. this particular cell would secret factors called ____. this factor damages the ____. This would affect the vitamin D metabolism and this would eventually result in ____ vitamin D.

this would cause defective mineralization. as you can see the histology, the darker black area indicated the mineralized are and the light blue area indicated the unmineralized area. so patients with osteomalacia you would able to see more of a ____ bone. this unmineralized bone eventually result in weak and soft.

Answer 30

phosphatonin (FGF23)
kidney
low
u
unmineralized

Question 31

Skeletal Cancer Metastasis

• Abnormal bone metabolism
  Bone breakdown
  • Radiolucent
  • ____

Bone deposition
• Radiopaque
• ____

Examples: Breast cancer; prostate cancer

breast/lung cancer has ____ to the bone; can ____ to the bone

Answer 31

lytic
sclerotic
affinity
metastasize