Acquired Metabolic Diseases of Bone Flashcards
Bone: Actively Metabolizing Tissue
- Need intact ____ supply
- Responds (poorly) to interruption of blood supply
- – Necrosis
- – New bone deposition
blood
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
intact
necrosis
bone
scar
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
1st
2nd
continuous
peak
maintain
damaged
calcium
mechanical
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
utero
bone remodeling unit (BRU)
osteocytes
lining cells
Bone remodeling
Bone homeostasis is the balance between bone ____ and bone ____
Entire ____ is renewed throughout our lifetime
formation
resorption
skeleton
Metabolic Bone Diseases
• Disorders of Bone:
– ____
– Proteins
– ____ Constituents
• Dysregulation of Major Functions:
– ____ (Support, Muscular attachment)
– ____ (Vital organs and bone marrow)
– ____ (Ion reserve, serum homeostasis)
minerals
cellular
mechanical
protective
metabolic
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:
- ____
osteoporosis
osteodystrophy
ectopic
osteogenesis imperfecta
fibrous dysplasia
antiresorptive induced-jaw osteonecrosis
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.
34
age
1.5
50
1/3
Aging
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 ____
little
excessive
decreased
increase
microarchitecture
Symptoms of Osteoporosis
- Asymptomatic bone loss (“____”)
- Bone fracture – ____ impact trauma (strain, bump and fall)
- Collapsed ____
- Severe back pain
- Loss of ____
- Spinal deformities
(e. g. ____)
silent disease low vertebrae height kypohsis
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 ____
progressive systemic quanity quality fragility preventable treatable
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
trabeculae
decreased
disjointed
increase
decrease
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.
estrogen
menopause
females
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.
osteoblast
osteoblast
hormones
osteoclast
bone formation
higher
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)
bone
disadvantage
consolidating
more
Model: Pathophysiology of Osteoporosis
____/ ____changes/ medication can decrease the bone ____ and bone ____ eventually leading to osteoporosis and eventually leading to low impact trauma and ____
post menopausal hormonal mass quality fracture
• ____
– 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.
bone mineral density (BMD)
1
doubling
-2.5
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.
> = -1
-2.5 and < -1
=< -2.5
MicroCT Assessment of Trabecular Bone Microstructure
____ bone biopsy by high resolution quantitative CT
non-invasive
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
increase
osteoporosis
age
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.
17
19
osteoporosis
etiological
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 ____
tubular
dialysis
homeostasis
balance
vitamin D
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 ____
decrease decrease increase turnover homeostasis
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 ____.
roots
serum chemistry
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
mineralization vitamin D decrease aluminum children pre-closure adults post-closure
Osteomalacia is restored post ____ therapy
In adults with osteomalacia, you will not see bowing but moreso ____
vitamin D
fractures
Oncogenic Osteomalacia
Acquired \_\_\_\_ syndrome – Disorder of bone \_\_\_\_ – \_\_\_\_ – Vitamin D-\_\_\_\_ osteomalacia – Induced by a bone/soft tissue \_\_\_\_ – Metabolic abnormality completely reversed with \_\_\_\_
paraneoplastic mineral osteopenia resistant tumor tumor removal
Oncogenic Osteomalacia
The tumor is ultimately impairing ____ metabolism
• Pathophysiology: (____ Effect)
– Renal ____ wasting
– Impaired synthesis of ____
This all leads to:
Poor bone ____, pain, ____
vitamin D
dual
phosphate
1,25(OH)2D3
mineralization
fractures
Oncogenic Osteomalacia
Patients may lose their ____
metacarpals
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.
phosphatonin (FGF23) kidney low u unmineralized
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
lytic
sclerotic
affinity
metastasize
