Metabolic Disorders of Bone Flashcards
What are some metabolic disorders of bone?
- Osteoporosis
- Vitamin D deficiency
- Vitamin D toxicity
- Vitamin C deficiency
When does the amount of bone in the body peak in life?
Around 25-35 years
What are some factors that influence higher bone mass/density peak?
- Males have higher peak in mass
- Ethnicity/genetics
- Activity
- Nutrition
- Hormones
After 35(ish), there is a decline of bone density for both sexes
Who will decline first?
Females lose density about 10 years earlier than males
What is the organic: inorganic ratio of bone in children?
How does this affect the structure and function of bones?
1:1
Lots of collagen, flexible/springy bones
What is the organic: inorganic ratio of bone in adults?
How does this affect the structure and function of bones?
1:4
Bones are hard, but have some give
What is the organic: inorganic ratio of bone in elderly (65+)?
How does this affect the structure and function of bones?
1:7
Bones lack collagen, no spring, more fragile
How does age affect our ability to make collagen?
Less able to make collagen as we age
What are some examples of decreased synthesis etiologies that decrease bone density?
- Decreased osteoblastic function: organic to inorganic ratio is maintained
- Decreased ability to make collagen with age, so less organic material to mineralize
The lack of ___ or ___ will decrease mineralization of osteoid
Vitamin D or calcium
What conditions come of a lack of Vitamin D or calcium?
Osteomalacia, hyperparathyroidism
What shift in activity of bone cells will cause increased destruction of bone density?
Balance of osteoclastic to osteoblastic activity
What is osteoporosis?
Decreased bone mass with normal quality (normal organic:inorganic ratio) where bones weaken
What is osteomalacia?
Vitamin D deficiency
Decreased bone mass with increased organic:inorganic ratio; decreased mineralization of osteoid; bones soften and weaken
Primary osteoporosis involves a change in what balance?
Osteoblast:osteoclast balance
What is type 1 primary osteoporosis?
Post-menopausal osteoporosis
How can post-menopause lead to type 1 primary osteoporosis?
Estrogen drop increases osteoclast activity
What is type 2 primary osteoporosis?
Senile osteoporosis: age related loss of osteoblast function
Besides decreased estrogen post-menopause and age related factors, what are some contributors to primary osteoporosis?
- Vitamin D
- Calcium intake and absorption (calbindin)
- Exercise
- Smoking
- Hypogonadism
In short, what is the function of estrogen in bone?
Major hormonal regulator of bone remodeling in both sexes
How does estrogen affect osteoclasts?
Blocks RANKL, suppressing osteoclastic activity
How does estrogen affect osteoblasts?
Inhibits osteoblast apoptosis and increases osteoblast lifespan
How does estrogen affect cytokines?
Decreases the production of bone-resorbing cytokines: IL-1, IL-6, TNF-a, and prostaglandins
How does hormone replacement therapy (HRT) affect bone for postmenopausal women with primary osteoporosis?
- Increased circulating calcitriol (tries to increase calcium)
- Increased calcium absorption
- Slows loss of bone, does not contribute to rebuilding
What is the effect of biphosphonates for primary osteoporosis?
- Decrease osteoclastic resorption, does not increase deposition
- Reduces risk of fracture, especially vertebral
What hormone plays a similar role to estrogen in bone?
Androgen
Besides estrogen, what are some important hormones for bone?
- Androgen
- Parathyroid hormone (PTH)
- Calcitonin
- Thyroid hormone
- Growth hormone
- Glucocorticoids
Where does calcitonin come from in the body?
Thyroid gland
Where does growth hormone come from in the body?
Pituitary gland
Where do glucocorticoids come from in the body?
Adrenal glands
How does primary osteoporosis affect ESR (erythrocyte sedimentation rate)?
Normal ESR
no inflammation
What does primary osteoporosis mean for calcium levels?
Normal serum calcium levels
less calcium in bone, however
What does primary osteoporosis mean for phosphate levels?
Normal serum phsophate levels
slow aging process
How does primary osteoporosis affect alkaline phosphatase?
Normal alkaline phosphatase levels
slow aging process
What are some exogenous causes of secondary osteoporosis?
- Disuse
- Endocrine and genetic abnormalities or malabsorption issues
- Chronic corticosteroids
- Multiple myeloma
- Complex regional pain syndrome
How can disuse due to casting affect bone?
Secondary osteoporosis with radiographically visible bone loss in 7-10 days, peaks 2-3 months
What are some examples of endocrine and genetic abnormalities or malabsorption issues that lead to secondary osteoporosis?
- Osteomalacia
- Hyperparathyroidism
- Cushing disease
How does chronic corticosteroid use, such as with prednisone, lead to secondary osteoporosis?
Inhibits osteoblastic activity, impairs calcium absorption
How does multiple myeloma lead to secondary osteoporosis?
Osteoblast inhibiting hormone released
What is the most significant clinical implication of osteoporosis?
How prevalent is this?
Increased fracture risk:
50% of women over 50 will have an osteoporotic fracture
20% of men over 50 will have an osteoporotic fracture
Which bones are most at risk for osteoporotic fracture?
- Hip
- Spine (compression fractures)
- Distal radius
What is the frequency of osteoporotic fracture of the hip in elderly patients?
250,000-300,000 in the US per year
With osteoporosis, ___ are dead within a year
25%
With osteoporosis, ___ are in a nursing home within a year
25%
With osteoporosis, ___ have some degree of limitation
Only ___ of elderly with a hip fracture can walk unaided across a room in one year
50% have limitation
only 15% can walk within a year
What are the fiscal implications of osteoporosis?
It is costly, more fractures will be more expensive
What is the purpose of radiographs for osteoporosis?
Primarily, visualizing fractures, but also finding osteopenia
Poor for assessing bone density
What imaging is used to quantify bone density?
Bone densitometry (dual energy X-ray absorptiometry (DEXA))
What are the two readings of DEXA (bone densitometry)?
- T-score
- Z-score
What does the T-score of DEXA indicate?
- Bone density compared with 18-25 year old of same race and sex
- Gives risk of fracture
What does the Z-score of DEXA indicate?
- Bone density compared with other people of same age, race, and sex
- Useful for premenopausal evaluation of density
- Useful for female athlete triad
What is the female athlete triad?
- Disordered eating (low energy)
- Amenorrhea (menstrual dysfunction/absence)
- Osteoporosis
What T-score readings of DEXA are normal, osteopenia, and osteoporosis?
+1 to -1 considered normal
-1 to -2.5 osteopenia
-2.5 or less osteoporosis
How do DEXA T-score values influence fracture risk?
-2 = 4x more likely
-3 = 8x more likely
-4 = 16x more likely
(exponents of 2)
What is Dowager’s Hump?
Osteoporotic hyperkyphosis leading to multiple compression fractures
Where does a Colles fracture occur?
Distal radius
What are four treatments for osteoporosis?
- Fall prevention
- Exercise
- Diet
- Drug/supplement therapy (HRT, calcitonin, bisphosphonates)
Can a chiropractor treat an osteoporotic patient?
Yes, can treat osteoporotic patients, but cannot directly treat osteoporosis
What are two categories of vitamin D disorders?
- Hypovitaminosis D
- Hypervitaminosis D
What are two results of hypovitaminosis D?
- Osteomalacia
- Rickets
What is osteomalacia?
What age group does it usually affect?
Decreased calcium absorption in the gut, inadequate mineralization of osteoid
Found in adults
What is rickets?
What age group does it usually affect?
Children/individuals with open growth plates
Inadequate cartilage and bone formation at the growth plate
hypovitaminosis D
What are some ways to acquire vitamin D deficiency?
- Inadequate sun
- Inadequate dietary intake
- Decreased absorption
What are some ways to inherit vitamin D deficiency?
- Vitamin D-dependent rickets type I
- Vitamin D-dependent rickets type II
How does vitamin D-dependent rickets type I cause deficiency?
Defective hydroxylation of metabolites in liver or kidney
How does vitamin D-dependent rickets type II cause deficiency?
End organ insensitivity to vitamin D
What are some etiologies of vitamin D deficiency that aren’t acquired or inherited?
- Tumor related osteomalacia (multiple endocrine neoplasia)
- Chronic renal disease
- Cirrhosis
- Anticonvulsant medications
How does decreased calbindin production affect absorption in the GI?
Decreased absorption of calcium and phosphate
If plasma levels of calcium decrease, what secretion increases in response?
PTH secretion increases
Decreased calcitriol (active vitamin D) means less ___ retrieved from bone
calcium
In the kidney, ___ is excreted in urine and ___ is mostly retained
phosphate is excreted in urine and calcium is mostly retained
Long term, vitamin D deficiency will result in ___ in phosphate and ___ in calcium levels
dramatic decrease in phosphate and modest decrease in calcium levels
What is the net effect of vitamin D deficiency on bone?
Why?
Decrease in bone mineralization
Excessive osteoid accumulates and is not well mineralized due to low levels of calcium and phosphate
What is the diagnostic profile shared between acquired vitamin D deficiency and vitamin D-dependent rickets type I?
- Slightly reduced plasma calcium
- Greatly reduced plasma phosphate
- Elevated levels of PTH
- Increased alkaline phosphatase
What is the treatment for the diagnostic profile of acquired or vitamin D-dependent rickets type I?
Megadosing vitamin D (Rx grade) or provide end stage metabolites
With osteomalacia, there is a relative ___ in organic and ___ in inorganic bone constituents
increase in organic and decrease in inorganic
Which vitamin D deficiency has marked, generalized osteopenia due to defective mineralization of bone in adults?
Osteomalacia
The following describes the clinical manifestations of what disease?
- No symptoms early
- Eventually, dull, aching bone pain
- Lower back, pelvis, hips, legs, ribs pain
- Pain may be worse at night or weight bearing
- Muscle weakness
- Patient adopts a waddling gait due to decreased muscle tone and leg weakness
Osteomalacia (a vitamin D deficiency)
What are some radiographic findings of osteomalacia?
- Generalized osteopenia
- Pseudofractures
- Corticomedullary indistinction
- Reversible, no/minimal deformity (may be irreversible)
What are four causes of pseudofractures?
PROF:
- Pagets
- Rickets
- Osteomalacia
- Fibrous dysplasia
What are the pseudofractures found in osteomalacia?
Unmineralized osteoid seam
With rickets, there is lack of control over ___
endplate growth
With rickets, decreased ___ and ___ contribute to lack of control over endplate growth
decreased cartilage formation and osteoid mineralization
Which disease presents with the following radiographic findings?
- Generalized osteopenia
- Widened growth plates
- Bowing of weight bearing bones, ribs
- Pseudofractures
- Discontinuities due to buckling, tearing of bone
Rickets (a vitamin D deficiency) is
What are the functional effects of rickets on lower extremities?
- Hypotonia
- Waddling gait
Hypervitaminosis D is also known as ___
vitamin D toxicity
Excessive sensitivity to vitamin D can lead to what disease?
Sarcoidosis (collections of granulomas)
What are the following clinical manifestations of?
- Hypercalcemia
- Increased urinary calcium excretion
- Nephrolithiasis
- Nephrocalcinosis
- Metastatic calcifications
Hypervitaminosis D
How does calcium affect the nervous system with hypercalcemia?
Calcium is a nervous system depressant
Given that calcium is a nervous system depressant, what are some symptoms of hypercalcemia?
- Dulled mentation
- Headaches
- Muscle weakness
- Hyporeflexia
- Lethargy
- Anorexia
- Constipation
- Generalized musculoskeletal pain
Hypervitaminosis D will have lab results of increased ___ and decreased ___
increased serum and urinary calcium levels and decreased PTH
What is a treatment for hypervitaminosis D?
Stop vitamin D and calcium supplementation and wait
Hypovitaminosis C is also known as ___
scurvy
Vitamin C is an important cofactor in the hydroxylation of ___ and ___
prolyl and lysyl residues in collagen
What is the stabilizing helical structure of collagen?
Hydroxyproline and hydroxylysine
What are the cross-linking tropocollagen fibers that create optimal molecular structure for collagen?
Hydroxyproline and hydroxylysine
Collagen lacks ___ strength
tensile strength
Historically, who was exceptionally vulnerable to scurvy?
Sailors
What modern populations would be most at risk for scurvy?
People prone to malnutrition; babies, children, and older people
The following are clinical manifestations of what disease?
- Vessel fragility and increased hemorrhage
- Subperiosteal bleeding
- Petechial hemorrhages, ecchymoses and purpura after mild trauma
- Swollen bleeding gums; alveolar resorption and tooth loss
Scurvy (hypovitaminosis C)
The following are clinical manifestations of what metabolic disorder of bone?
- Impaired bone growth
- Joint and muscle pain
- Delayed or impaired wound healing
Scurvy (hypovitaminosis C)
The following are radiographic findings in what disease?
- Generalized osteopenia
- White line of Frankel
- Wimberger’s ring
Scurvy (hypovitaminosis C)
The following are radiographic findings in what disease?
- Pelkin’s spurs
- Trummerfeld zone
- Subperiosteal hemorrhage
Scurvy (hypovitaminosis C)
What is the effect of estrogen on osteoclast activity?
Inhibits osteoclast activity during bone remodeling
blocks RANKL
Hypervitaminosis D is primarily a result of ___
over supplementation