7. Osteoporosis
What is the MOA for cortical bone loss in osteoporosis?
"trabecularization" of the inner cortex the small pores within the bony cortex, which normally represent Haversian canals and osteocyte lacunae, enlarge progressively until the cortex becomes cancellous-like, and assumes a trabecular structure
By what two mechanisms does estrogen prevent bone loss?
(a) pro-apoptotic effects on osteoclasts (b) anti-apoptotic effects on mature osteoblasts and osteocytes
After attainment of PBM physiologic bone loss occurs inevitably gradually over time. After 30 years of age, ______% of bone is lost every year independent of gender.
1%
How is trabecular structure changed in osteoporosis?
1. Thinning of individual trabeculae occurs first 2. Trabecular plates are transformed into rods by multiple perforations 3. Loss of the entire trabecular elements leads to loss of trabecular connectivity between vertical and horizontal trabeculae (an important feature of skeletal integrity)
What are the 4 main clinical presentations during symptomatic osteoporosis?
1. back pain 2. chronic dull back ache 3. loss of height or kyphosis 4. unsure gait
What are the three grades of vertebral fractures?
1. biconcave fractures 2. anterior wedging 3. compressive (crush) fracture
What are the 9 risk factors for osteoporosis?
1. genetics 2. race 3. sex 4. age 5. body size 6. lifestyle 7. calcium & vitamin D 8. cigarette smoking 9. medications
What are the 4 steps in the pathology of osteoporosis?
1. loss of trabecular connectivity 2. progression of osteoporosis in the cancellous bone 3. changes in trabecular structure 4. progression of osteoporosis in the compact bone
What are 3 radiographic features that suggest the presence of osteoporosis on lateral radiographs of the spine?
1. verticalization 2. picture frame 3. thinning of cortical bone
The loading capacity of a vertebral body approximates __________ kg in young adults but is markedly reduced in older people to about ________ kg.
1000 kg 100 kg
Type 1 osteoporosis affects women within ______ to _______ years of menopause.
15 to 20 years with a peak incidence in the 60s and early 70s
When we are born, our skeleton only contains _______ g of calcium and at age 30, our skeleton contains __________ g of calcium
25 grams 1000 grams
What percentage of cancellous bone is remodeled annually?
25% makes it a target for osteoporosis/exaggerated bone remodeling
X-rays are not appropriate for early diagnosis. Skeletal radiographs indicate bone loss only when the density has been reduced by ______%.
30-40%
Distal radius fractures represent the _______ most common type of osteoporotic fractures. How does this occur and what does it typically lead to?
3rd most common type following a fall on the outstretched hand (FOOSH) --> transverse fracture of the distal 2-3 cm of radius associated w/ dorsal displacement of wrist and hand ("colles fractures")
Postmenopausal women lose _____% of bone annually.
4%
From age 40 to 70 years, women lose _____% while men lose only _____% of their bone mass
40% 12%
What is the female to male ratio for risk of osteoporosis, gender as a risk factor?
4:1, women more at risk
What ages does postmenopausal osteoporosis occur?
50-70
After the age of 50 years, overall fracture incidence climbs steeply. Over ______% of all fractures in people older than 50 years are caused by osteoporosis
80%
_____% of vertebral crush fractures cause no pain and are discovered incidentally after a routine radiograph reveals the deformities.
80% (the majority)
What is the diagnostic criteria for preclinical osteoporosis?
BMD value of at least 2.5 SD below the young adult reference mean (T score -2.5 or more) **Fractures have not yet occurred but could do so at any time but effective antiresorbtive therapy should be administered immediately
What is the diagnostic criteria for established (severe, manifest) osteoporosis?
BMD value of greater than 2.5 SD below the young adult reference mean (T score -2.5 or more) WITH the presence of one or more fragility fractures
What race is at highest risk for osteoporosis?
Caucasians tend to have the lower bone mass and more common hip fractures. African Americans tend to have the highest bone density and lose bone less rapidly as they age
How is osteoporosis diagnosed?
DEXA scan that will measure bone mineral density (BMD)
What is verticalization as seen on x-ray in osteoporosis?
Loss of trabecular bone occurs in a predictable pattern The non-weight bearing (horizontal) trabeculae are resorbed first, which leads to a relative prominence of the weight-bearing (vertical) trabeculae
What locations in the body are high in trabecular bone?
Lumbar spine (75%) Heels (70%) Proximal Femur (50-75%) Distal Radius (25%) Middle Radius (<5%)
What is the difference between secondary and primary osteoporosis?
Patients are said to have primary osteoporosis when a secondary cause of osteoporosis cannot be identified Secondary osteoporosis occurs when an underlying disease, deficiency, or drug causes osteoporosis
How is age a risk factor for osteoporosis?
Risk increases with age. After age 30, bone resorption slowly begins to exceed new bone formation. This leads to bone loss
Bone mineral density is calculated in g/cm3 (i.e., weight of mineral for volume of bone), but it is reported as T score or Z score, not in absolute units. What is the T score for osteoporosis?
T-score is the number of standard deviations above or below the mean of peak adult bone mass (i.e., the BMD of a healthy 30-year-old adult of the same sex and ethnicity as the patient). A score of 0 means that the patient's BMD is equal to the norm for a healthy young adult.
What is the pathogenesis of JIO?
The exact pathogenesis of this disease is not known, but very low bone formation rate and decreased cancellous bone volume have been described Fewer remodeling cycles are initiated & Fewer osteoblast and osteoclast teams are recruited, and the amount of bone formed in each remodeling cycle is decreased, leading to the thinning of mature trabeculae
Why are osteoporotic fractures considered fragility fractures?
These fractures typically result from a low-energy trauma such as a fall from a standing height, i.e., occurring in absence of an adequate trauma.
What is the appearance of thinning cortical bone as seen on x-ray in osteoporosis?
Thinning of the cortical bone occurs in addition to changes in the trabecular bone, and the cortices appear paper thin.
True or False: Osteoporosis can be dormant and symptomless for extended period
True
True or False: Once the trabeculae are lost it is not possible to replace them.
True Trabecular bone is laid down within a cartilaginous matrix which is no longer present in adult bone. The anabolic therapy may replace the amount of bone that has been lost but cannot restore the trabecular architecture to its previous state
What manifestation of osteoporosis does this x-ray show?
Verticalization of vertebra increased presence of vertical weight bearing trabeculae
Why do patients with osteoporosis have an unsteady gait?
Walking becomes slow and unsure (because the body's center of gravity is displaced forward) with small steps to avoid transmitting shocks to the vertebral column The unsure gait carries with it an increased risk for falls and fractures
There are 7 trabecular groups in the proximal femur which indicate pressure or traction according to their orientation. Between them lies an area which is relatively poor in trabeculae called __________________. What does this structure lead to?
Ward's triangle with progression, the 7 groups of trabeculae are steadily resorbed Large gaps are produced in the cancellous area (spongiosa) that are located in the Ward's triangle and the great trochanter
What is a picture frame as seen on x-ray in osteoporosis?
With decreasing density, the trabecular bone becomes increasingly radiolucent, and the cortical rim of the vertebrae becomes more accentuated Therefore, the vertebrae may have a "picture frame" appearance
Bone mineral density is calculated in g/cm3 (i.e., weight of mineral for volume of bone), but it is reported as T score or Z score, not in absolute units. What is the Z score for osteoporosis?
Z-score is the number of standard deviations above or below the mean bone mineral density of people of the same age and gender as the patient.
What is a Fragility Fracture?
a pathological fracture that results from minimal trauma (e.g. a fall from a standing height) or no identifiable trauma at all, the fracture is both a sign and a symptom of osteoporosis
What is normal bone mineral density defined as?
a value less than 1 standard deviation below the young adult mean value. This corresponds to T score: negative 1.0 (or - 1.0)
What is juvenile idiopathic osteoporosis (JIO)?
a very rare condition of primary bone demineralization JIO is characterized by prepubertal onset, between 2 and 14 years of age, without sex predilection, and spontaneous remission with progression of puberty
What is the etiology of type II primary osteoporosis?
age related for men or women (over 75) that affects primarily cortical sites
Osteoporosis results from deficits in the amount of normally composed bone. Residual bone in osteoporosis is defective in ________ and _______ but not matrix composition or mineralization.
amount and distribution
What is the etiology of type I primary osteoporosis?
an accelerated phase of bone loss than begins at menopause and results in a loss of disproportionately more cancellous bone than compact bone Bone loss results mainly from trabecular perforation and loss of connectivity.
Bone trabeculae are ___________ with respect to its mechanical properties and architecture, meaning what?
anisotropic bone does not look or behave the same with rotation of 90 degrees
What is the measurement of bone mineral density by dual-energy x-ray absorptiometry (DEXA) used for?
as an index of bone mass, bone strength and fracture risk, and can be used to diagnose osteoporosis in some populations, such as postmenopausal women
What causes type II osteoporosis?
associated mainly with decreased bone formation due to loss of stem-cell bone precursors A decrease in osteoblast number leads to decreased bone formation, associated with an age-related decreased ability of the kidney to produce calcitriol
What is the most frequent reason for seeking medical attention with osteoporosis?
back pain, indicating a vertebral crush fracture **typically of sudden onset and severe lancing in character; worsening with movement and relieved by rest; radiating pain laterally following a dermatomal distribution and is accompanied by spasms of the paraspinal muscles
Changes in cortical bone during osteoporosis occur at a later time. The ______________ becomes thinner and the _______________________enlarges.
bone cortex medullary canal
___________ are the only clinical manifestation of osteoporosis
bone fractures w/o significant trauma
The large and rapid decrease in estrogen secretion at menopause leads to increased ________________.
bone turnover Bone resorption increases to a greater extent than does bone formation leading to rapid bone loss
When does our skeleton acquire maximal bone density ("peak bone mass")?
by the age of 30 years
What is a spinal biconcave fracture?
cause depression of the upper and lower endplates of the vertebral bodies (the first to appear)
After trabecular loss, the superior and inferior endplates of the ___________ attenuate leading to severe loss in mechanical competency in vertebral bodies.
cortical rim
Each bone consists of an outer portion of _______________ bone with a core of _________________________ bone. They undergo different rates of remodeling
cortical, compact cancellous or trabecular
What medications increase the risk for osteoporosis?
corticosteroids, lithium, isoniazid, carbamazepine/anti-epileptic drugs, heparin and warfarin, aluminum antacids, immunosuppressives like cyclosporin
The predilection of type I osteoporosis for women (male-to-female ratio is 1:6) and the temporal proximity to menopause implicates what?
estrogen deficiency as the etiologic agent
Family history of osteoporotic fractures is a ________ relative is risk factor for osteoporosis.
first degree
Osteoporosis does not often become clinically apparent until _________ occurs.
fragility fractures
Epidemiological and Twin studies have shown that __________ factors are responsible for 75% of the variation in peak bone mass among individuals.
genetic
Trabecular anisotropy reflects the manner in which ____________________________ are transmitted through the skeleton
gravitational stresses
In young people, ________-energy fractures of the __________ following major trauma predominate.
high energy long bones
During osteoporosis, ______________ trabeculae are lost out of proportion to _____________ trabeculae
horizontal vertical
In type II osteoporosis, increased bone resorption is a consequence of _______________________, mainly due to a lack of calcitriol.
hyperparathyroidism
How is osteoporosis different than osteomalacia?
in osteomalacia bone matrix is grossly under mineralized.
What age does secondary osteoporosis typically present?
in persons of any age
How can progression of osteoporosis be followed?
in the vertebral bodies Normal vertebral bodies show vertical trabeculae along the pressure lines and transverse trabeculae along the tension lines
In the vertebrae, where are the characteristic osteoporotic changes occurring first?
in the vertebral center and then radiating out
What are spinal compressive (crush) fractures?
last type to occur & results in vertical compression of the entire vertebral body
How is Calcium and Vitamin D intake a risk factor for osteoporosis?
lifetime diet low in Ca++ and Vitamin D increases the risk
The horizontal trabeculae connecting vertical trabeculae confer a several fold increase in what?
load-bearing capacity
What is osteoporosis characterized by?
low bone mass, microarchitectural disruption, skeletal fragility, w/ decreased bone strength and increased risk of fracture
Osteoporosis is a _________ disease of bone.
metabolic
In osteoporosis, loss of height or kyphosis (i.e., excessive convexity of the thoracic spine, resulting in humpback), are both outcomes of ______________________.
multiple vertebral fractures
In osteoporosis, levels of serum calcium, phosphate, and alkaline phosphatase are usually __________.
normal
What is a spinal anterior wedging fracture?
occurs following biconcavity and produces a loss of vertebral body height >50% on anterior side
A high _________________________ reduces osteoporosis risk later in life.
peak bone mass
Fracture incidence in the community is bimodal, meaning what?
peaks in youth and advanced age
How is lifestyle a risk factor for osteoporosis?
people w/ sedentary lifestyles @ higher risk
What sign of osteoporosis does this x ray show?
picture frame appearance due to trabeculae disappearing
Cancellous bone has a _________________ structure and a ______________ surface/volume ratio
porous large
What is the WHO definition of osteoporosis in postmenopausal women?
postmenopausal women w/ a T score value of -2.5 at the spine, hip, or forearm (2.5 SDs away from young adult mean) w/ or w/o the presence of fragility fracture
Lab tests are helpful in diagnosing which kind of osteoporosis?
secondary **Checking the serum levels of thyroxin, cortisol, and parathyroid hormone is prudent because hyperthyroidism, Cushing syndrome, and hyperparathyroidism are frequent causes of secondary osteoporosis
Where do fractures associated with type II osteoporosis typically occur?
sites that contain both cancellous and cortical bone, such as femoral neck, vertebral bodies, and long bones (proximal femur, humerus, and tibia)
Compact/cortical bone has a very ________ remodeling rate compared to trabecular bone
slow Only 2.5% of cortical bone is remodeled annually
How is body size a risk factor for osteoporosis?
smaller people at higher risk
How is cigarette smoking a risk factor for osteoporosis?
smoking cigarettes doubles risk
How does chronic back pain present in osteoporosis?
spinal osteoporosis that does not present as an acute fracture is often accompanied with a chronic dull back ache The pain is often difficult to localize accurately and may be explained by chronically aching muscles extended abnormally around the kyphotic deformity
Vertebral fractures occur in ____________ as a result of numerous microfractures which were not properly repaired
stages
_______________________ is a consequence of the collapse of the thoracic vertebrae (dowager's hump).
thoracic kyphosis
Loss of __________________ elements explains the exaggerated fragility of the skeleton in patients with osteoporosis.
trabecular
What is the diagnostic criteria for low bone mass (osteopenia)?
value of BMD more than 1 SD but less than 2.5 SD below the young adult female reference (T score between -1 and -2.5) **Patients with osteopenia are in no urgent need of therapy; Years may elapse before fractures occur in this group in the absence of preventive therapy
Where do osteoporotic fractures commonly occur and why?
vertebrae, hip, and forearm These bones have a large proportion of trabecular bone
Vertebral strength is primarily due to the volume fraction of the ______________ trabeculae
vertical Although horizontal trabeculae are shorter and thinner than vertical trabeculae in humans, they make an important contribution to trabecular strength
Because human locomotion is bipedal, the _____________ trabeculae are thicker (close to 200 μm) than ______________ trabeculae.
vertical horizontal
When are skeletal radiographs useful in osteoporosis?
very useful to detect the complications of osteoporosis i.e., to reveal previous fractures or compressions
What sign of osteoporosis does this x-ray show?
wedging/wedge fracture of the vertebra
