WO week 4 msk

1. Bone remodeling
2. Bone density changes across life cycle
3. Metabolic Bone disease
- Osteomalacia
 Osteomalacia means soft bones. Bone consists of a hard outer shell (the cortex) made
up of minerals, mainly calcium and phosphorus and a softer inner mesh (the matrix)
made up of collagen fibers.

When normal bone is formed, these fibers are coated with mineral (mineralization). The
strength of the new bone depens on the amount of mineral covering the collagen
matrix. The more mineral laid down, the stronger the bone.

Osteomalacia happens if mineralization doesn’t take place properly. In osteomalasia

more and more bone is made up of collagen matrix without a mineral covering, so the
bones become soft. These softened bones may bend and crack, and this can be very
painful.

There are rare types of osteomalacia these are usually due to problems in the kidneys
which result in loss of phosphorous from the body. This can be inherited through
parents genes but also can happen with other kidney problems and occasionally as a
side effect of treatment with some drugs.

Anyone who’s lacking vitamin D is likely to develop osteomalacia. Most of our vit. D
supply is produced by the body itself. Cholesterol, which is present naturally in the skin,
is converted to vit. D through the action of sunlight on the skin.

The people most at risk of osteomalacia are those who are not able to produce enough
vitamin D through exposure to sunlight.

Symptoms :

o Paun felt in the bones

o Muscle weakness
o Slight crack in the bone (partial fracture)

Bone pain is felt most ofthen in the legs, groin, upper thighs and knees and sometimes in
the feet when you stand, walk or run.
Muscle become weak or feel stiff. The weakness tends to affect the thighs and the
muscle in the shoulders and main trunk of the body.

Partial fractures linked with osteomalacia are called Looser’s zones, which can cause
pain. Occasionally these cracks can lead to full breaks (complete fracture)

In the much rarer inherited form of osteomalacia, muscle weakness is less common. The
main problem is that mineral laid down in the ligaments and tendos around the spine,
hips, and shoulders makes it difficult to move there joints.

- Ricket’s
 Ricket’s is the softening and weakening of bones in children. Usually because of an
extreme and prolonged vitamin D deficiency. The children need vitamin D to absorb
calcium and phosphorous from food.

Symptoms :
o Delayed growth
o Delayed motor skills
 o Pain in the spine, pelvis and legs
o Muscle weakness

Because of rickets softens the areas of growing tissues at the ends of a child’s bones
(growth plate), it can cause skeletal deformities such as:

o Bowed legs or knock knees

o Thickened writs and ankles
o Breastbone projection

- Osteoporisi
 Osteoporosis causes bones to become weak and brittle – so brittle that a fall or eve mild
stress such as bending over or coughing can cause a fracture. Osteoporosis-related
fractures most commonly occur in the hip, wrist or spine.

Osteoporosis occurs when the creation of new bone doesn’t keep up with the loss of old
bone.
The bones are in a constant state of renewal – new bone is made and old bone is broken
down. When you’re young, the body makes new bone faster than it breaks down old
bone and your bone mass increases. After early 20s this process slows, and most people
reach their peak bone mass by age 30. As people age, bone mass is lost faster than its
created.

How likely you are to develop osteoporosis depends partly on how much bone mass you
attained in your youth. Peak bone mass is somewhat inherited and varies also by ethnic
group. The higher your peak bone mass the more bone you have “in the bank” and the
less likely you are to develop osteoporosis as you age.
Osteoporosis is more common in people who have too much or too little of certain
hormones in their bodies, examples include:
o Sex hormones. Lowered sex hormone levels tend to weaken bone. The
reduction of esterogen levels in women at menopause is one of the strongest
risk factors for developing osteopororsis.
o Thyroid problems. Too much thyroid hormone can cause bone loss. This can
occur if your thyroid is overactive or if you take too much thyroid hormone
medication to treat an underactive thyroid.
o Other glands. Osteopororsis has also been associated with overactive
parathyroid and adrenal glands.
Symptoms :
o Back pain, caused by a fractured or collapsed vertebra
o Loss of height over time
o A stopped posture
o A bone that breaks much more easily than expected

4. Pathogenesis of Osteoporosis

5. Line out risk factors of osteogenesis

The risk of getting osteoporosis increases with age as bones naturally become thinner. After age 30,
the rate at which your bone tissue dissolves and is absorbed by the body slowly increases, while the
rate of bone building decreases. So overall you lose a small amount of bone each year after age 30.
In women, bone loss is more rapid and usually begins after monthly menstrual periods stop, when a
woman's production of the hormone estrogen slows down (usually between the ages of 45 and 55). A
 man's bone thinning typically starts to develop gradually when his production of the hormone
testosterone slows down, at about 45 to 50 years of age. Women typically have smaller and lighter
bones than men. As a result, women develop osteoporosis far more often than men. Osteoporosis
usually does not have a noticeable effect on people until they are 60 or older.
Whether a person develops osteoporosis depends on the thickness of the bones (bone density) in
early life, as well as health, diet, and physical activity later in life. Factors that increase the risk for
osteoporosis in both men and women include:

 Having a family history of osteoporosis. If your mother, father, or a sibling has been diagnosed with
osteoporosis or has experienced broken bones from a minor injury, you are more likely to develop
osteoporosis.
 Lifestyle factors. These include:
 Smoking. People who smoke lose bone density faster than nonsmokers.
 Alcohol use. Heavy alcohol use can decrease bone formation, and it increases the risk of falling.
Heavy alcohol use is more than 2 drinks a day for men and more than 1 drink a day for women. See
pictures of standard alcoholic drinks.
 Getting little or no exercise. Weight-bearing exercises—such as walking, jogging, stair climbing,
dancing, or lifting weights—keep bones strong and healthy by working the muscles and bones
against gravity. Exercise may improve your balance and decrease your risk of falling.
 Being small-framed or thin. Thin people and those with small frames are more likely to develop
osteoporosis. But being overweight puts women at risk for other serious medical conditions,
including type 2 diabetes, high blood pressure, and coronary artery disease (CAD). For more
information, see the topic Weight Management.
 A diet low in foods containing calcium and vitamin D.
 Having certain medical conditions. Some medical conditions, such
as hyperthyroidism or hyperparathyroidism, put you at greater risk for osteoporosis.
 Taking certain medicines. Several medicines, such as corticosteroids used for long periods, cause bone
thinning.
 Having certain surgeries, such as having your ovaries removed before menopause.
Other risk factors for osteoporosis may include:
 Being of European and Asian ancestry, the people most likely to have osteoporosis.
 Being inactive or bedridden for long periods of time.
 Excessive dieting or having an eating disorder, such as anorexia nervosa.
 Being a female athlete, if you have infrequent menstrual cycles due to low body fat.
Women who have completed menopause have the greatest risk for osteoporosis because their levels of
the estrogen hormone drop. Estrogen protects women from bone loss. Likewise, women who no longer have
menstrual periods—either because their ovaries are not working properly or because their ovaries have been
surgically removed—also can have lower estrogen levels.

6. Investigation findings in osteoporosis (laboratory, x ray, bone densitometry)

Densitometry

A bone density test is the only test that can diagnose osteoporosis before a broken bone occurs. This
test helps to estimate the density of your bones and your chance of breaking a bone. NOF
recommends a bone density test of the hip and spine by a central DXA machine to diagnose
osteoporosis. DXA stands for dual energy x-ray absorptiometry.
 Your bone density test results are reported using T-scores. A T-score shows how much your bone
density is higher or lower than the bone density of a healthy 30-year old adult. A healthcare provider
looks at the lowest T-score to diagnosis osteoporosis.

What Your T-score Means. According to the World Health Organization (WHO):

 A T-score of -1.0 or above is normal bone density. Examples are 0.9, 0 and -0.9.
 A T-score between -1.0 and -2.5 means you have low bone density or osteopenia. Examples are T-scores of -
1.1, -1.6 and -2.4.
 A T-score of -2.5 or below is a diagnosis of osteoporosis. Examples are T-scores of -2.6, -3.3 and -3.9.
 The lower a person’s T-score, the lower the bone density. A T-score of -1.0 is lower than a T-score of 0.5 and
a T-score of -3.5 is lower than a T-score of -3.0.

GUIDE TO UNDERSTANDING T-SCORES

Category T-scores

Range Examples

Normal Bone Density -1 and above +0.5

-1.0

Low Bone Density (Osteopenia) Between -1 and -2.5 -1.1

-1.5

-2.4

Osteoporosis -2.5 and below -2.5

-3.0

-4.0

Your bone density test result also includes a Z-score that compares your bone density to what is normal in
someone your age and body size. Among older adults low bone mineral density is common, so Z-scores can be
misleading.
Most experts recommend using Z-scores rather than T-scores for children, teens, women still having periods
and younger men. NOF does not recommend routine bone density testing in these age groups. A Z-score
above -2.0 is normal according to the International Society for Clinical Densitometry (ISCD). A diagnosis of
osteoporosis in younger men, premenopausal women and children should not be based on a bone density test
result alone.

Osteoporosis is essentially decreased bony tissue per unit volume of bone. There is no microstructural and
biochemical change as occurs in osteomalacia or rickets. Hence the mineral-to-osteoid ratio is normal
(cf. osteomalacia in which the mineral-to-osteoid ratio is decreased).

Osteoporosis can be localized or diffuse and be divided into:

 primary: no cause is identifiable

o postmenopausal (type 1): occurs in 50-65-year-olds females; disproportionate loss of cancellous bone
as compared to cortical bone resulting in more involvement of cancellous bone-rich areas, like
vertebrae and ends of long bones
o senile (type 2): occurs in the elderly; proportionate loss of cortical and cancellous bones affecting long
bones
o idiopathic juvenile osteoporosis
 secondary (type 3): occurs due to a range of causes including
o endocrine disease (e.g. Cushing syndrome, hyperthyroidism, hyperparathyroidism, diabetes mellitus) 7
o chronic illness (e.g. COPD, chronic liver disease, multiple sclerosis, celiac disease) 7
o inflammation
o medications (e.g. steroids, phenytoin)
o thalassemia major 4
o nutritional disturbances 6 (e.g. malnutrition, anorexia)
There is a different list of secondary causes for juvenile osteoporosis with some overlap with adult causes.

Radiographic features
Decreased bone density can be appreciated by decreased cortical thickness and loss of bony trabeculae in the
early stages in radiography. Bones like the vertebra, long bones (proximal femur), calcaneum and tubular
bones are usually looked at for evidence of osteoporosis.

Plain radiograph
 not a sensitive modality, as more than 30-50% bone loss is required to appreciate decreased bone density
on a radiograph
 vertebral osteoporosis manifests as
o pencilling of vertebrae
o loss of cortical bone (picture frame vertebra) and trabecular bone (ghost vertebra)
o compression fractures and vertebra plana
 loss of trabeculae in proximal femur area, which is explained by Singh's index (and can also be seen in the
calcaneum)
 in tubular bones (especially metacarpals), there will be thinning of the cortex
o cortical thickness <25% of the whole thickness of metacarpal signifies osteoporosis (normally 25-33%)
Bone mineral density measurement
Bone mineral density (BMD) measurement is the method of estimation of calcium hydroxyapatite. Multiple x-
ray based, gamma-ray based and ultrasonic methods are available:

 radiographic absorptiometry (RA)

 single photon and x-ray absorptiometry (SPA)
 dual energy x-ray absorptiometry (DEXA)
o most commonly-used and most reliable
 quantitative computed tomography can be used

MRI
Bone marrow signal takes on a heterogeneous appearance with rounded focal fatty lesions replacing normal
marrow with coalescence often occurring 5:

 T1: heterogeneously hyperintense

 T2: variable signal

Treatment and prognosis

As osteoporosis decreases bone strength, patients are at an increased risk of fracture, often with minimal
trauma, and commonly at the pelvis, hip and wrist.

Oral bisphosphonates are the most commonly prescribed medications and are effective in reducing the risk of
further osteoporotic fracture. There are a range of other medications that can also be used, including
intravenous bisphosphonates, selective estrogen receptor modulators (e.g. raloxifene), denosumab, strontium
ranelate, calcitonin, and parathyroid hormone-based treatments (e.g. teriparatide) 8.

Complications
Bisphosphonates and denosumab have been associated with rare, but serious, side effects
including bisphosphonate-related atypical femoral fractures and bisphosphonate-related osteonecrosis of the
jaw.

7. Management of osteoporosis

Treatments for established osteoporosis include:

 Weight-bearing exercise
 Calcium and vitamin D supplements
 Medications:
o Estrogen therapy
o Bisphosphonates: Fosamax® (aledronate sodium), Actonel®, Atelvia® (risedronate), Boniva®
(ibandronate), Reclast® (zoledronic acid)
o Selective estrogen receptor modulators: Evista® (raloxifene)
o Parathyroid hormone: Forteo® (teriparatide)
o Biologic therapy: Prolia® (denosumab)