Osteoporosis

Osteoporosis
Presented by
Khaled zaki
Aser mhamed kamal

Osteoporosis
• is a disease where decreased bone strength increases the risk
of a broken bone. It is the most common reason for a broken
bone among people who are old. Bones that commonly break
include the back bones, the bones of the forearm, and the
hip. Until a broken bone occurs there are typically no
symptoms. Bones may weaken to such a degree that a break
may occur with minor stress or spontaneously. Chronic
pain and a decreased ability to carry out normal activities may
occur following a broken bone.

• Osteoporosis may be due to lower than normal peak bone mass and greater than
normal bone loss. Bone loss increases after menopause due to lower levels
of estrogen. Osteoporosis may also occur due to a number of diseases or
treatments including alcoholism, anorexia, hyperthyroidism, surgical removal of
the ovaries, and kidney disease. Certain medications increase the rate of bone loss
including some anti seizure medications, chemotherapy, proton pump
inhibitors, selective serotonin reuptake inhibitors and steroids. Not enough
exercise and smoking are also risk factors. Osteoporosis is defined as a bone
density of 2.5 standard deviations below that of a young adult. This is typically
measured by dual-energy X-ray absorptiometry at the hip.
• Prevention of osteoporosis includes a proper diet during childhood and efforts to
avoid medications that cause the condition. Efforts to prevent broken bones in
those with osteoporosis include a good diet, exercise, and fall prevention. Lifestyle
changes such as stopping smoking and not drinking alcohol may help. Medication
of the bisphosphonate type are useful in those with previous broken bones due to
osteoporosis. In those with osteoporosis but no previous broken bones they are
less effective. A number of other medications may also be useful.

• Osteoporosis becomes more common with age. About 15% of white people in
their 50s and 70% of those over 80 are affected. It is more common in women
than men. In the developed world, depending on the method of diagnosis, 2%
to 8% of males and 9% to 38% of females are affected. Rates of disease in
the developing world are unclear. About 22 million women and 5.5 million
men in the European Union had osteoporosis in 2010. In the United States in
2010 about eight million women and one to two million men had
osteoporosis. White and Asian people are at greater risk. The word
osteoporosis is from the Greek terms for "porous bones"

Signs and symptoms :
• Osteoporosis itself has no
symptoms; its main consequence
is the increased risk of bone
fractures.
Osteoporotic fractures occur in
situations where healthy people
would not normally break a bone;
they are therefore regarded as
fragility fractures. Typical fragility
fractures occur in the vertebral
column, rib, hip and wrist.
• Osteoporosis is an age-related
disorder that causes the gradual
loss of bone density and strength.
When the thoracic vertebrae are
affected, there can be a gradual
collapse of the vertebrae. This
results in kyphosis, an excessive
curvature of the thoracic region

Fractures :
• Fractures are the most dangerous
aspect of osteoporosis. Debilitating
acute and chronic pain in the elderly is
often attributed to fractures from
osteoporosis and can lead to further
disability and early mortality. These
fractures may also be asymptomatic.
The most common osteoporotic
fractures are of the wrist, spine,
shoulder and hip. The symptoms of
a vertebral collapse ("compression
fracture") are sudden back pain, often
with radicular pain (shooting pain due
to nerve root compression) and rarely
with spinal cord compression or cauda
equina syndrome. Multiple vertebral
fractures lead to a stooped posture,
loss of height, and chronic pain with
resultant reduction in mobility.
•

• Fractures of the long bones acutely impair mobility and may
require surgery. Hip fracture, in particular, usually requires prompt surgery, as
serious risks are associated with it, such as deep vein
thrombosis and pulmonary embolism, and increased mortality.
• Fracture risk calculators assess the risk of fracture based upon several criteria,
including BMD, age, smoking, alcohol usage, weight, and gender. Recognized
calculators include FRAX] and Dubbo.
• The term "established osteoporosis" is used when a broken bone due to
osteoporosis has occurred. Osteoporosis is a part of frailty syndrome.

Falls risk :
• The increased risk of falling associated with aging leads to
fractures of the wrist, spine, and hip. The risk of falling, in
turn, is increased by impaired eyesight due to any cause
(e.g. glaucoma, macular degeneration), balance
disorder, movement disorders
• (e.g. Parkinson's disease), dementia, and sarcopenia (age-
related loss of skeletal muscle). Collapse (transient loss of
postural tone with or without loss of consciousness) leads to a
significant risk of falls; causes of syncope are manifold, but
may include cardiac arrhythmias (irregular heart
beat), vasovagal syncope, orthostatic hypotension (abnormal
drop in blood pressure on standing up), and seizures. Removal
of obstacles and loose carpets in the living environment may
substantially reduce falls. Those with previous falls, as well as
those with gait or balance disorders, are most at risk.

Risk factors :
• Risk factors for osteoporotic fracture can be split between
nonmodifiable and (potentially) modifiable. In addition,
osteoporosis is a recognized complication in specific diseases and
disorders. Medication use is theoretically modifiable, although in
many cases, the use of medication that increases osteoporosis risk
may be unavoidable. Caffeine is not a risk factor for osteoporosis
• It is more likely for a female to get osteoporosis than a male.
• 1- Nonmodifiable
Bone density peaks at about 30 years of age Women lose bone mass
more rapidly than men.

• The most important risk factors for osteoporosis are advanced age (in both
men and women) and female sex; estrogen deficiency following menopause
or oophorectomy is correlated with a rapid reduction in bone mineral density,
while in men, a decrease intestosterone levels has a comparable (but less
pronounced) effect.
• Race: While osteoporosis occurs in people from all ethnic
groups, European or Asian ancestry predisposes for osteoporosis.
• Heredity: Those with a family history of fracture or osteoporosis are at an
increased risk; the heritability of the fracture, as well as low bone mineral
density, are relatively high, ranging from 25 to 80%. At least 30 genes are
associated with the development of osteoporosis.
• Those who have already had a fracture are at least twice as likely to have
another fracture compared to someone of the same age and sex. Early
menopause/hysterectomy is another predisposing factor.
• Build: A small stature is also a nonmodifiable risk factor associated with the
development of osteoporosis

2- Potentially modifiable :
• Excess consumption of alcohol: Although small amounts of alcohol are
probably beneficial (bone density increases with increasing alcohol
intake), chronic heavy drinking (alcohol intake greater than three
units/day) probably increases fracture risk despite any beneficial effects
on bone density.
• Vitamin D deficiency: Low circulating Vitamin D is common among the
elderly worldwide. Mild vitamin D insufficiency is associated with
increased parathyroid hormone(PTH) production. PTH increases bone
resorption, leading to bone loss. A positive association exists between
serum 1,25-dihydroxycholecalciferol levels and bone mineral density,
while PTH is negatively associated with bone mineral density.
• Tobacco smoking: Many studies have associated smoking with
decreased bone health, but the mechanisms are unclear. Tobacco
smoking has been proposed to inhibit the activity of osteoblasts, and is
an independent risk factor for osteoporosis. Smoking also results in
increased breakdown of exogenous estrogen, lower body weight and
earlier menopause, all of which contribute to lower bone mineral
density.

• Malnutrition: Nutrition has an important and complex role in maintenance of
good bone. Identified risk factors include low dietary calcium and/or
phosphorus, magnesium, zinc, boron, iron, fluoride, copper, vitamins A, K, E
and C (and D where skin exposure to sunlight provides an inadequate supply).
Excess sodium is a risk factor. High blood acidity may be diet-related, and is a
known antagonist of bone. Some have identified low protein intake as
associated with lower peak bone mass during adolescence and lower bone
mineral density in elderly populations. Conversely, some have identified low
protein intake as a positive factor, protein is among the causes of dietary
acidity. Imbalance of omega-6 to omega-3 polyunsaturated fats is yet another
identified risk factor.
• High dietary protein from animal sources: Research has found an association
between diets high in animal protein and increased urinary calcium, and have
been linked to an increase in fractures. However, the relevance of this
observation to bone density is unclear, since higher protein diets tend to
increase absorption of calcium from the diet and are associated with higher
bone density. Indeed, it has recently been argued that low protein diets cause
poor bone health. No interventional trials have been performed on dietary
protein in the prevention and treatment of osteoporosis.

• Underweight/inactive: Bone remodeling occurs in response to physical stress,
so physical inactivity can lead to significant bone loss. Weight bearing exercise
can increase peak bone mass achieved in adolescence, and a highly significant
correlation between bone strength and muscle strength has been
determined. The incidence of osteoporosis is lower in overweight people.
• Endurance training: In female endurance athletes, large volumes of training
can lead to decreased bone density and an increased risk of osteoporosis. This
effect might be caused by intense training suppressing menstruation,
producing amenorrhea, and it is part of the female athlete triad. However, for
male athletes, the situation is less clear, and although some studies have
reported low bone density in elite male endurance athletes, others have
instead seen increased leg bone density.
• Heavy metals: A strong association between cadmium and lead with bone
disease has been established. Low-level exposure to cadmium is associated
with an increased loss of bone mineral density readily in both genders, leading
to pain and increased risk of fractures, especially in the elderly and in females.
Higher cadmium exposure results inosteomalacia (softening of the bone).
• Soft drinks: Some studies indicate soft drinks (many of which
contain phosphoric acid) may increase risk of osteoporosis, at least
in women. Others suggest soft drinks may displace calcium-containing drinks
from the diet rather than directly causing osteoporosis

3- Medical disorders:
• Many diseases and disorders have
been associated with osteoporosis. For
some, the underlying mechanism
influencing the bone metabolism is
straightforward, whereas for others
the causes are multiple or unknown.
• In general, immobilization causes bone
loss (following the 'use it or lose it'
rule). For example, localized
osteoporosis can occur after prolonged
immobilization of a fractured limb in a
cast. This is also more common in
active people with a high bone turn-
over (for example, athletes). Other
examples include bone loss
during space flight or in people who
are bedridden or use wheelchairs for
various reasons.
The body regulates calcium homeostasis with two pathways; one is signaled to
turn on when blood calcium levels drop below normal and one is the pathway
that is signaled to turn on when blood calcium levels are elevated.

• Hypogonadal states can cause secondary osteoporosis. These
include Turner syndrome, Klinefelter syndrome, Kallmann
syndrome,anorexia nervosa, andropause,
hypothalamic amenorrhea or hyperprolactinemia. In females, the
effect of hypogonadism is mediated by estrogen deficiency. It can
appear as early menopause (<45 years) or from prolonged
premenopausal amenorrhea (>1 year).
Bilateral oophorectomy (surgical removal of the ovaries)
and premature ovarian failure cause deficient estrogen production.
In males, testosterone deficiency is the cause (for example,
andropause or after surgical removal of the testes).
• Endocrine disorders that can induce bone loss include Cushing's
syndrome, hyperparathyroidism, hyperthyroidism,
hypothyroidism, diabetes mellitus type 1 and 2, acromegaly,
and adrenal insufficiency. In pregnancy and lactation can cause
reversible bone loss.

• Malnutrition, parenteral nutrition and malabsorption can lead to
osteoporosis. Nutritional and gastrointestinal disorders that can predispose
to osteoporosis include coeliac disease, Crohn's disease, Ulcerative
colitis, cystic fibrosis, lactose intolerance,
surgery (after gastrectomy, intestinal bypass surgery or bowel resection)
and severe liver disease (especially primary biliary cirrhosis). People
with bulimia can also develop osteoporosis. Those with an otherwise
adequate calcium intake can develop osteoporosis due to the inability to
absorb calcium and/or vitamin D. Other micronutrients such as vitamin
K or vitamin B12 deficiencymay also contribute.
• People with rheumatologic disorders such as rheumatoid
arthritis,] ankylosing spondylitis, systemic lupus erythematosus and
polyarticular juvenile idiopathic arthritis are at increased risk of
osteoporosis, either as part of their disease or because of other risk factors
(notably corticosteroid therapy). Systemic diseases such
as amyloidosis and sarcoidosis can also lead to osteoporosis.

• Renal insufficiency can lead to renal osteodystrophy.
• Hematologic disorders linked to osteoporosis are multiple myeloma and
other monoclonal
gammopathies lymphoma and leukemia, mastocytosis, hemophilia, sickle-cell
disease and thalassemia.
• Several inherited disorders have been linked to osteoporosis. These
include osteogenesis imperfecta, Marfan
syndrome, hemochromatosis, hypophosphatasia (for which it is often
misdiagnosed), glycogen storage diseases, homocystinuria, Ehlers–Danlos
syndrome, porphyria, Menkes' syndrome, epidermolysis
bullosa andGaucher's disease.
• People with scoliosis of unknown cause also have a higher risk of
osteoporosis. Bone loss can be a feature of complex regional pain syndrome.
It is also more frequent in people with Parkinson's disease and chronic
obstructive pulmonary disease.
• People with Parkinson's disease have a higher risk of broken bones. This is
related to poor balance and poor bone density. In Parkinson’s disease there
may be a link between the loss of dopaminergic neurons and altered calcium
metabolism (and iron metabolism) causing a stiffening of the skeleton
and kyphosis.

4- Medication:
• Certain medications have been associated with an increase in osteoporosis risk; only steroids and
anticonvulsants are classically associated, but evidence is emerging with regard to other drugs.
• Steroid-induced osteoporosis (SIOP) arises due to use of glucocorticoids – analogous to Cushing's
syndrome and involving mainly the axial skeleton. The synthetic glucocorticoid prescription
drug prednisone is a main candidate after prolonged intake. Some professional guidelines
recommend prophylaxis in patients who take the equivalent of more than 30 mg hydrocortisone
(7.5 mg of prednisolone), especially when this is in excess of three months. Alternate day use may
not prevent this complication.
• Barbiturates, phenytoin and some other enzyme-inducing antiepileptics – these probably
accelerate the metabolism of vitamin D.
• L-Thyroxine over-replacement may contribute to osteoporosis, in a similar fashion as
thyrotoxicosis does. This can be relevant in subclinical hypothyroidism.
• Several drugs induce hypogonadism, for example aromatase inhibitors used in breast
cancer, methotrexate and other antimetabolite drugs, depot progesterone and gonadotropin-
releasing hormone agonists.
• Anticoagulants – long-term use of heparin is associated with a decrease in bone
density, and warfarin (and related coumarins) have been linked with an increased risk in
osteoporotic fracture in long-term use.
• Proton pump inhibitors – these drugs inhibit the production of stomach acid; this is thought to
interfere with calcium absorption. Chronic phosphate binding may also occur with aluminium-
containing antacids.
• Thiazolidinediones (used for diabetes) – rosiglitazone and possibly pioglitazone, inhibitors
of PPARγ, have been linked with an increased risk of osteoporosis and fracture.
• Chronic lithium therapy has been associated with osteoporosis.

5- Evolutionary
• Age-related bone loss is common among humans due to exhibiting
less dense bones than other primate species. Because of the more
porous bones of humans, frequency of severe osteoporosis and
osteoporosis related fractures is higher. The human vulnerability to
osteoporosis is an obvious cost but it can be justified by the
advantage of bipedalism inferring that this vulnerability is the
byproduct of such. It has been suggested that porous bones help to
absorb the increased stress that we have on two surfaces compared
to our primate counterparts who have four surfaces to disperse the
force. In addition, the porosity allows for more flexibility and a
lighter skeleton that is easier to support. One other consideration
may be that diets today have much lower amounts of calcium than
the diets of other primates or the tetrapedal ancestors to humans
which may lead to higher likelihood to show signs of osteoporosis

Diagnosis :
• The diagnosis of osteoporosis can be made using conventional
radiography and by measuring the bone mineral density (BMD). The
most popular method of measuring BMD is dual-energy x-ray
absorptiometry. In addition to the detection of abnormal BMD, the
diagnosis of osteoporosis requires investigations into potentially
modifiable underlying causes; this may be done with blood tests.
Depending on the likelihood of an underlying problem, investigations
for cancer with metastasis to the bone, multiple myeloma, Cushing's
disease and other above-mentioned causes may be performed.
Multiple osteoporotic wedge fractures demonstrated on a lateral thoraco-
lumbar spine X-ray

Conventional radiography:
• Conventional radiography is useful, both by itself and in conjunction
with CT or MRI, for detecting complications of osteopenia (reduced
bone mass; preosteoporosis), such as fractures; for differential diagnosis
of osteopenia; or for follow-up examinations in specific clinical settings,
such as soft tissue calcifications, secondary hyperparathyroidism, or
osteomalacia in renal osteodystrophy. However, radiography is relatively
insensitive to detection of early disease and requires a substantial
amount of bone loss (about 30%) to be apparent on X-ray images.
• The main radiographic features of generalized osteoporosis are cortical
thinning and increased radiolucency. Frequent complications of
osteoporosis are vertebral fractures for which spinal radiography can
help considerably in diagnosis and follow-up. Vertebral height
measurements can objectively be made using plain-film X-rays by using
several methods such as height loss together with area reduction,
particularly when looking at vertical deformity in T4-L4, or by
determining a spinal fracture index that takes into account the number
of vertebrae involved. Involvement of multiple vertebral bodies leads to
kyphosis of the thoracic spine, leading to what is known as dowager's
hump.

Dual-energy X-ray :
• Dual-energy X-ray absorptiometry (DXA) is considered the gold
standard for the diagnosis of osteoporosis. Osteoporosis is
diagnosed when the bone mineral density is less than or equal to 2.5
standard deviations below that of a young (30–40-year-old), healthy
adult women reference population. This is translated as a T-score.
But because bone density decreases with age, more people become
osteoporotic with increasing age. The World Health Organization has
established the following diagnostic guidelines:
Category T-score range % young women
Normal T-score ≥ −1.0 85%
Osteopenia −2.5 < T-score < −1.0 14%
Osteoporosis T-score ≤ −2.5 0.6%
Severe osteoporosis
T-score ≤ −2.5 with fragility
fracture
• The International Society for Clinical Densitometry takes the position that
a diagnosis of osteoporosis in men under 50 years of age should not be
made on the basis of densitometric criteria alone. It also states, for
premenopausal women, Z-scores (comparison with age group rather
than peak bone mass) rather than T-scores should be used, and the
diagnosis of osteoporosis in such women also should not be made on the
basis of densitometric criteria alone

Prevention :
• Lifestyle prevention of osteoporosis is in many aspects the inverse of the potentially
modifiable risk factors. As tobacco smoking and high alcohol intake have been linked with
osteoporosis, smoking cessation and moderation of alcohol intake are commonly
recommended as ways to help prevent it.
• Nutrition
• Studies of the benefits of supplementation with calcium and vitamin D are conflicting,
possibly because most studies did not have people with low dietary intakes. A 2013 review
by the USPSTF found insufficient evidence to determine if supplementation with calcium
and vitamin D results in greater harm or benefit in men and premenopausal women. The
USPSTF did not recommend low dose supplementation (less than 1 g of calcium and 400 IU
of vitamin D) in postmenopausal women as there does not appear to be a difference in
fracture risk. It is unknown what effect higher doses have.
• While some meta-analyses have found a benefit of vitamin D supplements combined with
calcium for fractures, they did not find a benefit of vitamin D supplements alone.
• While supplementation does not appear to affect the risk of death, there is an increased
risk of myocardial infarctions, kidney stones, and stomach problems.
• Vitamin K deficiency is also a risk factor for osteoporotic fractures. The gene gamma-
glutamylcarboxylase (GGCX) is dependent on vitamin K. Functional polymorphisms in the
gene could attribute to variation in bone metabolism and BMD. Vitamin K2 is also used as a
means of treatment for osteoporosis and the polymorphisms of GGCX could explain the
individual variation in the response to treatment of vitamin K. Vitamin K supplementation
may reduce the risk of fractures in postmenopausal women; however, there is no evidence
for men.

Management
• Lifestyle
• Weight-bearing endurance exercise and/or exercises to strengthen muscles
improve bone strength in those with osteoporosis. Aerobics, weight bearing, and
resistance exercises all maintain or increase BMD in postmenopausal women Fall
prevention can help prevent osteoporosis complications. There is some evidence
for hip protectors specifically among those who are in care homes.
• Medications
• Bisphosphonates are useful in decreasing the risk of future fractures in those
who have already sustained a fracture due to osteoporosis. This benefit is
present when taken for three to four years. They have not been compared
directly to each other, though, so it is not known if one is better. Fracture risk
reduction is between 25 and 70% depending on the bone involved. There are
concerns of atypical femoral fractures and osteonecrosis of the jaw with long
term use, but these risks are low. With evidence of little benefit when used for
more than three to five years and in light of the potential adverse events, it may
be appropriate to stop treatment after this time in some.
• For those with osteoporosis but who have not had any fractures evidence does
not support a reduction of in fracture risk
with risedronate or etidronate. Alendronatedecreases fractures of the spine but
does not have any effect on other types of fractures. Half stop their medications
within a year.

• Teriparatide ( a recombinant parathyroid hormone ) has been shown to be
effective in treatment of women with postmenopausal osteoporosis. Some
evidence also indicatesstrontium ranelate is effective in decreasing the risk of
vertebral and nonvertebral fractures in postmenopausal women with
osteoporosis. Hormone replacement therapy, while effective for osteoporosis,
is only recommended in women who also have menopausal
symptoms. Raloxifene, while effective in decreasing vertebral fractures, does
not affect the risk of nonvertebral fracture. And while it reduces the risk
of breast cancer, it increases the risk of blood clots and strokes. Denosumab is
also effective for preventing osteoporotic fractures. In hypogonadal men,
testosterone has been shown to improve bone quantity and quality, but, as of
2008, no studies evaluated its effect on fracture risk or in men with a normal
testosterone levels. Calcitonin while once recommended is no longer due to
the associated risk of cancer with its use and questionable effect on fracture
risk.
• Certain drugs like alendronate, etidronate, risedronate, raloxifene and
strontium ranelate can be helpful for the preventing of osteoporotic fragility
fractures in postmenopausal women with osteoporosis.

References :
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3. WHO Scientific Group on the Prevention and Management of Osteoporosis (2000 : Geneva, Switzerland) (2003). "Prevention and
management of osteoporosis : report of a WHO scientific group" (PDF). p. 7, 31. ISBN 9241209216.
4. Wells, GA; Cranney, A; Peterson, J; Boucher, M; Shea, B; Robinson, V; Coyle, D; Tugwell, P (23 January 2008). "Alendronate for the
primary and secondary prevention of osteoporotic fractures in postmenopausal women.". The Cochrane database of systematic
reviews (1): CD001155. PMID 18253985.
5. Wells, G; Cranney, A; Peterson, J; Boucher, M; Shea, B; Robinson, V; Coyle, D; Tugwell, P (23 January 2008). "Risedronate for the
primary and secondary prevention of osteoporotic fractures in postmenopausal women.". The Cochrane database of systematic
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6. ^ Jump up to:a b Wells GA, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell P (Jan 23, 2008). "Etidronate for
the primary and secondary prevention of osteoporotic fractures in postmenopausal women". Cochrane Database of Systematic
Reviews (1): CD003376. doi:10.1002/14651858.CD003376.pub3. PMID 18254018.
7. Nelson HD, Haney EM, Chou R, Dana T, Fu R, Bougatsos C (2010). "Screening for Osteoporosis: Systematic Review to Update the
2002 U.S. Preventive Services Task Force Recommendation [Internet].". Agency for Healthcare Research and Quality.PMID 20722176.
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