In the United States, fugitive slaves or runaway slaves were terms used in the 18th and 19th centuries to describe people who fled slavery. The term also refers to the federal Fugitive Slave Acts of 1793 and 1850. Such people are also called freedom seekers to avoid implying that the enslaved person had committed a crime and that the slaveholder was the injured party.
Generally, they tried to reach states or territories where slavery was banned, including Canada, or, until 1821, Spanish Florida. Most slave laws tried to control slave travel by requiring them to carry official passes if traveling without an enslaver.
Passage of the Fugitive Slave Act of 1850
increased penalties against runaway slaves and those who aided them.
Because of this, some freedom seekers left the United States altogether,
traveling to Canada or Mexico. Approximately 100,000 enslaved Americans escaped to freedom.
An animation showing the free/slave status of U.S. states and territories, 1789–1861 (see separate yearly maps below). The American Civil War began in 1861. The 13th Amendment, effective December 1865, abolished slavery in the U.S.
The Fugitive Slave Act of 1793 is the first of two federal laws
that allowed for runaway slaves to be captured and returned to their
enslavers. Congress passed the measure in 1793 to enable agents for
enslavers and state governments, including free states, to track and
capture bondspeople. They were also able to penalize individuals with a
$500 (equivalent to $10,940 in 2022) fine if they assisted slaves in
their escape.
Slave hunters were obligated to obtain a court-approved affidavit in
order to apprehend an enslaved individual, giving rise to the formation
of an intricate network of safe houses commonly known as the Underground
Railroad.
Fugitive Slave Act of 1850
The Fugitive Slave Act of 1850, part of the Compromise of 1850,
was a federal law that declared that all fugitive slaves should be
returned to their enslavers. Because the slave states agreed to have California
enter as a free state, the free states agreed to pass the Fugitive
Slave Act of 1850. Congress passed the act on September 18, 1850, and
repealed it on June 28, 1864. The act strengthened the federal
government's authority in capturing fugitive slaves. The act authorized
federal marshals to require free state citizen bystanders to aid in the
capturing of runaway slaves. Many free state citizens perceived the
legislation as a way in which the federal government overstepped its
authority because the legislation could be used to force them to act
against abolitionist beliefs. Many free states eventually passed
"personal liberty laws", which prevented the kidnapping of alleged
runaway slaves; however, in the court case known as Prigg v. Pennsylvania,
the personal liberty laws were ruled unconstitutional because the
capturing of fugitive slaves was a federal matter in which states did
not have the power to interfere.
Many free state citizens were outraged at the criminalization of actions by Underground Railroad operators and abolitionists who helped people escape slavery. It is considered one of the causes of the American Civil War (1861–1865). Congress repealed the Fugitive Acts of 1793 and 1850 on June 28, 1864.
State laws
Many states tried to nullify
the acts or prevent the capture of escaped enslaved people by setting
up laws to protect their rights. The most notable is the Massachusetts
Liberty Act. This act was passed to keep escaped slaves from being
returned to their enslavers through abduction by federal marshals or
bounty hunters.
Wisconsin and Vermont also enacted legislation to bypass the federal
law. Abolitionists became more involved in Underground Railroad
operations.
Enslavers were outraged when an enslaved person was found missing,
many of them believing that slavery was good for the enslaved person,
and if they ran away, it was the work of abolitionists, with one enslaver arguing that "They are indeed happy, and if let alone would still remain so". (A new name was invented for the supposed mental illness of an enslaved person that made them want to run away: drapetomania.)
Enslavers would put up flyers, place advertisements in newspapers,
offer rewards, and send out posses to find them. Under the Fugitive
Slave Act, enslavers could send federal marshals into free states to
kidnap them. The law also brought bounty hunters
into the business of returning enslaved people to their enslavers; a
former enslaved person could be brought back into a slave state to be
sold back into slavery if they were without freedom papers. In 1851,
there was a case of a black coffeehouse waiter who federal marshals
kidnapped on behalf of John Debree, who claimed to be the man's
enslaver.
Capture
Fugitive slave Gordon during his 1863 medical examination in a U.S. Army camp.
Enslavers often harshly punished those they successfully recaptured,
such as by amputating limbs, whipping, branding, and hobbling.
Individuals who aided fugitive slaves were charged and punished under this law. In the case of Ableman v. Booth,
the latter was charged with aiding Joshua Glover's escape in Wisconsin
by preventing his capture by federal marshals. The Wisconsin Supreme
Court ruled that the Fugitive Slave Act of 1850 was unconstitutional,
requiring states to violate their laws. Ableman v. Booth was appealed by the federal government to the US Supreme Court, which upheld the act's constitutionality.
In 1786, George Washington complained that a Quaker tried to free one of his slaves. In the early 1800s, Isaac T. Hopper, a Quaker from Philadelphia, and a group of people from North Carolina established a network of stations in their local area.
In 1831, when Tice David was captured going into Ohio from Kentucky,
his enslaver blamed an "Underground Railroad" who helped in the escape.
Eight years later, while being tortured for his escape, a man named Jim
said he was going north along the "underground railroad to Boston."
Fellow enslaved people often helped those who had run away. They
gave signals, such as the lighting of a particular number of lamps, or
the singing of a particular song on Sunday, to let escaping people know
if it was safe to be in the area or if there were slave hunters nearby.
If the freedom seeker stayed in a slave cabin, they would likely get
food and learn good hiding places in the woods as they made their way
north.
Hiding places called "stations" were set up in private homes,
churches, and schoolhouses in border states between slave and free
states. John Brown had a secret room in his tannery to give escaped enslaved people places to stay on their way. People who maintained the stations provided food, clothing, shelter, and instructions about reaching the next "station". Often, enslaved people had to make their way through southern slave states on their own to reach them.
The network extended throughout the United States—including Spanish Florida, Indian Territory, and Western United States—and into Canada and Mexico.
The Underground Railroad was initially an escape route that would
assist fugitive enslaved African Americans in arriving in the Northern
states; however, with the passage of the Fugitive Slave Act of 1850, as
well as other laws aiding the Southern states in the capture of runaway
slaves, it became a mechanism to reach Canada. Canada was a haven for
enslaved African-Аmericans because it had already abolished slavery by
1783. Black Canadians were also provided equal protection under the law. The well-known Underground Railroad "conductor" Harriet Tubman is said to have led approximately 300 enslaved people to Canada. In some cases, freedom seekers immigrated to Europe and the Caribbean islands.
Harriet Tubman
One of the most notable runaway slaves of American history and conductors of the Underground Railroad is Harriet Tubman. Born into slavery in Dorchester County, Maryland,
around 1822, Tubman as a young adult, escaped from her enslaver's
plantation in 1849. Between 1850 and 1860, she returned to the South
numerous times to lead parties of other enslaved people to freedom,
guiding them through the lands she knew well. She aided hundreds of
people, including her parents, in their escape from slavery. Tubman followed north–south flowing rivers and the north star
to make her way north. She preferred to guide runaway slaves on
Saturdays because newspapers were not published on Sundays, which gave
her a one-day head-start before runaway advertisements would be
published. She preferred the winters because the nights were longer when
it was the safest to travel. Tubman wore disguises. She sang songs in different tempos, such as Go Down Moses and Bound For the Promised Land, to indicate whether it was safe for freedom seekers to come out of hiding. Many people called her the "Moses of her people." During the American Civil War, Tubman also worked as a spy, cook, and a nurse.
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone sterility, and consequent increase in fracture risk. It is the most common reason for a broken bone among the elderly. Bones that commonly break include the vertebrae in the spine, the bones of the forearm, the wrist, 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. After the broken bone heals, the person may have chronic pain and a decreased ability to carry out normal activities.
Prevention of osteoporosis includes a proper diet during childhood, hormone replacement therapy
for menopausal women, and efforts to avoid medications that increase
the rate of bone loss. 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. Bisphosphonate medications
are useful to decrease future broken bones in those with previous
broken bones due to osteoporosis. In those with osteoporosis but no
previous broken bones, they are less effective.They do not appear to affect the risk of death.
Osteoporosis becomes more common with age. About 15% of Caucasians 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 8 million women and between 1 and 2 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
Illustration depicting normal standing posture and osteoporosis
Osteoporosis has no symptoms and the person usually does not know that they have osteoporosis until a bone is broken. 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.
Examples of situations where people would not normally break a bone
include a fall from standing height, normal day-to-day activities such
as lifting, bending, or coughing.
Fractures
Fractures are a common symptom of osteoporosis and can result in disability.
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.
There is also an increased risk of mortality associated with hip
surgery, with the mean average mortality rate for Europe being 23.3%,
for Asia 17.9%, United States 21% and Australia 24.9%.
Fracture risk calculators assess the risk of fracture based upon several criteria, including bone mineral density, age, smoking, alcohol usage, weight, and gender. Recognized calculators include FRAX, the Garvan FRC calculator and QFracture as well as the open access FREM tool. The FRAX tool can also be applied in a modification adapted to routinely collected health data.
Progression of the shape of vertebral column with age in osteoporosis
There is an increased risk of falls associated with aging. These
falls can lead to skeletal damage at the wrist, spine, hip, knee, foot,
and ankle. Part of the fall risk is because of impaired eyesight due to
many causes, (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). 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.
Complications
As
well as susceptibility to breaks and fractures, osteoporosis can lead
to other complications. Bone fractures from osteoporosis can lead to
disability and an increased risk of death after the injury in elderly
people. Osteoporosis can decrease the quality of life, increase disabilities, and increase the financial costs to health care systems.
Risk factors
The
risk of having osteoporosis includes age and sex. Risk factors include
both nonmodifiable (for example, age and some medications that may be
necessary to treat a different condition) and modifiable (for example,
alcohol use, smoking, vitamin deficiency). In addition, osteoporosis is a
recognized complication of 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.
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 surgical removal of the ovaries is correlated with a rapid reduction in bone mineral density, while in men, a decrease in testosterone levels has a comparable (but less pronounced) effect.
Ethnicity: 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, is 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.
Build: A small stature is also a nonmodifiable risk factor associated with the development of osteoporosis.
Potentially modifiable
Alcohol:
Alcohol intake (greater than three units/day) may increase the risk of
osteoporosis and people who consumed 0.5-1 drinks a day may have 1.38
times the risk compared to people who do not consume alcohol.
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. Imbalance of omega-6 to omega-3 polyunsaturated fats is yet another identified risk factor.
A 2017 meta-analysis of published medical studies shows that higher
protein diet helps slightly with lower spine density but does not show
significant improvement with other bones. A 2023 meta-analysis sees no evidence for the relation between protein intake and bone health.
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 in osteomalacia (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.
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.
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.
Certain
medications have been associated with an increase in osteoporosis risk;
only glucocorticosteroids 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. It is recommended to use calcium or Vitamin D as prevention. Alternate day use may not prevent this complication.
L-Thyroxine over-replacement may contribute to osteoporosis, in a similar fashion as thyrotoxicosis does. This can be relevant in subclinical hypothyroidism.
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.
Chronic lithium therapy has been associated with osteoporosis.
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.
Fracture risk assessment
In
the absence of risk factors other than sex and age a BMD measurement
using dual-energy X-ray absorptiometry (DXA) is recommended for women at
age 65. For women with risk factors a clinical FRAX is advised at age
50.
Pathogenesis
Osteoporosis locations
The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation. In normal bone, matrix
remodeling of bone is constant; up to 10% of all bone mass may be
undergoing remodeling at any point in time. The process takes place in
bone multicellular units (BMUs) as first described by Frost & Thomas
in 1963. Osteoclasts are assisted by transcription factor PU.1 to degrade the bone matrix, while osteoblasts
rebuild the bone matrix. Low bone mass density can then occur when
osteoclasts are degrading the bone matrix faster than the osteoblasts
are rebuilding the bone.
The three main mechanisms by which osteoporosis develops are an
inadequate peak bone mass (the skeleton develops insufficient mass and
strength during growth), excessive bone resorption, and inadequate
formation of new bone during remodeling, likely due to mesenchymal stem
cells biasing away from the osteoblast and toward the marrow adipocyte lineage. An interplay of these three mechanisms underlies the development of fragile bone tissue.
Hormonal factors strongly determine the rate of bone resorption; lack
of estrogen (e.g. as a result of menopause) increases bone resorption,
as well as decreasing the deposition of new bone that normally takes
place in weight-bearing bones. The amount of estrogen needed to suppress
this process is lower than that normally needed to stimulate the uterus and breast gland. The α-form of the estrogen receptor appears to be the most important in regulating bone turnover. In addition to estrogen, calcium metabolism
plays a significant role in bone turnover, and deficiency of calcium
and vitamin D leads to impaired bone deposition; in addition, the parathyroid glands
react to low calcium levels by secreting parathyroid hormone
(parathormone, PTH), which increases bone resorption to ensure
sufficient calcium in the blood. The role of calcitonin, a hormone generated by the thyroid that increases bone deposition, is less clear and probably not as significant as that of PTH.
The activation of osteoclasts is regulated by various molecular signals, of which RANKL (receptor activator of nuclear factor kappa-B ligand) is one of the best-studied. This molecule is produced by osteoblasts and other cells (e.g. lymphocytes), and stimulates RANK (receptor activator of nuclear factor κB). Osteoprotegerin
(OPG) binds RANKL before it has an opportunity to bind to RANK, and
hence suppresses its ability to increase bone resorption. RANKL, RANK,
and OPG are closely related to tumor necrosis factor and its receptors. The role of the Wnt signaling pathway is recognized, but less well understood. Local production of eicosanoids and interleukins
is thought to participate in the regulation of bone turnover, and
excess or reduced production of these mediators may underlie the
development of osteoporosis. Osteoclast maturation and activity is also regulated by activation of colony stimulating factor 1 receptor (CSF1R). Menopause-associated increase production of TNF-α stimulates stromal cells to produce colony stimulating factor 1 (CSF-1) which activates CSF1R and stimulates osteoclasts to reabsorb bone.
Trabecular bone (or cancellous bone) is the sponge-like bone in the ends of long bones and vertebrae. Cortical bone
is the hard outer shell of bones and the middle of long bones. Because
osteoblasts and osteoclasts inhabit the surface of bones, trabecular
bone is more active and is more subject to bone turnover and remodeling.
Not only is bone density decreased, but the microarchitecture of bone
is also disrupted. The weaker spicules of trabecular bone break
("microcracks"), and are replaced by weaker bone. Common osteoporotic
fracture sites, the wrist, the hip, and the spine, have a relatively
high trabecular bone to cortical bone ratio. These areas rely on the
trabecular bone for strength, so the intense remodeling causes these
areas to degenerate most when the remodeling is imbalanced. Around the ages of 30–35, cancellous or trabecular bone loss begins. Women may lose as much as 50%, while men lose about 30%.
Light micrograph of an osteoclast displaying typical distinguishing characteristics: a large cell with multiple nuclei and a "foamy" cytosol.
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.
Conventional radiography
Conventional radiography is useful, both by itself and in conjunction with CT or MRI, for detecting complications of osteopenia
(reduced bone mass; pre-osteoporosis), 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 (DEXA scan) 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:
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.
Biomarkers
Chemical biomarkers are a useful tool in detecting bone degradation. The enzyme cathepsin K breaks down type-I collagen, an important constituent in bones. Prepared antibodies can recognize the resulting fragment, called a neoepitope, as a way to diagnose osteoporosis. Increased urinary excretion of C-telopeptides, a type-I collagen breakdown product, also serves as a biomarker for osteoporosis.
Quantitative computed tomography
(QCT) differs from DXA in that it gives separate estimates of BMD for
trabecular and cortical bone and reports precise volumetric mineral
density in mg/cm3 rather than BMD's relative Z-score. Among
QCT's advantages: it can be performed at axial and peripheral sites, can
be calculated from existing CT scans without a separate radiation dose,
is sensitive to change over time, can analyze a region of any size or
shape, excludes irrelevant tissue such as fat, muscle, and air, and does
not require knowledge of the patient's subpopulation in order to create
a clinical score (e.g. the Z-score of all females of a certain age).
Among QCT's disadvantages: it requires a high radiation dose compared to
DXA, CT scanners are large and expensive, and because its practice has
been less standardized than BMD, its results are more
operator-dependent. Peripheral QCT has been introduced to improve upon
the limitations of DXA and QCT.
Quantitative ultrasound
has many advantages in assessing osteoporosis. The modality is small,
no ionizing radiation is involved, measurements can be made quickly and
easily, and the cost of the device is low compared with DXA and QCT
devices. The calcaneus
is the most common skeletal site for quantitative ultrasound assessment
because it has a high percentage of trabecular bone that is replaced
more often than cortical bone, providing early evidence of metabolic
change. Also, the calcaneus is fairly flat and parallel, reducing
repositioning errors. The method can be applied to children, neonates,
and preterm infants, just as well as to adults. Some ultrasound devices can be used on the tibia.
Screening
The U.S. Preventive Services Task Force (USPSTF) recommend that all women 65 years of age or older be screened by bone densitometry. Additionally they recommend screening younger women with risk factors.
There is insufficient evidence to make recommendations about the
intervals for repeated screening and the appropriate age to stop
screening.
In men the harm versus benefit of screening for osteoporosis is unknown. Prescrire states that the need to test for osteoporosis in those who have not had a previous bone fracture is unclear.
The International Society for Clinical Densitometry suggest BMD testing
for men 70 or older, or those who are indicated for risk equal to that
of a 70‑year‑old. A number of tools exist to help determine who is reasonable to test.
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.
In people with coeliac disease adherence to a gluten-free diet decreases the risk of developing osteoporosis and increases bone density. The diet must ensure optimal calcium intake (of at least one gram daily) and measuring vitamin D levels is recommended, and to take specific supplements if necessary.
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 2018 review by the USPSTF found low-quality evidence that the routine
use of calcium and vitamin D supplements (or both supplements together)
did not reduce the risk of having an osteoporotic fracture in male and
female adults living in the community who had no known history of
vitamin D deficiency, osteoporosis, or a fracture. The USPSTF does 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. A 2015 review found little data that supplementation of calcium decreases the risk of fractures.
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 (800 IU/day or less) alone.While supplementation does not appear to affect the risk of death, an increased risk of myocardial infarctionskidney stones, and stomach problems is associated with calcium supplementation.
Vitamin K deficiency is also a risk factor for osteoporotic fractures. The gene gamma-glutamyl carboxylase (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.
Dietary sources of calcium include dairy products, leafy greens, legumes, and beans.
There has been conflicting evidence about whether or not dairy is an
adequate source of calcium to prevent fractures. The National Academy of
Sciences recommends 1,000 mg of calcium for those aged 19–50, and
1,200 mg for those aged 50 and above. A review of the evidence shows no adverse effect of higher protein intake on bone health.
Physical exercise
There is limited evidence indicating that exercise is helpful in promoting bone health.
There is some evidence that physical exercise may be beneficial for
bone density in postmenopausal women and lead to a slightly reduced risk
of a bone fracture (absolute difference 4%). Weight bearing exercise has been found to cause an adaptive response in the skeleton. Weight bearing exercise promotes osteoblast activity, protecting bone density.
A position statement concluded that increased bone activity and
weight-bearing exercises at a young age prevent bone fragility in
adults.
Bicycling and swimming are not considered weight-bearing exercise.
Neither contribute to slowing bone loss with age, and professional
bicycle racing has a negative effect on bone density.
Low-quality evidence suggests that exercise may reduce pain and
improve quality of life of people with vertebral fractures and there is
moderate-quality evidence that exercise will likely improve physical
performance in individuals with vertebral fractures.
Physical therapy
People with osteoporosis are at higher risk of falls due to poor postural control, muscle weakness, and overall deconditioning.
Postural control is important to maintaining functional movements such
as walking and standing. Physical therapy may be an effective way to
address postural weakness that may result from vertebral fractures,
which are common in people with osteoporosis. Physical therapy treatment
plans for people with vertebral fractures include balance training,
postural correction, trunk and lower extremity muscle strengthening
exercises, and moderate-intensity aerobic physical activity.
The goal of these interventions are to regain normal spine curvatures,
increase spine stability, and improve functional performance. Physical therapy interventions were also designed to slow the rate of bone loss through home exercise programs.
Whole body vibration
therapy has also been suggested as a physical therapy intervention.
Moderate to low-quality evidence indicates that whole body vibration
therapy may reduce the risk of falls. There are conflicting reviews as to whether vibration therapy improves bone mineral density.
Physical therapy can aid in overall prevention in the development
of osteoporosis through therapeutic exercise. Prescribed amounts of
mechanical loading or increased forces on the bones promote bone
formation and vascularization in various ways, therefore offering a
preventative measure that is not reliant on drugs. Specific exercise
interacts with the body's hormones and signaling pathways which
encourages the maintenance of a healthy skeleton.
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. Daily intake of calcium and vitamin D is recommended for postmenopausal women. Fall prevention can help prevent osteoporosis complications. There is some evidence for hip protectors specifically among those who are in care homes.
Pharmacologic therapy
The
US National Osteoporosis Foundation recommends pharmacologic treatment
for patients with hip of spine fracture thought to be related to
osteoporosis, those with BMD 2.5 SD or more below the young normal mean
(T-score -2.5 or below), and those with BMD between 1 and 2.5 SD below
normal mean whose 10-year risk, using FRAX, for hip fracture is equal or
more than 3%.
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 do not appear to change the overall risk of death. Tentative evidence does not support the use of bisphosphonates as a standard treatment for secondary osteoporosis in children. Different bisphosphonates have not been directly compared, therefore it is unknown if one is better than another. 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.
One medical organization recommends that after five years of
medications by mouth or three years of intravenous medication among
those at low risk, bisphosphonate treatment can be stopped. In those at higher risk they recommend up to ten years of medication by mouth or six years of intravenous treatment.
The goal of osteoporosis management is to prevent osteoporotic
fractures, but for those who have sustained one already it is more
urgent to prevent a secondary fracture.
That is because patients with a fracture are more likely to experience a
recurrent fracture, with marker increase in morbidity and mortality
compared.
Among the five bisphosphonates, no significant differences were found
for a secondary fracture for all fracture endpoints combined.
That being said, alendronate was identified as the most efficacious for
secondary prevention of vertebral and hip fractures while zoledronate
showed better performance for nonvertebral non-hip fracture prevention. There is concern that many people do not receive appropriate pharmacological therapy after a low-impact fracture.
For those with osteoporosis but who have not had a fracture, evidence does not support a reduction in fracture risk with risedronate or etidronate. Alendronate decreases fractures of the spine but does not have any effect on other types of fractures. Half stop their medications within a year. When on treatment with bisphosphonates rechecking bone mineral density is not needed. There is tentative evidence of benefit in males with osteoporosis.
Fluoride supplementation does not appear to be effective in
postmenopausal osteoporosis, as even though it increases bone density,
it does not decrease the risk of fractures.
Teriparatide (a recombinant parathyroid hormone) has been shown to be effective in treatment of women with postmenopausal osteoporosis. Some evidence also indicates strontium 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. It is not recommended for osteoporosis by itself. 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. While denosumab is effective at preventing fractures in women, there is not clear evidence of benefit in males.
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 and questionable effect on fracture risk. Alendronic acid/colecalciferol can be taken to treat this condition in post-menopausal women.
Romosozumab (sold under the brand name Evenity) is a monoclonal antibody against sclerostin.
Romosozumab is usually reserved for patients with very high fracture
risk and is the only available drug therapy for osteoporosis that leads
to simultaneous inhibition of bone resorption together with an anabolic effect.
Certain medications like alendronate, etidronate, risedronate,
raloxifene, and strontium ranelate can help to prevent osteoporotic
fragility fractures in postmenopausal women with osteoporosis. Tentative evidence suggests that Chinese herbal medicines may have potential benefits on bone mineral density.
Although people with osteoporosis have increased mortality due to the
complications of fracture, the fracture itself is rarely lethal.
Hip fractures can lead to decreased mobility and additional risks of numerous complications (such as deep venous thrombosis and/or pulmonary embolism, and pneumonia).
The six-month mortality rate for those aged 50 and above following hip
fracture was found to be around 13.5%, with a substantial proportion
(almost 13%) needing total assistance to mobilize after a hip fracture.
Vertebral fractures, while having a smaller impact on mortality,
can lead to severe chronic pain of neurogenic origin, which can be hard
to control, as well as deformity. Though rare, multiple vertebral
fractures can lead to such severe hunchback (kyphosis), the resulting pressure on internal organs can impair one's ability to breathe.
Apart from risk of death and other complications, osteoporotic fractures are associated with a reduced health-related quality of life.
The condition is responsible for millions of fractures annually,
mostly involving the lumbar vertebrae, hip, and wrist. Fragility
fractures of ribs are also common in men.
Fractures
Hip
fractures are responsible for the most serious consequences of
osteoporosis. In the United States, more than 250,000 hip fractures
annually are attributable to osteoporosis. A 50-year-old white woman is estimated to have a 17.5% lifetime risk of fracture of the proximal femur.
The incidence of hip fractures increases each decade from the sixth
through the ninth for both women and men for all populations. The
highest incidence is found among men and women ages 80 or older.
Between 35 and 50% of all women over 50 had at least one vertebral fracture.
In the United States, 700,000 vertebral fractures occur annually, but
only about a third are recognized. In a series of 9704 women aged 68.8
on average studied for 15 years, 324 had already sustained a vertebral
fracture at entry into the study and 18.2% developed a vertebral
fracture, but that risk rose to 41.4% in women who had a previous
vertebral fracture.
In the United States, 250,000 wrist fractures annually are attributable to osteoporosis. Wrist fractures are the third most common type of osteoporotic fractures. The lifetime risk of sustaining a Colles' fracture is about 16% for white women. By the time women reach age 70, about 20% have had at least one wrist fracture.
Fragility fractures of the ribs are common in men as young as age 35.
These are often overlooked as signs of osteoporosis, as these men are
often physically active and develop the fracture in the course of
physical activity, such as falling while water skiing or jet skiing.
Epidemiology
Age-standardised hip fracture rates in 2012.
Low (< 150 / 100 000)
Medium (150–250 / 100 000)
High (> 250 / 100 000)
It is estimated that 200 million people have osteoporosis. Osteoporosis becomes more common with age. About 15% of Caucasians 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.
Postmenopausal women have a higher rate of osteoporosis and fractures than older men. Postmenopausal women have decreased estrogen which contributes to their higher rates of osteoporosis. A 60-year-old woman has a 44% risk of fracture while a 60-year-old man has a 25% risk of fracture.
There are 8.9 million fractures worldwide per year due to osteoporosis. Globally, 1 in 3 women and 1 in 5 men over the age of 50 will have an osteoporotic fracture.
Data from the United States shows a decrease in osteoporosis within the
general population and in white women, from 18% in 1994 to 10% in 2006. White and Asian people are at greater risk.
People of African descent are at a decreased risk of fractures due to
osteoporosis, although they have the highest risk of death following an
osteoporotic fracture.
It has been shown that latitude affects risk of osteoporotic fracture.
Areas of higher latitude such as Northern Europe receive less Vitamin D
through sunlight compared to regions closer to the equator, and
consequently have higher fracture rates in comparison to lower
latitudes.
For example, Swedish men and women have a 13% and 28.5% risk of hip
fracture by age 50, respectively, whereas this risk is only 1.9% and
2.4% in Chinese men and women.
Diet may also be a factor that is responsible for this difference, as
vitamin D, calcium, magnesium, and folate are all linked to bone mineral
density.
There is also an association between Celiac Disease and increased risk of osteoporosis.
In studies with premenopausal females and males, there was a
correlation between Celiac Disease and osteoporosis and osteopenia.
Celiac Disease can decrease absorption of nutrients in the small
intestine such as calcium, and a gluten-free diet can help people with
Celiac Disease to revert to normal absorption in the gut.
About 22 million women and 5.5 million men in the European Union had osteoporosis in 2010. In the United States in 2010 about 8 million women and one to 2 million men had osteoporosis.
This places a large economic burden on the healthcare system due to
costs of treatment, long-term disability, and loss of productivity in
the working population. The EU spends 37 billion euros per year in
healthcare costs related to osteoporosis, and the US spends an estimated
US$19 billion annually for related healthcare costs.
History
The link between age-related reductions in bone density goes back to the early 1800s. French pathologist Jean Lobstein coined the term osteoporosis. The American endocrinologist Fuller Albright linked osteoporosis with the postmenopausal state.
Anthropologists
have studied skeletal remains that showed loss of bone density and
associated structural changes that were linked to a chronic malnutrition
in the agricultural area in which these individuals lived. "It follows
that the skeletal deformation may be attributed to their heavy labor in
agriculture as well as to their chronic malnutrition", causing the
osteoporosis seen when radiographs of the remains were made.
.jpg)
