Osteoporosis

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Adminஐﻬ:
Osteoporosis

~Definition
 Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures, especially of the hip, spine and wrist, although any bone can be affected.
 
~Prevalence
 Osteoporosis is a major public health threat for an estimated 44 million Americans, or 55 percent of the people 50 years of age and older. In the U.S., 10 million individuals are estimated to already have the disease and almost 34 million more are estimated to have low bone mass, placing them at increased risk for osteoporosis.

Of the 10 million Americans estimated to have osteoporosis, eight million are women and two million are men.

Significant risk has been reported in people of all ethnic backgrounds.

While osteoporosis is often thought of as an older person's disease, it can strike at any age.

~Women

Eighty percent of those affected by osteoporosis are women.

Twenty percent of non-Hispanic white and Asian women aged 50 and older are estimated to have osteoporosis, and 52 percent are estimated to have low bone mass.

Five percent of non-Hispanic black women over age 50 are estimated to have osteoporosis; an estimated additional 35 percent have low bone mass that puts them at risk of developing osteoporosis.

Ten percent of Hispanic women aged 50 and older are estimated to have osteoporosis, and 49 percent are estimated to have low bone mass.

Osteoporosis is under-recognized and under-treated not only in Caucasian women, but in African-American women as well.

 ~Men

Twenty percent of those affected by osteoporosis are men.

Seven percent of non-Hispanic white and Asian men aged 50 and older are estimated to have osteoporosis, and 35 percent are estimated to have low bone mass.

Four percent of non-Hispanic black men aged 50 and older are estimated to have osteoporosis, and 19 percent are estimated to have low bone mass.

Three percent of Hispanic men aged 50 and older are estimated to have osteoporosis, and 23 percent are estimated to have low bone mass.

~Fractures

One in two women and one in four men over age 50 will have an osteoporosis-related fracture in her/his remaining lifetime.

Osteoporosis is responsible for more than 1.5 million fractures annually, including:

over 300,000 hip fractures; and approximately

700,000 vertebral fractures;

250,000 wrist fractures; and

300,000 fractures at other sites.

Hip fracture risk is increasing most rapidly among Hispanic women. 

Women with a hip fracture are at a four-fold greater risk of a second one, and the risk factors are similar to those for the first hip fracture.

Osteoporotic fractures lower a patient’s quality of life. 
 
Cost The estimated national direct care expenditures (including hospitals, nursing homes, and outpatient services) for osteoporotic fractures is $18 billion per year in 2002 dollars, and costs are rising.
 
Symptoms Osteoporosis is often called a "silent disease" because bone loss occurs without symptoms.  People may not know that they have osteoporosis until their bones become so weak that a sudden strain, bump or fall causes a fracture or a vertebra to collapse.  Collapsed vertebrae may initially be felt or seen in the form of severe back pain, loss of height, or spinal deformities such as kyphosis or stooped posture.
 
Risk Factors Certain people are more likely to develop osteoporosis than others.  Factors that increase the likelihood of developing osteoporosis and fractures are called "risk factors."  These risk factors include: 

Personal history of fracture after age 50

Current low bone mass

History of fracture in a 1° relative

Being female

Being thin and/or having a small frame

Advanced age

A family history of osteoporosis

Estrogen deficiency as a result of menopause, especially early or surgically induced

Abnormal absence of menstrual periods (amenorrhea)

Anorexia nervosa

Low lifetime calcium intake

Vitamin D deficiency

Use of certain medications (corticosteroids, chemotherapy, anticonvulsants and others)

Presence of certain chronic medical conditions

Low testosterone levels in men

An inactive lifestyle

Current cigarette smoking

Excessive use of alcohol

Being Caucasian or Asian, although African Americans and Hispanic Americans are at significant risk as well

Women can lose up to 20 percent of their bone mass in the five to seven years following menopause, making them more susceptible to osteoporosis.
 
Detection Specialized tests called bone mineral density (BMD) tests can measure bone density in various sites of the body.  A BMD test can:

Detect osteoporosis before a fracture occurs

Predict chances of fracturing in the future

Determine rate of bone loss and/or monitor the effects of treatment if a DXA BMD test is conducted at intervals of one year or more 

Medicare reimburses for BMD testing every two years.

An increase in BMD testing and osteoporosis treatment was associated with a decrease in hip fracture incidence.

Bone density is an important determinant of fracture risk even in nursing home patients.

There has been a five-fold increase in office visits for osteoporosis (from 1.3 to 6.3 million) in the  past 10 years.
 
Prevention By about age 20, the average woman has acquired 98 percent of her skeletal mass.  Building strong bones during childhood and adolescence can be the best defense against developing osteoporosis later. There are five steps, which together can optimize bone health and help prevent osteoporosis.  They are:

A balanced diet rich in calcium and vitamin D

Weight-bearing and resistance-training exercises

A healthy lifestyle with no smoking or excessive alcohol intake

Talking to one’s healthcare professional about bone health

Bone density testing and medication when appropriate

A study of disease management in a rural healthcare population demonstrated that a preventive program was able to reduce hip fractures and save money.
 
Fractures The most typical sites of fractures related to osteoporosis are the hip, spine, wrist and ribs, although the disease can affect any bone in the body. 

The rate of hip fractures is two to three times higher in women than men; however, the one year mortality following a hip fracture is nearly twice as high  for men as for women.

A woman's risk of hip fracture is equal to her combined risk of breast, uterine and ovarian cancer.

In 2001, about 315,000 Americans age 45 and over were admitted to hospitals with hip fractures. Osteoporosis was the underlying cause of most of these injuries.

An average of 24 percent of hip fracture patients aged 50 and over die in the year following their fracture.

One in five of those who were ambulatory before their hip fracture requires long-term care afterward.

At six months after a hip fracture, only 15 percent of hip fracture patients can walk across a room unaided.

Not just hip fractures, but vertebral fractures are also linked with an increased risk of death.

One in five hip fracture patients ends up in a nursing home, a situation that participants in one study described as less desirable than death.

White women aged 65 or older have twice the incidence of fractures as African-American women.
 Medications Although there is no cure for osteoporosis, the following medications are approved by the FDA for postmenopausal women to prevent and/or treat osteoporosis:

~ANTIRESORPTIVE MEDICATIONS – BISPHOSPHONATES


Alendronate and alendronate plus vitamin D (brand names Fosamax® and Fosamax® plus D)

Alendronate is approved as a treatment for osteoporosis in men and is approved for treatment of glucocorticoid (steroid)-induced osteoporosis in men and women.
Ibandronate (brand name Boniva®)


Ibandronate is approved for the prevention and treatment of osteoporosis in postmenopausal women.
Risedronate and risedronate with calcium (brand names Actonel® and Actonel® with Calcium)

Risedronate is approved for prevention and treatment of glucocorticoid-induced osteoporosis in men and women.
Zoledronic Acid (brand name Reclast®)

Zoledronic acid is approved for the treatment of osteoporosis in postmenopausal women. It is the first and only once-a-year osteoporosis medication.
OTHER ANTIRESORPTIVE MEDICATIONS

Calcitonin (brand names Fortical® and Miacalcin®)

Calcitonin is approved for the treatment of osteoporosis in postmenopausal women who are at least five years beyond menopause.
Estrogen/Hormone Therapy
Multiple brand names available

Estrogen therapy (ET) and estrogen with progesterone hormone therapy (HT) are approved for the prevention of osteoporosis in postmenopausal women.
Because of side effects, the FDA recommends that women consider other medications for the prevention of osteoporosis. According to the FDA, estrogen should not be prescribed for the prevention of postmenopausal osteoporosis unless a woman is at significant risk of osteoporosis and cannot take non-estrogen medications. The FDA also recommends prescribing the lowest possible dose of ET/HT for the shortest period of time.
Selective Estrogen Receptor Modulators (SERMs)
Raloxifene (brand name Evista®)

Raloxifene is approved for the prevention and treatment of osteoporosis in postmenopausal women.
BONE FORMING (ANABOLIC) MEDICATIONS
Teriparatide – Parathyroid Hormone (brand name - Forteo®)

Teriparatide, a type of parathyroid hormone, is approved for the treatment of osteoporosis in postmenopausal women and in men who are at high risk for a fracture. [/size]

Adminஐﻬ:
Osteoporosis is a debilitating disease that can usually be prevented.

OSTEOPOROSIS is a disease people often do not know they have until they break a bone.

Bone thinning due to osteoporosis affects millions of people around the world. While 80% of those affected are women, men are also at risk, and the disease can strike at any age.

Osteoporosis literally means “porous bones” and it is a condition characterised by calcium-depleted bones that become fragile and weak.

Between 2-4% of a person’s skeleton is remodelled every year. This means that calcium and other minerals (magnesium, zinc, copper, boron, manganese) leave the bone in a process called resorption and then must be “remodelled” or replaced.

If not prevented or if left untreated, osteoporosis can progress painlessly until a bone breaks. These broken bones, also known as fractures, occur typically in the hip, spine, and wrist.

Any bone can be affected, but of special concern are fractures of the hip and spine. A hip fracture almost always requires hospitalisation and major surgery. It can impair a person’s ability to walk unassisted and may cause prolonged or permanent disability or even death. 

Spinal or vertebral fractures also have serious consequences, including loss of height, severe back pain, deformity and so on.

Whether due to poor nutrition or reduced hormone levels with the onset of ageing, the loss of calcium and other minerals from the bone creates tiny holes that make bones weak and brittle, particularly if collagen is lost. This is how osteoporosis develops.

Building and maintaining bone mass is paramount to avoiding osteoporosis. By about age 20, the average woman has acquired 98% of her skeletal mass.

Building strong bones during childhood and adolescence can be the best defence against developing osteoporosis later. 

There are five steps, which together, can optimise bone health and help prevent osteoporosis. They are:

Diet: Eating foods rich in calcium, magnesium, zinc, manganese, boron and copper such as milk, broccoli, fish and dark green vegetables.

Weight-bearing and resistance-training exercises: Bones, like muscles, grow stronger when regularly stressed.

A healthy lifestyle with no smoking or excessive alcohol intake.

If you are not meeting the required intake of calcium and other minerals through diet, you should consider taking supplements.

The importance of calcium supplementation has long been recognised in bone health. However, as important as calcium is to bone health, it is found that in the US, only 25% of women with osteoporosis are calcium deficient.

New evidence clearly shows that vitamin D, magnesium, copper, zinc, boron and manganese are also vital for maintaining strong and healthy bone.

These nutrients should all be consumed together for optimal bone metabolism. Even the absence of one nutrient can result in weak bones and osteoporosis.

Calcium plays an important role in maintaining bone. Calcium alone cannot prevent or cure osteoporosis, but it is an important part of an overall prevention or treatment program. The US RDA (recommended daily allowances) for calcium is as follows:

Adults and teenagers – 800 to 1200mg per day.

Pregnant and breast-feeding females – 1200mg per day.

Children four to 10 years of age – 800mg per day.

Children from birth to 3 years of age – 400 to 800mg per day.

Vitamin D helps body absorb calcium. Low levels of vitamin D are common in women, especially the elderly. Deficiencies of vitamin D can lead to calcium deficiencies, leading to soft bones (osteomalacia). Experts recommend a daily intake of between 400 and 800 international units (IU). 

Magnesium is essential for both the preservation and mobilisation of calcium in the bone and is required for the utilisation of vitamin D.

Magnesium deficiency is common and is a leading risk factor for osteoporosis. The US RDA for magnesium is 400mg per day.

Manganese is a trace mineral required for the synthesis of connective tissue that form the matrix upon which mineral deposition occurs. The recommended daily intake for manganese is 2mg.

Boron is needed to convert vitamin D into its active form, which explains why boron deficiency affects calcium metabolism and bone formation.

Boron reduces calcium loss from bones. Although there is no official RDA for boron, a dosage of 1.5 to 3.0mg daily is safe and adequate (Murray, 1996).

Zinc supports bone formation by enhancing the action of vitamin D. Zinc helps maintain bone structure and is involved in bone development.

Copper deficiency may lead to abnormal bone deposition. Copper helps form the building blocks of bone.

When shopping for a calcium supplement, do ensure that it also contains the other essential nutrients mentioned above in adequate amounts to support strong and healthy bones.

Prevention of osteoporosis should begin at birth by meeting the human dietary requirements for calcium and other nutrients and should continue thereafter.
 

Reference:

1. National Osteoporosis Foundation (nof.org

Adminஐﻬ:
Proton pump inhibitors and osteoporosis-related fractures
Laura E. Targownik, MD MSHS* and William D. Leslie, MD

*Assistant Professor of Medicine, Section of Gastroenterology; Professor of Medicine and Radiology, Sections of Endocrinology and Metabolism and Nuclear Medicine, University of Manitoba, Winnipeg, Man.

Two of the authors respond:

We thank Mathieu Forster for his interest in our article.1 He expressed concern about the possible influence of unmeasured variables, specifically smoking status, alcohol use and body mass index, on the association that we observed between use of proton pump inhibitors and the development of osteoporosis-related fractures. For an unmeasured variable to influence the results of the study, it would have to be associated both with the outcome of interest in the unexposed cohort and with the exposure of interest. It has previously been established that smoking, excessive alcohol use and low body mass index are associated with higher risk for osteoporosis and osteoporosis-related fractures,2–4 but for these factors to influence (positively or negatively) the relation between proton pump inhibitor use and osteoporosis-related fractures, they would also have to be independently associated with the use of proton pump inhibitors.

There are currently very little data available to confirm a relation between proton pump inhibitor use and any of the above factors. A recently published analysis of long-term use of proton pump inhibitors suggests a lack of a relation between use of proton pump inhibitors and both smoking and body mass index.5 However, smoking and alcohol use are both positively associated with gastresophageal reflux disease, the most common indication for proton pump inhibitor therapy. Conversely, gastresophageal reflux disease is also strongly associated with obesity,6 which is in fact protective against osteoporosis and osteoporosis-related fractures. Given the likelihood that these influences have opposing effects, it is very likely that the overall effect of these unmeasured variables on the detected association is minimal. We agree that further studies are required to determine whether the association between use of proton pump inhibitors and the development of osteoporosis and osteoporosis-related fractures is truly causal.

Footnotes

Competing interests: Laura Targownik has served on the national advisory board for AstraZeneca Canada. None declared for William Leslie.

REFERENCES

   1. Targownik LE, Lix LM, Metge CJ, et al. Use of proton pump inhibitors and risk of osteoporosis-related fractures. CMAJ 2008;179:319-26.[Abstract/Free Full Text]
   2. De Laet C, Kanis JA, Oden A, et al. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int 2005;16:1330-8.[CrossRef][Medline]
   3. Kanis JA, Johansson H, Johnell O, et al. Alcohol intake as a risk factor for fracture. Osteoporos Int 2005;16:737-42.[CrossRef][Medline]
   4. Kanis JA, Johnell O, Oden A, et al. Smoking and fracture risk: a meta-analysis. Osteoporos Int 2005;16:155-62.[CrossRef][Medline]
   5. Raghunath AS, Hungin AP, Mason J, et al. Symptoms in patients on long-term proton pump inhibitors: prevalence and predictors. Aliment Pharmacol Ther 2009;29:431-9.[CrossRef][Medline]
   6. El-Serag H. The association between obesity and GERD: a review of the epidemiological evidence. Dig Dis Sci 2008;53:2307-12.[CrossRef][Medline]
SOURCE:CMAJ

Adminஐﻬ:
May 14, 2009
Governor David A. Paterson has designated May as Osteoporosis Prevention Month in New York State to remind all New Yorkers to protect their bone health. Nearly three million New Yorkers over age 50 have osteoporosis or are at significant risk of developing osteoporosis. May is also National Osteoporosis Prevention Month.

"Maintaining strong bones should be a lifetime commitment," said State Health Commissioner Richard F. Daines, M.D. "Prevention through diet and exercise, along with early diagnosis and treatment can reduce the prevalence and debilitating affects of this disease."

Osteoporosis is a disease that causes bones to become thin and weak. This "silent disease" progresses without symptoms until a fracture occurs. If left untreated, osteoporosis can lead to debilitating pain, reduced mobility and a loss of quality of life. In 2006, more than 75,000 New Yorkers were hospitalized for falls, many of whom suffered bone fractures related to osteoporosis.

"An astonishing number of adults who break a bone -- as many as 95 percent -- are being treated without being evaluated for osteoporosis," said Commissioner Daines. "Too often, people believe that once they have osteoporosis or a fracture, there is nothing they can do to protect their bones. But there are steps everyone can take at any age to help prevent and treat osteoporosis."

The following steps are recommended to protect bone health:

* Maintain a balanced diet rich in calcium and vitamin D.

* Engage in regular physical activity, including weight-bearing exercise.

* Avoid smoking and excessive alcohol consumption.

* Have a bone mineral density test. Consult with your health care provider as to when and how often.

* Take osteoporosis medications as prescribed by your health care provider.

Nationally, nearly one in two women of Caucasian or Asian/Pacific Island descent, one in four women of African-American, Hispanic/Latina or American Indian/Alaskan Native descent, and one in four men over 50 years of age will have an osteoporosis-related fracture during their lifetime. It is projected that by the year 2020, the number of New Yorkers with either osteoporosis or low bone mass will increase by 25 percent to more than 3.7 million people.

Each year, the New York State Department of Health provides funding to support New York State Osteoporosis Prevention and Education Programs. These not-for-profit organizations and hospitals conduct outreach campaigns, provide education and information, and training and support to the general public and health professionals about the disease.

Adminஐﻬ:
Key Mechanism In Pathogenesis Of Osteoporosis Unraveled
May 20, 2009~
Osteoporosis, or bone loss, is a disease that is most common in the elderly population, affecting women more often than men. Until now, it was not clear exactly how the disease develops. Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now elucidated a molecular mechanism which regulates the equilibrium between bone formation and bone resorption. Dr. Jeske J. Smink, Dr. Valérie Bégay, and Professor Achim Leutz were able to show that two different forms of a gene switch – a short isoform and a long isoform – determine this process.

The MDC researchers hope these findings will lead to new therapies for this bone disease.

In osteoporosis, excessive bone resorption occurs. The bones lose their density and are therefore prone to breakage. Even minor falls can lead to serious bone fractures. The interplay between two cell types determines bone density: bone forming cells (osteoblasts) and bone resorbing cells (osteoclasts). The equilibrium between these two cell types is strictly regulated to prevent the formation of either too much or too little bone.

LAP and LIP maintain the balance

Dr. Smink, Dr. Bégay, and Professor Leutz have now elucidated a complicated mechanism which maintains the equilibrium between bone formation and bone resorption. Here, the gene switch C/EBPbeta plays a major role. It exists in different forms, differing in length and number of building blocks. LAP is the term researchers use to denote the full-length isoform of C/EBPbeta, and LIP is the term for the short isoform.

LAP activates another gene switch (MafB) which suppresses the formation of bone resorbing osteoclasts. In contrast, LIP, suppresses this gene switch and thus enhances the proliferation and activity of the osteoclasts. As a result, the osteoclasts resorb more bone substance than is built by the osteoblasts. The researchers suspect that imbalance in the ratio between LAP and LIP plays a role in osteoporosis.

The activity of a signaling molecule – mTOR – determines which of the two isoforms LAP and LIP is formed. The abbreviation mTOR stands for mammalian Target of Rapamycin. The drug rapamycin inhibits mTOR and thus suppresses the formation of bone resorbing osteoclasts. Unfortunately, rapamycin has severe side-effects on the immune system. "In the future, it may be possible to develop new drugs that regulate the activity of mTOR and, thus, remedy the disturbance in osteoclast function," Professor Leutz said.
Journal reference:

   1. Smink et al. Transcription factor C/EBPβ isoform ratio regulates osteoclastogenesis through MafB. The EMBO Journal, 2009; DOI: 10.1038/emboj.2009.127

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