osteoporosis

                                                             osteoporosis

INTRODUCTION

Osteoporosis is a disease of bone in which the bone mineral density(BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. Osteoporotic bones are more at  risk  of  fracture.  Osteoporosis  is  defined  by  the  WHO in women as a bone mineral density 2.5 standard deviations below peak bone mass (20-year-old sex-matched healthy person average) as measured by DXA; the term "established osteoporosis" includes the presence of a fragility fracture. While treatment modalities are becoming available (such as the bisphosphonates), prevention is still considered the most important way to reduce fracture. Due to its hormonal component, more women, particularly after menopause, suffer from osteoporosis than men. In addition it may be caused by various hormonal conditions, smoking and (specifically glucocorticoids) as well as many chronic diseases. Osteo' means bone, and 'porosis' thinning or becoming more porous, so osteoporosis literally means 'thinning of bone.' It is commonly confused with the word osteoarthritis, which is a form of arthritis that results in breakdown of thecartilagecovering the ends of bones. In contrast, osteoporosis is a condition where bone itself breaks down.  Bones then become thin, brittle and easily broken.

1.1  Anatomy of Bones:

Introduction  Bone (anatomy),  hard connective  tissues, the  major  component  of  almost all   skeletal systems in adult vertebrate animals. However, bone actually is a dynamic structure composed of both living tissues, such as bone cells, fat cells, and blood vessels, and nonliving materials, including water and minerals.Bones are multipurpose structures that play diverse, vital roles in vertebrates. They provide a framework for the body, supporting it and giving it shape. They store calcium, a mineral essential for the activity of nerve and muscle cells. The soft core of bone, the bone marrow, is the site of formation of red blood cells, certain white blood cells, and blood platelets .

           

                                      

                                   

                                                            

                                                          

                                                               

                                                                  

                                            Figure 1:Anatomy of Bones

An adult human has 206 bones, which account for 14 percent of the body total weight. The longest and strongest bone is the thighbone, which at maturity is about 50 cm (20 in) long and 2.5 cm (1 in) wide. The smallest bone, the stirrup bone, is one of three tiny bones buried within the middle ear; it is only 0.18 cm (0.07 in) long.   Bone consists of living cells widely scattered within a nonliving material called the matrix. The matrix is formed by osteoblasts, cells that are constantly renewed in the bone. Osteoblasts make and secrete the protein collagen, which makes bones elastic so that they can give under

the stresses generated by walking, lifting, and other activities. Osteoblasts also secrete mineral salts formed from calcium and phosphorus, which impart hardness so that bones do not break easily. If more bone is needed, new osteoblasts carry out the task of building it. As bone tissue matures, osteoblasts transform into osteocytes, mature bone cells that carry out daily cellular activities. During the early development of a baby within its  body, the skeletal structure consists of cartilage. At about the eighth week of fetal development, calcium and phosphorus salts begin to deposit around the cartilage. At 40 weeks of development, however, the fetal bones still consist primarily of soft cartilage. The skull consists of several cartilage plates that are not completely joined. The spaces between the cartilage plates are called soft spots, or fontanels. The soft cartilage and the fontanels enable the skull to be compressed as it passes through the birth canal. During childhood, cartilage gradually is replaced by bone through the activity of osteoblasts. More than 300 bones are present in an infant, several of which fuse as the infant matures.

 1.2 :Deterioration

A variety of diseases affect bones. One of the most common bone diseases is osteoporosis, which is characterized by a thinning of bone tissue, causing bones to become weak, brittle, and prone to fractures. Many factors can cause osteoporosis, including menopause, lack of exercise, low calcium intake, smoking, use of steroid drugs, and excessive consumption of alcohol.Dietary deficiencies of calcium, phosphorus, and vitamin D cause rickets, a disease characterized by abnormal bone formation and skeletal deformities. Rickets is most common in children. Dietary deficiencies of these nutrients in adults-or metabolic disorders that cause poor absorption of the nutrients-can result in an abnormal softening of bone, a condition called osteomalacia.Infections of bones called osteomyelitis usually are caused by bacteria, especially Staphylococcus, which enters the body through open wounds and may destroy bone tissues. Tumors, or abnormal growths, occur in bone tissue, though most are benign. Cancerous tumors can be caused by excessive radiation; many radioactive substances have an affinity for bone, particularly the marrow, and are readily stored there. Most cancerous tumors in bones, however, are

tumors that spread from cancer in other parts of the body. Cancers that arise in bone, cartilage, and other connective tissues are called sarcomas.

 

OSTEOPOROSIS

Osteoporosis is a disease of bone in which the bone mineral density(BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. Osteoporotic bones are more at  risk  of  fracture.  Osteoporosis  is  defined  by  the  WHO in women as a bone mineral density 2.5 standard deviations below peak bone mass (20-year-old sex-matched healthy person average) as measured by DXA; the term "established osteoporosis" includes the presence of a fragility fracture. While treatment modalities are becoming available (such as the bisphosphonates), prevention is still considered the most important way to reduce fracture. Due to its hormonal component, more women, particularly after menopause, suffer from osteoporosis than men. In addition it may be caused by various hormonal conditions, smoking and (specifically glucocorticoids) as well as many chronic diseases. Osteo' means bone, and 'porosis' thinning or becoming more porous, so osteoporosis literally means 'thinning of bone.' It is commonly confused with the word osteoarthritis, which is a form of arthritis that results in breakdown of thecartilagecovering the ends of bones. In contrast, osteoporosis is a condition where bone itself breaks down.  Bones then become thin, brittle and easily broken.

OSTEOPOROSIS

Osteoporosis (oss-tee-oh-puh-ro-sis) is a condition that means your bones are weak, and you’re more likely to break a bone. Since there are no symptoms, you might not know your bones are getting weaker until you break a bone!                                                                                       The bones in the wrist, hip and spine are most often affected by osteoporosis.      Over time the bones in the spine can collapse.  When a bone in the spine collapses it is called a compression (pronounced com-pre-shun) fracture.  This can result in a person becoming shorter. The bones most commonly affected by osteoporosis are those in the hip, wrist and back (the vertebrae - pronounced ver-te-bray), particularly those in the mid-back.  As vertebrae become thin, they are prone to collapse from relatively minor forces. Usually the fronts of the vertebrae break, leading to a state called wedging, which causes a person to stoop forward and develop a hump-like deformity on the upper spine. Those people who do not develop wedging may notice a progressive loss of height as bone collapse occurs.

warning signs

Ø  Many people do not realize they have osteoporosis until they have had it for a long period of time.

Ø  If you have osteoporosis the first warning sign might be a sudden sharp pain in your back that seems to have come on for no reason.

Ø  After a fall or accident, you could get a sharp pain in your back, ribs, hip or wrist that does not go away.  This could mean one of your bones has broken, even though you might think that the accident was not serious enough to cause a break.

 Pregnancy-associated osteoporosis:

Pregnancy-associated osteoporosis is believed to be a rare condition that is usually found in the third trimester of a woman’s pregnancy or after giving birth. It usually occurs during a woman’s first pregnancy, is temporary, and does not happen again.

Women affected usually complain of back pain, have a loss of height, and have vertebral fractures. Things that may cause this condition, such as genetic factors or steroid use, are being studied. Even though there is stress on a pregnant woman’s calcium supply, and calcium leaves her body more often because of frequent urination, other changes during pregnancy, like increases in estrogen and weight gain, may actually help bone density. There is much more to be learned about how a woman’s bone density is affected by pregnancy.

Risk factors for osteoporosis include:

·     Female sex

·     Age > 70 years

·     Caucasian or Asian race

·     Early onset of menopause

·     Longer postmenopausal interval

History

The link between age-related reductions in bone density and fracture risk goes back at least to Astley Cooper, and the term "osteoporosis" and recognition of its pathological appearance is generally attributed to the French pathologist Lobstein The American endocrinolgist Fuller Albright linked osteoporosis with the postmenopausal state.

 2.1 Classification

       The following three types categories of osteoporosis have been established: 

(1)    TypeI or Post Menopausal Osteoporosis:

        It affects primarily woman within the first 15-20 years following menopause.fractures of the vertebral and distal forearm are seen most frequently in this type ofosteoporosis                                                                 

(2)   Type II or Senile Osteoporosis:

        It affects man and woman older than age 70.the clinical manifestations of  type II   

      

        Osteoporosis are multiple wedge,hip and radius fractures. in which bone loss is

        accelerated over that predicted for age and sex. 

   (3) Type III or Secondary Osteoporosis:            

       Osteoporosis secondary to other diseases or mediators occurs in either sex to any               

       age. secondary osteoporosis results from a variety of identifiable conditions that may

       include:

·     Metabolic bone disease, such as hyperparathyroidism

·     Neoplasia, as with multiple myeloma or metastatic carcinoma

·     Malnutrition

·     Drug therapy, as with corticosteroids

·     Prolonged immobilization

·     Weightlessness with space travel

Consequences of Osteoporosis:

Osteoporotic bone is histologically normal in its composition--there is just less bone. This results in weakened bones that are more prone to fractures with trauma, even minor trauma. The areas most affected are:

·     Hip (femoral head and neck)

·     Wrist

·     Vertebrae

Hip fractures that occur, even with minor falls, can be disabling and confine an elderly person to a wheelchair. It is also possible to surgically put in a prosthetic hip joint. Wrist fractures are common with falls forward with arms extended to break the fall, but the wrist bones break too. Vertebral fractures are of the compressed variety and may be more subtle. Vertebral fractures may result in back pain. Persons suffering fractures are at greater risk for death, not directly from the fracture, but from the

complications that come from hospitalization with immobilization, such as pulmonary thromboembolism and pneumonia.

2.2 Etiology

Family history of fracture or low bone mass are probably the most important etiological factors of primary osteoporosis. The heritability of the fracture as well as low BMD are relatively high, ranging from 25 to 80 percent.estrogen deficiency following menopause is correlated with a rapid reduction in BMD. This, plus the increased risk of falling associated with aging, leads to fractures of the wrist, spine and hip. Other hormone deficiency states can lead to osteoporosis, such as testosterone deficiency. Glucocorticoid or thyroxine excess states also lead to osteoporosis. Lastly, calcium and/or vitamin D deficiency from malnutrition increases the risk of osteoporosis.

Ø  Hypogonadal states - Turner syndrome, Klinefelter syndrome, Kallmann syndrome, anorexia nervosa, hypothalamic amenorrhea, hyperprolactinemia

Ø  Other endocrine disorders - Cushing's syndrome, hyperparathyroidism, thyrotoxicosis, insulin-dependent diabetes mellitus, acromegaly, adrenal insufficiency

Ø  Nutritional and gastrointestinal disorders - malnutrition, parenteral nutrition, malabsorption syndromes (e.g. coeliac disease), gastrectomy, severe liver disease (especially primary biliary cirrhosis)

Ø  Rheumatologic disorders - rheumatoid arthritis, ankylosing spondylitis

Ø  Hematologic disorders/malignancy - multiple myeloma, lymphoma and leukemia, mastocytosis, hemophilia, thalassemia.

Ø  Inherited disorders - osteogenesis imperfecta, Marfan syndrome, hemochromatosis, hypophosphatasia, glycogen storage diseases, homocystinuria, Ehlers-Danlos syndrome, porphyria, Menkes' syndrome, epidermolysis bullosa.

Ø  Medication:

Ø  Steroid-induced osteoporosis (SIOP) due to use of glucocorticoids - analogous to Cushing's syndrome and involving mainly the axial skeleton Barbiturates (due to accelerated metabolism of vitamin D) and some other antiepileptics

Causes of  osteoporosis 

There are many factors that are involved in causing osteoporosis.  Having a combination of factors present increases a person's risk of bone loss and osteoporosis:

Ø  Aging 
Bone is a living tissue that is continually growing and being removed.  Bones usually reach their maximum mass when people are in their mid-thirties. At about age 40, more bone is removed (about 1% per year) than is made, and so the bones start to become weaker. In women the bone loss may reach 3 - 5 % per year during the first five to six years after menopause.

Ø  Family history :
Some people with osteoporosis have other family members with it, which suggests that heredity may be a factor. Heredity also plays a role in a person's body type; having a small frame and bone structure may increase the chances of getting osteoporosis.

Ø   Lack of exercise:
Because bone is a living tissue it needs exercise to stay strong. Normally through the activities of daily living such as walking, bending, stretching, and exercising, forces are imposed upon the bones. Bone responds to these forces by restructuring itself and becoming stronger. 

Ø  Hormone changes:
Osteoporosis can also be linked to changes in hormones.  Certain hormones, such as estrogen, allow women to get pregnant. Estrogen is also a hormone that is important to maintaining bone strength.  

Ø  Diet
 Bones need nourishment from calcium, vitamin D, and phosphorous..

Ø  Medication 
 Some medications, when taken in high doses, can influence how your body deals with calcium and so contribute to bone loss. These medications include cortisone/corticosteroids, anticoagulants, thyroid supplements, and some anti-convulsive drugs.   

Ø   Other illnesses or diseases, such over-active thyroid, diabetes and rheumatoid arthritis may also cause bone loss.  A disease such as anorexia nervosa or bulimia can cause changes in a person's estrogen level and lead to osteoporosis. 

2.3 Pathogenesis:

The underlying mechanism in all cases of osteoporosis is an imbalance between bone resorption and bone formation. Either bone resorption is excessive, and/or bone formation is diminished. Bone matrix is manufactured by the osteoblast cells, whereas bone resorption is accomplished by osteoclast cells. The mechanisms influencing the formation of the disease are complex. Most cases do not result from inadequate calcium intake, but include other factors affecting bone matrix formation and reabsorption. These include: (1) cigarette smoking, which inhibits the activity of osteoblasts; (2) sedentary lifestyle with little weight bearing exercise, such as walking; (3) a family history of osteoporosis; and being age 30 or older. Trabecular bone is the sponge-like bone in the center of long bones and vertebrae. Cortical bone is the hard outer shell of bones. Because osteoblasts and osteoclasts inhabit the surface of bones, trabecular bone is more active, more subject to bone turnover, to remodeling. Long before any overt fractures occur, the small spicules of trabecular bone break and are reformed in the process known as remodeling. Bone will grow and change shape in response to physical stress. The bony prominences and attachments in runners are different in shape and size than those in weightlifters. It is an accumulation of fractures in trabecular bone that are incompletely repaired that leads to the manifestation of osteoporosis. 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 trabecular bone for strength.

Low peak bone mass is important in the development of osteoporosis. Bone mass peaks in both men and women between the ages of 25 and 35, thereafter diminishing. Achieving a higher peak bone mass through exercise and proper nutrition during adolescence is important for the prevention of osteoporosis.Bone remodeling is heavily influenced by nutritional and hormonal factors. Calcium and vitamin D are nutrients required for normal bone growth. Parathyroid hormone regulates the mineral composition of bone, with higher levels causing resorption of calcium and bone. Glucocorticoid hormones cause osteoclast activity to increase, causing bone resorption. Calcitonin, estrogen and testosterone increase osteoblast activity, causing bone growth. The loss of estrogen following menopause causes a phase of rapid bone loss. Similarly, testosterone levels in men diminish with advancing age and are related to male osteoporosis. In addition to estrogen, follicle-stimulating hormone (FSH) affects BMD. In mice, lower levels of FSH mean less resorption by osteoclasts.^[4]

Physical activity causes bone remodeling. People who remain physically active throughout life have a lower risk of osteoporosis. Conversely, people who are bedridden are at a significantly increased risk. Physical activity has its greatest impact during adolescence, affecting peak bone mass most. In adults, physical activity helps maintain bone mass, and can increase it by 1 or 2%.

2.4  Epidemiology

 2.4.1   Disease burden

It is estimated that 1 in 3 women and 1 in 12 men over the age of 50 worldwide have osteoporosis. It is responsible for millions of fractures annually, mostly involving the lumbar vertebrae, hip, and wrist.

2.4.2   Natural history

Today, many cases of osteoporosis in developed countries are diagnosed before symptoms develop. This is due to widespread screening for osteoporosis using the DXA scan. With treatment, bone mineral density increases, and fracture risk decreases.

In the absence of treatment, overt osteoporosis is heralded by a fracture. Some fractures, like vertebral compression fractures or sacral insufficiency fractures, may not be apparent at first, appearing to patient and physician as a very bad back ache or completely without symptoms. Hip fractures and wrist fractures are more obvious.

Hip fractures are responsible for the most serious consequences of osteoporosis. In the United States, osteoporosis causes a predisposition to more than 250,000 hip fractures yearly. It is estimated that a 50-year-old white woman has 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 those men and women ages 80 or older.

An estimated 700,000 women have a first vertebral fracture each year. The lifetime risk of a clinically detected symptomatic vertebral fracture is about 15% in a 50-year-old white woman. However, because symptoms are often overlooked or thought to be a normal part of getting older, it is believed that only about one-third of vertebral compression fractures are actually diagnosed.

Distal radius fractures, usually of the Colles type, are the third most common type of osteoporotic fractures. In the United States, the total annual number of Colles' fractures is about 250,000. 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.

   

SYMPTOMS AND DIAGNOSIS

Sign and symptoms

The mentioned in various sources for Osteoporosis includes the 13 symptoms listed below:

Early symptoms:

• No early symptoms - in many cases there is no indication of gradually thinning bones
• Joint aches
• Muscle aches
• Symptoms of bone weakness from advanced osteoporosis:
• Thin bones
• Brittle bones
• Weak bones
• Fractures
• Fracturing easily
• Backache
• Loss of height

Osteoporosis has been called a “silent thief" because often the first obvious symptom of osteoporosis is a bone fracture. This is why osteoporosis specialists encourage anyone with key risk factors to get a diagnostic assessment that typically includes a bone scan. Using measurements of bone density, a doctor and patient together can take steps to avoid the ultimate symptom of osteoporosis - bone fracture. 

                      

 Risk factors

A number of factors can increase the likelihood that you'll develop osteoporosis, including:

·      Sex. Fractures from osteoporosis are about twice as common in women as they are in men. That's because women start out with lower bone mass and tend to live longer.. From age 75 on, osteoporosis is as common in men as it is in women.

·     Age. The older you get, the higher your risk of osteoporosis. Your bones become weaker as you age.

·     Race. You're at greatest risk of osteoporosis if you're white or of Southeast Asian descent. Black and Hispanic men and women have a lower but still significant risk.

·     Family history. Osteoporosis runs in families. For that reason, having a parent or sibling with osteoporosis puts you at greater risk, especially if you also have a family history of fractures.

·     Frame size. Men and women who are exceptionally thin or have small body frames tend to have higher risk because they may have less bone mass to draw from as they age.

·     Tobacco use. The exact role tobacco plays in osteoporosis isn't clearly understood,

·     Lifetime exposure to estrogen. The greater a woman's lifetime exposure to estrogen, the lower her risk of osteoporosis.

·     Eating disorders. Women and men with anorexia nervosa or bulimia are at higher risk of lower bone density in their lower backs and hips.

·     Corticosteroid medications. Long-term use of corticosteroid medications, such as prednisone, cortisone, prednisolone and dexamethasone, is damaging to bone. These medications are common treatments for chronic conditions such as asthma, rheumatoid arthritis and psoriasis.

·     Thyroid hormone. Too much thyroid hormone also can cause bone loss. This can occur either because your thyroid is overactive (hyperthyroidism) or because you take excess amounts of thyroid hormone medication to treat an underactive thyroid (hypothyroidism).

·      Diuretics. Drugs that prevent buildup of fluids in your body — diuretics — cause the kidneys to excrete more calcium, leading to thinning bones. Diuretics that cause calcium loss include furosemide (Lasix), bumetanide (Bumex), ethacrynic acid (Edecrin) and torsemide (Demadex). If.

·      Other medications. Long-term use of the blood-thinning medication heparin, the drug methotrexate, some anti-seizure medications and aluminum-containing antacids also can cause bone loss.

·      Breast cancer. Postmenopausal women who have had breast cancer are at increased risk of osteoporosis, especially if they were treated with chemotherapy or aromatase inhibitors such as anastrozole, letrozole and exemestane, which suppress estrogen..

·       Low calcium intake. A lifelong lack of calcium plays a major role in the development of osteoporosis..

·       Medical conditions and procedures that decrease calcium absorption. Stomach surgery (gastrectomy) can affect your body's ability to absorb calcium. So can conditions such as Crohn's disease, hyperparathyroidism, anorexia nervosa and Cushing's disease — a rare disorder in which your adrenal glands produce excessive corticosteroid hormones.

·      Sedentary lifestyle. Bone health begins in childhood. Children who are physically active and consume adequate amounts of calcium-containing foods

have the greatest bone density. Any weight-bearing exercise is beneficial, but jumping and hopping seem particularly helpful for creating healthy bones

·     Excess soda consumption. The link between osteoporosis and caffeinated sodas isn't clear, but caffeine may interfere with calcium absorption and its diuretic effect may increase mineral loss. In addition, the phosphoric acid in soda may contribute to bone loss by changing the acid balance in the blood.

·     Chronic alcoholism. For men, alcoholism is one of the leading risk factors for osteoporosis..

·     Depression. People who experience serious depression have increased rates of bone loss.

Diagnosis

Dual energy X-ray absorptiometry (DXA, formerly DEXA) is considered the gold standard for diagnosis of osteoporosis. Diagnosis is made when the bone mineral density is less than or equal to 2.5 standard deviations below that of a young adult reference population. This is translated as a T-score. The World Health Organization has established diagnostic guidelines as T-score -1.0 or greater is "normal", T-score between -1.0 and -2.5 is "low bone mass" (or "osteopenia") and -2.5 or below as osteoporosis. When there has also been a low trauma or osteoporotic fracture, defined as one that occurs as a result of a fall from a standing height, the term "severe or established" osteoporosis is used. This is very important, because a person who has already had a fracture is at least 4 times as likely to have another fracture as another person of the same age and bone density. The absolute risk of fracture depends strongly on age as well as bone density and factors which affect strength and falling.

The rate of bone turnover can be measured with urine NTx, a byproduct of bone cartilage breakdown. Urine NTx greater than 40 may indicate osteoporosis.

In order to differentiate between "primary" (post-menopausal, regardless of age, or senile - related to age) and "secondary" osteoporosis, blood tests and X-rays are usually

done to rule out cancer with metastasis to the bone, multiple myeloma, Cushing's disease and other causes mentioned above.

Screening

The U.S. Preventive Services Task Force (USPSTF) recommends that all women 65 years of age or older should be screened with bone densitometry (PMID 12230355). The Task Force recommends screening women 60 to 64 years of age who are at increased risk. The best risk factor for indicating increased risk is lower body weight (weight < 70 kg).

Diagnosis of osteoporosis is made by three methods:

1.  Radiographic measurement of bone density

2.  Laboratory biochemical markers

3.  Bone biopsy with pathologic assessment

Of these three the best is radiographic bone density measurement. A variety of techniques are available, including single-photon absorptiometry, dual-photon absorptiometry, quantitative computed tomography, dual x-ray absorptiometry, and ultrasonography. Most often, site specific measurements are performed. The most common sites analyzed are those with greatest risk for fracture: hip, wrist, and vertebrae. The forearm and heel that are easily measured using single-photon absorptiometry, quantitative computed tomography, and ultrasonography can be inexpensive, but these sites are typically unresponsive to therapy and give less information about response to therapy. Increased risk for fracture correlates with decreasing bone density. Serial measurements over time can also give an indication of the rate of bone loss and prognosis.

The two main biochemical markers for bone formation are serum alkaline phosphatase and serum osteocalcin. Markers for bone resorbtion include urinary calcium and urinary hydroxyproline:

·         Alkaline phosphatase, which reflects osteoclast activity in bone, is measured in serum, but it lacks sensitivity and specificity for osteoporosis, because it can be elevated or decreased with many diseases. It is increased with aging. Fractionating alkaline phosphatase for the fraction more specific to bone doesn't increase usefulness that much.

·         Osteocalcin, also known as bone gamma-carboxyglutamate. It is synthesized by osteoblasts and incorporated into the extracellular matrix of bone, but a small amount is released into the circulation, where it can be measured in serum. The levels of circulating osteocalcin correlate with bone mineralization, but are influenced by age, sex, and seasonal variation. Laboratory methods also vary.

·         Urinary calcium can give some estimate of resorbtion (loss of) bone, but there are many variables that affect this measurement. Thus, it is more specific for osteoporosis when measured following overnight fasting.

·         Urinary hydroxyproline is derived from degradation of collagen, which forms extracellular bone matrix. However, hydroxyproline measurement is not specific for bone, because half of the body's collagen is outside the bony skeleton. It is also influenced by many diseases, as well as diet.

TREATMENT AND PREVENTION

Treatment :

Persons with osteoporosis may benefit from an improved diet, including supplementation with vitamin D and calcium, and moderate exercise to help slow further bone loss.Most drug therapies work by decreasing bone resorbtion. At any given time, there is bone that has been resorbed but not replaced, and this accounts for about 5 to 10% of bone mass. By decreasing resorbtion of bone, a gain in bone density of 5 to 10% is possible, taking about 2 to 3 years. However, no drug therapy will restore bone mass to normal. Women past menopause with accelerated bone loss may benefit from hormonal therapy using estrogen with progesterone. The estrogen retards bone resorption and thus diminishes bone loss. This effect is most prominent in the first years after menopause.One of the more common non-estrogen therapies is the use of biphosphonates such as alendronate or risedronate that act an an inhibitor of osteoclastic activity. Biphosphonates may be beneficial, particularly in women who cannot tolerate estrogen therapy. Biphosphonaes are effective in inhibiting bone loss after menopause. In one study risedronate has shown effectiveness in reducing the risk of hip fracture among elderly women with osteoporosis.Raloxifene is a selective estrogen receptor modulator (SERM) that may also replace estrogen therapy. Raloxifene can act in concert with estrogen in bone to inhibit resorbtion and decrease the risk for fractures. Though raloxifene inhibits bone resorbtion, it does not have an anabolic effect. Additional potential benefits from raloxifene therapy include decreased risk for breast cancer, because raloxifene acts antagonistically to estrogen on the uterus. Conversely, raloxifene acts in concert with estrogen to protect against and reduce atherogenesis.Patients at risk for osteoporosis (e.g. steroid use) are generally treated with vitamin D and calcium supplements. In osteoporosis (or a very high risk), bisphosphonate drugs are prescribed. Other medicines prescribed for prevention of osteoporosis include raloxifene ,a selective estrogen receptor modulator (SERM). Estrogen replacement remains a good treatment for prevention of osteoporosis but, at this time, is not recommended unless there are other indications for its use as well.

There is uncertainty and controversy about whether estrogen should be recommended in women in the first decade after the menopause; hopefully new research will provide guidance.

Recently, teriparatide (Forteo®, recombinant parathyroid hormone 1-34) has been shown to be effective in osteoporosis. It is used mostly for patients who have already fractured, have particularly low BMD or several risk factors for fracture or cannot tolerate the oral bisphosphonates. It is given as a daily injection with the use of a pen-type injection device. Teriparatide is only licensed for treatment if bisphosphonates have failed or are contraindicated.

Oral Strontium ranelate (Protelos® - Servier) is the first in a new class of drugs called a Dual Action Bone Agents (DABA's), and has proven efficacy in the prevention of vertebral and non-vertebral fractures (including hip fracture). Strontium Ranelate works by stimulating the proliferation of osteoblast (bone building) cells (there is some debate about this), and inhibiting the proliferation of osteoclast (bone absorbing) cells. This means that strontium Ranelate increases BMD by forming new bone, rather than just preserving existing bone. In comparison to bisphosphonates which only act on one aspect of bone remodeling, strontium ranelate also preserves bone turnover, allowing the microarchitecture of the bone to be continuously repaired as it would in healthy bone.

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Antiresorptive Medications

For more detailed information on the actions, administration and possible side effects for each of the following medications, please consult the Package Insert, available on-line and at pharmacies.

The information provided here regarding particular medications is intended solely for general information and should NOT be relied upon for any particular diagnosis,

treatment, or care. Inclusion in this list does not imply an endorsement by NOF of any particular medication or manufacturer.

Bisphosphonates:

Much like estrogen, this group of drugs can inhibit bone breakdown, preserve bone mass, and even increase bone density in your spine and hip, reducing the risk of fractures.

Alendronate Sodium (brand name Fosamax®)

Alendronate Sodium Plus 2,800 IU Vitamin D3 (brand name Fosamax®)

Alendronate is approved for both the prevention (5 mg per day or 35 mg once a week) and treatment (10 mg per day or 70 mg once a week or 70 mg once a week plus D) of postmenopausal osteoporosis. Alendronate reduces bone loss, increases bone density and reduces the risk of spine, wrist and hip fractures.

Alendronate also is approved for treatment of glucocorticoid-induced osteoporosis in men and women as a result of long-term use of these medications (i.e., prednisone and cortisone) and for the treatment of osteoporosis in men.

Alendronate Sodium Plus 2,800 IU Vitamin D3 (brand name Fosamax® Plus D)

Alendronate plus D is approved for the treatment of osteoporosis in postmenopausal women (70 mg once a week plus D), and for treatment to improve bone mass in men with osteoporosis.

Ibandronate Sodium (brand name Boniva®)

Ibandronate is approved for the prevention and treatment of postmenopausal osteoporosis. Taken as a once-a-month pill (150 mg), ibandronate should be taken on the same day each month. Ibandronate reduces bone loss, increases bone density and reduces the risk of spine fractures.

Later this year, ibandronate will be available as an infusion administered every three months.

Risedronate Sodium (brand name Actonel®)

Risedronate Sodium with 500 mg of Calcium Carbonate (brand name Actonel® or Actonel® with Calcium)

Risedronate is approved for the prevention and treatment of postmenopausal osteoporosis. Taken daily (5 mg dose) or weekly (35 mg dose or 35 mg dose with calcium), risedronate slows bone loss, increases bone density and reduces the risk of spine and non-spine fractures.

Risedronate also is approved for use by men and women to prevent and/or treat glucocorticoid-induced osteoporosis that results from long-term use of these medications (i.e., prednisone or cortisone).

Administration and Side Effects of Bisphosphonates

Side effects for alendronate, ibandronate and risedronate are uncommon but may include gastrointestinal problems, abdominal or musculoskeletal pain, nausea, heartburn, or irritation of the esophagus. There have been a few reports of osteonecrosis of the jaw (learn more about this disease) and of visual disturbances, which should be reported to the healthcare provider as soon as possible.

Alendronate and risedronate must be taken on an empty stomach, first thing in the morning, with eight ounces of water (no other liquid), at least 30 minutes before eating or drinking. Patients must remain upright during this 30-minute period.  Ibandronate must be taken on an empty stomach, first thing in the morning, with eight ounces of water (no other liquid) at least 60 minutes before eating or drinking. Patients must remain upright for at least one hour after taking this medication.

Calcitonin:

A hormone produced by your thyroid gland.(Brand name Miacalcin®, Calcimar® or Fortical®)Calcitonin is a naturally occurring hormone involved in calcium regulation and bone metabolism. In women who are more than 5 years beyond menopause, calcitonin slows bone loss, increases spinal bone density, and, according to anecdotal reports, may relieve the pain associated with bone fractures. Calcitonin reduces the risk of spinal fractures but has not been shown to decrease the risk of non-spine fractures. Studies on fracture reduction are on going. Because calcitonin is a protein, it cannot be taken orally as it would be digested before it could work. Calcitonin is available as an injection (50-100 IU daily) or nasal spray (200 IU daily).While it does not affect other organs or systems in the body, injectable calcitonin may cause an allergic reaction and unpleasant side effects including flushing of the face and hands, urinary frequency, nausea and a skin rash. Side effects for nasal calcitonin are not common but may include nasal irritation, backache, bloody nose, and headaches.

Estrogen Therapy (ET) and Hormone Therapy (HT):
Estrogen therapy (ET)/Hormone therapy (HT) is approved for the prevention of osteoporosis. ET has been shown to reduce bone loss, increase bone density in both the spine and hip, and reduce the risk of hip and spinal fractures in postmenopausal women. ET is administered most commonly in the form of a pill or skin patch that delivers a low dose of approximately 0.3 mg daily or a standard dose of approximately 0.625 mg daily and is effective even when started after age 70.

Teriparatide:

 This powerful drug, an analog of parathyroid hormone, treats osteoporosis in postmenopausal women who are at high risk of fractures. Unlike other available therapies for osteoporosis, it works by stimulating new bone growth, as opposed to preventing

further bone loss. Teriparatide is given once a day by injection under the skin on the thigh or abdomen.

Raloxifene :

(Brand name Evista®)Raloxifene, 60 mg a day, is approved for the prevention and treatment of postmenopausal osteoporosis. It is from a class of drugs called Selective Estrogen Receptor Modulators (SERMs) that have been developed to provide the beneficial effects of estrogens without their potential disadvantages. Raloxifene increases bone mass and reduces the risk of spine fractures. Data are not yet available to demonstrate that raloxifene can reduce the risk of hip and other non-spine fractures.

 Parathyroid: 

(Brand name Fortéo®)Teriparatide, a form of parathyroid hormone, is approved for the treatment of osteoporosis in postmenopausal women and men who are at high risk for a fracture. This medication stimulates new bone formation and significantly increases bone mineral density.

S.No	Drug Formulation	Indication	Mechanism of            act       Action
1.	Conjugated oestrogens(female sex hormone) -Tablet -Injection	Osteoporosis due to abnormally low bone mass(post menopausal)	Given as hormone replacement therapy
2.	Oestrogen patch	Osteoporosis (post menopauseal)	hormonereplacement therapy
3.	Nandrolone (anabolic and androgenic steroid)	Senile osteoporosis	Retards bone loss
4.	Reloxifene HCI(selective oestrogen receptor modulator or SERM) Tablete	Osteoporosis (post menopauseal)	It inhibits bone resorption.
5.	Alendronate sodium (bisphosphonate) -Tablet	Osteoporosis (post menopauseal)	Inhibits bone mineralization
6.	Etidronate disodium Tablet Injection	Osteoporosis	Inhibits bone mineralization
7.	Salmon  calcitonin Injection	Osteoporosis (post menopauseal)	It inhibits bone resorption
8.	Vitamin D(Vitamin D2& D3)Tablets,Capsule,Injection Syrup.	Severe osteoporosis	Help in calcium absorption

Table 1: Drug commonly emloyed in the treatment of osteoporosis in india

Prevention

Preventing osteoporosis is much easier than curing it. Recognizing that this condition can occur, young people should take measures to prevent osteoporosis. If a person builds excellent quality bones when young, he or she will have bone reserves that may be able to withstand changes that can occur later in life, such as taking medicines, inactivity, etc. The critical age to be building good bones is between 10 and 30 years of age. It can be much more difficult to start improving bone health later in life.

If your doctor thinks you have osteoporosis, he or she will perform a physical examination.  To confirm the diagnosis certain tests, such as x-rays and blood and urine tests, may be ordered. Other tests may be done to measure the density of your bones.  Correct diagnosis is important as there may be other medical conditions causing your symptoms, or that are contributing to the osteoporosis.

·     If you have osteoporosis your doctor may suggest hormone replacement therapy.  Hormone replacement therapy can reduce the rate of bone loss.  Estrogen can be taken alone, or along with another hormone called progesterone (pronounced pro-jes-ter-own).

 Bisphosphonates have shown to be helpful in rebuilding bone.  They are often given to women with osteoporosis who cannot or do not want to take hormone replacement therapy. Bisphosphonates can also be useful in treating osteoporosis that has resulted from steroids, such as found in other types of medication.
 

·     Calcitonin (pronounced cal-si-tone-in) can help rebuild bones. It also can relieve the pain that results from fractures of the spine.

Calcitonin is a hormone that occurs naturally within the body.  It helps increase bone density by affecting the levels of calcium in the blood.  It can also relieve pain resulting from spine fractures.  To treat osteoporosis it is usually given in doses much higher than normally occurs within the body.  Often calcitonin from eel or salmon is used, as it is many times stronger than the human form.  

Diet

·     Eat a well-balanced diet, and foods rich in calcium. 

·     Foods rich in calcium are milk, cheese, yogurt, salmon, sardines, almonds, dark green leafy vegetables and broccoli.

To find out whether you are getting sufficient calcium, you can get calcium tables and checklists from your doctor, dietician, public health office or the local chapter of the Osteoporosis Society of Canada. Your calcium intake should be at different levels depending on your age: 

Child (ages 1-12)	800 mg/day
Teen (ages 13-18)	700 – 1200 mg/day
Adult	700 - 1000 mg/day
Pregnant woman	1200 mg/day
Woman during & post menopause	800-1500 mg/day

Foods rich in calcium are milk and milk products such as cheese and yogurt. Other calcium rich foods include canned salmon with bones, sardines, almonds, dark green leafy vegetables, and broccoli.

Exercise

·     Exercise helps rebuild bone and strengthens muscles.

·     Walking, dancing, low-impact aerobics and stationary cycling are all good forms of exercise. Swimming or other exercises done in the water may be best if you have pain as a result of osteoporosis.

·     Your doctor can help you find the exercise that best meets your needs.

Protect Your Body

·     Be kind to your body.  After doing heavy work, or doing the same task over and over, stop.  Use your back, arms and legs in safe ways to avoid putting stress on joints. .

·     Use helpful devices such as a cart to carry your grocery bags, or an enlarged handle that fits over a knife handle so you can hold it easily.  A cart will help you to walk more safely. 

·     Maintain a healthy weight to avoid putting extra stress on your bones.

                    

      

   

SUMMARY

The best course for patient at risk for osteoporosis fractures is prevention through an early intervention.Hence Osteoporosis is a disease of bone in which the bone mineral density(BMD) is reduced, bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. Osteoporotic bones are more at  risk  of  fracture.  Osteoporosis  is  defined  by  the  WHO in women as a bone mineral density 2.5 standard deviations below peak bone mass (20-year-old sex-matched healthy person average) as measured by DXA; the term "established osteoporosis" includes the presence of a fragility fracture. While treatment modalities are becoming available (such as the bisphosphonates), prevention is still considered the most important way to reduce fracture. Due to its hormonal component, more women, particularly after menopause, suffer from osteoporosis than men.

In addition it may be caused by various hormonal conditions, smoking and (specifically glucocorticoids) as well as many chronic diseases. Osteo' means bone, and 'porosis' thinning or becoming more porous, so osteoporosis literally means 'thinning of bone.' It is commonly confused with the word osteoarthritis, which is a form of arthritis that results in breakdown of thecartilagecovering the ends of bones. In contrast, osteoporosis is a condition where bone itself breaks down.  Bones then become thin, brittle and easily broken.

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