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com/article/330598overview#showall Background
Osteoporosis, a chronic progressive disease of multifactorial etiology (see Etiology), is the most common metabolic bone disease in the United States. It has been most frequently recognized in elderly white women, although it does occur in both sexes, all races, and all age groups. This disease is considered a "silent thief" that generally does not become clinically apparent until a fracture occurs (see Clinical Presentation). Screening at-risk populations is, therefore, essential (see Workup). Osteoporosis can affect almost the entire skeleton. It is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility.[1] The disease often does not become clinically apparent until a fracture occurs. Osteoporosis represents an increasingly serious problem in the United States and around the world. Many individuals, male and female, experience pain, disability, and diminished quality of life as a result of having this condition. The economic burden the disease imposes is already considerable and will only grow as the population ages.[2] Despite the adverse effects of osteoporosis, it is a condition that is often overlooked and undertreated, in large part because it is so often clinically silent before manifesting in the form of fracture. For example, a Gallup survey performed by the National Osteoporosis Foundation revealed that 75% of all women aged 45-75 years have never discussed osteoporosis with their physicians. Failure to identify at-risk patients, to educate them, and to implement preventive measures may lead to tragic consequences. Medical care includes calcium, vitamin D, and antiosteoporotic medication such as bisphosphonates and parathyroid hormone. Antiresorptive agents currently available for osteoporosis treatment include bisphosphonates, the selective estrogen-receptor modulator (SERM) raloxifene, calcitonin, and denosumab. One anabolic agent, teriparatide (see Medication), is available as well. Surgical care includes vertebroplasty and kyphoplasty. (See Treatment and Management.) Osteoporosis is a preventable disease that can result in devastating physical, psychosocial, and economic consequences. Prevention and recognition of the secondary causes of osteoporosis are first-line measures to lessen the impact of the disease (see the images below). Osteoporosis of the spine. Observe the considerable reduction in overall vertebral bone density and note the lateral wedge fracture of L2. Osteoporosis of the spine. Note the lateral wedge fracture in L3 and the central burst fracture in L5. The patient had suffered a recent fall.

For more information, see Pediatric Osteoporosis, as well as Osteoporosis in Solid Organ Transplantation, Utility of Bone Markers in Osteoporosis, and Nonoperative Treatment of Osteoporotic Compression Fractures.

Anatomy
Cortical and trabecular (cancellous) bone differ in architecture but are similar in molecular composition. Bone consists of cells and an extracellular matrix with mineralized and nonmineralized components. The composition and architecture of the extracellular matrix is what imparts mechanical properties to bone. Bone strength is determined by collagenous proteins (tensile strength) and mineralized osteoid (compressive strength).[3] The greater the concentration of calcium, the greater the compressive strength.

Pathophysiology
Osteoporosis is a condition in which bone mass is low and microarchitectural deterioration of bone tissue occurs, leading to bone fragility and an increased risk of fracture. It results from hereditary and environmental factors that affect both bone mass and bone quality. Traditionally, osteoporosis was described as type I (postmenopausal) or type II (senile). Postmenopausal osteoporosis (PMO) is primarily due to estrogen deficiency; senile osteoporosis is primarily due to an aging skeleton and calcium deficiency. However, it is increasingly recognized that multiple pathogenetic mechanisms interact in the development of the osteoporotic state, regardless of age. Understanding the pathogenesis of osteoporosis starts with knowing how bone formation and remodeling occur.

Normal bone formation and remodeling

Homeostasis of bone, a living tissue, is maintained by osteoclasts, which are responsible for bone resorption, and osteoblasts, which are responsible for bone formation. Osteoblasts are derived from mesenchymal stem cells, whereas osteoclasts are derived from hematopoietic precursors. The 2 types of cells are dependent on each other for production. In fact, the development of osteoclasts from hematopoietic precursors cannot be accomplished unless mesenchymal cells are present. Mesenchymal cells with the potential to become osteoblasts also have the potential to become fibroblasts, chondrocytes, adipocytes, or muscle cells. This potential for differentiation allows the osteoblast to secrete the same cytokines and colony-stimulating factors produced by fibroblasts. Hematopoietic granulocyte-macrophage colony-forming units (CFUs) produce osteoclasts and give rise to monocytes and macrophages. As such, the osteoclasts produce the same cytokines that monocytes produce. Interleukin (IL)-6 is produced, in part, by osteoblasts that stimulate osteoclastic activity. This phenomenon is one proposed mechanism for certain diseases that

exhibit increased bone resorption. Two examples of diseases that result in osteoporosis by this mechanism are multiple myeloma and rheumatoid arthritis. Bone is continually remodeled throughout life because bones sustain recurring microtrauma. Bone remodeling occurs at discrete sites within the skeleton and proceeds in an orderly fashion. Bone resorption is always followed by bone formation, a phenomenon referred to as coupling. In osteoporosis, this coupling mechanism is thought to be unable to keep up with the constant microtrauma to trabecular bone. In adults, approximately 25% of trabecular bone is resorbed and replaced every year, compared with only 3% of cortical bone. Osteocytes, which are terminally differentiated osteoblasts embedded in mineralized bone, direct the timing and location of remodeling. Osteoblasts not only secrete and mineralize osteoid but also appear to control the bone resorption carried out by osteoclasts. Osteoclasts require weeks to resorb bone, whereas osteoblasts need months to produce new bone. Therefore, any process that increases the rate of bone remodeling results in net bone loss over time.[4] Furthermore, in periods of rapid remodeling (eg, after menopause), bone is at an increased risk for fracture because the newly produced bone is less densely mineralized, the resorption sites are temporarily unfilled, and the isomerization and maturation of collagen is impaired.[5] Molecular biologists have begun to elucidate the mechanisms of bone remodeling. For example, it is now understood that the receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK)/osteoprotegerin (OPG) system is the final common pathway for bone resorption. Osteoblasts and activated T cells in the bone marrow produce the RANKL cytokine. RANKL binds to the RANK receptor expressed by osteoclasts and osteoclast precursors to promote osteoclast differentiation. Osteoprotegerin is a soluble decoy receptor that inhibits RANKRANKL by binding and sequestering RANKL. Bone mass peaks by the third decade of life and slowly decreases afterward. The failure to attain optimal bone strength by this point is one factor that contributes to osteoporosis. Therefore, nutrition and physical activity are important during growth and development. Nevertheless, hereditary factors play the principal role in determining an individual's peak bone strength. In fact, genetics account for up to 80% of the variance in peak bone mass between individuals.[6]

Alterations in bone formation and resorption

The hallmark of osteoporosis is a reduction in skeletal mass caused by an imbalance between bone resorption and bone formation. Under physiologic conditions, bone formation and resorption are in a fair balance. A change in eitherthat is, increased bone resorption or decreased bone formationmay result in osteoporosis. Osteoporosis can be caused both by a failure to build bone and reach peak bone mass as a young adult and by bone loss later in life. Accelerated bone loss can occur in perimenopausal women and elderly men and women and can occur secondary to various disease states and medications.

Loss of gonadal function and aging are the 2 most important factors contributing to the development of osteoporosis. Studies have shown that bone loss in women accelerates rapidly in the first years after menopause. The lack of gonadal hormones is thought to up-regulate osteoclast progenitor cells. Estrogen deficiency not only accelerates bone loss in postmenopausal women but also plays a role in bone loss in men. Estrogen deficiency can lead to excessive bone resorption accompanied by inadequate bone formation. Osteoblasts, osteocytes, and osteoclasts all express estrogen receptors. In addition, estrogen affects bones indirectly through cytokines and local growth factors. The estrogen-replete state may enhance osteoclast apoptosis via increased production of transforming growth factor (TGF)-beta. In the absence of estrogen, T cells promote osteoclast recruitment, differentiation, and prolonged survival via IL-1, IL-6, and tumor necrosis factor (TNF)-alpha. A murine study, in which either the mice's ovaries were removed or sham operations were performed, found that IL-6 and granulocyte-macrophage CFU levels were much higher in the ovariectomized mice.[7] This finding provided evidence that estrogen inhibits IL-6 secretion, and IL-6 contributes to the recruitment of osteoclasts from the monocyte cell line, thus contributing to osteoporosis. IL-1 has also been shown to be involved in the production of osteoclasts. The production of IL-1 is increased in bone marrow mononuclear cells from ovariectomized rats. Administering IL-1 receptor antagonist to these animals prevents the late stages of bone loss induced by the loss of ovarian function, but it does not prevent the early stages of bone loss. The increase in the IL-1 in the bone marrow does not appear to be a triggered event, but is a result of removal of the inhibitory effect of sex steroids on IL-6 and other genes directly regulated by sex steroids. T cells also inhibit osteoblast differentiation and activity and cause premature apoptosis of osteoblasts through cytokines such as IL-7. Finally, estrogen deficiency sensitizes bone to the effects of parathyroid hormone (PTH; see below). In contrast to postmenopausal bone loss, which is associated with excessive osteoclast activity, the bone loss that accompanies aging is associated with a progressive decline in the supply of osteoblasts in proportion to the demand. This demand is ultimately determined by the frequency with which new multicellular units are created and new cycles of remodeling are initiated. After the third decade of life, bone resorption exceeds bone formation and leads to osteopenia and, in severe situations, osteoporosis. Women lose 30-40% of their cortical bone and 50% of their trabecular bone over their lifetime, as opposed to men, who lose 15-20% of their cortical bone and 25-30% of trabecular bone. Calcium, vitamin D, and PTH help maintain bone homeostasis. Insufficient dietary calcium or impaired intestinal absorption of calcium due to aging or disease can lead to secondary hyperparathyroidism. PTH is secreted in response to low serum calcium levels. It increases calcium resorption from bone, decreases renal calcium excretion, and increases renal production of 1,25-dihydroxyvitamin D (1,25[OH]2 D)an active hormonal form of vitamin D that

optimizes calcium and phosphorus absorption, inhibits PTH synthesis, and plays a minor role in bone resorption. Vitamin D deficiency can result in secondary hyperparathyroidism via decreased intestinal calcium absorption. Interestingly, the effects of PTH and 1,25[OH]2 D on bone are mediated via binding to osteoblasts and stimulating the RANKL/RANK pathway. Osteoclasts do not have receptors for PTH or 1,25[OH]2 D.[3] Endocrinologic conditions or medications that lead to bone loss (eg, glucocorticoids) can cause osteoporosis. Corticosteroids inhibit osteoblast function and enhance osteoblast apoptosis.[8] Polymorphisms of IL-1, IL-6 and TNF-alpha, as well as their receptors, have been found to influence bone mass. Other factors implicated in the pathogenesis of osteoporosis include polymorphisms in the vitamin D receptor; alterations in insulin-like growth factor-1, bone morphogenic protein, prostaglandin E2, nitrous oxide, and leukotrienes; collagen abnormalities; and leptin-related adrenergic signaling.[4] Osteoporotic fractures represent the clinical significance of these derangements in bone. They can result both from low-energy trauma, such as falls from a sitting or standing position, and from high-energy trauma, such as a pedestrian struck in a motor vehicle accident. Fragility fractures, which occur secondary to low-energy trauma, are characteristic of osteoporosis. Fractures occur when bones fall under excess stress. Nearly all hip fractures are related to falls.[9] The frequency and direction of falls can influence the likelihood and severity of fractures. The risk of falling may be amplified by neuromuscular impairment due to vitamin D deficiency with secondary hyperparathyroidism or corticosteroids. Vertebral bodies are composed primarily of cancellous bone with interconnected horizontal and vertical trabeculae (see Anatomy). Osteoporosis not only reduces bone mass in vertebrae but also decreases interconnectivity in their internal scaffolding.[3] Therefore, minor loads can lead to vertebral compression fractures. An understanding of the biomechanics of bone provides greater appreciation as to why bone may be susceptible to an increased risk of fracture. When vertical loads are placed on bone, such as tibial and femoral metaphyses and vertebral bodies, a substantial amount of bony strength is derived from the horizontal trabecular cross-bracing system. This system of horizontal crossbracing trabeculae assists in supporting the vertical elements, thus limiting lateral bowing and fractures that may occur with vertical loading. Disruption of such trabecular connections is known to occur preferentially in patients with osteoporosis, particularly in postmenopausal women, making females more at risk than males for vertebral compression fractures. Rosen and Tenenhouse studied the unsupported trabeculae and their susceptibility to fracture within each vertebral body and found an extraordinarily high prevalence of trabecular fracture

callus sites within vertebral bodies examined at autopsy, typically 200-450 healing or healed fractures per vertebral body.[10] These horizontal trabecular fractures are asymptomatic, and their accumulation reflects the impact of lost trabecular bone and greatly weakens the cancellous structure of the vertebral body. The reason for preferential osteoclastic severance of horizontal trabeculae is unknown. Some authors have attributed this phenomenon to overaggressive osteoclastic resorption. Osteoporosis may be confused with osteomalacia. The normal human skeleton is composed of a mineral component, calcium hydroxyapatite (60%), and organic material, mainly collagen (40%). In osteoporosis, the bones are porous and brittle, while in osteomalacia the bones are soft. This difference in bone consistency is related to the mineral-to-organic material ratio. In osteoporosis, the mineral-to-collagen ratio is within the reference range, whereas in osteomalacia, the proportion of mineral composition is reduced relative to organic mineral content.

WHO definition of osteoporosis

Bone mineral density (BMD) in a patient is related to peak bone mass and, subsequently, bone loss. The World Health Organization (WHO) has established the following definitions of osteoporosis based on BMD measurements in white women:

Normal - BMD within 1 standard deviation (SD) of the mean bone density for young adult women (T-score at -1 and above) Low bone mass (osteopenia) - BMD between 1-2.5 SD below the mean for young adult women (T-score between -1 and -2.5) Osteoporosis - BMD 2.5 SD or more below the normal mean for young adult females (Tscore at or below -2.5) Severe or "established" osteoporosis - BMD 2.5 SD or more below the normal mean for young adult females (T-score at or below -2.5) in a patient who has already experienced 1 or more fractures

The WHO definition applies to postmenopausal women and men aged 50 years or older. Although these definitions are necessary to establish the prevalence of osteoporosis, they should not be used as the sole determinant of treatment decisions. This diagnostic classification should not be applied to premenopausal women, men younger than 50 years, or children. Whereas the T-score is the bone density compared with the BMD of control subjects who are at their peak BMD, the Z-score reflects a bone density compared with that of patients matched for age and sex.[11, 12, 13, 14] Z-scores should be used in premenopausal women, men younger than 50 years, and children. Zscores adjusted for ethnicity or race should be used, with Z-scores of -2.0 or lower defined as "below the expected range for age" and those above -2.0 being "within the expected range for

age." The diagnosis of osteoporosis in these groups should not be based on densitometric criteria alone.

Etiology
Osteoporosis has been divided into several classifications according to etiology and localization in the skeleton. Osteoporosis is initially divided into localized and generalized categories. These 2 main categories are classified further into primary and secondary osteoporosis. Postmenopausal osteoporosis (PMO) is primarily due to estrogen deficiency; senile osteoporosis is primarily due to an aging skeleton and calcium deficiency.

Primary osteoporosis
Primary osteoporosis occurs in patients in whom a secondary cause of osteoporosis cannot be identified, including juvenile and idiopathic osteoporosis. Idiopathic osteoporosis can be further subdivided into postmenopausal (type I) and age-associated or senile (type II) osteoporosis, as follows:

Juvenile osteoporosis usually occurs in children or young adults of both sexes. These patients have normal gonadal function. The age of onset usually is 8-14 years. The hallmark characteristic of juvenile osteoporosis is abrupt bone pain and/or a fracture following trauma. Type I osteoporosis (postmenopausal osteoporosis) occurs in women aged 50-65 years. This type of osteoporosis is characterized by a phase of accelerated bone loss. This bone loss occurs primarily from trabecular bone. In this phase, fractures of the distal forearm and vertebral bodies are common. Type II osteoporosis (age-associated or senile) occurs in women and men older than 70 years. This form of osteoporosis represents bone loss associated with aging. Fractures occur in cortical and trabecular bone. In addition to wrist and vertebral fractures, hip fractures are often seen in patients with type II osteoporosis.

Secondary osteoporosis
Secondary osteoporosis occurs when an underlying disease, deficiency, or drug causes osteoporosis. Up to one third of postmenopausal women, as well as many men and premenopausal women, have a coexisting cause of bone loss.[15, 16] Genetic (congenital) causes of osteoporosis include the following:

Cystic fibrosis Ehlers-Danlos syndrome Glycogen storage disease Gaucher disease

Hemochromatosis Homocystinuria Hypophosphatasia Idiopathic hypercalciuria Marfan syndrome Menkes steely hair syndrome Osteogenesis imperfecta Porphyria Riley-Day syndrome Hypogonadal states (see below)

Hypogonadal states that can cause osteoporosis include the following:

Androgen insensitivity Anorexia nervosa/bulimia nervosa Female athlete triad Hyperprolactinemia Panhypopituitarism Premature menopause Turner syndrome Klinefelter syndrome

Endocrine disorders that can cause osteoporosis include the following[17] :

Acromegaly Adrenal insufficiency Cushing syndrome Estrogen deficiency Diabetes mellitus Hyperparathyroidism Hyperthyroidism

Hypogonadism Pregnancy Prolactinoma

Deficiency states that can cause osteoporosis include the following:

Calcium deficiency Magnesium deficiency Protein deficiency Vitamin D deficiency[17, 18] Bariatric surgery Celiac disease Gastrectomy Malabsorption Malnutrition Parenteral nutrition Primary biliary cirrhosis

Inflammatory diseases that can cause osteoporosis include the following:

Inflammatory bowel disease Ankylosing spondylitis Rheumatoid arthritis Systemic lupus erythematosus

Hematologic and neoplastic disorders that can cause osteoporosis include the following:

Hemochromatosis Hemophilia Leukemia Lymphoma Multiple myeloma Sickle cell anemia

Systemic mastocytosis Thalassemia Metastatic disease

Medications known to cause or accelerate bone loss include the following:

Anticonvulsants - Phenytoin, barbiturates, carbamazepine (these agents are associated with treatment-induced vitamin D deficiency) Antipsychotic drugs Antiretroviral drugs Aromatase inhibitors - Exemestane, anastrozole Chemotherapeutic/transplant drugs - Cyclosporine, tacrolimus, platinum compounds, cyclophosphamide, ifosfamide, methotrexate Furosemide Glucocorticoids and corticotropin[19] - Prednisone (5 mg/d for 3 mo)[20] Heparin (long-term) Hormonal/endocrine therapies - Gonadotropin-releasing hormone (GnRH) agonists, luteinizing hormone-releasing hormone (LHRH) analogs, depomedroxyprogesterone, excessive thyroid supplementation Lithium Methotrexate Selective serotonin reuptake inhibitors Thyroxine (excessive)

Miscellaneous causes of osteoporosis include the following:

Alcoholism Amyloidosis Chronic metabolic acidosis Congestive heart failure Depression Emphysema Chronic or end-stage renal disease

Chronic liver disease HIV disease/AIDS Idiopathic calciuria Idiopathic scoliosis Immobility Multiple sclerosis Ochronosis Organ transplantation Pregnancy/lactation Sarcoidosis Weightlessness

Risk factors
Risk factors for osteoporosis, such as advanced age and reduced bone mineral density (BMD), have been established by virtue of their direct and strong relationship to the incidence of fractures; however, many other factors have been considered risk factors based on their relationship to BMD as a surrogate indicator of osteoporosis. Risk factors for osteoporosis include the following[21, 22, 23] :

Advanced age (50 years or older) Female sex White or Asian ethnicity Genetic factors, such as a family history of osteoporosis Thin build or small stature (eg, body weight less than 127 pounds) Amenorrhea Late menarche Early menopause Postmenopausal state Physical inactivity or immobilization[24] Use of drugs - Anticonvulsants, systemic steroids, thyroid supplements, heparin, chemotherapeutic agents, insulin

Alcohol and tobacco use Androgen[25] or estrogen deficiency Calcium deficiency

A study by Cummings et al in evaluated 9516 white women aged 65 years for an average of 4.1 years and found an indirect relationship between the number of risk factors and bone density values.[26] The study also identified factors that did not increase the risk of fracture, including hair color, number of children breastfed, prior smoking history, or use of short-acting benzodiazepines. One very interesting finding of this study was that dietary intake of calcium was not correlated to the risk of hip fracture; however, the authors of the study did agree with other experts that dietary calcium would only help if the patient was calcium deficient. A longitudinal and prospective cohort study, including a subcohort, evaluated the effect of dietary calcium on fracture incidence and osteoporosis in 61,433 women. The results found that low vitamin D intake was associated with a more pronounced rate of fracture in the first quintile. The risk of fractures of any type, or of osteoporosis, was not further reduced in the highest quintile of calcium intake but was associated with a higher rate of hip fracture. The study concludes that gradual increases in dietary calcium intake did not further reduce fracture risk or osteoporosis in women.[27] One study sought to determine if the femoral neck BMD score and the World Health Organization Fracture Risk Algorithm (FRAX) score are associated with hip and nonspine fracture risk in older adults with type 2 diabetes mellitus (DM). Using data from 3 prospective observational studies, statistics from self-reported incidence of fractures in 9449 women and 7436 men in the United States were analyzed. The results found that participants with type 2 DM had a higher fracture risk and T score than those without type 2 DM, concluding that the femoral neck BMD T score and FRAX score were associated with higher hip and nonspine fracture risk in older adult patients with type 2 DM.[28]

Epidemiology
United States statistics
According to the National Osteoporosis Foundation (NOF), 10 million Americans have osteoporosis. Another 34 million have low bone mass, which leaves them at increased risk for osteoporosis.[29] Each year in the United States, 1.5 million osteoporotic fractures occur. Of these, 700,000 occur in the spine, 300,000 occur in the hip, and 200,000 occur in the wrist. The remainder of fractures occur at other sites in the body. Most studies assessing the prevalence and incidence of osteoporosis use the rate of fracture as a marker for the presence of this disorder, although BMD also relates to risk of disease and fracture. The risk of new vertebral fractures increases by a factor of 2-2.4 for each SD decrease

of BMD measurement. Women and men with metabolic disorders associated with secondary osteoporosis have a 2- to 3-fold higher risk of hip and vertebral fractures (see the images below). Normal femoral anatomy. Stable intertrochanteric fracture of the femur

International statistics
Osteoporosis is by far the most common metabolic bone disease in the world and is estimated to affect over 200 million people worldwide.[30] An estimated 75 million people in Europe, the United States, and Japan have osteoporosis.[31] One in 3 women older than 50 years will eventually experience osteoporotic fractures, as will 1 in 5 men.[32] By 2050, the worldwide incidence of hip fracture is projected to increase by 240% in women and 310% in men.[33]

Age distribution for osteoporosis

Risk for osteoporosis increases with age, as BMD declines. Senile osteoporosis is most common in persons aged 70 years or older. Secondary osteoporosis, however, can occur in persons of any age. Although bone loss in women begins slowly, it speeds up around the time of menopause, typically at about or after age 50 years. The frequency of postmenopausal osteoporosis is highest in women aged 50-70 years. The number of osteoporotic fractures increases with age. Wrist fractures typically occur first, when individuals are aged approximately 50-59 years. Vertebral fractures occur more often in the seventh decade of life. Jensen et al studied Danish women aged 70 years and found a 21% prevalence of vertebral fractures.[34] Melton et al reported that 27% of women in their study had evidence of vertebral fractures by age 65 years.[35] Hip fractures occur more often in the eighth decade of life; 90% of such fractures occur in persons aged 50 years or older.[36]

Sex distribution for osteoporosis

Women are at a significantly higher risk for osteoporosis. In primary osteoporosis, the female-tomale ratio is 5:1. Men have a higher prevalence of secondary osteoporosis, with an estimated 4560% being a consequence of hypogonadism, alcoholism, or glucocorticoid excess.[19] Only 3540% of osteoporosis diagnosed in men is considered primary in nature. Overall, osteoporosis has a female-to-male ratio of 4:1.[29] Fifty percent of all women and 25% of all men older than 50 years experience an osteoporosisrelated fracture in their lifetime. Eighty percent of hip fractures occur in women.[36] Women have a 2-fold increase in the number of fractures resulting from nontraumatic causes, compared with men of the same age.

Racial differences in incidence

Osteoporosis can occur in persons of all races and ethnicities. In general, however, whites (especially of northern European descent) and Asians are at increased risk. In particular, non-Hispanic white women and Asian women are at higher risk for osteoporosis. An estimated one half of all hip fractures will occur in Asia in the next century. Twenty percent of non-Hispanic white and Asian women aged 50 years or older are estimated to have osteoporosis, and 52% have low bone mass. Ten percent of Hispanic women aged 50 years or older are estimated to have osteoporosis, and 49% have low bone mass. Five percent of nonHispanic black women older than 50 years are estimated to have osteoporosis, and 35% have low bone mass. Seven percent of non-Hispanic white and Asian men aged 50 years or older have osteoporosis, and 35% have low bone mass. Four percent of non-Hispanic black men aged 50 years or older have osteoporosis, and 19% have low bone mass. Three percent of Hispanic men aged 50 years or older have osteoporosis, and 23% have low bone mass.[37, 38, 39] Melton et al reported that the prevalence of hip fractures is higher in white populations, regardless of geographic location.[40] Another study indicated that the incidence of hip fractures was lower among African Americans in the United States and South Africa compared to agematched white populations within the same continent. A study of Japanese American women in Hawaii found a 5% incidence of vertebral fractures each year among individuals aged 80 years.

Prognosis
The prognosis for osteoporosis is good if bone loss is detected in the early phases and proper intervention is undertaken. Patients can increase BMD and decrease fracture risk with the appropriate antiosteoporotic medication. In addition, patients can decrease their risk of falls by participating in a multifaceted approach that includes rehabilitation and environmental modifications, among others. Worsening of medical status can be prevented by providing appropriate pain management and, if indicated, orthotic devices.

Effect of fractures on prognosis

Many individuals experience morbidity associated with the pain, disability, and diminished quality of life caused by osteoporosis-related fractures. According to a 2004 Surgeon General's report, osteoporosis and other bone diseases are responsible for about 1.5 million fractures per year. Osteoporosis-related fractures result in annual direct care expenditures of $12.2-$17.9 billion (in 2002 dollars).[41] In 2005, over 2 million osteoporosis-related fractures occurred in the United States.[42] Osteoporosis is the leading cause of fractures in the elderly. Women aged 50 years have a 40% lifetime fracture rate as a result of osteoporosis. Osteoporosis is associated with 80% of all the fractures in people aged 50 years or older. If full recovery is not achieved, osteoporotic fractures may lead to chronic pain, disability, and, in some cases, death. This is particularly true of vertebral and hip fractures.

Vertebral compression fractures (see the images below) are associated with increased morbidity and mortality rates. In addition, the impact of vertebral fractures increases as they increase in number. As posture worsens and kyphosis progresses, patients experience difficulty with balance, back pain, respiratory compromise, and an increased risk of pneumonia. Overall function declines, and patients may lose their ability to live independently. Osteoporosis. Lateral radiograph demonstrates multiple osteoporotic vertebral compression fractures. Kyphoplasty has been performed at one level. Osteoporosis. Lateral radiograph of the patient seen in previous image following kyphoplasty performed at 3 additional levels. In one study, Cooper et al found that vertebral fractures increased the 5-year risk of mortality by 15%.[43] In a subsequent study, Kado et al[44] demonstrated that women with one or more fractures had a 1.23-fold increased age-adjusted mortality rate, while women with 5 or more vertebral fractures had a 2.3-fold increased age-adjusted mortality rate. Furthermore, mortality rate was correlated with number of vertebral fractures, with 19 per 1000 woman-years in women with no fracture and 44 per 1000 woman-years in women with 5 or more fractures. Vertebral fractures were related to risk of subsequent cancer and pulmonary death, and severe kyphosis was further correlated with pulmonary deaths. Only one third of people with radiographic vertebral fractures are diagnosed clinically.[45] Symptoms of vertebral fracture may include back pain, height loss, and disabling kyphosis. Compression deformities can lead to restrictive lung disease, abdominal pain, and early satiety. More than 250,000 hip fractures are attributed to osteoporosis each year.[26] Like vertebral fractures, they are associated with significantly increased morbidity and mortality rates in men and women. In the year following hip fracture, excess mortality rates can be as high as 20%.[43, 46] Men have higher mortality rates following hip fracture than do women. Patients with hip fractures incur decreased independence and a diminished quality of life. Of all patients with hip fracture, approximately 20% require long-term nursing care.[29] Among women who sustain a hip fracture, 50% spend time in a nursing home while recovering. Approximately 50% of previously independent individuals become partially dependent, and one third become completely dependent.[47] Only one third of patients return to their prefracture level of function.[48] Secondary complications of hip fractures include nosocomial infections and pulmonary thromboembolism. Patients who have sustained one osteoporotic fracture are at increased risk for developing additional osteoporotic fractures.[49] For example, the presence of at least one vertebral fracture results in a 5-fold increased risk of developing another vertebral fracture. One in 5 postmenopausal women with a new vertebral fracture incurs another vertebral fracture within one year.[50]

Patients with previous hip fracture have a 2-fold[51] to 10-fold increased risk of sustaining a second hip fracture. In addition, patients with ankle, knee, olecranon, and lumbar spine fractures have a 1.5-, 3.5-, 4.1-, and 4.8-fold increased risk of subsequent hip fracture, respectively.

WHO fracture-risk algorithm

The World Health Organization fracture-risk algorithm (www.shef.ac.uk/FRAX/) was developed to calculate the 10-year probability of a hip fracture and the 10-year probability of any major osteoporotic fracture (defined as clinical spine, hip, forearm, or humerus fracture) in a given patient. These calculations account for femoral neck bone mineral density (BMD) and other clinical risk factors, as follows[52] :

Age Sex Personal history of fracture Low body mass index Use of oral glucocorticoid therapy Secondary osteoporosis (ie, coexistence of rheumatoid arthritis) Parental history of hip fracture Current smoking status Alcohol intake (3 or more drinks per day)

The National Osteoporosis Foundation (NOF) recommends osteoporosis treatment in patients with low bone mass in whom a US-adapted WHO 10-year probability of a hip fracture is 3% or more or in whom the risk for a major osteoporosis-related fracture is 20% or more.[29] Algorithms such as the FRAX algorithm are useful in identifying patients with low bone mass (T-scores in the osteopenic range) who are most likely to benefit from treatment. A study by Leslie et al demonstrated the effects of including a patient's 10-year fracture risk along with DXA results in Manitoba, Canada.[53] The authors found an overall reduction in dispensation of osteoporosis medications as more women were reclassified into lower fracture risk categories.

Patient Education
Patient education is paramount in the treatment of osteoporosis. Many patients are unaware of the serious consequences of osteoporosis, including increased morbidity and mortality, and only become concerned when osteoporosis manifests in the form of fracture; accordingly, it is important to educate them regarding these consequences. Early prevention and treatment are essential in the appropriate management of osteoporosis.

The focus of patient education is on the prevention of osteoporosis. Prevention has 2 components, behavior modification and pharmacologic interventions. Appropriate preventive measures may include adequate calcium and vitamin D intake, exercise, cessation of smoking, and moderation of alcohol consumption. Patients should be educated about the risk factors for osteoporosis, with a special emphasis on family history and the effects of menopause. Patients also need to be educated about the benefits of calcium and vitamin D supplements. All postmenopausal women should be offered bone densitometry, and they should understand the benefits of bone density monitoring. Society at large also should be educated about the benefits of exercise with regard to osteoporosis. For patient education resources, see the following:

Osteoporosis and Bone Health Center Eating Disorders Center Esophagus, Stomach, and Intestine Center Women's Health Center Osteoporosis Anorexia Nervosa Inflammatory Bowel Disease Menopause Hormone Replacement and Osteoporosis