INTRODUCTION

1.1 Background Osteoporosis, also known as decreased density of bone, most commonly affected with osteoporosis postmenopausal white women. Osteoporosis can be present without any symptoms until bone fractures. To prevent the fractures, it is important to know effect of estrogen deficiency on the individuals postmenopausal. 1.2 Problems How the estrogen deficiency can effect of the bone growth and development?

1.3 Limitation of problems What is osteoporosis? What are risk factors of osteoporosis? How growth and development of bone and effect of estrogen?

1.4 Objectives To know what Osteoporosis is. To know the risk factors of osteoporosis To know the effect of estrogen deficiency

1.5 Method of writing In the making of this writing, writer uses some updated and reliable sources, such as multimedia studies (internet), interviews and library research. This writing is still open for many updated information.

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OSTEOPOROSIS Definition Osteoporosis is a disease characterized by decreased density of bone and impaired the structural integrity of trabecular bone. Its leading to bone fragility and an increased susceptibility to fractures, especially of the hip, spine, and wrist, although any bone can be affected. The World Health Organization (WHO) has defined osteoporosis based on the bone density below 648 mg/cm2. Severe osteoporosis is identified when there has been a fragility fracture. The disease can be generalized or regional. Certain people are more likely to develop osteoporosis than others. Risk Factor Female gender Osteoporosis is more common in women (80%) than men (20%). In women, bone loss is more rapid in the first years after menopause but persists throughout the postmenopausal years. Men lose bone density with aging but because they begin with a higher bone density. They reach osteoporotic levels at an older age than do females. Older age Osteoporosis can affect people of all ages, but it is more common in older people than younger people. Relating between age and bone loss begins in the fourth decade. The cause remains unclear, but it is known that decreased serum growth hormone (GH) and insulin-like growth hormone (IGF) levels along with increased binding of RANKL and decreased OPG affect osteoblast and osteoclast function. Men have approximately 30%

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more bone mass than women, which may be a factor in their later involvement with osteoporosis.

B
Figure 1 (A) Bone loss in men and women. (B) Mechanism of loss of trabecular bone in women and trabecular thinning in men.

Family history of osteoporosis Research suggests that heredity and genetics play a major role in osteoporosis. If either of your parents had osteoporosis or a history of broken bones, you are more likely to get it too. And also, if one of your parents had a noticeable amount of height loss or a spine that curved forward, they may have had osteoporosis.

Caucasian or Asian race While osteoporosis affects all races and ethnicities, people in the U.S. who are Caucasian or Asian descent are more likely to develop osteoporosis than those of Africans heritage. It is because Africans have a higher bone density than Caucasian or Asian.

Low body weight/being small and thin Women and men with small bones are more likely than larger people to have osteoporosis.

Low sex hormone

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Estrogen levels In women, the sex hormone estrogen protects bones. Estrogen is important n maintaining bone density. When estrogen levels drop after menopause, loss of bone density accelerates and that is a major cause of osteoporosis in women.

Amenorrhea The young women who dont have regular periods, this could mean low estrogen levels. It may cause exercising too much, eating so little that you become too thin, disorders of the ovaries or the pituitary.

Testosterone levels In man, testosterone protects bone. Estrogen levels in men are also important. Low levels of these hormones can lead to bone loss. A number of factors can cause levels to be low, including eating too little or drinking too much alcohol.

Diet Low calcium and phosphorous intake Low vitamin D intake

Inactive lifestyle People who are inactive or do not exercise are at high risk of osteoporosis. Certain kinds of regular exercise can help keep your bones strong. Muscle contraction is the dominant source of skeletal loading, it is logical that resistance exercise such as weight training are more effective stimuli for increasing bone mass than repetitive endurance activities such

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as jogging. Certainly the decreased physical activity that is associated with aging contributes to senile osteoporosis. Smoking The chemicals in cigarettes are bad for your bone cells. Smoking also might make it harder to absorb calcium. For women, smoking can prevent estrogen from protecting the bones. Alcohol abuse Drinking heavily can reduce bone formation. Drinking may also affect your bodys calcium supply. Normal Bone Development The bone-forming cells include the osteoprogenitor cells, osteoblasts, and osteocytes. The generation and stimulation of these cells are regulated by cytokines and growth factors such as bone morphogenic proteins (BMPs), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), insulin-like growth factor, and transforming growth factor- (TGF-). Osteoprogenitor cells are pluripotent mesenchymal stem cells that are located in the vicinity of all bony surfaces. The process of osteoblastic differentiation is initiated and governed by the transcription factor core binding factor, which activates osteoblastsspecific gene expression. Osteoblasts and surface lining cells are located on the surface of bone and synthesize, transport, and arrange the many proteins of matrix detailed later. Osteoblasts express cellsurface receptors that bind many hormones (PTH, vitamin D, and estrogen), cytokines, growth factors, and extracellular matrix proteins. Metabolically active osteoblasts have a

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life span of approximately 3 months and their undergo apoptosis, become surrounded by matrix an transform into osteocytes, or become quiescent, flattened, bone surface-lining cells. Osteocytes cells processes traverse the canaliculi, and their contact along gap junctions allow the transfer of surface membrane potential and substrates. The large number of osteocytic processes and their distribution throughout bone tissue enable them to be key cells in several biological processes. Osteoclast is the cell responsible for bone resorption. The cytokines and growth factor crucial for osteoclast differentiation and maturation in human include interleukin (IL-1, IL-3, IL-6, IL-11), tumor necrosis factor (TNF), granulocyte-macrophage colonystimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF). These factor works by either stimulating osteoclasts progenitor cells or participating in a paracrine system in which osteoblasts and marrow stromal cells play a central role. This paracrine system is essential to bone metabolism, and its mediators include the molecules RANK (Receptor Activator for Nuclear factor B), RANK ligand (RANKL), and osteoprotegerin (OPG). RANK is a receptor expressed mainly on cells of macrophage/monocytic lineage such as proteoclasts. When the receptors bind its specific ligand (RANKL) through cell-to-cell contact, osteoclastogenesis is initiated. RANKL is major role in bone metabolism is stimulation of osteoclast formation, fusion, differentiation, activation, and survival. The actions of RANKL can be blocked by osteoprotegrin (OPG), which is inhibits osteoclastogenesis by acting as a decoy receptor that binds to RANKL, thus preventing the interaction of RANK with RANKL. The balance between RANKL and OPG is regulated by cytokines and hormones, and alterations of the RANKL/RANK/OPG system can lead to dysregulationand pathologica condition.
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Figure 2 OPG/RANK/RANKL system

POSTMENOPAUSAL OSTEOPOROSIS Definition Menopause is perhaps the most widely recognized and most studied age-related change in all of biology. The mean age of menopause, or the cessation of menstrual cycling, has increased steadily to the present age of approximately 50 years. In the decade after menopause, yearly reduction in bone mass may reach up to 2% of cortical bone and 9% of trabecular bone. Woman may lose as much as 35% of their cortical bone and 50% of their trabecular bone within the 30 to 40 years after menopause. Pathogenesis Postmenopausal osteoporosis is characterized by increased bone resorption, leading to sustained bone loss, resulting from estrogen deficiency. Estrogen deficiency plays the major role, and estrogen replacement at menopause is protective against bone loss. The effects of estrogen on bone mass are mediated by cytokines. Decreased estrogen levels result in
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increased secretion of IL-1, IL-6, and TNF. These cytokines are potent stimulators of osteoclasts recruitment and activity. They act by increasing the levels of RANK and RANKL and diminishing the quantity of OPG. RANKL expression is inversely correlated with serum level of 17 -estradiol. So estradiol deficiency will make RANKL is increased.

Figure 3 Pathophysiology of postmenopausal and senile osteoporosis

In the absence of estrogen, T cells promote osteoclast recruitment, differentiation, and prolonged survival via interleukin [IL]1, IL-6, and tumor necrosis factor (TNF)alpha. 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). Clinical Manifestations Osteoporosis can be present without any symptoms for decades because osteoporosis doesnt cause symptoms until bone fractures. The most common manifestation is bone deformity. Pain tends to occur only when there is a fragility fractures. Fractures are likely to occur because the trabeculae of spongy bone became thin and sparse and compact bone become porous. Vertebral collapse causes kyphosis (hunchback) and diminished height.fractures of the long bones (femur and humerus), distal radius, ribs, vertebrae are most

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common. Fracture of the neck of the femur (broken hip)tends to occur in older or elderly women with osteoporosis. Evaluation and Treatment Generally, osteoporosis is detected radio-graphically as increased radiolucency of bone. The National Osteoporosis Foundation, the American Medical Association recommend a dual-energy X-ray absorption scan (DXA/DEXA). DXA measures bone density in the hip and the spine. The score is called T score and osteoporosis is defined as a bone density T score of -2.5 or below. The prevention and treatment of senile and postmenopausal osteoporosis include exercise, appropriate calcium and vitamin D intake, and pharmacologic agents, including estrogen replacing agents, bisphosphonates, and recombinant PTH.

SUMMARY Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fractures. Bone strength is based on bone density and other factors, such as remodeling frequency, bone size and area, degree of bone mineralization, and hormone (estrogen). Decreased estrogen levels are potent stimulators of osteoclasts recruitment and activity. Osteoporosis can be present without any symptoms for decades because osteoporosis doesnt cause symptoms until bone fractures. The National Osteoporosis Foundation recommend a dual-energy X-ray absorption scan (DXA/DEXA) to detect osteoporosis with increased radiolucency of bone. The prevention and treatment of postmenopausal osteoporosis include exercise, appropriate calcium and vitamin D intake, and pharmacologic agents, including estrogen replacing agents, bisphosphonates, and recombinant PTH.

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REFERENCES 1. American Medical Association. Pathophysiology Osteoporosis. Available at:

http://www.ama-cmeonline.com/osteo_mgmt/module03/pdf/osteo_mgmt_03.pdf. Accessed December 8,2009 2. Kumar V, Abul KA, Nelson F. Robbins and Cotran Pathologic Basis of Disease . 7thed. China: Elsevier Mosby;2004. p.1507-13 3. McCance KL, Sue EH. Pathophysiology The Biologic Basic for Disease in Adults and Children. 5th ed. USA: Elsevier Mosby;2006. p.1274-84 4. National Osteoporosis Foundation. Osteoporosis. Osteoporosis. Available at: at: http://www.nof.org/osteoporosis/index.htm. Accessed December 8,2009. 5. MedicineNet.com. Available http://www.medicinenet.con/osteoporosis/index.htm. Accessed December 8,2009 6. Rowe JW, Richard WB. Health and Disease in Old Age. USA: Little Brown and Company;1992.p.246-54 7. Emedicine.com. Osteoporosis. Available at: http://emedicine.medscape.com/article/330598-overview. Accessed December 18,2009

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