Osteoporosis and Normal Bone Physiology - Essay Example

Student’s Name Instructor’s Name Course Date Osteoporosis Osteoporosis is nowadays a serious disorder that has become prevalent particularly in developed countries due to the changing lifestyles standards that have rendered people to become less active and change their eating habits. According to Binkley (2009, 755) osteoporosis refers to a systemic skeletal disease characterized by micro-architectural deterioration and low bone mass of the bone tissue with a subsequent increase in susceptibility to bone fracture and bone fragility. Historically, this disorder was referred to as a ‘woman’s disease’ in that significant percentage of women, 40-45%, sustained osteoporotic fractures during their lifetime. However, research by various researchers has established that approximately 25% of men do as well sustain osteoporosis-related fractures. In both genders, the incidences of developing osteoporosis-related fractures increase dramatically with advancement in age. A Case in point is in the United States where approximately 2 million men have osteoporosis accounting for about 20% of clinical vertebral fractures and 30% of hip. Osteoporosis develops in case peak bone mass is not achieved, excessive resorption of bone leading to reduction of bone mass as well as structural damage, or insufficient formation bone in respect to bone resorption. In regard to the above, this essay takes a closer look the basic physiology and functions of bones in the first section and the pathophysiology of osteoporosis in the second section. Normal Bone Physiology Notably it is possible for any bone to be affected by osteoporosis although the most common body parts are for instance wrist, hip, upper arm, pelvis, ribs and spine. In most cases osteoporotic fractures leads may lead to development of a stoop on the back rendering a change in posture, height loss, and bone deformity and muscle weakness. In addition, the fractures can also lead to disability, kyphosis, back pain, emotional difficulties and even premature death. In respect to physiology, bone is a living tissue and its strength is based on the normal functioning of three crucial bone cells which include osteoclasts, osteocytes and osteoblasts. This illustrated in the figure 1 below. Figure 1. Illustrative figure of bone physiology Osteoblasts and osteoclasts are key constituent cells of Bone Multicellular Unit (BMU) in which case reconstruction and remodelling of the bone occurs. It is at BMU that small packages of damaged and old bone tissues are removed through bone resorption by the osteoclasts. As such, osteoblasts are henceforth recruited into the hollow site in order to fill with young, new and healthy bone tissues. This process is commonly referred to as bone formation and it take place constantly all over the skeleton and is crucial in safeguarding normal bone strength. Basically, the functions of both the osteoblasts and osteoclasts is sufficiently coupled or coordinated. On the other hand, osteocytes are the most abundant and longest living bone cells and they come in handy as skeleton mechanosensors. Mechanosensors are in real sense developed from senescent osteoblasts and of their major role is to create an elaborate communication network amongst them and also with the exterior bone surface. In response to structural and mechanical demands, mechanosensors directs when and where bone remodelling is supposed to be initiated. The time required for osteoclasts to initiate bone resorption is quite short whereas time required to osteoblasts to imitate bone formation is quite long (months). As a result, an increase in the rate of bone remodelling results in net bone loss. On the other hand, an increase in the number of unfilled excavation sites stress risers are formed thereby becoming much more vulnerable to and can easily be perforated hence results in overall micro fractures of the bone. Furthermore, extreme bone resorption may as well result in comprehensive waste of trabecular plates thereby leaving no template on which formation of bone can occur. Constant and comprehensive damage of trabecular structures is especially common amongst postmenopausal women whereas in the case of men they do experience trabeculae thinning instead of total waste. During puberty and childhood increased rates of bone resorption is parallel by increased rates of bone formation although with advancement in age the response of osteoblast to bone resorption is insufficient with it outdoing bone formation. Becker (2006) argues that such significant failure of the osteoblasts is a key factor for triggering osteoporosis development. Lately, the essential molecular mechanisms through which osteoblasts and osteoclasts coordinate their activities at the BMU has been proposed by Roodman (2004) as illustrated in the figure below. Receptor Activator of Nuclear factor-kB ligand (RANKL), a crucial cytokine, is generated by activated T cells and osteoblasts within the bone marrow thereby play a vital role during intercellular communication network. Subsequently, RANKL attaches itself on the receptor activator of nuclear factor kB (RANK) receptor which is exhibited on the surfaces of osteoclasts and osteoclasts precursors. Upon binding of RANKL onto the RANK, variation of osteoclast precursors is promoted from an early maturation stages into fully functional, multinucleated and mature osteoclasts. Besides, RANKL as well activates mature osteoclasts exciting them to commence bone resorption. Subsequently, RANKL is capable of binding itself to osteoprotegerin (OPG) which is a soluble decoy receptor generated by several hematopoietic cells. Through isolation and prevention of RANKL to bind to RANK, OPG acts as a potent anti-resorptive cytokine. As such, RANKL/RANK/OPG process seems to be the ultimate mutual path through several processes that excite bone resroption should take. Pathophysiology of osteoporosis According to Kasturi (2009, p.254) osteoporosis was for quite some time categorised into two –primary and secondary. In respect to primary osteoporosis is further divide into two; Type I –a postmenopausal disorder in women and ‘idiopathic’ in men and they are common among those between the age of 50 and 70 years. Mainly it occurs on trabecular bones thus leading to wrist and vertebral fractures; Type II also called senile osteoporosis occurs on both trabecular and cortical bones of individuals aged at least 70 years it is a common cause of hip fractures. The basis upon which pathophysiology of osteoporosis can clearly be discussed is through appreciating the main moderators of bone metabolism. These moderators include oestrogen, testosterone, vitamin D, calcium, parathyroid hormone, thyroid hormone, and calcitriol. Besides, the concept of peak bone mass, bone reconstruction and remodelling cycles are as well important. Bone mass has a high correlation to the strength of the bone. Normally peak bone mass is attained between 25 and 30 years and thereafter it reduces gradually in both women and men. Although peak bone mass is to large extent effected by genetic factors, environmental factors for instance physical activity, calcium and vitamin D also plays a great role. Delayed puberty, delayed menarche, premature menopause, reduced physical activity, oestrogen deficiency manifested by eating disorders and amenorrhea, and nutritional deficiencies may cause achievement of peak bone mass which is lower than normal. In respect to bone remodelling encompasses continued resorption and redesortpion of phosphorus and calcium in the bone in order to regulate acidosis, give response to variations in mechanical forces and repair micro damages. According to Kasturi (2009), the main purpose of bine remodelling is repairs fatigue microdamages and at any time, 10% of skeleton is remodelled. At initial activation stages of the cycle, osteoblastic precursors and osteoplastic precursors are activated. Osteoclasts are responsible for resorption leading to irregular cavities of the bone surface. Consequently, in a reversal phase, further collagen degradation is casued by mononuclear cells. During the process, osteoblasts results from differentiation of mesenchymal precursor cells during resorption phase thereby forming a bony matrix. Regulation of bone remodelling is through local and systemic factors. Local regulatory factors include RANK ligand, osteoprotegerin, prostaglandins and cytokines. Systemic regulatory factors include parathyroid hormones, vitamin D, oestrogen, testosterone, thyroid hormone, and glucocorticoids. Any abnormality or deficiency in any of the above factors leads to abnormal bone remodelling cycle. As such, this disorder is a result of failure to attain optimal peak bone mass during young age, extreme bone resorption after achieving peak bine mass, and/or impairment of bone formation process throughout remodelling cycle. In the case of oestrogen, Sipos et al. (2099), notes that play a key role of both extra skeletal and skeletal activities and in case of its deficiency, osteoporosis results. Skeletal activities includes direct activities that are dependent on oestrogen receptors contained in both osteoblasts and osteoblasts and indirect skeletal activities of oestrogens are facilitated by oestrogen receptors on several other cell types such as stromal cells that controls OPG when exposed to oestrogen, and immune cell systems that regulates homeostasis. Among postmenopausal women, oestrogen deficiency leads to upward regulation of RANKL within the bone marrow cells. Ranksl is a key determinant of heightened bone resorption whereas on the other hand oestrogen excites production of OPG within osteoblasts thereby exerting anti-resorptive influences on the bones (Appendix A) illustrated in the figure below. Extra skeletal oestrogen deficiency is mainly influenced by increase in renal calcium excretion as well as reduced absorption of calcium within the intestines. Besides, oestrogen deficiency goes alongside continuous increase in serum parathyroid hormone (PTH) levels. Through interaction between bone cells and immune system, deficiency of oestrogen causes T cells to release various types if inflammatory cytokines. For instance tumour necrosis factor-α, interleukin (IL)-1, and IL-6 enhances recruitment of osteoclasts, their differentiation, and prolonged lifetime compared to IL-7 which inhibits differentiation and activity of osteoblasts thereby causing premature death commonly known as apoptosis. Hence according to Becker (2006) this causes postmenopausal osteoporosis which manifest itself as inflammatory autoimmune disease. As illustrated in the above discourse, osteoporosis has been explained as disorder that affects the composition of bones rendering them weak. This particularly affects the skeletal system and it is common in old age in both genders. Besides, in terms of pathophysiology, oestrogen deficiency is the common cause of that leads to pathogenesis of osteoporosis whereas others are for instance abnormal variations of testosterone, vitamin D, calcium, parathyroid hormone, thyroid hormone and calcitriol. In this regard, this is a serious disorder that requires a lot is attention with the increasing changing lifestyle. Works Cited Becker, Carolyn. “Pathophysiology and Clinical Manifestations of Osteoporosis.” Clinical Cornerstone 9.2 (2006): 42-50. Binkley, Neil. “A perspective on male osteoporosis.” Best Practice & Research Clinical Rheumatology 23 (2009): 755–768 Kasturi C. Gopi, David X. Cifu and Robert A. Adler. ‘A Review of Osteoporosis: Part I. Impact, Pathophysiology, Diagnosis and Unique Role of the Physiatrist.” Physical Medicine and Rehabilitation Journal 1.3 (2009): 254-260. Print. Roodman GD. “Mechanisms of bone metastasis.” N Engl J Med 350 (2004): 1655–1664. Sipos Wolfgang, Peter Pietschmann, Martina Rauner, Katharina Kerschan-Schindl, and Janina Patsch. “Pathophysiology of osteoporosis.” Wien Med Wochenschr 159.9–10 (2009): 230–234. Appendix A: Effects of oestrogen deficiency leading to bone loss Read More