A Research of Bone Metabolism in Osteoporosis

Introduction

The human skeleton is composed of roughly 206 bones. The axial skeleton and appendicular skeleton together make up the adult skeleton. Bones are active tissues that are being broken down and rebuilt all the time. Bones have an enormous variety and due to this they have more than one function. They provide the body structural support, cover and protect organs such as the heart and lungs and enables us to move. Bones are predominately made of collagen which is a protein. Bone metabolism is ongoing natural process of bone growth and resorption this is vital for repair, growth and maintenance. This complex process is carried out by osteoclasts and osteoblasts. Osteoclasts break down bone tissue and absorb them whilst osteoblasts are in charge of building new bone tissue. Imbalances in the activity of resorption and growth can weaken bones leading to diseases such as osteoporosis. Osteoporosis is a condition that causes bones to weaken and more vulnerable to breaking. This essay will give a detail explanation of what bone metabolism is, osteoporosis and its diagnosis and risk factors involved in it. 

Bone metabolism is a lifelong process where the synthesis and destruction of tissue gives bones its mature structure. Ossification is known as the synthesis of bone tissue while bone resorption is the destruction of bone tissue. After injuries, bone metabolism can also replace and change the shape of bones. Osteoblasts are large cells with a single nucleus that are responsible for the synthesis and mineralisation of bone during initial bone formation and later bone remodelling. Osteoblasts develop into a compact layer on the exterior of the bone, from which cellular processes extend through the developing bone (Osteoblast, 2018). They need to be in groups of connected cells to function and individual osteoblast cells cannot form a fully developed bone. An osteon is a collection of osteoblasts that work together with the bone. Mesenchymal stem cells that are specialised and permanently differentiated form the osteoblasts. The enzymes alkaline phosphate and collagenase, growth factors, hormones such as osteocalcin, and collagen which forms the matrix of the bone are produced by osteoblasts. In the end the osteoblast is enclosed by the growing bone matrix and as the material calcifies, the cell is surrounded in a space called a lacuna forming an osteocyte (Osteoblast, 2018). Osteoclasts are large multinucleated cells that break down bone tissue. Bone is continuously broken down in response to micro-damage and the body’s requirement for calcium. Osteoclasts are found in a small depression on the bone exterior called Howship lacunae. The lacunae are caused by erosion of the bone by osteoclasts’ enzymes. The combination of many cells from monocytes in the blood help to form the osteoclasts. Microvilli extends onto the bone’s surface that is nearest to the side of the cell. Osteoclasts form several enzymes including acid phosphatase that dissolve both the organic collagen and the inorganic calcium and phosphorus of the bone. Digestion of the fragmented mineralised bones using cytoplasmic vacuoles occurs when the osteoclast engulfs the fragments. Calcium and phosphorus are let into the bloodstream after the breakdown of the mineralised bone. 

Osteoporosis, is a skeletal disorder that occurs when the correct functioning of bone remodelling is compromised. Typically, bone density increases until the age of 20, when bones are at their strongest and healthiest. After young adult life, bone density starts to slowly decrease over time. However, for some individuals, this happens more rapidly than the rest of the population, which leads to osteoporosis. In fact, this disease sees the loss of mineral and ostheoid components of bone mass, caused by far more significant reabsorption than the appositive phase. In other words, this is due when the osteoblasts do not work as efficiently as the osteoclasts within the BMU, which results in the production of too little bone or the loss of too much bone mass or both (National Osteoporosis Foundation, 2019). Ultimately, this leads to reduced bone matrix due to the reduction of osteoblastic activity as well as the increase activity of osteoclasts. 

Furthermore, the disease causes micro-architectural alterations of the bone, where the difference between healthy bone tissue compared to one affected by osteoporosis is shown. Here, the left shows a compact tissue with small perforations, contrasting to much larger holes presented in the right picture. In fact, the noun osteoporosis derives from ancient Greek where the noun pores translates into an orifice or an opening (www.dictionary.com, 2019). Therefore, bone density decreases and they become more fragile, increasing the risk of fractures and breaks from low impacts. Other symptoms include, stooped posture or progressive loss of height caused by vertebral crush fractures which may lead in difficulties in breathing and back pain. 

The disease is classified into primary osteoporosis (Type I) and secondary osteoporosis (Type II). Type I is associated with the process of ageing alone, such as hormonal changes within the body as one grows old. On the other hand, type II is caused by a pre-existing medical conditions or drugs which may lead to abnormalities in bone reformation. Some of the diseases associated with osteoporosis are some endocrine disorders, gastrointestinal, hepatic and nutritional disorders, hematological disorders, renal disorders and some autoimmune disorders. Moreover, medications that may lead to osteoporosis include hormones and drugs with actions on the endocrine system, drugs with actions on the central nervous system, drugs with actions on the immune system, anticoagulants; heparin, diuretics: loop diuretics, drugs with actions on the gastrointestinal tract (Mirza and Canalis, 2015). The most common way to determine whether a patient is affected by the disease, is to perform a quick and noninvasive dual energy x-ray absorptiometry (DEXA) scan. This measures the bone mineral density (BMD) through small dose of ionizing radiation by producing a picture of the inside of the body. Results are then given in the forms of two scores, the Z-score and the T-score. The latter one compares the patient’s bone mass to the one of a young adult of the same gender who has peak bone mass. This comparison is done in the form of a number by which a score of -1.0 and above is considered to be healthy. Contrarily, less than -1.1 to -2.4 defines the early stage of osteoporosis called osteopenia. Finally, a score of -2.5 and below represents osteoporosis. On the other hand, the Z-score is a number that compares one’s bone mass to the people in the same age group and of the same gender and size. Here, if the score is significantly higher or lower, it may imply the presence of a condition such as osteoporosis, thus the need of further tests.

Treatments for osteoporosis include vitamin D and calcium, weight-bearing exercises and drugs such as bisphosphonates. It is important to consume an adequate amount of nutrients in an individual’s diet who are suffering from osteoporosis, supplements include vitamin D and calcium. Vitamin D helps the body to absorb calcium before maximum bone density is reached. Bones contain minerals such as phosphorus and calcium, which makes them hard and dense. To maintain bone mass the body requires a certain amount of calcium. Lots of vitamin D is required to absorb calcium from our diet and incorporate it into bones. 

To prevent osteoporosis drugs such as bisphosphonates are used. This drug is useful for treating all types of osteoporosis and it also reduces the risk of fractures in individuals. Those people who have a sedentary lifestyle are at a higher risk for osteoporosis. Examples of weight-bearing exercises are walking, swimming and other exercises do not increase bone density but it increases core strength. Long term use of steroids such as glucocorticoids can lead to a loss of bone tissues. High dose of drugs which are taken for a long period can cause less calcium being available to the bones. Those people who are given thyroid hormones must do routine tests to determine if the bone mass is decreasing. Hormonal therapy includes estrogen and progesterone which are produced by a woman’s ovaries. If women take estrogen without a progestogen it will increase the risk of endometrial cancer. So it is important to take estrogen with progestogen as it will reduce the risk. It is important for smokers to quit smoking as it increases rates of bone loss. Some studies have shown that women who smoke tend to have earlier menopause and have a lower level of estrogen in their body than non-smokers. Women’s lose bone rapidly in their first few years after the menopause. When the estrogen level decreases in women at the stage of menopause the risk of osteoporosis and bone loss can increase. Bone density is an issue in female athletes as the level of estrogen drops and can lead to lower mineral counts. High intensity can cause the athletes to suffer fractures. Ageing is another reason for osteoporosis in men and women. If the body is unable to take a certain amount of bone formation, bones will continue to lose its density and this can cause osteoporosis. 

Conclusion 

Current findings suggest that new treatments such as monoclonal antibodies could be used for the treatment of osteoporosis. Romosuzumab, is a monoclonal antibody that binds to sclerostin. Sclerostin is a glycoprotein which plays a key role in skeletal growth, which is secreted by osteocytes. By binding to the sclerostin it prevents it from inhibiting the WNT signaling which leads to bone formation and bone mineral density gain. Research found that sclerostin deficiency syndrome in humans and animals are characterized by high bone mass of normal quality. This highlighted that high levels of sclersotin and RANKL were linked to osteoporosis. The clinical trial for Romosozumbab evaluated treatments effects in postmenopausal women aged 55-90 with osteoporosis. They were randomly assigned to receive subcutaneous doses of romosozumtab or placebo injections, followed by subcuntaneous denosumab every 6 months for 12 months. The bone mineral density at the lumbar spine and total hip had increased and reduced the risk of clinical fractures. The Romosumnab produced good results and it was found to be a highly effective treatment alongside Denosumab for postmenopausal women with osteoporosis. In an experts opinion it shows promise in the treatment of osteoporosis. 

To conclude osteoporosis is one of many bone diseases which form a large group of disorders of bone metabolism, it causes the bones to become brittle and fragile from loss of tissue as a result of hormonal changes, or deficiency of calcium or vitamin D. This is why osteoporosis can have a huge impact on day to day life, it can cause fractures and intense amount of pain due to lack of bone density, It is most commonly seen in women as they have smaller bones especially women after they experience menopause. Bone metabolism aids bone remodeling which is initiated by osteocytes and follows an orderly sequence of osteoclastic bone removal and then osteoblastic bone formation. Although there is no cure yet for osteoporosis, many treatments and lifestyle changes can slow down the rate of bone loss. Over the years there has been ground-breaking research into treatments for osteoporosis and many are now FDA approved such as Romosozumab.