It has been estimated that 2 million women who have osteoporosis in England and Wales and it affects 1 in 3 women aged more than 50 years and 1 in 12 men aged larger than 50 years [B1, B31]. The clinical disorder is heterogeneous with range of origins, including hormone loss, physical and genetic factor[C2] and often these conditions overlap within individual patients and they are the major factors in affecting the choice of treatments and preventions. So, what are the present treatments for osteoporosis?
Figure 1 Normal bone matrix and osteopororsis[C1]
A Possible Solution
Screening and testing
Every individual above 40 is encouraged to go for screening for their Bone Mass Density (BMD). Before the screening test, the doctor would evaluate the patient's family history, lifestyle and tests concerning the nutrients in the body. Next, the patients would be introduced to several methods of screening such as dual-energy X-ray absorptiometry (DEXA) and X-ray absorptiometry (SXA).
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Figure 2: DEXA screening[C32]In DEXA, X-ray machine scan the lower spine and hop area with the patients lying on a bed with clothes on.(Figure 2) In contrast, SXA used a smaller X-ray machine to measure the BMD at the heel, shin bone ad kneecap only. SXA is reliable as a low BMD at hips often indicates low BMD at the other parts of the body[C32]. However, DXA may be carried out to confirm the bone mineral deposit.
It is proven that with low BMD, one will has increased bone fragility and increased risk of fracture[B2]. Doctor will usually begin with careful history to determine if one is having osteoporosis. One will also be asked a variety of questions concerning lifestyle and other conditions while blood tests are usually used to measure contents of various nutrients in the body. Any individuals whose hip having BMD lower than or equal to 2.5 SD is diagnosed to be having osteoporosis
Antiresorptive agents- Bisphosphonates
There are several types of antiresorptive agents which work with different mechanisms such as Bisphosphonates, Hormonal estrogen replacement (HRT), SERM (Selective Estrogen Receptor Modulator) and Calcitonin[C3]. However, bisphosphonate is focused in this report as it is the first line therapy for osteoporosis.
Bisphosphonates, or known as diphosphonates, reduce bone turnover marker by selectively binding to bone and inhibit the osteoclasts-mediated bone resorption[C4,C7], which further reduces the risk of osteoporotic fractures by preventing the decrease in BMD[C6].
Osteoclasts and osteoblasts are the cells that regulate the bone density and they balance the bone formation and bone absorption. When the bone absorption of osteoblasts is greater than bone-forming activity of osteoblast, more bone is absorbed than produced; hence, BMD decreases, leading to osteoporosis.
Generally, there are two classes of bisphosphonates: nitrogen containing bisphosphonates which include tiledronate, etidronate and clodronate or the other hand, the non-nitrogen containing bisphosphonates which include pamidronate, neridronate, olpadronate, alendronate, ibandronate, risedronate, and zoledronate.
The non-nitrogen containing bisphosphonates are first metabolized to cytotoxic(non-hydrosable analogs of ATP) when they are internalized into osteoclasts via endocytosis and these toxic by products interfere mitochondrial function of osteoclasts and lead to their apoptosis. On the other hand, the nitrogen-containing bisphosphonates function by inhibiting the key enzymes-farnesyl pyrophosphate synthase (FPPS) that further prevent the prenylation and activation of small Guanosine Triphosphate-binding Proteins (GTPases), which are crucial for the survival of osteoclasts and bone-resorbing activity[C5]. Bisphosphonates have the ability to selectively adhere to and retain within the bone before endocytosis into osteoclasts and it occurs only in osteoclasts. When the osteoclasts activity has been suppressed, the osteoblast form more bone, leading to rise in BMD and decrease in fracture risk.
Table 1: Relative risk reduction of bone after
oral bisphosphonate treatment[C9]There are data suggesting that long-term use of bisphosphonate instead of specific use of bisphosphonate is the most important factor in determining the effectiveness of treatment for limiting fracture risk[C8]. The ability of nitrogen-containing bisphosphonate is generally more potent than non-nitrogen containing bisphosphonates though their ability to suppress osteoclasts activity varies.
For example, alendronate and risedronate are shown to be able to reduce the number of vertebral and hip fractures, progression of vertebral deformities, and height loss in postmenopausal women with osteoporosis[C8] whereas Ibandronate, has been demonstrated to reduce only the risk of vertebral fracture[C8]. (Table 1)
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During the 3-year Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) study period, annual IV administration of zoledronic acid led to significant decrease in vertebral (70% reduction), hip (41% reduction), and nonvertebral (25% reduction) fractures, with significant increase in BMD at the lumbar spine, hip, and femoral neck.
Besides that, there are studies showing improvement in rate of spine fractures with various bisphosphonates in elderly subjects. However, some of the trials compared young women to older women, and with alendronate and zoledronate the younger women had a better response. (Graph 1)
Graph 1: Percentage of women during study with different bisphosphonates and placebo[C10]
As shown in Graph 2, the probability of fracture remains unchanged to approximately 0.50 and then declines with a shallow slope for their MPR values from 0.50 till 1.00. The model fits a continuing substantial reduction in fracture rate up to a maximum level of MPR.
Graph 2: Probability of fracture in 24 months in the bisphosphonate-treated patients[C11]
MPR = medication possession ratioAlthough nearly all osteoporosis trials, which used bisphosphonate therapy, involved post-menopausal women, trials examining men have also demonstrated similar responses. From the studies conducted, bisphosphonate has been an effective treatment for osteoporosis.
Social and Economic implications
Osteoporosis does not only cause depression but also anxiety among the patients as they lose their confidence due to their inability to play their role in their workplace and home. Besides that, the patients experience stress and fear of falling for fracture. Due to their fear, they became inactive[A2,C33] and may develop other illnesses such as obesity. Hence, bisphosphonate help to improve psychological conditions of the patients because when their fractures risk is decreased, they have more confidence to live normally carrying their daily life[C12].
Osteoporotic patients who had experienced bone fractures need to spend much on artificial bones, surgery and follow-up treatment which cost up to £1.7 billion per year and is expected to increase to £2.1 billion by 2010 in England and Wales[C31]. Hence, using bisphosphonates as an early prevention could save the society millions of dollars. It could also maintain the productivity of the country as the patients could work normally and not afraid of having bone fractures[C13].
Therefore, I think it is important for the government to encourage public to do screening tests and to provide subsidized tests in reducing the rate of hip fracture for both acute and chronic care. With that, the whole country may save up to billion per year.
Table 2: Resource utilization and cost for the acute management of hip fracture at SPSS at 2007 [C34]
Benefits and Risks
Bisphosphonate is the first line treatment and prevention for both genders[B1]. Despite of the increase of the BMD in the patients, it also improves their psychological conditions and the work force of a country.
The administration of the newer bisphosphonates is much more convenient than the previous class as it can be taken according to the patients' preference: weekly, monthly or yearly via intravenous (IV) method[A1]. Besides that, compared to the cost of surgery and other treatments, bisphosphonates are cheaper and more affordable for poor families[C35, C36]. Besides that, bisphosphonate are used to treat osteitis deformans (Paget's disease of the bone), bone metastasis (with or without hypercalcaemia), multiple myeloma, and other conditions that feature bone fragility
On the other hand, there are side effects with the use of bisphosphonates. Oral nitrogen-containing bisphosphonates can cause stomach upset, nausea, vomiting, abdominal pain, and erosions of the esophagus[C14] while the IV administered bisphosphonates can cause fever and flu-like symptopms after the first infusion. Another well known side effect of bisphosphonates is the osteonecrosis of the jaw which is frequent in IV administration[C28]. There are also studies showing atrial fibrillation in female patients. However, till now the benefits of bisphosphonates outweigh its side effects and their side effects are much more minor compared to other treatments' side effects[C27].
Behavior therapy works by practicing healthy lifestyle. Any other treatment alone is unlikely to help the patients to prevent or treat osteoporosis fully unless they practice a healthy lifestyle. A behavior therapy includes :
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b.) Taking diet containing sufficient calcium, magnesium, Vitamin K and Vitamin D
c.) Limit alcohol intake
Exercise, especially those involving weight-bearing physical activity strengthens muscles and improves reflex action. The patients who exercise are less likely to fall as they can react faster by balancing themselves before a fall and reduce the risk of bone fracture[A1]. There are also studies conducted showing that running could strengthen the leg of both the elders and the young[C15,C16]Â.Besides that, intensive exercise training can lead to improvement in strength and function in elder patients who have had hip replacement surgery due to hip fracture[A1].
Figure 3: Importance of exercise [C17]
Magnesium[C18], calcium, vitamin K and vitamin D are vital nutrients to maintain the BMD in a healthy range and prevent osteoporosis. Calcium is the main element of bone while Vitamin D[C19] and magnesium help the body to absorb calcium. Meanwhile, Vitamin K[C20] is used to maintain calcium in the bone[A3].
Fortunately, osteoporosis is preventable for most people, and getting enough calcium in your diet is the first place to start.
Moderate alcohol intake is found to be linked to high BMD but excessive alcohol appears to reduce BMD[C21]. However, excessive drinking prevents the body from taking in calcium by interfering with the liver enzymes responsible for the conversion of vitamin D to active form that is able to absorb calcium into the body. Nevertheless, it poisons the osteoblasts and interferes the sexual hormone of both genders. Some professors suggested that it is the silicon and antioxidant in the moderate drinking that protects the bone[C22].
"Previous research suggests that moderate alcohol consumption in older men and post-menopausal women may protect against BMD loss, a major risk factor for osteoporosis"
Anabolic agents- Parathyroid hormone
Anabolic agents have been used to prevent and treat osteoporosis[C23]. Anabolic agents such as parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) are critical in bone growth, regulation of calcium homeostasis and bone resorption[C24]. However, both of them have different therapeutic effects on calcium and bone metabolism and are found naturally in human body.
When PTH is produced too much, osteoporosis is likely to occur[C25]. However, if it is given an intermittent burst, osteoporosis effect is eliminated and bone-building effect occurs.
Currently, there are anolog to this hormone, known as teriparatide and has been approved for use by Food and Drug Administration (FDA) in November 2002 to resemble the naturally gained PTH found in human body. It is administered through injection into the subcutaneous tissue and it is mainly used to grow bone. It has been proven to reduce the risk of vertebral fracture among women (Graph 3 and Table 4).
Graph 3: Percentage of patients from different group having non-vertebral osteoporotic fracture[C26] I feel that the choice of treatments used should suit the patients themselves as each individual vary with each other. The primary objective for the treatment and prevention of osteoporosis is to reduce the risk of fracture and hence, minor side effects are tolerable for the greater later benefit.
Table 4: Reduction in vertebral fractures by teriparatide[C37]
Evaluation of sources
Personally, I think that http://courses.washington.edu/bonephys/ophome.html is a very useful website as it focuses on osteoporosis from several factors. It is last reviewed on 17 Jun 2010 and had been certified by HON code[C29] (Health on the Net Foundation). Therefore, the information smut be correct. Besides that, the site is maintained by Susan Ott, MD, an Associate Professor of Department of Medicine University of Washington.
Besides that, http://www.mayoclinic.com/ is a website which provides information for diagnosis and treatment of many type of complex illness. Furthermore, the staff members who themselves are specialist often seek and update the latest information from doctors, specialists and health care professionals. Hence, it should be accurate and up to date. Besides that, http://www.mayoclinic.com/health/ osteoporosis-treatment/WO00127, which provides specific information on osteoporosis is last updated on. 27 Aug 2009, and reviewed by Kurt Kennel, M.D., a specialist in endocrinology at Mayo Clinic. This source agrees with many other popular internet sources, such as http://osteoporosis.emedtv.com and http://orthopedics.about.com/od/osteoporosis/tp/ osteoporosis.htm. Nevertheless, Mayo Clinic itself has its own university, research centre and medical centre that always seek for the latest information regard the illness.
I have also evaluated on the book "Drug Therapy for Osteoporosis" written by Michael Kleerekoper. The book was first published in United Kingdom in 2005 and is considered reliable because it has been considered as a good reference for health professionals seeking information for the drugs for osteoporosis by http://www.theannals.com/cgi/content/full/39/11/1958-a. The book has also used various references available in 2004, which is a year before the book is published. Besides that, the book has been found to be cited in several journals relating to osteoporosis, proving that the book is a reliable source.
Compston J. (1999), Family Dorctor Guide to Osteoporosis, London, 1(2): 46-48
Kleerekoper M. (2005) Drug Therapy for Osteoporosis, United Kingdom, 1(1):63-86
Burckharadt P., Dawson-Hughes B., P.Heavney R. (2004) Nutritional Aspects of Osteoporosis, 1(1): 211-220
Boonen, S., Body, JJ., Boutsen, Y., Devogelaer, JP., Goemaere, S., Kaufman, JM., Rozenberg, S., & Reginster, JY. (2005) International Osteoporosis Foundation and National Osteoporosis Foundation 2005. Evidence-based guidelines for treatment of postmenopausal osteopororsis: a consensus document, (1)1;1-2
Miller, P.D. & Derman R.J. (2010) International Osteoporosis Foundation and National Osteoporosis Foundation 2005. What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis? 1(1):1-3
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