Osteonecrosis of Jaw: Story of Bisphosphonates
Introduction:
Bisphosphonates (BPs), also known as diphosphonates are class of drugs used for prevention and treatment of bone related disorders. They came into existence in 19th century and were primarily used as detergents, water softener, anticorrosive, and antiscaling agents (Russell, Watts, Ebetino, & Rogers, 2008). In 1960s, after understanding their properties and mechanism of action their use was determined in humans. BPs acted as antiresorptive agents with high affinity towards skeletal tissue. Their unique characteristics of controlling calcium and phosphate dissolution thereby preventing of loss of mineralized tissue attracted many industries and created potential market for their development. BPs were developed and used in the treatment of bone diseases such as Paget’s disease, multiple myeloma, hypercalcemia of malignancy, and osteoporosis.
Structure and mechanism of action:
BPs has a P-C-P backbone. They are synthetic analogs of inorganic pyrophosphate in which the oxygen is substituted by carbon. The R1 and R2 side-chains attached to the carbon atom are responsible for the large range of activity observed among the BPs. R1 enhances the binding to hydroxyapatite while R2 determines anti-resorptive properties and carbon enhances chemical stability and resistance to enzymatic degradation (Russell et al., 2008). Source: http://en.wikipedia.org/wiki/File:BisphosStruct.svg
There are 2 main types of BPs: nitrogen containing and non nitrogen containing. Depending on their type the mode of action differs. The nitrogen containing BPs are more potent and exert their action via inhibition of the mevalonate pathway which is by binding and blocki...
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...Watts, N. B., Ebetino, F. H., & Rogers, M. J. (2008). Mechanisms of action of bisphosphonates: Similarities and differences and their potential influence on clinical efficacy. Osteoporosis International, 19(6), 733-759.
Schwartz, H. C. (2005). Bisphosphonate-associated osteonecrosis of the jaws. Journal of Oral and Maxillofacial Surgery, 63(10), 1555-1556.
Silverman, S. L., & Landesberg, R. (2009). Osteonecrosis of the jaw and the role of bisphosphonates: A critical review. The American Journal of Medicine, 122(2S), 33-45.
V.M. Cartsos, S. Zhu and A.I. Zavras,. (2008). Bisphosphonate use and the risk of adverse jaw outcomes: A medical claims study of 714,217 people. J Am Dent Assoc, 139, 23-30.
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Osteoporosis is the loss of bone mass and deterioration of bone matrix resulting in brittle and fragile bones (Weber & Kelley, 2014). The rate of bone resorption is greater than the rate of bone formation, therefore, causing bones to become porous and under stress, can fracture (Drake, Clarke, & Lewiecki, 2015). Conditions that contribute to osteoporosis include poor nutrition, menopause, long-term use of glucocorticoid therapy, and hyperthyroidism are only a few conditions. These conditions all have several related factors that contribute to osteoporosis, breakdown of bone or prevention of bone remodeling. For instance, inadequate dietary intake of vitamin D and calcium can lead to osteoporosis because they are necessary for bone
Bisphenol A (BPA) is a synthetic compound used worldwide in the manufacturing of plastics and epoxy resins. Derivatives of BPA are present in resin-based sealants and composites used in dentistry.1 Some of these compounds include bis-DMA (BPA dimethacrylate), bis-GMA (BPA glycidyl methacrylate) and BADGE (BPA diglycidylether).1
Roux C, Dougados M. Treatment of patients with Paget’s disease of Bone. Drugs. 1999 Nov; 58 (5): 823-830.
Osteonecrosis has become a subject of interest amongst orthopaedic surgeons predominantly during the last four to five decades.
Osteoporosis is a condition, which advances with age, resulting in fragile, weak bones due to a decrease in bone mass. Externally osteoporotic bone is shaped like normal bone, however it’s internal appearance differs. Internally the bone becomes porous due to a loss in essential minerals, including phosphate and calcium. The minerals are loss more quickly than they can be replaced and in turn cause the bones to become less dense and weak. The bones become prone to fracture, due to their weakness. Therefore the awareness of the disease tends to occur after a fracture has been sustained. The bones most commonly affected are the ribs, wrist, pelvis and the vertebrae.
By definition, "osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased risk of fractures of the hip, spine, and wrist" (National Institute of Health- Osteoporosis and Related Bone Diseases, 2012). Both Berarducci (2008) and Hansberger’s (2005) article note that osteoporosis is the most common disease of all bone disorders, affecting both men and women. The incidence of the disease is growing in the United States with almost 44 million affected Americans and an estimate incidence rate of 10 to 14 million by 2020. Deemed a "silent" epidemic, there is a low level of diagnosis, and even lower level of treatment. Walker (2010) supports Hansberger (2005) that the disease causes pain, depression, anxiety, loss of mobility, and ultimately fractures. It is crucial that Advanced Practice Nurses/Nurse Practitioners have a solid understanding of the disease and are able to identify risk factors, order the proper diagnostic testing, and treat their patients.
Osteoporosis is a condition, in which bones are weak from deterioration, loss of bone mass, and quality-bone strength. Osteoporosis usually triggers postmenopausal women (women who have not had their period for a whole year), or older men and women. Some risks both older men and women endure when experiencing Osteoporosis are decrease of calcium and bone fractures. These symptoms or effects can all be caused by weight loss, smoking, age, ethnicity, genetics, medications, bone structure, and certain diseases that can later on contribute to Osteoporosis, such as rheumatoid arthritis. Osteoporosis may be prevented by going to drug therapy to stop alcoholism and smoking, a sufficient amount of calcium intake, and exercising; such as jogging, walking,
Osteoporosis is a common problem worldwide. It affects people of all races and ages. Older people are particularly prone to the disease because the ageing process involves bone weakening,
Osteoporosis is a systemic, debilitating disease of the skeleton, characterized by significantly decreased bone mass in combination with the deterioration of bone microarchitecture. Osteoporosis has three types of categories the first category is type 1 which occurs in women after menopause and results from declining levels of estrogen and other sex hormones in the body, this could also occur in men due to low levels of the sex hormone testosterone. Type 2 is called Senile Osteoporosis, which occurs in elderly men as well as elderly women because of decreased bone formation due to aging. Type 3 is caused by long term use of medication usually with steroids and drugs to treat elipsy. Osteoporosis which literally means “Porous Bone”,
It was coined by French pathologist Jean G. C. F. M. Lobstein in the 1820s in the context of osteitis (inflammation of the bone). It was derived from the Greek osteon(bone), to which he added poros (little hole). Thus, osteoporosis meant “porous bone,” a condition that Lobstein had observed in patients.” After more research was done on how bones are formed and how the skeletal system works, it laid the foundation to understand Osteoporosis better and to develop treatment.
The alveolar bone resorb faster, after tooth extraction, when bone density is low affecting the quality of life in patients with mouth prosthetic (dentures). Osteoporosis is a chronic disease that up to date cannot be cured, but some drugs therapy help with prevention and stopping bone loss. The most used medications to slow bone resorption are bisphosphonates, which include alendronate, alendronate plus vitamin D (Fosamax and Fosamax Plus D), ibandronate sodium (Boniva), risendronate sodium, risendronate sodium with calcium carbonate (actonel, actonel with calcium and atelvia), and zoledronic acid (reclast). Unfortunately, the American Association of Oral and Maxillofacial Surgeons had reported that some patients under bisphosphonates therapy had shown dental complications such as osteonecrosis of the jaw (ONJ). The osteonecrosis of the jaw is a painful infection of the bone caused by slow healing of the jaw bone after tooth extractions or any invasive surgery that involve jaw and/or maxillary bone. The National Osteoporosis Foundation highlight that “of all the cases reported to date in 2007, 95% were in cancer patients who had taken higher dose of intravenous bisphosphonate, than the given for osteoporosis”. Since osteonecrosis of the jaw is not only a side effect of antiresorptive drugs, there are also other medications such antiangiogenic agents, in June of 2014 the Oral Surgeon
Thus, the recommended treatment for a patient with osteoporosis would receive supplementary calcium (1,000 to 1,500 mg of calcium daily) as confirmed in the National Institutes of Health Consensus Development Conference on osteoporosis in 1984. But studies have shown that as humans age their ability to absorb calcium starts to diminish making this treatment almost ineffective in some elderly patients. Patients of this time, with little treatment options were forced to endure many fracture related injuries; most commonly fractures of the hip which is a very complicated fracture requiring hospitalisation and a surgical practice would be required. Even if the surgery had been successful the patient would not be able to return to the previous levels of activity they were once at; forcing the patient from self-care to supervised living situations/nursing
Osteomyelitis is an infection of the bone or bone marrow. Osteomyelitis is a very destructive disease that affects the skeletal system. Most commonly affected bones of the skeletal system are the long bones. Osteomyelitis can be caused from a broken bone, or even from a hospital stay. The total prevalence of osteomyelitis in the general population is about 1 in 5,000 patients, while in newborns it is about 1 in 1,000. (Mantero) This paper will explain the types, causes, individuals at risk, signs and symptoms, diagnosis, treatment, and prognosis of osteomyelitis.
This paper researches information from a selection of sources about the pathology osteomyelitis. Osteomyelitis is the inflammation and infection of bone, bone marrow, and inadvertently the surrounding soft tissue. It can occur in any bone of the body. It is caused by bacteria and occasionally fungus. Symptoms can be difficult to determine and the illness can occur from differentiating factors. Without treatment, infection can spread throughout the body and possibility of amputation is prevalent. Most imaging modalities can be used in some respect to diagnose the disease. Magnetic resonance imaging (MRI), nuclear medicine (Nuc Med), and positron emission tomography (PET) are
Gandhi, S., et al., Pattern of maxillofacial fractures at a tertiary hospital in northern India: a 4-year retrospective study of 718 patients. Dent Traumatol, 2011. 27(4): p. 257-62.