CD68 is a protein expressed by cells in the monocyte lineage, by circulating macrophages, by tissue macrophages. Human CD68 is a transmembrane glycoprotein glycosylated in its extracellular domain, with a molecular weight of 110 kD, its primary sequence consists of 354 amino acids with predicted molecular weight of 37.4 kD if it were not glycosylated. The human CD68 protein is encoded by the "CD68" gene which maps to Chromosome 17. Other names or aliases for this gene in humans and other animals include: CD68 Molecule, CD68 Antigen, GP110, Scavenger Receptor Class D, Member 1, SCARD1, LAMP4; the mouse equivalent is known as "macrosialin". CD68 is functionally and evolutionarily related to other gene/protein family members, as follows: the hematopoietic mucin-like family of molecules that includes leukosialin/CD43 and stem cell antigen CD34. Functionally, the CD68 protein binds to tissue- and organ-specific lectins or selectins, allowing macrophages to home in on particular targets, it is thought that rapid recirculation of CD68 from endosomes and lysosomes to the plasma membrane allows macrophages to crawl over selectin-bearing substrates or other cells.
Immunohistochemistry can be used to identify the presence of CD68, found in the cytoplasmic granules of a range of different blood cells and myocytes. It is useful as a marker for the various cells of the macrophage lineage, including monocytes, giant cells, Kupffer cells, osteoclasts; this allows it to be used to distinguish diseases of otherwise similar appearance, such as the monocyte/macrophage and lymphoid forms of leukaemia. Its presence in macrophages makes it useful in diagnosing conditions related to proliferation or abnormality of these cells, such as malignant histiocytosis, histiocytic lymphoma, Gaucher's disease. Anti-CD68 monoclonal antibodies that react with tissues of rodent and other species include ED1, FA-11, KP1, 6A326, 6F3, 12E2, 10B1909, SPM130. Monoclonals that react with humans include, Ki-M7, PG-M1, 514H12, ABM53F5, 3F7C6, 3F7D3, Y1/82A, EPR20545, CDLA68-1, LAMP4-824. ED1 is the most used monoclonal antibody clone directed against the rat CD68 protein and is used to identify macrophages, Kupffer cells, osteoclasts and activated microglia in rat tissues.
In this species, it is expressed in most macrophage populations and thus ED1 is used as a pan-macrophage marker. However, in some cell types it is detectable only when up-regulated, such as activated but not quiescent microglia, can thus be used as a marker of inflammatory conditions and immune reactions in those instances. Commercial suppliers report that ED1 is used for detection of the CD68 protein by immunohistochemical staining, flow cytometry, western blot methods and that in addition to rat it cross-reacts with bovine species; the ED1 anti-CD68 antibody is not to be confused with the fibronectin extra domain ED1. Cluster of differentiation Lysosome-associated membrane glycoprotein Scavenger receptor
Hematoxylin and eosin stain or haematoxylin and eosin stain is one of the principal stains in histology. It is the most used stain in medical diagnosis and is the gold standard. A combination of hematoxylin and eosin, it produces blues and reds; the staining method involves application of hemalum, a complex formed from aluminium ions and hematein. Hemalum colors nuclei of cells blue, along with a few other objects, such as keratohyalin granules and calcified material, which turns blue when exposed to alkaline water; the nuclear staining is followed by counterstaining with an aqueous or alcoholic solution of eosin Y, which colors eosinophilic structures in various shades of red and orange. The staining of nuclei by hemalum is ordinarily due to binding of the dye-metal complex to DNA, but nuclear staining can be obtained after extraction of DNA from tissue sections; the mechanism is different from that of nuclear staining by basic dyes such as thionine or toluidine blue. Staining by basic dyes occurs only from solutions that are less acidic than hemalum, it is prevented by prior chemical or enzymatic extraction of nucleic acids.
There is evidence to indicate that co-ordinate bonds, similar to those that hold aluminium and hematein together, bind the hemalum complex to DNA and to carboxy groups of proteins in the nuclear chromatin. The eosinophilic structures are composed of intracellular or extracellular protein; the Lewy bodies and Mallory bodies are examples of eosinophilic structures. Most of the cytoplasm is eosinophilic. Red blood cells are stained intensely red; the structures do not have to be basic to be called basophilic and eosinophilic. Other colors, e.g. yellow and brown, can be present in the sample. Some structures do not stain well. Basal laminae need to be stained by PAS stain or some silver stains, if they have to be well visible. Reticular fibers require silver stain. Hydrophobic structures tend to remain clear. Hematoxylin is a dark blue or violet stain, basic/positive, it binds to basophilic substances. DNA/RNA in the nucleus, RNA in ribosomes in the rough endoplasmic reticulum are both acidic because the phosphate backbones of nucleic acids are negatively charged.
These backbones form salts with basic dyes containing positive charges. Therefore, dyes stain them violet. Eosin is a red or pink stain, acidic and negative, it binds to acidophilic substances such as positively charged amino-acid side chains. Most proteins in the cytoplasm of some cells are basic because they are positively charged due to the arginine and lysine amino-acid residues; these form salts with acid dyes containing negative charges, like eosin. Therefore, eosin stains them pink; this includes cytoplasmic filaments in muscle cells, intracellular membranes, extracellular fibers. So, in optical microscopy, one can observe: Nuclei in blue/purple Basophils in purplish red Cytoplasm in red Muscles in dark red Erythrocytes in cherry red Collagen in pale pink Mitochondria in pale pink Papanicolaou stain, another popular staining technique Cytopathology Acid-fast Baker JR Experiments on the action of mordants. 2. Aluminium-haematein. Quart. J. Microsc. Sci. 103: 493–517. Kiernan JA Histological and Histochemical Methods: Theory and Practice.
4th ed. Bloxham, UK: Scion. Lillie RD, Pizzolato P, Donaldson PT Nuclear stains with soluble metachrome mordant lake dyes; the effect of chemical endgroup blocking reactions and the artificial introduction of acid groups into tissues. Histochemistry 49: 23–35. Llewellyn BD Nuclear staining with alum-hematoxylin. Biotech. Histochem. 84: 159–177. Marshall PN, Horobin RW The mechanism of action of "mordant" des – a study using preformed metal complexes. Histochemie 35: 361–371. Puchtler H, Meloan SN, Waldrop FS Application of current chemical concepts to metal-haematein and -brazilein stains. Histochemistry 85: 353–364. SIGMA-ALDRICH H&E Informational Primer Routine Mayer's Hematoxylin and Eosin Stain Hematoxylin & Eosin Staining Protocol Rosen Lab, Department of Molecular and Cellular Biology, Baylor College of Medicine) Step by step protocol
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the outer surfaces of organs and blood vessels throughout the body, as well as the inner surfaces of cavities in many internal organs. An example is the outermost layer of the skin. There are three principal shapes of epithelial cell: squamous and cuboidal; these can be arranged in a single layer of cells as simple epithelium, either squamous, columnar, or cuboidal, or in layers of two or more cells deep as stratified, either squamous, columnar or cuboidal. In some tissues, a layer of columnar cells may appear to be stratified due to the placement of the nuclei; this sort of tissue is called pseudostratified. All glands are made up of epithelial cells. Functions of epithelial cells include secretion, selective absorption, transcellular transport, sensing. Epithelial layers contain no blood vessels, so they must receive nourishment via diffusion of substances from the underlying connective tissue, through the basement membrane.
Cell junctions are well employed in epithelial tissues. In general, epithelial tissues are classified by the number of their layers and by the shape and function of the cells; the three principal shapes associated with epithelial cells are—squamous and columnar. Squamous epithelium has cells; this is found as the lining of the mouth, the blood vessels and in the alveoli of the lungs. Cuboidal epithelium has cells whose height and width are the same. Columnar epithelium has cells taller. By layer, epithelium is classed as either simple epithelium, only one cell thick or stratified epithelium having two or more cells in thickness or multi-layered – as stratified squamous epithelium, stratified cuboidal epithelium, stratified columnar epithelium, both types of layering can be made up of any of the cell shapes. However, when taller simple columnar epithelial cells are viewed in cross section showing several nuclei appearing at different heights, they can be confused with stratified epithelia; this kind of epithelium is therefore described as pseudostratified columnar epithelium.
Transitional epithelium has cells that can change from squamous to cuboidal, depending on the amount of tension on the epithelium. Simple epithelium is a single layer of cells with every cell in direct contact with the basement membrane that separates it from the underlying connective tissue. In general, it is found where filtration occur; the thinness of the epithelial barrier facilitates these processes. In general, simple epithelial tissues are classified by the shape of their cells; the four major classes of simple epithelium are: simple squamous. Simple squamous. Simple cuboidal: these cells may have secretory, absorptive, or excretory functions. Examples include small collecting ducts of kidney and salivary gland. Simple columnar. Non-ciliated epithelium can possess microvilli; some tissues are referred to as simple glandular columnar epithelium. These secrete mucus and are found in stomach and rectum. Pseudostratified columnar epithelium; the ciliated type is called respiratory epithelium as it is exclusively confined to the larger respiratory airways of the nasal cavity and bronchi.
Stratified epithelium differs from simple epithelium. It is therefore found where body linings have to withstand mechanical or chemical insult such that layers can be abraded and lost without exposing subepithelial layers. Cells flatten as the layers become more apical, though in their most basal layers the cells can be squamous, cuboidal or columnar. Stratified epithelia can have the following specializations: The basic cell types are squamous and columnar classed by their shape. Cells of epithelial tissue are scutoid shaped packed and form a continuous sheet, they have no intercellular spaces. All epithelia is separated from underlying tissues by an extracellular fibrous basement membrane; the lining of the mouth, lung alveoli and kidney tubules are all made of epithelial tissue. The lining of the blood and lymphatic vessels are of a specialised form of epithelium called endothelium. Epithelium lines both the outside and the inside cavities and lumina of bodies; the outermost layer of human skin is composed of dead stratified squamous, keratinized epithelial cells.
Tissues that line the inside of the mouth, the esophagus, the vagina, part of the rectum are composed of nonkeratinized stratified squamous epithelium. Other surfaces that separate body cavities from the outside environment are lined by simple squamous, columnar, or pseudostratified epithelial cells. Other epithelial cells line the insides of the lungs, the gastrointestinal tract, the reproductive and urinary tracts, make up the exocrine and endocrine glands; the outer surface of the cornea is covered with fast-growing regenerated epithelial cells. A specialised form of epithelium – endothelium forms the inner lining of blood vessels and the heart, is known as vascular endotheliu
An osteoclast is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance and remodelling of bones of the vertebral skeleton; the osteoclast disassembles and digests the composite of hydrated protein and mineral at a molecular level by secreting acid and a collagenase, a process known as bone resorption. This process helps regulate the level of blood calcium. An odontoclast is an osteoclast associated with absorption of the roots of deciduous teeth. An osteoclast is a large multinucleated cell and human osteoclasts on bone have five nuclei and are 150–200 µm in diameter; when osteoclast-inducing cytokines are used to convert macrophages to osteoclasts large cells that may reach 100 µm in diameter occur. These may have dozens of nuclei, express major osteoclast proteins but have significant differences from cells in living bone because of the not-natural substrate; the size of the multinucleated assembled osteoclast allows it to focus the ion transport, protein secretory and vesicular transport capabilities of many macrophages on a localized area of bone.
In bone, osteoclasts are found in pits in the bone surface which are called resorption bays, or Howship's lacunae. Osteoclasts are characterized by a cytoplasm with "foamy" appearance; this appearance is due to a high concentration of vacuoles. These vacuoles include lysosomes filled with acid phosphatase; this permits characterization of osteoclasts by their staining for high expression of tartrate resistant acid phosphatase and cathepsin K. Osteoclast rough endoplasmic reticulum is sparse, the Golgi complex is extensive. At a site of active bone resorption, the osteoclast forms a specialized cell membrane, the "ruffled border", that opposes the surface of the bone tissue; this extensively folded or ruffled border facilitates bone removal by increasing the cell surface for secretion and uptake of the resorption compartment contents and is a morphologic characteristic of an osteoclast, resorbing bone. Since their discovery in 1873 there has been considerable debate about their origin. Three theories were dominant: from 1949 to 1970 the connective tissue origin was popular, which stated that osteoclasts and osteoblasts are of the same lineage, osteoblasts fuse together to form osteoclasts.
After years of controversy it is now clear that these cells develop from the self fusion of macrophages. It was in the beginning of 1980 that the monocyte phagocytic system was recognized as precursor of osteoclasts. Osteoclast formation requires the presence of RANKL and M-CSF; these membrane-bound proteins are produced by neighbouring stromal cells and osteoblasts, thus requiring direct contact between these cells and osteoclast precursors. M-CSF acts through its receptor on the osteoclast, c-fms, a transmembrane tyrosine kinase-receptor, leading to secondary messenger activation of tyrosine kinase Src. Both of these molecules are necessary for osteoclastogenesis and are involved in the differentiation of monocyte/macrophage derived cells. RANKL is a member of the tumour necrosis family, is essential in osteoclastogenesis. RANKL knockout mice exhibit a phenotype of osteopetrosis and defects of tooth eruption, along with an absence or deficiency of osteoclasts. RANKL activates NF-κβ and NFATc1 through RANK.
NF-κβ activation is stimulated immediately after RANKL-RANK interaction occurs and is not upregulated. NFATc1 stimulation, begins ~24–48 hours after binding occurs and its expression has been shown to be RANKL dependent. Osteoclast differentiation is inhibited by osteoprotegerin, produced by osteoblasts and binds to RANKL thereby preventing interaction with RANK, it may be important to note that while osteoclasts are derived from the hematopoietic lineage, osteoblasts are derived from mesenchymal stem cells. Once activated, osteoclasts move to areas of microfracture in the bone by chemotaxis. Osteoclasts lie in small cavities called Howship's lacunae, formed from the digestion of the underlying bone; the sealing zone is the attachment of the osteoclast's plasma membrane to the underlying bone. Sealing zones are bounded by belts of specialized adhesion structures called podosomes. Attachment to the bone matrix is facilitated by integrin receptors, such as αvβ3, via the specific amino acid motif Arg-Gly-Asp in bone matrix proteins, such as osteopontin.
The osteoclast releases hydrogen ions through the action of carbonic anhydrase through the ruffled border into the resorptive cavity and aiding dissolution of the mineralized bone matrix into Ca2+, H3PO4, H2CO3, water and other substances. Dysfunction of the carbonic anhydrase has been documented to cause some forms of osteopetrosis. Hydrogen ions are pumped against a high concentration gradient by proton pumps a unique vacuolar-ATPase; this enzyme has been targeted in the prevention of osteoporosis. In addition, several hydrolytic enzymes, such as members of the cathepsin and matrix metalloprotease groups, are released to digest the organic components of the matrix; these enzymes are released into the compartment by lysosomes. Of these hydrolytic enzymes, cathepsin K is of most importance. Cathepsin K is a collagenolytic, papain-like, cysteine protease, expressed in osteoclasts, is secreted into the resorptive pit. Cathepsin K is the major protease involved in the degradation of
Apoptosis is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to death; these changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, chromosomal DNA fragmentation, global mRNA decay. The average adult human loses between 70 billion cells each day due to apoptosis. For an average human child between the ages of 8 to 14 year old 20 to 30 billion cells die per day. In contrast to necrosis, a form of traumatic cell death that results from acute cellular injury, apoptosis is a regulated and controlled process that confers advantages during an organism's lifecycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic bodies that phagocytic cells are able to engulf and remove before the contents of the cell can spill out onto surrounding cells and cause damage to them; because apoptosis cannot stop once it has begun, it is a regulated process.
Apoptosis can be initiated through one of two pathways. In the intrinsic pathway the cell kills itself because it senses cell stress, while in the extrinsic pathway the cell kills itself because of signals from other cells. Weak external signals may activate the intrinsic pathway of apoptosis. Both pathways induce cell death by activating caspases, which are proteases, or enzymes that degrade proteins; the two pathways both activate initiator caspases, which activate executioner caspases, which kill the cell by degrading proteins indiscriminately. Research on apoptosis has increased since the early 1990s. In addition to its importance as a biological phenomenon, defective apoptotic processes have been implicated in a wide variety of diseases. Excessive apoptosis causes atrophy, whereas an insufficient amount results in uncontrolled cell proliferation, such as cancer; some factors like Fas receptors and caspases promote apoptosis, while some members of the Bcl-2 family of proteins inhibit apoptosis.
German scientist Karl Vogt was first to describe the principle of apoptosis in 1842. In 1885, anatomist Walther Flemming delivered a more precise description of the process of programmed cell death. However, it was not until 1965. While studying tissues using electron microscopy, John Foxton Ross Kerr at the University of Queensland was able to distinguish apoptosis from traumatic cell death. Following the publication of a paper describing the phenomenon, Kerr was invited to join Alastair R. Currie, as well as Andrew Wyllie, Currie's graduate student, at University of Aberdeen. In 1972, the trio published a seminal article in the British Journal of Cancer. Kerr had used the term programmed cell necrosis, but in the article, the process of natural cell death was called apoptosis. Kerr and Currie credited James Cormack, a professor of Greek language at University of Aberdeen, with suggesting the term apoptosis. Kerr received the Paul Ehrlich and Ludwig Darmstaedter Prize on March 14, 2000, for his description of apoptosis.
He shared the prize with Boston biologist H. Robert Horvitz. For many years, neither "apoptosis" nor "programmed cell death" was a cited term. Two discoveries brought cell death from obscurity to a major field of research: identification of components of the cell death control and effector mechanisms, linkage of abnormalities in cell death to human disease, in particular cancer; the 2002 Nobel Prize in Medicine was awarded to Sydney Brenner and John E. Sulston for their work identifying genes that control apoptosis; the genes were identified by studies in the nematode C. elegans and homologues of these genes function in humans to regulate apoptosis. In Greek, apoptosis translates to the "falling off" of leaves from a tree. Cormack, professor of Greek language, reintroduced the term for medical use as it had a medical meaning for the Greeks over two thousand years before. Hippocrates used the term to mean "the falling off of the bones". Galen extended its meaning to "the dropping of the scabs".
Cormack was no doubt aware of this usage. Debate continues over the correct pronunciation, with opinion divided between a pronunciation with the second p silent and the second p pronounced, as in the original Greek. In English, the p of the Greek -pt- consonant cluster is silent at the beginning of a word, but articulated when used in combining forms preceded by a vowel, as in helicopter or the orders of insects: diptera, etc. In the original Kerr, Wyllie & Currie paper, there is a footnote regarding the pronunciation: "We are most grateful to Professor James Cormack of the Department of Greek, University of Aberdeen, for suggesting this term; the word "apoptosis" is used in Greek to describe the "dropping off" or "falling off" of petals from flowers, or leaves from trees. To show the derivation we propose that the stress should be on the penultimate syllable, the second half of the word being pronounced like "ptosis", which comes from the same root "to fall", is used to describe the drooping of the upper eyelid."
The initiation of apoptosis is regulated by activation mechanisms, because once apoptosis has begun, it leads to the death of the cell. The two best-understood activation mechanisms are the extrinsic pathway; the intrinsic pathway is activated by intracellular signals generated when cells are stressed and depends on the release of proteins from th
A micrograph or photomicrograph is a photograph or digital image taken through a microscope or similar device to show a magnified image of an object. This is opposed to a macrograph or photomacrograph, an image, taken on a microscope but is only magnified less than 10 times. Micrography is the art of using microscopes to make photographs. A micrograph contains extensive details of microstructure. A wealth of information can be obtained from a simple micrograph like behavior of the material under different conditions, the phases found in the system, failure analysis, grain size estimation, elemental analysis and so on. Micrographs are used in all fields of microscopy. A light micrograph or photomicrograph is a micrograph prepared using an optical microscope, a process referred to as photomicroscopy. At a basic level, photomicroscopy may be performed by connecting a camera to a microscope, thereby enabling the user to take photographs at reasonably high magnification. Scientific use began in England in 1850 by Prof Richard Hill Norris FRSE for his studies of blood cells.
Roman Vishniac was a pioneer in the field of photomicroscopy, specializing in the photography of living creatures in full motion. He made major developments in light-interruption photography and color photomicroscopy. Photomicrographs may be obtained using a USB microscope attached directly to a home computer or laptop. An electron micrograph is a micrograph prepared using an electron microscope. Micrographs have micron bars, or magnification ratios, or both. Magnification is a ratio between the size of an object on its real size. Magnification can be a misleading parameter as it depends on the final size of a printed picture and therefore varies with picture size. A scale bar, or micron bar, is a line of known length displayed on a picture; the bar can be used for measurements on a picture. When the picture is resized the bar is resized making it possible to recalculate the magnification. Ideally, all pictures destined for publication/presentation should be supplied with a scale bar. All but one of the micrographs presented on this page do not have a micron bar.
The microscope has been used for scientific discovery. It has been linked to the arts since its invention in the 17th century. Early adopters of the microscope, such as Robert Hooke and Antonie van Leeuwenhoek, were excellent illustrators. After the invention of photography in the 1820s the microscope was combined with the camera to take pictures instead of relying on an artistic rendering. Since the early 1970s individuals have been using the microscope as an artistic instrument. Websites and traveling art exhibits such as the Nikon Small World and Olympus Bioscapes have featured a range of images for the sole purpose of artistic enjoyment; some collaborative groups, such as the Paper Project have incorporated microscopic imagery into tactile art pieces as well as 3D immersive rooms and dance performances. Close-up Digital microscope Macro photography Microphotograph Microscopy USB microscope Make a Micrograph – This presentation by the research department of Children's Hospital Boston shows how researchers create a three-color micrograph.
Shots with a Microscope – a basic, comprehensive guide to photomicrography Scientific photomicrographs – free scientific quality photomicrographs by Doc. RNDr. Josef Reischig, CSc. Micrographs of 18 natural fibres by the International Year of Natural Fibres 2009 Seeing Beyond the Human Eye Video produced by Off Book - Solomon C. Fuller bio Charles Krebs Microscopic Images Dennis Kunkel Microscopy Andrew Paul Leonard, APL Microscopic Cell Centered Database - Montage Nikon Small World Olympus Bioscapes Other examples
Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most prescribed drugs used to treat osteoporosis, they are called bisphosphonates. They are thus called diphosphonates. Evidence shows. Bone tissue undergoes constant remodeling and is kept in balance by osteoblasts creating bone and osteoclasts destroying bone. Bisphosphonates inhibit the digestion of bone by encouraging osteoclasts to undergo apoptosis, or cell death, thereby slowing bone loss; the uses of bisphosphonates include the prevention and treatment of osteoporosis, Paget's disease of bone, bone metastasis, multiple myeloma, primary hyperparathyroidism, osteogenesis imperfecta, fibrous dysplasia, other conditions that exhibit bone fragility. Bisphosphonates are used to treat osteoporosis, osteitis deformans, bone metastasis, multiple myeloma, other conditions involving fragile, breakable bone. In osteoporosis and Paget's, the most popular first-line bisphosphonate drugs are alendronate and risedronate.
If these are ineffective or if the person develops digestive tract problems, intravenous pamidronate may be used. Strontium ranelate or teriparatide are used for refractory disease; the use of strontium ranelate is restricted because of increased risk of venous thromboembolism, pulmonary embolism and serious cardiovascular disorders, including myocardial infarction. In postmenopausal women, the selective estrogen receptor modulator raloxifene is administered instead of bisphosphonates. Bisphosphonates are beneficial in reducing the risk of vertebral fracture in steroid induced osteoporosis. Bisphosphonates are recommended as a first line treatments for post-menopausal osteoporosis. Long-term treatment with bisphosponates produces anti-fracture and bone mineral density effects that persist for 3–5 years after an initial 3–5 years of treatment; the bisphosphonate alendronate reduces the risk of hip and wrist fractures by 35-39%. Risedronate has been shown to reduce the risk of hip fractures. After five years of medications by mouth or three years of intravenous medication among those at low risk, bisphosphonate treatment can be stopped.
In those at higher risk ten years of medication by mouth or six years of intravenous treatment may be used. Bisphosphonates reduce the risk of fracture and bone pain in people with breast and other metastatic cancers as well as in people with multiple myeloma. In breast cancer there is mixed evidence regarding. A 2017 Cochrane review found that for people with early breast cancer, bisphosphonate treatment may reduce the risk of the cancer spreading to the persons' bone, for people who had advanced breast cancer bisphosphonate treatment did not appear to reduce the risk of the cancer spreading to the bone. Side effects associated with bisphosphonate treatment for people with breast cancer are mild and rare. Bisphosphonates can reduce mortality in those with multiple myeloma and prostate cancer. Evidence suggests that the use of bisphosphonates would be useful in the treatment of complex regional pain syndrome, a neuro-immune problem with high MPQ scores, low treatment efficacy and symptoms which can include regional osteoporosis.
In 2009 bisphosphonates were "among the only class of medications that has survived placebo-controlled studies showing statistically significant improvement with therapy."Bisphosphonates have been used to reduce fracture rates in children with the disease osteogenesis imperfecta and to treat otosclerosis by minimizing bone loss. Other bisphosphonates, including medronate and oxidronate, are mixed with radioactive technetium and injected, as a way to image bone and detect bone disease. Oral bisphosphonates can cause upset stomach and inflammation and erosions of the esophagus, the main problem of oral N-containing preparations; this can be prevented by remaining seated upright for 30 to 60 minutes after taking the medication. Intravenous bisphosphonates can give fever and flu-like symptoms after the first infusion, thought to occur because of their potential to activate human γδ T cells. Bisphosphonates, when administered intravenously for the treatment of cancer, have been associated with osteonecrosis of the jaw, with the mandible twice as affected as the maxilla and most cases occurring following high-dose intravenous administration used for some cancer patients.
Some 60% of cases are preceded by a dental surgical procedure, it has been suggested that bisphosphonate treatment should be postponed until after any dental work to eliminate potential sites of infection. A number of cases of severe bone, joint, or musculoskeletal pain have been reported, prompting labeling changes. Recent studies have reported bisphosphonate use as a risk factor for atrial fibrillation in women; the inflammatory response to bisphosphonates or fluctuations in calcium blood levels have been suggested as possible mechanisms. Until now, the benefits of bisphosphonates, in general, outweigh this risk, although care must be taken in certain populations at high risk of serious adverse effects from atrial fibrillation. FDA has not yet confirmed a causal relat