Skeletal fluorosis
Encyclopedia
Skeletal fluorosis is a bone
disease caused by excessive consumption of fluoride
. In advanced cases, skeletal fluorosis causes pain and damage to bones and joints.
can be isolated in two different forms including the molecular, diatomic gas, F2, and the ionic form, F−. It is very difficult to isolate Fluorine in its atomic form due to its high reactivity and electronegativity
.
(8 electrons in the outer s and p shells). This extra electron could come from anything. Because of this, Fluorine is the strongest known oxidizer. It is only found naturally on earth as 19F, its only stable isotope
.
Aqueous HF [Hydrofluoric acid], is weakly acidic. This acid will dissociate in water, but only to small extent. In its dissociated form, F−, it is a fairly strong base. Anhydrous HF (hydrogen fluoride) is a strong acid and its strength can be greatly increased through the addition of a lewis acid
such as antimony pentafluoride
.
, which is the major source of Fluorine on earth.
Fluorine can be produced in its ionic and diatomic gas forms. This is done by a method developed by Henri Moissan
in 1886. The method begins by reacting Potassium Fluoride and Hydrogen Fluoride, KF and HF respectively, to form Potassium Bifluoride
, KHF2. This compound is produced in an aqueous solution and is further electrolyzed to form gaseous Hydrogen, gaseous Fluorine, and ionic Fluorine in an aqueous solution, H2, F2, and F− respectively.
Fluorine is known to react violently with Hydrogen and alkali metals. It will react with alkali earth metals less violently and may form an insoluble salt. It is also know to form covalent bonds with transition metals, noble gases, and organic compounds.
Due to its high reactivity, gaseous Fluorine must be kept under dry conditions. If it comes in contact with moisture it will decompose to form HF gas.
), consumption of fluoride from drinking water (naturally occurring levels of fluoride in excess of the CDC recommended safe levels), and consumption of fluoride from the drinking of tea, particularly brick tea
.
In India
, the most common cause of fluorosis is fluoride-laden water derived from deep bore wells. Over half of ground water sources in India have fluoride above recommended levels.
In Tibet
, excessive consumption of poor-quality pu-erh tea
is reported to cause fluorosis.
by which Fluorine breaks down bones and causes Skeletal Fluorosis is in a step-wise fashion.
and China
- UNICEF estimates that "fluorosis is endemic in at least 25 countries across the globe. The total number of people affected is not known, but a conservative estimate would number in the tens of millions."
The World Health Organization
recently estimated that 2.7 million people in China
have the crippling form of skeletal fluorosis. In India
, 20 states have been identified as endemic areas, with an estimated 60 million people at risk and 6 million people disabled; about 600,000 might develop a neurological disorder as a consequence.
Although skeletal fluorosis has been studied intensely in other countries for more than 40 years, virtually no research has been done in the U.S. to determine how many people are afflicted with the earlier stages of the disease, particularly the preclinical stages. Because some of the clinical symptoms mimic arthritis, the first two clinical phases of skeletal fluorosis could be easily misdiagnosed. Even if a doctor is aware of the disease, the early stages are difficult to diagnose. Given this, it may be beneficial for general physicians and neuromuscular specialists to familiarize themselves with this uncommon disease and monitor fluoride levels in patients diagnosed with arthritis over time.
Fluorine can also damage the thyroid gland leading to hyperparatthyroidisme, the uncontrolled secretion of parathyroid hormones. These hormones regulate Calcium concentration in the body. An elevated parathyroid hormone concentration results in a depletion of Calcium in bone structures and thus a higher Calcium concentration in the blood. As a result, bone flexibility decreases making the bone more amenable to fractures.
Concluding, Fluorine also has the potential to exist as the ion, F−. This ion is very reactive as a base with organic molecules, resulting in possible reactions with any molecule in the body which can lead to damage at the tissue level.
Treatment of side effects is also very difficult. For example, a patient with a bone fracture cannot be treated according to standard procedures, because the bone is very brittle. In this case, recovery will take a very long time and a pristine healing is aleatory.
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
disease caused by excessive consumption of fluoride
Fluoride
Fluoride is the anion F−, the reduced form of fluorine when as an ion and when bonded to another element. Both organofluorine compounds and inorganic fluorine containing compounds are called fluorides. Fluoride, like other halides, is a monovalent ion . Its compounds often have properties that are...
. In advanced cases, skeletal fluorosis causes pain and damage to bones and joints.
Forms
FluorineFluorine
Fluorine is the chemical element with atomic number 9, represented by the symbol F. It is the lightest element of the halogen column of the periodic table and has a single stable isotope, fluorine-19. At standard pressure and temperature, fluorine is a pale yellow gas composed of diatomic...
can be isolated in two different forms including the molecular, diatomic gas, F2, and the ionic form, F−. It is very difficult to isolate Fluorine in its atomic form due to its high reactivity and electronegativity
Electronegativity
Electronegativity, symbol χ , is a chemical property that describes the tendency of an atom or a functional group to attract electrons towards itself. An atom's electronegativity is affected by both its atomic number and the distance that its valence electrons reside from the charged nucleus...
.
Reactivity
Fluorine is the most reactive of the halogens. Fluorine is the most electronegative element currently known. This means the elemental form, F, will actively seek another electron to satisfy the octet ruleOctet rule
The octet rule is a chemical rule of thumb that states that atoms of low The octet rule is a chemical rule of thumb that states that atoms of low The octet rule is a chemical rule of thumb that states that atoms of low (The octet rule is a chemical rule of thumb that states that atoms of low (...
(8 electrons in the outer s and p shells). This extra electron could come from anything. Because of this, Fluorine is the strongest known oxidizer. It is only found naturally on earth as 19F, its only stable isotope
Isotope
Isotopes are variants of atoms of a particular chemical element, which have differing numbers of neutrons. Atoms of a particular element by definition must contain the same number of protons but may have a distinct number of neutrons which differs from atom to atom, without changing the designation...
.
Aqueous HF [Hydrofluoric acid], is weakly acidic. This acid will dissociate in water, but only to small extent. In its dissociated form, F−, it is a fairly strong base. Anhydrous HF (hydrogen fluoride) is a strong acid and its strength can be greatly increased through the addition of a lewis acid
Lewis acid
]The term Lewis acid refers to a definition of acid published by Gilbert N. Lewis in 1923, specifically: An acid substance is one which can employ a lone pair from another molecule in completing the stable group of one of its own atoms. Thus, H+ is a Lewis acid, since it can accept a lone pair,...
such as antimony pentafluoride
Antimony pentafluoride
Antimony pentafluoride is the inorganic compound with the formula SbF5. This colourless, viscous liquid is a valuable Lewis acid and a component of the superacid fluoroantimonic acid, the strongest known acid...
.
Synthesis
Fluorine is not produced in a monatomic, uncharged form. It is generally always manufactured from the mineral FluoriteFluorite
Fluorite is a halide mineral composed of calcium fluoride, CaF2. It is an isometric mineral with a cubic habit, though octahedral and more complex isometric forms are not uncommon...
, which is the major source of Fluorine on earth.
Fluorine can be produced in its ionic and diatomic gas forms. This is done by a method developed by Henri Moissan
Henri Moissan
Ferdinand Frederick Henri Moissan was a French chemist who won the 1906 Nobel Prize in Chemistry for his work in isolating fluorine from its compounds.-Biography:...
in 1886. The method begins by reacting Potassium Fluoride and Hydrogen Fluoride, KF and HF respectively, to form Potassium Bifluoride
Potassium bifluoride
Potassium bifluoride is the inorganic compound with the formula KHF2. This colourless salt consists of the potassium cation and the bifluoride anion. The salt is used in etchant for glass...
, KHF2. This compound is produced in an aqueous solution and is further electrolyzed to form gaseous Hydrogen, gaseous Fluorine, and ionic Fluorine in an aqueous solution, H2, F2, and F− respectively.
Reactions
Molecular Fluorine will act as an oxidant in most reactions. In electrochemistry, strong oxidizers have a high standard reduction potential. This value refers to the tendency of the compound or element in question to be reduced, or gain electrons. Fluorine has the highest standard reduction potential, +2.87V, making it the strongest oxidizer.Fluorine is known to react violently with Hydrogen and alkali metals. It will react with alkali earth metals less violently and may form an insoluble salt. It is also know to form covalent bonds with transition metals, noble gases, and organic compounds.
Due to its high reactivity, gaseous Fluorine must be kept under dry conditions. If it comes in contact with moisture it will decompose to form HF gas.
Available forms
Fluorine can be very dangerous in its gaseous form. However, it is still available for purchase from chemical suppliers around the world. It can also be obtained by the purchase of Fluorine containing compounds. It would have to be produced by one method or another of chemical conversion and isolation from these compounds.Causes
Common causes of fluorosis include inhalation of fluoride dusts/fumes by workers in industry, use of coal as an indoor fuel source (a common practice in ChinaChina
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
), consumption of fluoride from drinking water (naturally occurring levels of fluoride in excess of the CDC recommended safe levels), and consumption of fluoride from the drinking of tea, particularly brick tea
Tea brick
Tea bricks or compressed tea are blocks of whole or finely ground black tea, green tea, or post-fermented tea leaves that have been packed in molds and pressed into block form...
.
In India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
, the most common cause of fluorosis is fluoride-laden water derived from deep bore wells. Over half of ground water sources in India have fluoride above recommended levels.
In Tibet
Tibet
Tibet is a plateau region in Asia, north-east of the Himalayas. It is the traditional homeland of the Tibetan people as well as some other ethnic groups such as Monpas, Qiang, and Lhobas, and is now also inhabited by considerable numbers of Han and Hui people...
, excessive consumption of poor-quality pu-erh tea
Pu-erh tea
Pu'er, Pu-erh, Puer, also Po Lei or Bolay is a variety of post-fermented tea produced in Yunnan province, China. Post-fermentation is a tea production style in which the tea leaves undergo a microbial fermentation process after they are dried and rolled. This is a Chinese specialty and is sometimes...
is reported to cause fluorosis.
Mechanism of Action
The best way to view the mechanism of actionMechanism of action
In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...
by which Fluorine breaks down bones and causes Skeletal Fluorosis is in a step-wise fashion.
- Fluorine enters the body by two paths: Ingestion or respiration. Both paths lead to corrosion of exposed tissue in high concentrations. Since the most likely form of Fluorine to enter the body is Hydrogen Fluoride gas, this is what starts the process. Exposed tissues will be utilized by HF in neutralizationNeutralizationIn chemistry, neutralization, or neutralisation is a chemical reaction in which an acid and a base react to form a salt. Water is frequently, but not necessarily, produced as well. Neutralizations with Arrhenius acids and bases always produce water:Y and X represent a monovalent cation and anion...
reactions. - This will leave F− free to pass further into the body.
- It reacts with the concentrated HCl in the stomach to form the weak acid, HF.
- This compound is then absorbed by the gastro-intestinal tract and passes into the liver via the portal vein. Since F is the strongest oxidizer known currently, it is immune to phase 1 metabolic reactionsDrug metabolismDrug metabolism is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products...
, which are generally oxidation reactions, in the liver. These reactions are the body’s first line of defense to biotransform harmful compounds into something more hydrophilic and more easily excreted. - The HF is now free to pass into the blood stream and be distributed to all tissues including bones.
- Bones are largely composed of Ca compounds, particularly carbonated hydroxyapatite (Ca10(PO4)6(OH)2); the reaction of Ca and HF forms an insoluble salt, CaF2Calcium fluorideCalcium fluoride is the inorganic compound with the formula CaF2. This ionic compound of calcium and fluorine occurs naturally as the mineral fluorite . It is the source of most of the world's fluorine. This insoluble solid adopts a cubic structure wherein calcium is coordinated to eight fluoride...
. - This salt must be cleared by the body and as a result washes away some of the calcium that would be part of the bone matrix.
- This process results in increased densityDensityThe mass density or density of a material is defined as its mass per unit volume. The symbol most often used for density is ρ . In some cases , density is also defined as its weight per unit volume; although, this quantity is more properly called specific weight...
, but decreased strength in bones.
Epidemiology
In some areas, skeletal fluorosis is endemic. While fluorosis is most severe and widespread in the two largest countries - IndiaIndia
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
and China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
- UNICEF estimates that "fluorosis is endemic in at least 25 countries across the globe. The total number of people affected is not known, but a conservative estimate would number in the tens of millions."
The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
recently estimated that 2.7 million people in China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
have the crippling form of skeletal fluorosis. In India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
, 20 states have been identified as endemic areas, with an estimated 60 million people at risk and 6 million people disabled; about 600,000 might develop a neurological disorder as a consequence.
Although skeletal fluorosis has been studied intensely in other countries for more than 40 years, virtually no research has been done in the U.S. to determine how many people are afflicted with the earlier stages of the disease, particularly the preclinical stages. Because some of the clinical symptoms mimic arthritis, the first two clinical phases of skeletal fluorosis could be easily misdiagnosed. Even if a doctor is aware of the disease, the early stages are difficult to diagnose. Given this, it may be beneficial for general physicians and neuromuscular specialists to familiarize themselves with this uncommon disease and monitor fluoride levels in patients diagnosed with arthritis over time.
Skeletal fluorosis phases
| Osteosclerotic phase | Ash concentration (mgF/kg) | Symptoms and signs |
| Normal Bone | 500 to 1,000 | Normal |
| Preclinical Phase | 3,500 to 5,500 | Asymptomatic; slight radiographically Radiography Radiography is the use of X-rays to view a non-uniformly composed material such as the human body. By using the physical properties of the ray an image can be developed which displays areas of different density and composition.... -detectable increases in bone mass |
| Clinical Phase I | 6,000 to 7,000 | Sporadic pain Pain Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."... ; stiffness of joint Joint A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:... s; osteosclerosis Osteosclerosis Osteosclerosis, an elevation in bone density, is normally detected on an X-ray as an area of whiteness, and is where the bone density has significantly increased... of pelvis and vertebral spine |
| Clinical Phase II | 7,500 to 9,000 | Chronic joint pain; arthritic Arthritis Arthritis is a form of joint disorder that involves inflammation of one or more joints.... symptoms; slight calcification Calcification Calcification is the process in which calcium salts build up in soft tissue, causing it to harden. Calcifications may be classified on whether there is mineral balance or not, and the location of the calcification.-Causes:... of ligaments' increased osteosclerosis and cancellous bones; with/without osteoporosis Osteoporosis Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered... of long bones |
| Phase III: Crippling Fluorosis | 8,400 | Limitation of joint movement; calcification of ligaments of neck vertebral column; crippling deformities of the spine and major joints; muscle wasting; neurological defects/compression of spinal cord |
Symptoms and side effects
Symptoms are mainly promoted in the bone structure. Due to a high Fluorine concentration in the body, the bone is hardened and thus less elastic, resulting in an increased frequency of fractures. Other symptoms include thickening of the bone structure and accumulation of bone tissue, which both contribute to impaired joint mobility. Most patients suffering from skeletal fluorosis show side effects from the high Fluorine dose such as ruptures of the stomach lining and nausea.Fluorine can also damage the thyroid gland leading to hyperparatthyroidisme, the uncontrolled secretion of parathyroid hormones. These hormones regulate Calcium concentration in the body. An elevated parathyroid hormone concentration results in a depletion of Calcium in bone structures and thus a higher Calcium concentration in the blood. As a result, bone flexibility decreases making the bone more amenable to fractures.
Concluding, Fluorine also has the potential to exist as the ion, F−. This ion is very reactive as a base with organic molecules, resulting in possible reactions with any molecule in the body which can lead to damage at the tissue level.
Effects on animals
The histological changes which are induced through Fluorine on rats resemble those of humans. That has been observed in an experiment with young and old rats. NaF was dissolved in their drinking water. Young rats have shown to be more susceptible to skeletal Fluorosis, because their bones react faster with the Fluorine. Further aspects are major changes in teeth morphology, defects on dental enamel and abrasion of the incisors and porous compression of the upper and lower jaw.Treatment
As of now, there are no established treatments for skeletal fluorosis patients. However, it is reversible in some cases, depending on the progression of the disease. If Fluorine intake is stopped, the Fluorine existing in bone structures will deplete and be excreted via urine. However, it is a very slow process to eliminate the Fluorine from the body completely. Minimal results are seen in patients.Treatment of side effects is also very difficult. For example, a patient with a bone fracture cannot be treated according to standard procedures, because the bone is very brittle. In this case, recovery will take a very long time and a pristine healing is aleatory.