| Skeletal fluorosis | |
|---|---|
 | |
| Fluorosis patient in the industrial city of Raigarh, India | |
| Specialty | Rheumatology  |
Skeletal fluorosis is a bone disease caused by excessive accumulation of fluoride leading to weakened bones. [1] In advanced cases, skeletal fluorosis causes painful damage to bones and joints.
Symptoms are mainly promoted in the bone structure. Due to a high fluoride 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. Ligaments and cartilage can become ossified. [2] Most patients with skeletal fluorosis show side effects from the high fluoride dose such as ruptures of the stomach lining and nausea. [3] Fluoride can also damage the parathyroid glands, leading to hyperparathyroidism, 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 susceptible to fractures. [4]
The clinical symptoms of fluoride toxicity in the bones are indistinguishable from arthritis. Even low level exposure to fluoride can cause or worsen the symptoms in consumers with vulnerable genotypes. [5] [6] [7]
Common causes of fluorosis include inhalation of fluoride dusts or fumes by workers in industry and consumption of fluoride from drinking water (levels of fluoride in excess of levels that are considered safe. [8] )
In India, especially the Nalgonda region (Telangana), a common cause of fluorosis is fluoride-rich drinking water that is sourced from deep-bore wells. Over half of groundwater sources in India have fluoride above recommended levels. [9]
Fluorosis can also occur as a result of volcanic activity. The 1783 eruption of the Laki volcano in Iceland is estimated to have killed about 22% of the Icelandic population, and 60% of livestock, as a result of fluorosis and sulfur dioxide gases. [10] The 1693 eruption of Hekla also led to fatalities of livestock under similar conditions. [11]
| 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-detectable increases in bone mass |
| Clinical Phase I | 6,000 to 7,000 | Sporadic pain; stiffness of joints; osteosclerosis of pelvis and vertebral column |
| Clinical Phase II | 7,500 to 9,000 | Chronic joint pain; arthritic symptoms; slight calcification of ligaments' increased osteosclerosis and cancellous bones; with/without osteoporosis of long bones |
| Clinical Phase III | 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 |
As of now, there are no established treatments for skeletal fluorosis patients. [12] However, it is reversible in some cases, depending on the progression of the disease. If fluorine intake is stopped, the amount in bone will decrease 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 cannot be guaranteed. [13] However, further fluorosis can be prevented by drinking defluoridated water. It is recently suggested that drinking of defluoridated water from the "calcium amended-hydroxyapatite" defluoridation method may help in the fluorosis reversal. [14] Defluoridated water from this suggested method provides calcium-enriched alkaline drinking water as generally fluoride contaminated water has a low amount of calcium mineral and drinking alkaline water helps in eliminating the toxic fluoride from the body. [14]
In some areas, skeletal fluorosis is endemic. While fluorosis is most severe and widespread in the world's two most populous countries – India 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." [15]
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. [9]
The histological changes which are induced through fluorine on rats resemble those of humans. [16]
Fluoride is an inorganic, monatomic anion of fluorine, with the chemical formula F−
, whose salts are typically white or colorless. Fluoride salts typically have distinctive bitter tastes, and are odorless. Its salts and minerals are important chemical reagents and industrial chemicals, mainly used in the production of hydrogen fluoride for fluorocarbons. Fluoride is classified as a weak base since it only partially associates in solution, but concentrated fluoride is corrosive and can attack the skin.
Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes parathyroid hormone in response to a low blood calcium, which plays a key role in regulating the amount of calcium in the blood and within the bones.
Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.
Disorders of calcium metabolism occur when the body has too little or too much calcium. The serum level of calcium is closely regulated within a fairly limited range in the human body. In a healthy physiology, extracellular calcium levels are maintained within a tight range through the actions of parathyroid hormone, vitamin D and the calcium sensing receptor. Disorders in calcium metabolism can lead to hypocalcemia, decreased plasma levels of calcium or hypercalcemia, elevated plasma calcium levels.
Calcium fluoride is the inorganic compound of the elements calcium and fluorine with the formula CaF2. It is a white solid that is practically insoluble in water. It occurs as the mineral fluorite (also called fluorspar), which is often deeply coloured owing to impurities.
Water fluoridation is the controlled adjustment of fluoride to a public water supply solely to reduce tooth decay. Fluoridated water contains fluoride at a level that is effective for preventing cavities; this can occur naturally or by adding fluoride. Fluoridated water operates on tooth surfaces: in the mouth, it creates low levels of fluoride in saliva, which reduces the rate at which tooth enamel demineralizes and increases the rate at which it remineralizes in the early stages of cavities. Typically a fluoridated compound is added to drinking water, a process that in the U.S. costs an average of about $1.26 per person-year. Defluoridation is needed when the naturally occurring fluoride level exceeds recommended limits. In 2011, the World Health Organization suggested a level of fluoride from 0.5 to 1.5 mg/L, depending on climate, local environment, and other sources of fluoride. Bottled water typically has unknown fluoride levels.
Fluoride toxicity is a condition in which there are elevated levels of the fluoride ion in the body. Although fluoride is safe for dental health at low concentrations, sustained consumption of large amounts of soluble fluoride salts is dangerous. Referring to a common salt of fluoride, sodium fluoride (NaF), the lethal dose for most adult humans is estimated at 5 to 10 g. Ingestion of fluoride can produce gastrointestinal discomfort at doses at least 15 to 20 times lower than lethal doses. Although it is helpful topically for dental health in low dosage, chronic ingestion of fluoride in large amounts interferes with bone formation. In this way, the most widespread examples of fluoride poisoning arise from consumption of ground water that is abnormally fluoride-rich.
Parathyroidectomy is the surgical removal of one or more of the (usually) four parathyroid glands. This procedure is used to remove an adenoma or hyperplasia of these glands when they are producing excessive parathyroid hormone (PTH): hyperparathyroidism. The glands are usually four in number and located adjacent to the posterior surface of the thyroid gland, but their exact location is variable. When an elevated PTH level is found, a sestamibi scan or an ultrasound may be performed in order to confirm the presence and location of abnormal parathyroid tissue.
Bone char is a porous, black, granular material produced by charring animal bones. Its composition varies depending on how it is made; however, it consists mainly of tricalcium phosphate 57–80%, calcium carbonate 6–10% and carbon 7–10%. It is primarily used for filtration and decolorisation.
Sodium fluoride (NaF) is an inorganic compound with the formula NaF. It is a colorless or white solid that is readily soluble in water. It is used in trace amounts in the fluoridation of drinking water to prevent tooth decay, and in toothpastes and topical pharmaceuticals for the same purpose. In 2020, it was the 265th most commonly prescribed medication in the United States, with more than 1 million prescriptions. It is also used in metallurgy and in medical imaging.
Fluoride or fluorine deficiency is a disorder which may cause increased dental caries and possibly osteoporosis, due to a lack of fluoride in diet. Common dietary sources of fluoride include tea, grape juice, wine, raisins, some seafood, coffee, and tap water that has been fluoridated. The extent to which the condition truly exists, and its relationship to fluoride poisoning has given rise to some controversy. Fluorine is not considered to be an essential nutrient, but the importance of fluorides for preventing tooth decay is well-recognized, despite the effect is predominantly topical. Prior to 1981, the effect of fluorides was thought to be largely systemic and preeruptive, requiring ingestion. Fluoride is considered essential in the development and maintenance of teeth by the American Dental Hygienists' Association. Fluoride incorporates into the teeth to form and harden teeth enamels. This makes the teeth more acid resistant, as well as more resistant to cavity forming bacteria. Caries-inhibiting effects of fluoride were first noticed 1902, when fluoride in high concentrations was found to stain teeth and prevent tooth decay.
Fluoride therapy is the use of fluoride for medical purposes. Fluoride supplements are recommended to prevent tooth decay in children older than six months in areas where the drinking water is low in fluoride. It is typically used as a liquid, pill, or paste by mouth. Fluoride has also been used to treat a number of bone diseases.
Dental fluorosis is a common disorder, characterized by hypomineralization of tooth enamel caused by ingestion of excessive fluoride during enamel formation.
Renal osteodystrophy is currently defined as an alteration of bone morphology in patients with chronic kidney disease (CKD). It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder (CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and kidney failure.
Osteitis fibrosa cystica is a skeletal disorder resulting in a loss of bone mass, a weakening of the bones as their calcified supporting structures are replaced with fibrous tissue, and the formation of cyst-like brown tumors in and around the bone. Osteitis fibrosis cystica (OFC), also known as osteitis fibrosa, osteodystrophia fibrosa, and von Recklinghausen's disease of bone, is caused by hyperparathyroidism, which is a surplus of parathyroid hormone from over-active parathyroid glands. This surplus stimulates the activity of osteoclasts, cells that break down bone, in a process known as osteoclastic bone resorption. The hyperparathyroidism can be triggered by a parathyroid adenoma, hereditary factors, parathyroid carcinoma, or renal osteodystrophy. Osteoclastic bone resorption releases minerals, including calcium, from the bone into the bloodstream, causing both elevated blood calcium levels, and the structural changes which weaken the bone. The symptoms of the disease are the consequences of both the general softening of the bones and the excess calcium in the blood, and include bone fractures, kidney stones, nausea, moth-eaten appearance in the bones, appetite loss, and weight loss.
Tertiary hyperparathyroidism is a condition involving the overproduction of the hormone, parathyroid hormone, produced by the parathyroid glands. The parathyroid glands are involved in monitoring and regulating blood calcium levels and respond by either producing or ceasing to produce parathyroid hormone. Anatomically, these glands are located in the neck, para-lateral to the thyroid gland, which does not have any influence in the production of parathyroid hormone. Parathyroid hormone is released by the parathyroid glands in response to low blood calcium circulation. Persistent low levels of circulating calcium are thought to be the catalyst in the progressive development of adenoma, in the parathyroid glands resulting in primary hyperparathyroidism. While primary hyperparathyroidism is the most common form of this condition, secondary and tertiary are thought to result due to chronic kidney disease (CKD). Estimates of CKD prevalence in the global community range from 11 to 13% which translate to a large portion of the global population at risk of developing tertiary hyperparathyroidism. Tertiary hyperparathyroidism was first described in the late 1960s and had been misdiagnosed as primary prior to this. Unlike primary hyperparathyroidism, the tertiary form presents as a progressive stage of resolved secondary hyperparathyroidism with biochemical hallmarks that include elevated calcium ion levels in the blood, hypercalcemia, along with autonomous production of parathyroid hormone and adenoma in all four parathyroid glands. Upon diagnosis treatment of tertiary hyperparathyroidism usually leads to a surgical intervention.
The calcium-sensing receptor (CaSR) is a Class C G-protein coupled receptor which senses extracellular levels of calcium ions. It is primarily expressed in the parathyroid gland, the renal tubules of the kidney and the brain. In the parathyroid gland, it controls calcium homeostasis by regulating the release of parathyroid hormone (PTH). In the kidney it has an inhibitory effect on the reabsorption of calcium, potassium, sodium, and water depending on which segment of the tubule is being activated.
Fluorine may interact with biological systems in the form of fluorine-containing compounds. Though elemental fluorine (F2) is very rare in everyday life, fluorine-containing compounds such as fluorite occur naturally as minerals. Naturally occurring organofluorine compounds are extremely rare. Man-made fluoride compounds are common and are used in medicines, pesticides, and materials. Twenty percent of all commercialized pharmaceuticals contain fluorine, including Lipitor and Prozac. In many contexts, fluorine-containing compounds are harmless or even beneficial to living organisms; in others, they are toxic.
Defluoridation is the downward adjustment of the level of fluoride in drinking water. Worldwide, fluoride is one of the most abundant anions present in groundwater. Fluoride is more present in groundwater than surface water mainly due to the leaching of minerals. Groundwater accounts for 98 percent of the earth's potable water. An excess of fluoride in drinking water causes dental fluorosis and skeletal fluorosis. The World Health Organization has recommended a guideline value of 1.5 mg/L as the concentration above which dental fluorosis is likely. Fluorosis is endemic in more than 20 developed and developing nations.
Topical fluorides are fluoride-containing drugs indicated in prevention and treatment of dental caries, particularly in children's primary dentitions. The dental-protecting property of topical fluoride can be attributed to multiple mechanisms of action, including the promotion of remineralization of decalcified enamel, the inhibition of the cariogenic microbial metabolism in dental plaque and the increase of tooth resistance to acid dissolution. Topical fluoride is available in a variety of dose forms, for example, toothpaste, mouth rinses, varnish and silver diamine solution. These dosage forms possess different absorption mechanisms and consist of different active ingredients. Common active ingredients include sodium fluoride, stannous fluoride, silver diamine fluoride. These ingredients account for different pharmacokinetic profiles, thereby having varied dosing regimes and therapeutic effects. A minority of individuals may experience certain adverse effects, including dermatological irritation, hypersensitivity reactions, neurotoxicity and dental fluorosis. In severe cases, fluoride overdose may lead to acute toxicity. While topical fluoride is effective in preventing dental caries, it should be used with caution in specific situations to avoid undesired side effects.
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