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. Most patients suffering from skeletal fluorosis show side effects from the high fluoride dose such as ruptures of the stomach lining and nausea. 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.
Common causes of fluorosis include inhalation of fluoride dusts/fumes by workers in industry, consumption of fluoride from drinking water (levels of fluoride in excess of levels that are considered safe), and consumption of fluoride from drinking tea, particularly brick tea. Skeletal fluorosis can be caused by cryolite (Na3AlF6, sodium hexafluoroaluminate), and the disease was first recognized among workers processing cryolite.
In India, most in Nalgonda (Telangana), the most common cause of fluorosis is fluoride-laden drinking water which is sourced as groundwater from deep-bore wells. Over half of groundwater sources in India have fluoride above recommended levels.
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. The 1693 eruption of Hekla also led to fatalities of livestock under similar conditions.
Mechanism of action
The best way to view the mechanism of action by which fluorine breaks down bones and causes skeletal fluorosis is in a stepwise fashion.
- Fluoride 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 fluoride to enter the body is hydrogen fluoride (HF) gas, this is what starts the process. Exposed tissues will be utilized by HF in neutralization 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 elemental F is one of the strongest oxidizers currently known, the anion F−
is immune to phase 1 metabolic reactions, 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 (Ca
3(OH)); the reaction of Ca2+ ions and HF forms an insoluble salt, CaF
- This salt must be cleared by the body, which concomitantly leaches out some of the calcium that would be part of the bone matrix.
- This process results in increased density, but decreased strength in bones.
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-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|
|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. 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. 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. 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.
In some areas, skeletal fluorosis is endemic. While fluorosis is most severe and widespread in the two largest 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."
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.
Effects on animals
The histological changes which are induced through fluorine on rats resemble those of humans.
- Kalia LV, Lee L, Kalia SK, Pirouzmand F, Rapoport MJ, Aviv RI, Mozeg D, Symons SP. Thoracic myelopathy from coincident fluorosis and epidural lipomatosis. Canadian Journal of Neurological Sciences. 2010 March; 37(2):276–278.
- Gönnewicht, Daniela (2005). "Untersuchung eines Zusammenhanges von Fluoridkonzentrationen in privaten Trinkwasserversorgungsanlagen und Kariesentwicklung im Raum Ascheberg (Südliches Münsterland/Westfalen)" (PDF). Dissertation. Universität Münster, Fachbereich Medizinische Fakultät.
- Teotia SP, Teotia M (March 1973). "Secondary hyperparathyroidism in patients with endemic skeletal fluorosis". Br Med J. 1 (5854): 637–40. doi:10.1136/bmj.1.5854.637. PMC 1588649. PMID 4692708.
- "CDC – National Research Council (NRC) Report – Safety – Community Water Fluoridation – Oral Health". Cdc.gov. Retrieved 2013-09-04.
- Naveen Kakumanu, M.D. & Sudhaker D. Rao, M.B., B.S. (2013-03-21). "Skeletal Fluorosis Due to Excessive Tea Drinking". New England Journal of Medicine. 368 (12): 1140. doi:10.1056/NEJMicm1200995. PMID 23514291.CS1 maint: Multiple names: authors list (link)
- Skeletal fluorosis
- Reddy DR (2009). "Neurology of endemic skeletal fluorosis". Neurol India. 57 (1): 7–12. doi:10.4103/0028-3886.48793. PMID 19305069.
- Klemetti, Erik (7 June 2013). "Eruptions Local and Global Impacts of the 1783–84 Laki Eruption in Iceland". Wired. Retrieved 3 November 2014.
- Eruption History
- "Fluorine". Retrieved 2011-03-18.
- Whitford GM (1994). "Intake and Metabolism of Fluoride". Advances in Dental Research. 8 (1): 5–14. doi:10.1177/08959374940080011001. PMID 7993560.
- Whyte MP, Essmyer K, Gannon FH, Reinus WR (January 2005). "Skeletal fluorosis and instant tea". Am. J. Med. 118 (1): 78–82. doi:10.1016/j.amjmed.2004.07.046. PMID 15639213.
- Grandjean P, Thomsen G (November 1983). "Reversibility of skeletal fluorosis". Br J Ind Med. 40 (4): 456–61. doi:10.1136/oem.40.4.456. PMC 1009220. PMID 6626475.
- "UNICEF – Water, environment and sanitation – Common water and sanitation-related diseases". Retrieved 2007-09-17.
- Franke J, Runge H, Fengler F, Wanka C (1972). "[Experimental bone fluorosis]". Int Arch Arbeitsmed (in German). 30 (1): 31–48. doi:10.1007/bf00539123. PMID 5084923.