Skeletal fluorosis

Skeletal fluorosis is a bone disease caused by excessive accumulation of fluoride in the bones. In advanced cases, skeletal fluorosis causes pain and damage to bones and joints.

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 China), consumption of fluoride from drinking water (levels of fluoride in excess of levels that are considered safe^[1]), and consumption of fluoride from drinking tea,^[2] particularly brick tea. Skeletal fluorosis can be caused by cryolite (Na₃AlF₆, sodium hexafluoroaluminate), and the disease was first recognized among workers processing cryolite.^[3]

In India, 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.^[4]

Fluorosis can also occur as a result of volcanic activity.^[5] 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.^[6] The 1693 eruption of Hekla also led to fatalities of livestock under similar conditions.^[7]

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.

1. 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 (HF) gas, this is what starts the process. Exposed tissues will be utilized by HF in neutralization reactions.^[8]
2. This will leave F−
   free to pass further into the body.
3. It reacts with the concentrated HCl in the stomach to form the weak acid, HF.
4. 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.
5. The HF is now free to pass into the blood stream and be distributed to all tissues including bones.
6. Bones are largely composed of Ca compounds, particularly carbonated hydroxyapatite (Ca
   5(PO
   4)
   3(OH)); the reaction of Ca²⁺ ions and HF forms an insoluble salt, CaF
   2.
7. This salt must be cleared by the body, which concomitantly leaches out some of the calcium that would be part of the bone matrix.
8. This process results in increased density, but decreased strength in bones.^[9]

Epidemiology

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."^[10]

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.^[4]

Skeletal fluorosis phases

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. Ligaments and cartilage can become ossified.^[11] Most patients suffering from skeletal fluorosis show side effects from the high fluorine dose such as ruptures of the stomach lining and nausea.^[12] Fluorine 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 amenable to fractures.^[13]

Effects on animals

Moroccan cow with fluorosis, from industrial contamination

The histological changes which are induced through fluorine on rats resemble those of humans.^[14]

Treatment

As of now, there are no established treatments for skeletal fluorosis patients.^[15] 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 cannot be guaranteed.^[16]

See also

• Dental fluorosis
• Fluoride poisoning
• Kaj Roholm

References