Focus on Dangerous Skeletal Fluorosis, how it Can be Prevented in Humans

Fluorosis is endemic in areas where people drink water containing fluoride above the recommended standard of 1.0 ppm or 1.5 ppm and/or people who are exposed to air-borne fluoride or any other fluoride sources for long periods of time. In this disease, primarily the teeth and bones are affected to varying degrees, depending on the fluoride level and its duration and frequency of exposure. Whatever the case, fluorosis primarily manifests as dental fluorosis and skeletal fluorosis. The latter form develops when fluoride accumulates excessively on various bones of the skeleton and is extremely painful. Actually, skeletal fluorosis is a bone disease caused by excessive accumulation of fluoride which causes the bones to become weak. In advanced state, skeletal fluorosis causes painful damage to the bones and joints and is extremely painful. In this disease the bones become harder and less flexible, resulting in increased frequency of fractures. Thickening of the bone structure and accumulation of bone tissue, both of which contribute to decreased joint mobility. Ligaments and cartilage can become ossified. Skeletal fluorosis is of utmost importance as it reduces mobility at a very early age by causing gradual changes in the bones such as periosteal exostosis, osteosclerosis, osteoporosis, and osteophytosis. These changes manifest clinically as vague pain in the body and joints. Excess accumulation of fluoride in the muscles also reduces mobility and the condition leads to disability or crippling. In its advanced stage, neurological complications such as paraplegia and quadriplegia and limbs deformities, such as genu-varum (outward bowing of legs at the knee) and genu-valgum (inward bowing of legs at the knee) syndromes also result from regular excessive fluoride accumulation in the bones and is the worst form of skeletal fluorosis. Once skeletal fluorosis develops it lasts a lifetime and is not curable. The presented editorial focuses on how skeletal fluorosis is dangerous and how it can be prevented in the humans. The purpose of this editorial is to provide scientific information and create awareness about this fluorosis disease among people living in fluoride endemic areas.

It is well known that fluoride is universally found at varying levels in water, soil, air and foods. This may be due to geologic processes and/or anthropogenic or industrial activities. Fluoride intake has both beneficial and negative effects in humans that depend on the concentration of fluoride. Consumption of water containing fluoride in the range of 0.5 to 1.0 ppm is beneficial and reduces the chances and incidence of dental caries [1,2], but its excessive intake through drinking water contains fluoride more than the recommended or standard value of 1.0 ppm or 1.5 ppm then it leads to genesis of dangerous and highly painful fluorosis disease [3-5]. Globally, water-borne fluorosis (hydrofluorosis) is the most common and widespread disease in humans [3]. But industrial fluorosis is limited to specific areas or regions due to exposure to fluoride emitted from various industrial activities [6,7]. Fluorosis occurs not only in humans [8–22] but also in herbivorous wild [23–29] and domestic animals [30–55] if they are exposed to fluoride for long periods of time.

Once fluoride enters the body it is absorbed by the digestive and/or respiratory tract and then eventually reaches all parts of the body through the blood. More than 50% of the absorbed fluoride is excreted through feces, urine, and sweat, while the rest is retained in the body where it is deposited in various organs. However, its maximum accumulation is found in calcified organs, bones and teeth compared to non-calcified organs. Bio-accumulation of fluoride causes diverse toxic effects or pathological changes and interference with various physiological and metabolic processes and ultimately triggers the occurrence of adverse reversible and non-reversible health effects in people of all age groups. This fluoride induced toxic or health changes are collectively called fluorosis [3-5]. Various fluoride induced anomalies or deformities in teeth and bones are permanent, irreversible and not curable and can be easily observed. But fluoride-induced changes in soft tissues or organs are mostly reversible and disappear when the source of fluoride exposure is removed. Chronic fluoride exposure through ingestion of drinking water containing high fluoride levels (>1.0 or 1.5 ppm) can lead to three forms of fluorosis in man and animals, dental fluorosis (dental mottling), skeletal fluorosis (bone deformities) and non-skeletal Fluorosis [56,57]. But it is not necessary that all these three forms exist in the same person. However, among the various forms of fluorosis, skeletal fluorosis is a relatively more dangerous and highly painful bone disease in both humans and animals [56,57].

Excessive fluoride intake or fluoride bioaccumulation alters the balance between bone formation and resorption. This physiological process is accomplished with the participation of certain regulatory determinants and signaling pathways, leading to various bone malformations (lesions) known as skeletal fluorosis. Severity and different phases of skeletal fluorosis is much depending on the amount of fluoride accumulation in bones (mg F/kg). There will be no changes in bones at bone ash fluoride concentrations of 500 to 1,000 mg F/kg. Above this range, various signs and symptoms of bone changes or deformities in various clinical phases are shown in Table 1 [58]. This entity of chronic fluoride intoxication or skeletal fluorosis is very painful and more dangerous than other forms of fluorosis and is of utmost importance because it reduces mobility at a very early age by causing gradual changes in the bones such as periosteal exostosis, osteoporosis, osteoporosis, and osteophytosis (Figure 1) [59-61]. These changes manifest clinically as vague pain in the body and joints. Excessive accumulation of fluoride in muscles also reduces mobility and the condition leads to disability or crippling (Figure 2). In its advanced stage, neurological complications such as paraplegia and quadriplegia and syndromes of genu-valgum and genu-varum also result from regular fluoride exposure and is the worst form of skeletal fluorosis.

Table 1: Various clinical phases and symptoms and signs of skeletal fluorosis at different range of bone ash fluoride concentration. Source: [58].

Figure 1: Radiographs of different bones of subjects, afflicted with skeletal fluorosis. Cervical and dorsal spines showing extreme osteosclerosis, lipping and osteophytosis (a, e); osteosclerosis of the pelvis with calcification of ligaments (e); contrast of the osteosclerosis in bony cage with radiolucent lungs and clavicular involvement (b); calcification of interosseous membrane (arrow) between radius and ulna bones of forearm (c); bony exostosis in tibia (d). The calcification of interosseous membrane (arrow) is the most ideal and confirmative indication of skeletal fluorosis.

Figure 2: Subjects afflicted with severe skeletal fluorosis characterised with invalidism, kyphosis, genu-varum (a, b, d, e), genu-valgum (c), crippling with paraplegia and quadriplegia (a, d), and crossing or scissor-shaped legs (e).

These fluoride-induced bone changes can appear in people of any age. However, children are more sensitive to changes in these bones. Interestingly, all these bone deformities or changes in humans persist throughout their life span and cannot be corrected by any treatment. Many people with skeletal fluorosis in rural areas are unable to perform daily tasks and have higher rates of bone fractures. Women may also face problems in delivery due to skeletal fluorosis. The severity of skeletal fluorosis depends not only on the fluoride concentration and its duration and frequency of exposure, but also on gender, food, nutrients, chemicals in the water, individual fluoride sensitivity or tolerance and genetics, environmental factors, etc. [62-72]. Whatever the case, disability, neurological complications (paraplegia and quadriplegia) and limb deformities, such as genu-varum (outward bowing of legs at the knee) and genu-valgum (inward bowing of legs at the knee) syndromes are found to be extremely painful and not treatable and may persist throughout life in subjects suffering from severe skeletal fluorosis.

Prevention of skeletal fluorosis

It is well documented that all types of fluoride induced bone deformities (crippling, neurological complications, limbs deformities, etc.) are irreversible and not curable. But their further progress or severity in people can be prevented or controlled by adopting and implementing the following potentially effective and feasible methods: (a) regular supply or providing of fluoride free treated drinking water, (b) control of entry of fluoride in the body from different sources such  air-borne fluoride (industrial fluoride emissions) and various food items, such as alcohol, tea, rock salt, tobacco, and betel nuts, which naturally contain high amounts of fluoride, (c) providing nutritious foods containing ample amount of calcium, vitamin C, vitamin E nutrients, and antioxidants, and (d) to disseminate current knowledge about fluorosis and create general awareness among people towards preventive measures of fluoride poisoning with the help of well-trained volunteers, students, and teachers [3].

Defluoridation technology can be used or adopted for regular supply of fluoride free drinking water in the community or population inhabiting fluoride endemic areas. However, several defluoridation techniques have been developed that are readily available [73,74]. However, among these techniques, “Nalgonda Defluoridation Technique” is an ideal technique as it is simple, effective, and low cost which can be used at both household and community levels [75,76]. In India, where hydro fluorosis disease is endemic in almost all rural areas, this Nalgonda technique is most successful in the prevention and control of hydro fluorosis disease. However, this technique is cheap and gives good results but its success rate at the community level is poor due to lack of public participation, lack of responsibility for its supervision and lack of proper monitoring and maintenance [76]. Instead of adopting any defluoridation technique, the author believes that harvesting and conservation of rainwater is a better option to get low fluoride or fluoride free water regularly. Perennial freshwater reservoirs also allow regular supply of fluoride-free water to the community as their water contains only trace amounts of fluoride [3]. Nevertheless, collective efforts are needed to control fluorosis, while monitoring and evaluation of fluorosis control projects also needs to be done honestly.

Long-term exposure to fluoride or excessive intake of fluoride through drinking water and industrial fluoride emissions causes serious fluorosis disease which can develop in all age groups, children, adolescents, adults, and older people. Even low levels of fluoride can also develop fluorosis in humans. This disease is endemic in many countries, especially in their rural areas. Among the various forms of fluorosis, skeletal fluorosis is the most dangerous and highly painful. Excessive bioaccumulation of fluoride in bones leads to the development of various bone deformities, such as disability, neurological complications (paraplegia and quadriplegia) and limb deformities, and they persist throughout life and they are also irreversible or incurable. This state is the worst form of skeletal fluorosis. Thousands of people in rural areas of many fluorides endemic countries suffer from this bone disease. Prevention is the only cure or solution to this dreadful disease. Prevention of this disease in human population is possible by providing regular supply or availability of fluoride free drinking water, checking the entry of fluoride into the body, providing nutritious food, and spreading current knowledge about fluorosis and creating awareness among people about preventive measures.

Funding sources

No any funding sources for this work.

Acknowledgements

The author thanks to Prof. Darshana Choubisa, Department Prosthodontics and Crown & Bridge, Geetanjali Dental and Research Institute, Udaipur, Rajasthan 313002, India for their cooperation.