bubble_chart Overview

Fluorine is one of the important trace elements in the human body, and fluorides are closely related to human life activities as well as the metabolism of teeth and skeletal tissues. Scholars both domestically and internationally have reported that long-term excessive intake of fluorides can lead to fluorosis. In 1932, Danish researchers Moller and Gudjonsson first proposed the term "fluorosis." Subsequently, many scholars discovered that this condition has strong regional characteristics and is closely related to the fluoride content in drinking water, hence naming it endemic fluorosis. Once patients develop skeletal damage and nervous system lesions, it is referred to as skeletal fluorosis. In China, the prevalence of skeletal fluorosis is widespread, with reports from urban and rural areas, mountains and plains, coastal and inland regions. Additionally, with the rapid development of industrialization, environmental pollution has become one of the disease causes of skeletal fluorosis. Therefore, this condition and its prevalence should be given high attention.

bubble_chart Etiology

Fluorides are widely present in nature, and those related to fluorosis are mainly fluorides dissolved in drinking water. In high-fluoride areas, the high concentration of fluoride in water can easily lead to the prevalence of fluorosis. It is generally believed that the main sources of fluoride causing fluorosis are: fluoride in drinking water and the environment, especially water and air in polluted environments; high-fluoride foods, etc. Therefore, the World Health Organization (WHO) sets the hygienic standard for fluoride content in drinking water with a lower limit of 0.5～1.0×10^-6 and an upper limit of 1.5～1.7×10^-4. The fluoride hygiene standard for drinking water proposed in China is 0.5～1.0^-6, and levels above 1.0×10^-6 may cause damage due to high fluoride.

bubble_chart Pathological Changes

Chronic fluorosis can manifest as various pathological changes under different pathological conditions: osteosclerosis, osteoporosis, osteomalacia, and secondary hyperparathyroid bone lesions. Long-term excessive fluoride intake can increase bone formation, but the newly formed bone is often irregularly arranged, leading to a dissociation between bone quality and quantity. Epidemiological surveys have confirmed the existence of such pathological changes. In animal experiments, long-term administration of small doses of fluoride can induce osteosclerosis in rats. If large doses of fluoride are administered in experiments while providing a normal dose of calcium or restricting calcium intake, the fluoride stimulates osteoblast activity and increases bone matrix formation, thereby raising the animal's calcium demand. However, the actual calcium intake is relatively insufficient, resulting in calcium deficiency. Additionally, fluoride can combine with calcium to form calcium fluoride, which precipitates and cannot be absorbed, exacerbating calcium deficiency and leading to osteoporosis and/or osteomalacia. The imbalance of calcium homeostasis in the body can secondarily induce hyperparathyroidism, causing a series of pathological changes in bone tissue.

However, epidemiological investigations have demonstrated that in the pathogenesis of skeletal fluorosis, excessively high fluoride levels in drinking water are not the sole pathological factor. In some regions, residents' drinking water contains relatively low fluoride levels, yet the incidence of skeletal fluorosis remains high. This indicates that, besides fluoride, other contributing factors—such as nutritional factors, calcium metabolism balance, the dose and duration of fluoride intake—also play a role in the development of skeletal fluorosis.

bubble_chart Clinical Manifestations

Dental fluorosis

Under normal circumstances, the human body requires a certain amount of fluoride, which has a good preventive effect on dental caries. However, excessive fluoride directly damages the developing ameloblasts, hindering enamel development and affecting the normal calcification process of teeth. This causes the loss of the enamel's unique luster, roughens the tooth surface, and leads to the appearance of white chalk-like spots, streaks, and patches. If pigmentation occurs, yellow, brown, or tan spots and patches may appear, which are referred to as dental fluorosis. The texture of fluorotic teeth becomes brittle, with sparrow-beak-like pits, and may exhibit varying degrees of tooth defects, uneven surfaces, susceptibility to wear and fracture, and early脱落等。

It is generally believed that the incidence and severity of dental fluorosis are directly proportional to the high fluoride concentration in drinking water—the higher the fluoride concentration, the more severe the damage. Additionally, dental fluorosis rarely occurs in deciduous teeth, and when it does, the severity is mild, likely due to the placental barrier protecting the fetus from high fluoride exposure. If permanent teeth are exposed to high-fluoride water for more than two years during their development, dental fluorosis may occur. However, once permanent teeth have fully erupted, the teeth undergo little further change.

Bone tissue damage

The damage of skeletal fluorosis to bone tissue primarily manifests as a series of clinical symptoms and signs, including lumbago and leg pain, bone and joint pain with stiffness, skeletal deformities, and compression of spinal nerve roots. Patients may experience persistent pain in the limbs, spine, and other joints, which often alleviates with activity and worsens at rest. Morning stiffness is common, making immediate movement difficult. Typically, there is no accompanying redness, swelling, heat, or migratory arthralgia. The pain is often described as soreness or distending pain, and in severe cases, stabbing pain or electric shock-like pain may occur. During episodes, patients may refuse to be touched and even avoid turning over or coughing. Those with a prolonged course may develop rigidity in the spine and limb joints, scoliosis or kyphosis, and varus or valgus deformities of the knees. Skeletal fluorosis patients often also exhibit damage to the lower limb skeletal muscles, leading to muscle atrophy, primarily due to disuse atrophy and nutritional impairment caused by nerve compression. Additionally, fluoride poisoning can directly damage muscles, and electromyography may reveal abnormalities.

Approximately 10% of patients may develop secondary neurological disorders due to pathological changes in bone tissue, manifesting as compression of the spinal cord and nerve roots. Symptoms include numbness, stabbing pain, abnormal sensations in the extremities, and a girdle-like sensation around the torso. Reduced muscle strength, increased muscle tone, and hyperactive tendon reflexes may also occur. In severe cases, patients may experience incontinence or even paraplegia. Patients with severe skeletal fluorosis often exhibit extensive bone hyperplasia and fusion in the spine, narrowing of the intervertebral foramina, and calcification or ossification of paravertebral ligaments and soft tissues, leading to significant spinal canal stenosis.

bubble_chart Auxiliary Examination

Blood and Urine Fluoride Measurement Approximately 85% of the fluoride in the human body is excreted through urine. In patients with fluoride poisoning, both blood and urine fluoride concentrations will increase, with elevated urine fluoride levels being a key diagnostic criterion for skeletal fluorosis. The normal range for urine fluoride is 1.0–3.0 mg/24h, and the normal range for blood fluoride is 0.15–1.0 mg/L. In high-fluoride areas, if blood and urine fluoride concentrations exceed the normal range, the possibility of skeletal fluorosis should be considered. It must be noted that many factors can increase urine fluoride levels, especially foods with high fluoride content, so a single elevated urine fluoride reading should not be used as the sole basis for diagnosing skeletal fluorosis. Additionally, urine fluoride levels fluctuate throughout the day, generally peaking in the late evening, while morning urine fluoride levels are close to the daily average. Therefore, morning urine testing can serve as a reliable indicator for diagnosing skeletal fluorosis.

Blood Generation and Transformation Measurement Fluoride stimulates osteoblasts, increasing new bone formation and leading to bone hyperplasia and sclerosis. This results in elevated serum alkaline phosphatase (AKP) activity, which reflects osteoblast activity. Fluoride can also bind with calcium, magnesium, and phosphates to form insoluble complexes, causing serum calcium, magnesium, and phosphorus levels to drop below normal. However, prolonged low blood calcium levels may induce hyperparathyroidism, increasing intestinal and bone calcium absorption, which can subsequently raise serum calcium and phosphorus levels.

Kidney Function Measurement Excessive fluoride intake has a direct toxic effect on the kidneys, causing varying degrees of renal dysfunction. This can lead to elevated blood urea nitrogen, decreased creatinine clearance, positive urine protein, and the presence of cells and casts in the urine.

Nail and Hair Fluoride Measurement Quantitative fluoride measurements in nails and hair accurately reflect the body's fluoride levels and are significant for diagnosing endemic skeletal fluorosis.

Iliac Bone Biopsy Non-decalcified bone biopsies reveal thickened bone trabeculae, while decalcified sections show disordered bone plate arrangement. Bone chemical analysis indicates increased fluoride, calcium, and magnesium content, with bone and blood phosphorus levels within the normal range.

Imaging Examination

X-ray changes in skeletal fluorosis include osteoporosis, osteosclerosis, osteomalacia, periosteal hyperplasia, soft tissue calcification or ossification, degenerative joint changes, bone developmental disorders, and deformities.

Osteoporosis often occurs in the long bones, with coarse and sparse trabeculae. Osteosclerosis is more common in the spine, pelvis, ribs, and skull base, and less frequent in the long bones, manifesting as granular or coarse bone texture. Severe cases show extensive osteosclerosis, but the structure is often blurred and rarely uniform like ivory. Osteomalacia primarily affects the spine and pelvis, presenting as reduced bone density, blurred trabeculae, biconcave vertebral deformities, pelvic narrowing, and pseudofractures. Osteosclerosis and osteomalacia may coexist. Periosteal hyperplasia is common in the long bones, particularly the upper fibula, appearing as localized new bone formation with a spindle or lace-like pattern, often accompanied by adjacent interosseous membrane calcification. Soft tissue calcification or ossification mainly occurs in interosseous membranes, ligaments, and tendons, initially appearing as low-density wavy or clustered protrusions, then progressing to rose-thorn-like formations, and finally fusing into lace-like or irregular shapes. Their density starts slightly higher than soft tissue and gradually increases to near bone density. Degenerative joint changes are seen in the spine and limbs, presenting as bone spurs, narrowed joint spaces, hardened joint surfaces, intra-articular loose bodies, and joint capsule calcification. Bone developmental disorders manifest as growth arrest lines and delayed bone age, while bone deformities include scoliosis and kyphosis, leading to pelvic retroversion. Genu varum and genu valgum are also common.

bubble_chart Diagnosis

1. Living in and drinking high-fluoride water in endemic fluorosis areas for more than two years, or suffering from dental fluorosis.

2. Clinical manifestations consistent with typical symptoms and signs of skeletal fluorosis.

3. Radiological examination reveals specific skeletal changes.

4. Positive laboratory tests with diagnostic significance.

5. Bone biopsy consistent with skeletal fluorosis.

Classification of Skeletal Fluorosis

Grade I: Patients with only clinical symptoms but no obvious signs of skeletal fluorosis.

Grade II: Patients with typical clinical manifestations such as bone and joint pain and dysfunction, but still able to perform some labor.

Grade III: Patients with skeletal fluorosis who have lost the ability to work.

bubble_chart Treatment Measures

Principles of treatment: (1) Reduce the body's absorption of fluorine; (2) Enhance the body's metabolism and promote the excretion of fluoride; (3) Alleviate symptoms and improve signs; (4) If nerve roots or spinal cord tissues are compressed, leading to paralysis or limb dysfunction, surgical decompression should be performed; (5) Strengthen nutrition, improve the body's disease resistance, and restore high-intensity labor capacity.

Aluminum hydroxide: Aluminum hydroxide can bind with fluorine in the intestines to form insoluble aluminum compounds, reducing fluorine absorption. Generally, aluminum hydroxide gel is used, 10ml each time, 3–4 times a day.

Calcium: Calcium binds with fluorine in the intestines to form insoluble calcium fluoride, which reduces fluorine absorption and also regulates calcium balance, treating osteomalacia or osteoporosis-type fluorosis. The dose is 2–3g, three times a day. It is often combined with citrate, 2g each time, three times a day.

Magnesium: Magnesium ions can chelate with fluoride ions to form insoluble compounds, reducing fluoride deposition in bones. Commonly, a mixture of magnesium-containing minerals, such as serpentine powder, 50mg dissolved in water, is taken twice daily.

Halogen salt: This is a complex salt containing magnesium, calcium, sodium, chlorine, and other elements, with multifaceted effects.

Boron: Binds with fluorine in the intestines and bone tissues to form BF4, reducing fluorine toxicity.

Adjuvant therapy: Includes avoiding high-fluoride water, improving nutrition, supplementing proteins and vitamins, encouraging outdoor exercise, and increasing physical activity.

Orthopedic surgery: Once nerve tissues are compressed, especially when severe clinical symptoms and signs such as paraplegia appear, timely surgical decompression often yields good results.

Chinese medicine treatment: Its principles include tonifying the kidneys, strengthening bones and muscles, promoting blood circulation, and relieving pain.

bubble_chart Prevention

Fluorosis is primarily caused by excessive fluoride content in drinking water, so as long as low-fluoride water is consumed or fluoride is removed from high-fluoride water as much as possible, fluorosis can be completely prevented and treated. Additionally, after reducing fluoride intake, the kidneys still have a strong ability to excrete fluoride. Once blood fluoride levels decrease, the excess fluoride accumulated in bone tissues and teeth can be released into the blood and excreted through the kidneys, thereby improving the symptoms and signs of fluorosis patients. Therefore, preventing and treating fluorosis by reducing the fluoride content in drinking water is not only necessary but also feasible.

Avoid drinking high-fluoride water. Residents in high-fluoride areas should try not to consume high-fluoride water and seek alternative low-fluoride water sources, such as deep well water, tap water, rainwater (2nd solar term), or snow water, while also regularly testing water quality.

Chemical methods for removing fluoride from water include the following measures:

1. Aluminum sulfate + an appropriate amount of lime can produce aluminum hydroxide precipitate, and fluoride ions are adsorbed onto the precipitate and removed.

2. Activated alumina has a large surface area and strong ion exchange capacity, providing effective adsorption of fluoride ions.

3. Basic aluminum chloride can be directly added to drinking water to form colloidal polymers. Fluoride ions precipitate with the polymers, and the supernatant becomes low-fluoride water.

There are many chemical methods for fluoride removal, but none are ideal, and the costs are relatively high, making long-term application difficult to sustain.