Fluoride Action Network

Variability in Radiographic Appearance of Skeletal Fluorosis

F.A.N. | June 2012 | By Michael Connett

Osteosclerosis (dense bone) is the bone change typically associated with skeletal fluorosis, particularly in the axial skeleton (spine, pelvis, and ribs). Research shows, however, that skeletal fluorosis produces a spectrum of bone changes, including osteomalacia, osteoporosis, exostoses, changes resulting from secondary hyperparathyroidism, and combinations thereof. In some studies, the percentage of skeletal fluorosis patients with osteoporosis, osteomalacia, or osteoarthritis exceeds the percentage of fluorosis patients with axial osteosclerosis. (e.g., Sang 2010; Liu 2006; Savas 2001).

Although the reason for this radiographic variability is not yet fully understood, it is believed to relate to the dose of fluoride, sufficiency of calcium intake, exposure to aluminum, repetitive stress, age, sex, presence of kidney disease, and genetic susceptibility. (See below).

Variability in Radiographic Appearance:

“114 patients with moderate endemic skeletal fluorosis were [examined]. . . . All X-ray features of endemic skeletal fluorosis appeared in the X-ray of the 114 patients with moderate endemic skeletal fluorosis. Osteosclerosis: 4 cases in forearm, 7 in calf,4 in pelvis, 4 in lumbar vertebrae; Osteoporosis and bone softening: 23 cases in forearm patients, 23 in calf, 5 in pelvis, 8 in lumbar vertebrae; Mixed changes: 6 cases in forearm, 9 in calf, 10 in pelvis, 1 in lumbar vertebrae patients; Joint changes: 107 cases in forearm, 47 in calf, 28 in pelvis, 19 in lumbar vertebrae. ”
SOURCE: Sang ZC, et al. (2010). [X-ray analysis on 114 patients with moderate endemic skeletal fluorosis by treatment of Guo’s Chinese herbal]. [Article in Chinese]. Zhongguo Gu Shang. 23(5):379-82.

“A variety of conditions are associated with SF including osteosclerosis, osteomalacia, osteoporosis, and secondary hyperparathyroidism.”
SOURCE: Qin X, et al. (2009). Child Skeletal Fluorosis from Indoor Burning of Coal in Southwestern China. Journal of Environmental and Public Health  doi:10.1155/2009/969764

The X-rays of patients with skeletal fluorosis from drinking “brick tea” (a tea drink that contains high levels of both fluoride and aluminum) showed that 61.29% had degenerative joints, 33.87% had interosseous membrane calcification, 29.03% had osteoporosis, and just 8.06% and osteosclerosis.
SOURCE: Liu QB, et al. (2006). Investigation on combined toxicosis of fluorine-aluminum in Ewenke Qi Inner Mongolia. Chinese Journal of Control of Endemic Diseases. Available online at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-DYBF200605010.htm

X-rays of 28 skeletal fluorosis patients revealed: “17 cases with main quantitative increase in bones, 11 cases with main quantitative decrease in bones, 5 cases with blurred bone structure, 9 cases with osteoporosis of cortical bones, 19 cases with osteosclerosis of cancellous bones, 7 cases with concave shaped vertebral bodies at both ends, 6 cases with pelvic malformation, 4 cases with false fracture, 7 cases with dysplastic bones.”
SOURCE:  Liu J, et al. (2004). Imaging value on bone turnover of skeletal fluorosis. Foreign Medical Sciences-Section of Medgeography. Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-GONE200402017.htm

“To determine the effect of high level fluoride in drinking water on bone mineral density (BMD), thereby finding a method for screening endemic fluorosis. Methods: 80 female residents in the endemic fluorosis area and 71 women in urban area were recruited randomly as subjects and controls, respectively. Fluoride concentration in urine was determined, and single photon absorptionetry (SPA) was used to determine the BMD of the forearms. The difference in BMD and detection rate of osteoporosis between the two groups was analyzed. Results: Compared with the controls, the difference in the mean value of BMD was inconsistent in different age groups, without regularity, however, the rate of osteoporosis is higher in the subjects of endemic fluorosis area than in the controls (P < 0.001). Conclusion: High concentration of fluoride in the drinking water may result in the variation of BMD in the forearm by population levels. The rate of osteoporosis that was detected in the female group is higher in the endemic fluorosis area than in the normal population . . . .”
SOURCE: Zhan Z, et al. (2003). Bone mineral density of forearm of female residents in endemic fluorosis area. Chinese Journal of Osteoporosis. Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZGZS200302013.htm

“The main radiological features of the patients with endemic fluorosis were degenerative changes [of the knee joint]. . . . Twenty-five (44.6%) patients wtih endemic fluorosis had polyp-like osteophytes at the medial non-weight-bearing margin of the femoral condyle. This kind of osteophyte was not detected in controls. . . . Two patients (3.6%) with endemic fluorosis had axial osteosclerosis and five (8.9%) had interosseous membrane calcification of the forearm. . . . In our study, some radiological findings such as osteosclerosis, interosseous membrane calcification, or ligament calcification, which are accepted as hallmarks of skeletal fluorosis were not found as frequently as in the literature.”
SOURCE: Savas S, et al. (2001). Endemic fluorosis in Turkish patients: relationship with knee osteoarthritis. Rheumatology International 21: 30-5.

“To find out the skeletal radiologic appearances of high aluminum fluorosis caused by burning coal as domestic fuel. Materials and methods: Thirty-nine cases of high aluminum fluorosis caused by eating corn baked by coal and china clay were studied. . . . The skeletal radiographic appearances were very complicated. The main change was osteomalacia. Osteoporosis, osteosclerosis and dysplastic bone were also found. . . . We suggest that high aluminum fluorosis is a special type of fluorosis presenting as osteomalacia.”
SOURCE: Chen X, et al. (1996). Skeletal radiographic appearances of high aluminum fluorosis caused by domestic coal fuel (analysis of 39cases). Chinese Journal of Radiology. Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZHGS604.015.htm

“Skeletal fluorosis caused by endemic fluorine poisoning was once thought to result merely in osteosclerosis, causing marblelike changes. Later, various radiologic features were found, including osteosclerosis, osteomalacia, and osteoporosis. Although this disorder has a wide variety of appearances, little attention has been given to the spectrum of radiologic appearances… The pathogenesis of these diverse radiologic appearances remains unclear.”
SOURCE: Wang Y, et al. (1994). Endemic fluorosis of the skeleton: radiographic features in 127 patients. American Journal of Roentgenology 162: 93-8.

“Typical descriptions of skeletal radiology in endemic fluorosis have emphasized osteosclerosis (especially of the spine), membranous and ligamentous calcification, and exostoses… Our study showed in addition a wide variety of radiological patterns: …[T]he pelvis showed the appearance of both osteosclerosis and osteopenia. Osteosclerosis was present in the central area of the pelvis while the lateral part showed considerable osteopenia. Vertebral bodies showed an osteopenic central region bordered by a sclerotic zone at the vertebral margin.”
SOURCE: Mithal A, et al. (1993). Radiological spectrum of endemic fluorosis: relationship with calcium intake. Skeletal Radiology 22: 257-61.

Examination of the bone mineral content in the forearm of 128 skeletal fluorosis patients, “showed that the bone mineral content of the cases was lower than that of normal controls. It was also found that, even among the cases of endemic skeletal fluorosis, their bone mineral contents varied with their four types of roentgen rays (early osteopathic changes, osteosclerosis, osteoporosis and mixed osteopathic changes), bone mineral contents being arranged, in order from high to low levels, as follows: osteosclerosis > early osteopathic changes > mixed osteopathic changes > osteoporosis.”
SOURCE: Tian JY, et al. (1993). Analysis of Bone Mineral Content in Human Cases of Endemic Skeletal Fluorosis with Different Types of Roentgen Rays. Endemic Disease Bulletin. Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-DFBT199303015.htm

A radiologic analysis was made on 23 inhabitants of an area with high content of fluorine in drinking water, where they lived over 40 years.The fluorosis could be recognized with bone change in 8 cases; osteoporosis without coarsening of trabeculae in 5 cases; no change of bone tissue in 10 and ossification or calcification of the tissue surrounding the bone in 23 cases. The author considers that it is not suitable to make radiologic classification of endemic fluorosis only on the basis of changes of the bone itself without consideration of the change to surrounding tissue.
SOURCE: Bai X. (1992). Radiological analysis in 23 cases of endemic fluorsis. Chinese Journal of Endemiology. Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZDFB199204012.htm

“High F intakes have been associated wtih a wide spectrum of bone diseases including osteosclerosis, osteoporosis, osteomalacia and exostoses… The pathogenic mechanisms underlying fluorosis of the mineralizing tissues have been studied extensively, but are still a matter of controversy.”
SOURCE: Kragstrup J, et al. (1989). Effects of fluoride on cortical bone remodeling in the growing domestic pig. Bone 10:421-424.

“We suggest that bone fluorosis be classified roentgenologically on the basis of these 3 features into 3 types: the osteosclerosis type (53 cases, 36.3%), osteoporosis type (18 cases, 12.3%), and mixed type (51 cases, 34.9%)… In mixed type fluorosis, osteosclerosis, osteoporosis and osteomalacia exist in one patient.”
SOURCE: Xu JC, et al. (1987). X-ray findings and pathological basis of bone fluorosis. Chinese Medical Journal 100:8-16.

“A combination of osteosclerosis, osteomalacia and osteoporosis of varying degrees as well as exostoses formation characterzes the bone lesions. In a proportion of cases secondary hyperparathyroidism is observed with associated characteristic bone changes.”
SOURCE: Krishnamachari KA. (1986). Skeletal fluorosis in humans: a review of recent progress in the understanding of the disease. Progress in Food and Nutrition Sciences 10(3-4):279-314.

“It is very interesting to observe that in the majority of our cases, osteosclerosis in the spine and pelvis was always combined with osteoporosis of the long bones. It might be an indication that the axial skeleton undergoes a quite different pathological process from the appendicular skeleton…”
SOURCE: Lian ZC, Wu EH. (1986). Osteoporosis–an early radiographic sign of endemic fluorosis. Skeletal Radiology 15:350-3.

73 patients with skeletal fluorosis were compared with 73 non-fluorosis patients. The incidence of radiographically detectable osteopenia (manifested as osteoporosis, trabecular thickening and porosis or reduced mineral content) in the fluorosis group was 68.4%, which was significantly higher than that in the non-fluorosis group (43.8%), p < 0.01.This indicated that fluorosis increased the occurance of osteopenia.”
SOURCE: Hebei Province Baoding Antiepidemic Station. (1985). Relationships between osteofluorosis and osteopenia. Chinese Journal of Endemiology. Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZDFB198503012.htm

“Radiographic appearances varied between individuals. Conflicting changes such as both decreased and increased density, coarsened, thinned and blurred trabeculae, coexisted not only in different bones of one individual, but also in one and the same bone. Some cases showed axial osteosclerosis exclusively, others axial osteosclerosis in association with peripheral osteoporosis or osteomalacia… Combinations of various changes produced a wide sprectrum of radiological changes.”
SOURCE: Daijei H. (1984). Further observations on radiological changes of endemic foodborne skeletal fluorosis. Fluoride 17: 9-14.

The frequency of bony peripheral tissue change and arthralgias in osteosclerosis-type fluorosis was sligbtly less than in the osteoporosis and mixed-type fluorosis.
SOURCE: Huang S, et al. (1984). Evaluation of the diagnosis classification and differentiation of fluorosis on bony peripheral tissue change and athralgias. Ningxia Medical Journal. Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-NXYX198403000.htm

“[N]ew bone formed under the stimulus of fluoride administration may exhibit various degrees of osteosclerosis, osteoporosis, osteomalacia, and architectural disorganization. Of these manifestations, only osteosclerosis increases bone strength. When fluoride is used therapeutically, therefore, it is obvious that conditions must be carefully chosen so as to maximize the development of osteosclerosis and to minimize the undesirable manifestations of osteoporosis and osteomalacia.”
SOURCE: Riggs BL. (1983). Treatment of osteoporosis with sodium fluoride: An appraisal. Bone and Mineral Research. 2: 366-393.

X-ray analysis of 407 patients with confirmed skeletal fluorosis found four types of bone changes: (1) osteoporosis; (2) osteosclerosis, (3) Mixed-type, and (4) Osteomalacia. Each type of bone change was classified into three stages: mild, moderate, and severe.
SOURCE: Liu Z, et al. (1982). X-ray analysis of 407 cases of skeletal fluorosis. Shaanxi Journal of Medicine. Available at: http://www.cnki.com.cn/Article/CJFDTOTAL-SXYZ198206024.htm

“The changes described did not always develop in a progressive, predictable pattern to the adult stage of osteofluorosis.”
SOURCE: Christie DP. (1980). The spectrum of radiographic bone changes in children with fluorosis. Radiology 136:85-90.

“The considerable individual variability of skeletal response to excessive fluoride ingestion implies that causative factors other than total daily ingestion of fluoride exist.”
SOURCE: Christie DP. (1980). The spectrum of radiographic bone changes in children with fluorosis. Radiology 136:85-90.

“The osseous changes in fluorosis have been described as osteosclerosis, exostosis, hyperostosis, osteoporosis, osteomalacia, and rickets.'”
SOURCE: Krook L, Maylin GA. (1979). Industrial fluoride pollution. Chronic fluoride poisoning in Cornwall Island cattle. Cornell Veterinarian 69(Suppl 8): 1-70.

“In several patients we failed to notice evidence of typical sclerosis in the radiogram. Instead, the picture of so-called ‘hypertrophic atrophy‘ was found as in the following case: Patient G.M., 62 years-old, had been working for 20 years in an aluminum smelter. X-rays showed typical hypertrophic atrophy with slight periosteal appositions on the forearms and lower legs. . . .  We observed similar findings following therapy with sodium fluoride for osteoporosis. It is likely that a previously existing osteoporosis is superimposed upon fluorosis or the predominance of the fluoride-induced bone resorption in conjunction with thickening of the statically loaded bone structure may be responsible.”
SOURCE: Franke J, et al. (1975). Industrial Fluorosis. Fluoride 8:61-85.

“The findings of osteosclerosis, osteomalacia and increased bone resorption have been confirmed in experimental fluorosis in animals. It can be seen, therefore, that fluoride bone disease could mimic renal osteodystrophy.”
SOURCE: Cordy PE, et al. (1974). Bone disease in hemodialysis patients with particular reference to the effect of fluoride. Transactions of the American Society of Artifical Internal Organs 20: 197-202.

“In the final analysis it would be surprising if the complicated effects of fluoride on bone did not reflect the versatility of fluorine, the most reactive and the most stronly electronegative of all elements.”
SOURCE: Faccini JM, Teotia SPS. (1974). Histopathological assessment of endemic skeletal fluorosis. Calcified Tissue Research 16: 45-57.

“To this day, many investigators still think of fluorosis exclusively in terms of osteosclerosis, whether crippling or non-crippling. This attitude is no longer valid, because osteosclerosis is only one of many skeletal abnormalities that can be induced by fluoride.”
SOURCE: Marier JR, Rose D. (1971). Environmental fluoride. National Research Council of Canada, Publication No. 12,226, Ottawa.

“The osteofluorotic lesions may be porosis, sclerosis, hyperostosis, osteophytosis, and malacia, depending on the interacting factors influencing the degree of fluorosis.”
SOURCE: Shupe JL, Olson AE. (1971). Cinical aspects of fluorosis in horses. Journal of the American Veterinary Association. 158: 167-174.

“Skeletal fluorosis has been likened to a number of bone diseases. The dense radiographic picture of the skeleton has resulted in comparison with osteosclerosis; the presence of broad osteoid seams has suggested osteomalacia; the way in which bone formation may proceed side by side with bone destruction is reminiscent of Paget’s disease and the often excessive resorption points to osteoporosis.”
SOURCE: Jolly SS. (1970). Hydric fluorosis in Punjab. In: TL Vischer. (1970). Fluoride in Medicine. Hans Huber, Bern. pp. 106-121.

“Areas of intense sclerosis coexist with those of marked osteoporosis in the same bone. This is highly characteristic of the disease (‘wine fluorosis’).”
SOURCE: Soriano, M. (1968). Periostitis deformans due to wine fluorosis. Fluoride 1: 56-64.

“In certain human cases of long-standing high level exposures to fluoride, small portions of the bone become radiolucent giving a moth-eaten appearance, in contrast to the usual picture of increased density. In experimental animals given fluoride doses much higher in proportion than the human exposures just referred to, osteomalacia or osteoporosis have frequently been recorded.”
SOURCE: Hodge HC, Smith FA. (1965). Fluorine chemistry, Volume 4. Academic Press, New York.

“the findings in spontaneous and experimental fluorosis are, in part, contradictory. Human patients are usually diagnosed as having osteosclerosis whereas animals are described as having osteoporosis or ‘osteomalacia‘. Our radiograms might indicate that both processes are taking place, the sclerosis predominating over the greater part of most of the bones but osteoporosis being evident near the ends of some long bones.”
SOURCE: Kilborn LG, et al. (1950). Fluorosis with report of an advanced case. Canadian Medical Association Journal 62: 135-141.

“Chronic fluorosis presented by some 10,000 inhabitants of the Argentine Republic is an anomaly of calcium metabolism involving not only the teeth but in addition the entire osseous system and characterized by generalized osteoporosis.”
SOURCE: Silva LL, et al. (1940). Fluorosis and tuberculosis. La Semana Medica 24: 1413-1434.

“The osseous tissue displays a curious double reaction: sometimes an increased precipitation of mineral salts accompanied by stimulated growth, sometimes a reduced mineralization with mostly atrophying processes.”
SOURCE: Roholm K. (1937). Fluoride intoxication: a clinical-hygienic study with a review of the literature and some experimental investigations. London: H.K. Lewis Ltd.

Reasons for the Individual Variability Are Unclear:

“Although this disorder has a wide variety of appearances, little attention has been given to the spectrum of radiologic appearances… The pathogenesis of these diverse radiologic appearances remains unclear.”
SOURCE: Wang Y, et al. (1994). Endemic fluorosis of the skeleton: radiographic features in 127 patients. American Journal of Roentgenology 162: 93-8.

“The pathogenic mechanisms underlying fluorosis of the mineralizing tissues have been studied extensively, but are still a matter of controversy.”
SOURCE: Kragstrup J, et al. (1989). Effects of fluoride on cortical bone remodeling in the growing domestic pig. Bone 10:421-424.

“Many questions arise as to why sometimes one type of osteopathy is induced and another at other times. The pathogenesis of the osseous changes in fluorosis has not been uncovered. Hodge and Smith (1965) commented on the cellular mechanisms whereby the bone lesions are induced in fluorosis: ‘Questions are many, and answers are few, indeed, practically non-existent.'”
SOURCE: Krook L, Maylin GA. (1979). Industrial fluoride pollution. Chronic fluoride poisoning in Cornwall Island cattle. Cornell Veterinarian 69(Suppl 8): 1-70.

“It appears that there are some factors yet unknown which a play a part in determining the pattern of skeletal changes.”
SOURCE: Makhni SS, et al. (1977). Long-term effects of fluoride administration: an experimental study. Fluoride 10:82-86.

“The histopathogenesis of the bone disease produced by chronic fluoride intoxication remains incompletely understood despite innumerable reports in the literature of the results of animal experimentation… In the final analysis it would be surprising if the complicated effects of fluoride on bone did not reflect the versatility of fluorine, the most reactive and the most stronly electronegative of all elements…Most probably all these factors are involved.”
SOURCE: Faccini JM, Teotia SPS. (1974). Histopathological assessment of endemic skeletal fluorosis. Calcified Tissue Research 16: 45-57.

“Despite the large volume of research, however, the effects of fluoride on bone are complicated and are still not fully understood.”
SOURCE: Faccini JM. (1969). Fluoride and bone. Calcified Tissue Research 3:1-16.

“It is extremely probable that fluorine acts on the metabolism in various ways and that the symptoms of chronic intoxication have a complicated genesis.”
SOURCE: Roholm K. (1937). Fluoride intoxication: a clinical-hygienic study with a review of the literature and some experimental investigations. London: H.K. Lewis Ltd

Explanations Offered for Variability:

a) Multifactorial: 

In this animal study, “the main influential factors which led up to various types of skeletal fluorosis were total fluoride intake, malnutrition (protein and calcium insufficiency) and high intake of aluminum compounds.”
SOURCE: Zhang H, et al. (1999). Study on the pathogenesis of osteotransformation in children’s skeletal fluorosis. Modern Preventive Medicine. Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-XDYF199903012.htm

“It is generally thought that several factors influence the type of bone change seen in fluoride intoxication. These include the nature, dose, and duration of fluoride exposure; nutritional status; hormonal responses; age; sex; type of bone affected (cortical or otherwise); and dietary habits… The different appearances of this disease probably represent different combinations of these variables.”
SOURCE: Wang Y, et al. (1994). Endemic fluorosis of the skeleton: radiographic features in 127 patients. American Journal of Roentgenology 162: 93-8.

b) Dose of Fluoride:

“We found that fluoride increased cancellous bone area in the rat at the lower dose and reduced cancellous bone volume at the higher dose… Our findings suggest that the optimal concentration of fluoride that increases bone resorption is higher than the concentration that increases formation. If this is correct, the effects of fluoride on bone formation and resorption may be mediated through different mechanisms and may be dissociable.”
SOURCE: Turner RT, et al. (1989). The effects of fluoride on bone and implant histomorphometry in growing rats. Journal of Bone and Mineral Research 4: 477-484.

“Osteosclerotic picture is evident when small doses of fluoride are ingested over a long period of time during which calcium intakes are apparently normal while osteoporotic forms are common in pediatric age group and with higher body load of the element.”
SOURCE: Krishnamachari KA. (1986). Skeletal fluorosis in humans: a review of recent progress in the understanding of the disease. Progress in Food and Nutrition Sciences 10:279-314.

“Roholm (1937) realised, however, that an increase in bone growth and calcification resulted from comparatively small doses of fluorides, while large doses produced an atrophic state with a reduction in calcification.”
SOURCE: Faccini JM. (1969). Fluoride and bone. Calcified Tissue Research 3:1-16.

“The osteoporotic stage of the disease occurs only when fluoric intoxication is very severe.”
SOURCE: Soriano, M. (1968). Periostitis deformans due to wine fluorosis. Fluoride 1: 56-64.

“In the adult the osteosclerotic process seems to be produced by comparatively small quantities of fluorine, the osteoporotic process seems to be produced by comparatively large quantities.”
SOURCE: Roholm K. (1937). Fluoride intoxication: a clinical-hygienic study with a review of the literature and some experimental investigations. London: H.K. Lewis Ltd.

c) Nutritional Status: 

“The toxic effects of fluoride were more severe and more complex and the incidence of metabolic bone disease (rickets, osteoporosis, Parathyroid Hormone bone disease) and bony leg deformities (genu valgum, genu varum, bowing, rotational and wind-swept) was greater (>90%) in children with calcium deficiency as compared to in children with adequate calcium who largely had osteoslcerotic form of skeletal fluorosis…”
SOURCE: Teotia M, Teotia SP, Singh KP. (1998). Endemic chronic fluoride toxicity and dietary calcium deficiency interaction syndromes of metabolic bone disease and deformities in India: year 2000. Indian Journal of Pediatrics 65:371-81.

Nourishment and endemic skeletal fluorosis were surveyed in 4 high fluoride drinking water villages in China. The investigation revealed that the most of patients with x-ray evidence of osteosclerosis were better nourished than those with osteoporosis, as evident by differences in blood and urinary calcium levels. Based on the findings, the authors conclude that the “mechanism of endemic skeletal fluorosis could be influenced by nutritional insufficency, epsecially low calcium intake.”
SOURCE: Fan J, et al. (1994). The Relationship between Nutritional Factors and Endemic Skeletal Fluorosis. Tianjing Medical Journal. Available online at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-TJYZ199412003.htm

“On the basis of our results, we suggest that fluoride toxicity in subjects with a reasonable calcium intake leads to typical osteosclerosis, while a calcium – (and protein-) deficient diet together with fluoride excess may be responsible for the osteopenic forms of the disease.”
SOURCE: Mithal A, et al. (1993). Radiological spectrum of endemic fluorosis: relationship with calcium intake. Skeletal Radiology 22: 257-61.

“It is considered that low dietary Ca intake is an es-sential factor in the development of osteomalacic skeletal fluorosis, that the changes of calciotropic hormones secondary to the hypocalcemia aggravate the severity of osteomalacia, and that improvement of Ca nutrition state ofthe inhabitants can play an important role inthe control of endemic fluorosis.”
SOURCE: Sun M, et al. (1993). Pathogenesis of osteomalacic skeletal fluorosis an experimental study. Chinese Journal of Endemiology. Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZDFB199303001.htm

“Besides reduction of fluoride intake, the supplement of adequate calcium and the improvement of collagen metabolism are the effective approaches to the enhancement of body tolerance to fluoride and the prevention of fluoride-induced osteomalacia.”
SOURCE: Li GS, et al. (1988). Conditions and factors affecting the development of osteomalacic skeletal fluorosis: an experimental study. Endemic Disease Bulletin. Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-DFBT198802002.htm

“Osteosclerotic picture is evident when small doses of fluoride are ingested over a long period of time during which calcium intakes are apparently normal while osteoporotic forms are common in pediatric age group and with higher body load of the element.”
SOURCE: Krishnamachari KA. (1986). Skeletal fluorosis in humans: a review of recent progress in the understanding of the disease. Progress in Food and Nutrition Sciences 10:279-314.

d) Aluminum Exposure

“Based on the result, we suggest that aluminum plays a role in the pathogenesis of fluorosis. The combined effect of F-Al is an important condition for occurring of fluorosis.”
SOURCE: Song S, et al. (1991). Experimental study on the role of aluminum in the pathogenesis of fluorosis. Journal of Guiyang Medical College. Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-GYYB199103009.htm

“Fluoride may interact with aluminum to worsen the osteomalacic lesion.”
SOURCE: Ng AHM, et al. (2004). Association between fluoride, magnesium, aluminum and bone quality in renal osteodystrophy. Bone 34: 216-224.

“To find out the skeletal radiologic appearances of high aluminum fluorosis caused by burning coal as domestic fuel. Materials and methods: Thirty-nine cases of high aluminum fluorosis caused by eating corn baked by coal and china clay were studied. . . . The skeletal radiographic appearances were very complicated. The main change was osteomalacia. Osteoporosis, osteosclerosis and dysplastic bone were also found. . . . We suggest that high aluminum fluorosis is a special type of fluorosis presenting as osteomalacia.”
SOURCE: Chen X, et al. (1996). Skeletal radiographic appearances of high aluminum fluorosis caused by domestic coal fuel (analysis of 39cases). Chinese Journal of Radiology. Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZHGS604.015.htm

“We consider that the appearance of patients with serious osteomalacia in the fluorosis area is the result of fluoride aluminium combined toxicity.”
SOURCE: Chen X, et al. (1991). [Bone x-ray analysis of patients with combined fluoride-aluminium toxicosis. Journal of Guiyang Medical College.] Available at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-GYYB199103005.htm

e) Repetitive Stress:

For more discussion on the role of repetitive stress in fluorosis, click here.

“Radiological changes in industrial fluorosis suggest that physical strain on bones, ligaments, and joints plays an important role in the development of the lesions. The reason for the selective knee involvement in our patients may be fluoride’s selectivity for the most stressed joints. Sitting habits like hyperflexion sitting and ritual worship in our population may stress the knees and cause vulnerability to fluorotic damage.”
SOURCE: Savas S, et al. (2001). Endemic fluorosis in Turkish patients: relationship with knee osteoarthritis. Rheumatology International 21(1):30-5.

“it appears that the development of new fluorotic bone occurs at those sites most subjected to strain and minor trauma.”
SOURCE: Littleton J. (1999). Paleopathology of skeletal fluorosis. American Journal of Physical Anthropology 109: 465-483.

“It is notable that the symptoms and radiological changes occur first in areas of greater muscular activity… Both Siddiqui and Singh et al noted… the selective effect of this halide on the joints which are most used.”
SOURCE: Anand JK, Roberts JT. (1990). Chronic fluorine poisoning in man: a review of literature in English (1946-1989) and indications for research. Biomedicine & Pharmacotherapy 44: 417-420.

In “Indian basket weavers exposed to fluoride, it was observed that the much used left arm and wrist were particularly susceptible to fluorotic exostosis… [T]he areas suffering repeated or constant stress or trauma, and as a result requiring ongoing repair, may be areas of increased circulation and metabolism and, as a consequence, increased deposition of fluorides.”
SOURCE: Carnow BW, Conibear SA. (1981). Industrial fluorosis. Fluoride 14: 172-181.

“Radiological changes in industrial fluorosis suggest that physical strain on bones, ligaments, and joints play an important role in the development of the lesions.”
SOURCE: Boillat MA, et al. (1980). Radiological criteria of industrial fluorosis. Skeletal Radiology 5: 161-165.

“The degree of osteosclerosis was found to be related to the duration of intoxication and the concentration of fluorine in the water. Physical strain was also found responsible: the greater the strain, the more pronounced were the changes observed… Pain and stiffness were more severe in the joints used most by the individual – for example, the wrists, shoulders, and neck in the females, who were mostly engaged in household work: and the lumbar spine and the joints of the lower limbs in the males working in the fields.”
SOURCE: Siddiqui AH. (1955). Fluorosis in Nalgonda district, Hyderabad-Deccan. British Medical Journal ii (Dec 10): 1408-1413.

f) Genetics

“Fluoride incorporation into bone depends on many factors, including ingestion from sources in addition to water, age, duration of residency, renal function and other disease states, remodeling rate, and genetic susceptibility. About 40% of the population in areas with water supplies naturally fluoridated at very high levels are unaffected by skeletal fluorosis, and about a third of patients who receive fluoride as a therapy for osteoporosis are described as ‘nonresponders,’ indicating that intrinsic susceptibility to fluoride varies with the individual. A genetic basis for these differences is supported by research with different strains of mice. In a large, diverse urban center like Toronto, therefore, one would expect that the population would display a range of genetic susceptibilities to fluoride…”
SOURCE: Chachra D, et al. (2010). The long-term effects of water fluoridation on the human skeleton. Journal of Dental Research 89:1219-1223.