Skeletal fluorosis in Vavuniya District : an observational study

Methods In 98 volunteers we detected 60 with clinical features of pre-skeletal and skeletal fluorosis. Clinical examination, biochemical and radiographic investigations were performed. Forty four with confounding factors were excluded. The balance 16 had radiographic investigation for fluoride bone disease, and assessment of clinical features for pre-skeletal fluorosis. The radiographic criteria of skeletal fluorosis were trabecular haziness, osteosclerosis, osteophytes, cortical thickening and ligamentous or muscle attachment ossification. All 16 had “spot” samples of 15 ml of venous blood taken for biochemical tests and fluoride estimation; and 30 ml of urine, and water from 16 dug wells for fluoride.


Introduction
Fluoride toxicity is a worldwide health problem of gigantic proportions, manifesting as dental and skeletal fluorosis.For example, in India alone, about 60 million in over 200 Districts are at risk of developing skeletal fluorosis, and about 6 million are disabled by the disease.Similar results have been reported from many other countries [1].
The crucial aetiological factor for fluoride toxicity is the high fluoride content in groundwater.For development of pre-skeletal and skeletal fluorosis other determinants contribute, including duration of exposure, strenuous physical activity, and strontium in groundwater [3].
Before the onset of overt skeletal fluorosis, there is a long pre-skeletal phase during which joint pains, neck stiffness, and muscle weakness occur that mimic symptoms of familiar arthritic conditions, leading to prolonged misdiagnosis, since the overwhelming majority of doctors have never encountered a case of fluorosis.Hence serum and urine fluoride studies are never done in such cases [1,3].
Vengalcheddikulam, in Vavuniya District, has all the predisposing conditions conducive to development of fluoride toxicity: high levels of groundwater fluoride, high average daytime temperature over 35°C, a harsh ambience with many residents engaged in farming or other labourintensive employment, requiring strenuous physical exertion and drinking copious amounts of well water.

Methods
Average daytime temperature in the Vavuniya District is about 35°C, often exceeding 37°C.Residents of Vengalcheddikulam (VC), a Divisional Secretary Division of Vavuniya District, were selected for our study.They obtained drinking water from dug wells, and in 82 randomly selected wells in Vengalcheddikulam, 22 (26.8%) had between 1.6 mg/l and 4.15 mg/l fluoride in water, with a mean of 1.59  0.69 mg/dl [2].
Sixty long-standing residents of Vengalcheddikulam with radiographic criteria of skeletal fluorosis in axial skeleton and long bones, namely trabecular haziness, cortical thickening, osteosclerosis, osteophytes and ligamentous or muscle attachment ossification, and symptoms of pre-skeletal fluorosis, such as failure to stand unaided from squatting position or when seated on a chair, neck pain or stiffness, low back pain, and pain on flexion of either wrist, elbow, knee or hip, inability to walk unaided, were investigated.The investigations included history and examination, examination of a "spot" 15 ml sample of blood for creatinine, urea, e-GFR, calcium, phosphate, alkaline phosphatase and fluoride; a 30 ml "spot" sample of urine for creatinine/albumin ratio and fluoride; and groundwater samples from 16 relevant dug wells for fluoride.
Fluoride estimations were performed at the Department of Geology, Faculty of Science, University of Peradeniya by Professor Rohana Chandrajith.Other biochemical investigations were performed at the Nawaloka Metropolis Laboratories, Vavuniya.Radiographic imaging was by a qualified radiographer, advised by a Consultant Radiologist (PBH).
As symptoms and signs of patients in the pre-skeletal phase (Table 2) we used the observational data from previous studies.None of them give validated criteria for evaluation of symptoms.Four signs gleaned from these studies, namely ability to walk unaided, flexion of the spine to touch a point 10 cm below the patella, and standing from a chair and from a squatting position unaided, could be more objectively assessed [1,4].
"Normal" values for urinary and serum fluoride given by authors vary widely.We have used urinary fluoride level between 0.6 and 2.0 mg/l, and serum fluoride level between 0.02 and 0.18 mg/l, as our reference values [1,4].
Although initially all 60 individuals were investigated, we excluded from the study those who had surrogate markers of renal osteodystrophy, namely, hypocalcaemia, hyperphosphataemia, ALP >120U/l, and eGFR<60 ml/min/ 1.73 m 2 , because renal osteodystrophy would confound radiographic confirmation of bone fluorosis.Individuals in whom radiographic diagnosis confirmed other nonfluorosis bone diseases were also excluded, leaving 16 individuals conforming to the criteria of skeletal or preskeletal fluorosis.
Approval for our study was obtained from the Sri Lanka Medical Association (ERC/14 -032).

Results
From 98 volunteers for the study we detected 60 with clinical features suggestive of pre-skeletal and skeletal fluorosis for biochemical and radiological investigation.Confounding factors were detected in 44 individuals, who were excluded from further study.
The 16 selected (11 males) had BMI between 20.6 and 31.9 kg/m 2 , and were between 22 and 84 years ( 59.9  20.4).They used water from domestic dug wells for drinking.All had adequate renal function.All serum and urine samples had raised fluoride levels way above the reference ranges for serum (0.02 -0.18 mg/l) and urine (0.6 -2.0 mg/l).The 16 water samples showed a mean fluoride content of 2.90  0.93 mg/l.The mean serum calcium value of the 16 individuals was 8.77  0.30 mg/dl, of phosphate 4.33  0.47 mg/dl, and alkaline phosphatase 96.4  16.20 IU.Serum fluoride ranged between 0.40 and 2.14 mg/l ( 1.0  0.42), and urinary fluoride ranged from 0.88 to 3.26 mg/l ( 1.90  0.53).A summary of the biochemical investigations and demographic details of all 16 individuals is given in Table 1.The symptoms elicited and results of four tests we have performed are given in Table 2.All had neck pain or stiffness and low back pain, while pain on wrist flexion was recorded in 14, and pain on hip flexion in 13.Among the four physical signs tested, all had inability to stand unaided from squatting, 10 inability to stand from a low chair, 10 could not walk unaided, and spine flexion was limited in 9.These are the most useful diagnostic criteria for pre-skeletal and skeletal fluorosis.Their conglomeration demands testing blood and urine for fluoride and radiographic investigation [4].All 16 despaired about the disabilities, which prevented them from sustaining livelihood.All had severe dental fluorosis according to Dean's Index Codes and Criteria [5].
Ten individuals had typical symptoms and signs of pre-skeletal fluorosis without radiographic evidence of skeletal fluorosis, while the other 6 gave a long history of pre-skeletal fluorosis and had definitive radiological evidence of skeletal fluorosis.

Discussion
Although initially 60 individuals were investigated, we excluded those with renal osteodystrophy.Also excluded were individuals in whom initial radiographic diagnosis was osteoporosis, degenerative bone disease, and chronic osteoarthritis [3].
When the radiographic diagnosis confirmed skeletal fluorosis, and the signs and symptoms were compatible, 6 were diagnosed as having skeletal fluorosis.When the radiographic diagnosis was non-contributory, and the signs and symptoms were compatible, 10 were diagnosed Original article as having pre-skeletal fluorosis.All individuals had been diagnosed as having one or more of the following by numerous hospital doctors for periods varying between 4 and 15 years: osteoarthritis, cervical spondylosis, rheumatoid arthritis, gout, idiopathic skeletal hyperostosis, and ankylosing spondylitis [4].
Although the rigorous measures we have taken to exclude confounders has reduced the number that could be confidently diagnosed as pre-skeletal and skeletal fluorosis to 16, the probability that several of the 44 individuals excluded from the study also had pre-skeletal or skeletal fluorosis remains an unresolved enigma.

Conclusions
Our study is focused on 16 individuals resident in Vengalcheddikulam, in Vavuniya District, in whom we have confirmed 10 had pre-skeletal fluorosis and 6 skeletal fluorosis.They were selected from a cohort of 60 with features suggestive of fluoride toxicity, who were further investigated after exclusion of confounders.The principal aetiological culprit is drinking water with a high level of fluoride over a long period.Both forms of fluoride toxicity had rendered the individuals disabled, and their families destitute.Among 44 individuals who were not subjected to investigation because they had radiographic and biochemical evidence of confounders, some may well have had bone fluorosis, in particular pre-skeletal fluorosis, which has no radiographic features.
The results of this study, and a previous study point to the prevalence of significant endemic fluorosis toxicity in residents of Vavuniya District, emphasising the need for a proper epidemiological study [2].As succinctly stated by an authority on fluoride toxicity, this disabling disorder is easily preventable by providing potable water with reduced fluoride content [6].Doctors in the Northern Province and Vavuniya District need to consider fluoride toxicity in the differential diagnosis of musculo-skeletal and arthritic disorders.
Journal 2018; 63: 120-123 DOI: http://doi.org/10.4038/cmj.v63i3.8723x = Interpretation In a cohort of 60 individuals in Vavuniya with symptoms suggestive of skeletal fluoride toxicity, 6 had skeletal fluorosis, 10 had pre-skeletal fluorosis, and groundwater sources had fluoride levels much higher than W HO recommended upper limit for drinking water.Residents in Vavuniya are predisposed to preskeletal and skeletal fluorosis.All 16 had been misdiagnosed as various types of arthritis.