Skeletal fluorosis: an uncommon cause, yet a rescue treatment?

PURPOSE: Skeletal fluorosis (SF) results from chronic exposure to fluoride (F-) causing excessive aberrantly mineralized brittle bone tissue, fractures, and exostoses. There is no established treatment other than avoiding the source of F-. Still, excess F- can persist in bone for decades after exposure ceases. CASE PRESENTATION: A 50-year-old woman presented with multiple, recurrent, low AQ2 trauma fractures yet high radiologic bone mineral density. Serum F- was elevated, and osteomalacia was documented by non-decalcified transiliac biopsy. She reported intermittently "huffing" a keyboard cleaner containing F- (difluoroethane) for years. Following cessation of her F- exposure, we evaluated the administration of the parathyroid hormone analog, abaloparatide, hoping to increase bone remodeling and diminish her skeletal F- burden. CONCLUSION: Due to the prolonged half-life of F- in bone, SF can cause fracturing long after F- exposure stops. Anabolic therapy approved for osteoporosis, such as abaloparatide, may induce mineralized bone turnover to replace the poorly mineralized osteomalacic bone characteristic of SF and thereby diminish fracture risk. Following abaloparatide treatment for our patient, there was a decrease in bone density as well as a reduction in F- levels.

Associations of cumulative voriconazole dose, treatment duration, and alkaline phosphatase with voriconazole-induced periostitis.

OBJECTIVE: To investigate the associations of cumulative voriconazole dose, treatment duration, and alkaline phosphatase with voriconazole-induced periostitis. MATERIALS AND METHODS: One hundred and thirty-one patients with voriconazole use were identified using a clinical informatics tool. Health record data including age, sex, immune status, alkaline phosphatase, voriconazole levels, voriconazole dose, frequency, and treatment duration were collected. Imaging studies during the duration of treatment were reviewed by two radiology trainees and imaging features of voriconazole-induced periostitis were confirmed by a board-certified musculoskeletal radiologist. The length, location in the body, location in the bone, type, and morphology of periostitis lesions were recorded. Incident voriconazole-induced periostitis was defined as new periostitis on imaging after 28 days or more of voriconazole treatment in the absence of an alternative diagnosis. Univariate Firth's logistic regression models were performed using cumulative voriconazole dose, treatment duration, and average ALP as predictors and incident VIP as the outcome. RESULTS: There were nine patients with voriconazole-induced periostitis and 122 patients without voriconazole-induced periostitis. The most common lesion location in the body was the ribs (37%) and morphology was solid (44%). A 31.5-g increase in cumulative voriconazole dose was associated with 8% higher odds of incident periostitis. Increased treatment duration (63 days) and higher average alkaline phosphatase (50 IU/L) were associated with 7% higher odds of periostitis and 34% higher odds of periostitis, respectively. CONCLUSION: Increased cumulative voriconazole dose, treatment duration, and average alkaline phosphatase were associated with higher odds of voriconazole-induced periostitis.

LDL receptor-related protein 5 rs648438 polymorphism is associated with the risk of skeletal fluorosis.

To investigate the potential association between LRP5 rs648438 polymorphism and the risk of skeletal fluorosis (SF) was evaluated in a cross-sectional case-control study conducted in Shanxi, China, in 2019. A total of 973 individuals were enrolled in this study, in which cases and controls were 346 and 627, respectively. SF was diagnosed according to the standard WS/192-2008 (China). The LRP5 rs648438 was detected by the multiple PCR and sequencing. LRP5 rs648438 was found to follow a dominant genetic model using a web-based SNP-STATS software. Logistic regression analysis found that the TC/CC genotype of LRP5 rs648438 might be a protective factor for SF. When stratified by gender, this protective effect of TC/CC genotype in rs648438 was pronounced in males. There was an interaction between gender and rs648438 on risk of SF. Our study suggested that TC/CC genotype of rs648438 might be a protective factor for water-drinking-type skeletal fluorosis, especially in male participants.

Association between mtDNA haplogroups and skeletal fluorosis in Han population residing in drinking water endemic fluorosis area of northern China.

To investigate the association between mtDNA genetic information and the risk of SF, individuals were conducted in the drinking water endemic fluorosis area in northern China, sequenced the whole genome of mtDNA, identified the SNPs and SNVs, analyzed the haplogroups, and diagnosed SF, and then, the effect of mtDNA genetic information on the risk of SF was evaluated. We find that, D5 haplogroup and its specific SNPs reduced the risk, while the D4 haplogroup and its specific SNPs increased the risk of SF. The number of SNVs in coding regions of mitochondrial respiratory chain (MRC) is different between the controls and cases. This suggests that D5 haplogroup may play a protective role in the risk of SF, while the opposite is observed for the D4 haplogroup, this may relate to their specific SNPs. And SNVs that encode the MRC complex may also be associated with the risk of SF.

Association between polymorphism and haplotype of ATP2B1 gene and skeletal fluorosis in Han population.

To evaluate the association between ATP2B1 gene polymorphisms and skeletal fluorosis, a cross-sectional study was conducted. In China, 962 individuals were recruited, including 342 cases of skeletal fluorosis. Four TP2BA1 polymorphisms (rs2070759, rs12817819, rs17249754, and rs7136259) were analysed. The results suggested that rs17249754 and rs7136259 were associated with skeletal fluorosis. After controlling confounders, the protective effect of GG genotype in rs17249754 was apparent in individuals over 45 years old, female, with urine fluoride concentration below 1.6 mg/L, serum calcium above 2.25 mmol/L or serum phosphorus between 1.1 and 1.3. Heterozygote TC in rs7136259 increased the risk of skeletal fluorosis in subjects who are elderly, female, with urinary fluoride more than 1.6 mg/L, serum calcium more than 2.25 mmol/L and blood phosphorus between 1.1 and 1.3 mmol/L. Four loci were found to be tightly related by linkage disequilibrium analysis, and the frequency of distribution of haplotype GCGT was lower in the skeletal fluorosis group.

Association between Bone Morphogenetic Protein 2 Gene Polymorphisms and Skeletal Fluorosis of The Brick-tea Type Fluorosis in Tibetans and Kazakhs, China.

To investigate the potential association between BMP2 single nucleotide polymorphisms (SNPs) and brick-tea-type skeletal fluorosis risk in cross-sectional case-control study conducted in Sinkiang and Qinghai, China, a total of 598 individuals, including 308 Tibetans and 290 Kazakhs, were enrolled. Using the standard WS/192-2008 (China), 221 skeletal fluorosis cases were diagnosed, including 123 Tibetans and 98 Kazakhs. Logistic regressions 2 analysis did not find the association between SNPs (Rs235764, Rs235739 and Rs996544) and skeletal fluorosis. Genetic models, linkage disequilibrium (LD) and haplotype analysis were not found to be associated with risk of skeletal fluorosis after adjustment by age and sex (P>0.05).Our data suggested that Rs 235764, Rs 235739 and Rs 996544 were not linked susceptibility for skeletal fluorosis in our cross-sectional case-control study.

Neuro-medical manifestations of fluorosis in populations living in the Main Ethiopian Rift Valley.

Prolonged exposure to higher concentrations of fluoride (> 1.5 mg/L) is associated with dental and skeletal fluorosis. The effects of fluoride on dental and skeletal system have been studied extensively; however, the neurological consequences of fluoride in population-based studies are limited. The study aims to assess the epidemiology of neurological and other manifestations of fluorosis among rural populations living in the Main Ethiopian Rift valley. In this cross-sectional study, we enrolled 316 individuals from 23 rural communities in the Main Ethiopian Rift valley. Fluoride concentration was measured in drinking water samples collected from 23 community wells. Association between fluoride concentrations and clinical features of fluorosis was assessed using student t test, chi square, multivariable regression using adjusted odds ratio (OR). The mean fluoride concentration in the drinking water was 6.8 ± 4.3 mg/L (range: 0.3-15.5 mg/L). At least one clinical sign of skeletal fluorosis was observed in 54.4% (n = 175) of the study participants. Headache and joint pain reported by 67.1% and 56.3% of the participants as the most common neurological manifestation, and skeletal fluorosis symptom, respectively. The mean fluoride level was higher for those individuals who reported paresthesia compared to those with no-paresthesia. Loss of appetite, constipation, and fatigue were reported by 48.0%, 45.6%, and 56.6% of the participants, respectively. Signs of crippling fluorosis were observed in small proportion (1.6%) of the participants. Individuals who reported headache are most likely exposed to higher fluoride concentrations in drinking water compared to those reported no-headache (p < 0.001). The study demonstrates high prevalence of neuro-medical manifestations of fluorosis in population living in the Main Ethiopian Rift valley. Fluoride concentration in drinking water and joint pain were independent predictors of fluorosis.

miR-486-3p regulates CyclinD1 and promotes fluoride-induced osteoblast proliferation and activation.

Fluoride is a persistent environmental pollutant, and its excessive intake contributes to skeletal and dental fluorosis. The mechanisms underlying fluoride-induced abnormal osteoblast proliferation and activation, which are related to skeletal fluorosis, have not yet been fully clarified. As important epigenetic regulators, microRNAs (miRNAs) participate in bone metabolism. On the basis of our previous miRNA-seq results and bioinformatics analysis, this study investigated the role and specific molecular mechanism of miR-486-3p in fluoride-induced osteoblast proliferation and activation via CyclinD1. Herein, in the fluoride-challenged population, we observed that miR-486-3p expression decreased while CyclinD1 and transforming growth factor (TGF)-ß1 increased, and miR-486-3p level correlated negatively with the expression of CyclinD1 and TGF-ß1 genes. Further, we verified that sodium fluoride (NaF) decreases miR-486-3p expression in human osteoblasts and overexpression of miR-486-3p reduces fluoride-induced osteoblast proliferation and activation. Meanwhile, we demonstrated that miR-486-3p regulates NaF-induced upregulation of CyclinD1 by directly targeting its 3'-untranslated region (3'-UTR). In addition, we observed that NaF activates the TGF-ß1/Smad2/3/CyclinD1 axis and miR-486-3p mediates transcriptional regulation of CyclinD1 by TGF-ß1/Smad2/3 signaling pathway via targeting TGF-ß1 3'-UTR in vitro. This study, thus, contributes significantly in revealing the mechanism of miR-486-3p-mediated CyclinD1 upregulation in skeletal fluorosis and sheds new light on endemic fluorosis treatment.

Progress of Signaling Pathways, Stress Pathways and Epigenetics in the Pathogenesis of Skeletal Fluorosis.

Fluorine is widely dispersed in nature and has multiple physiological functions. Although it is usually regarded as an essential trace element for humans, this view is not held universally. Moreover, chronic fluorosis, mainly characterized by skeletal fluorosis, can be induced by long-term excessive fluoride consumption. High concentrations of fluoride in the environment and drinking water are major causes, and patients with skeletal fluorosis mainly present with symptoms of osteosclerosis, osteochondrosis, osteoporosis, and degenerative changes in joint cartilage. Etiologies for skeletal fluorosis have been established, but the specific pathogenesis is inconclusive. Currently, active osteogenesis and accelerated bone turnover are considered critical processes in the progression of skeletal fluorosis. In recent years, researchers have conducted extensive studies in fields of signaling pathways (Wnt/ß-catenin, Notch, PI3K/Akt/mTOR, Hedgehog, parathyroid hormone, and insulin signaling pathways), stress pathways (oxidative stress and endoplasmic reticulum stress pathways), epigenetics (DNA methylation and non-coding RNAs), and their inter-regulation involved in the pathogenesis of skeletal fluorosis. In this review, we summarised and analyzed relevant findings to provide a basis for comprehensive understandings of the pathogenesis of skeletal fluorosis and hopefully propose more effective prevention and therapeutic strategies.

Association between ALOX15 gene polymorphism and brick-tea type skeletal fluorosis in Tibetans, Kazaks and Han, China.

To evaluate the association between ALOX15 gene polymorphism and skeletal fluorosis (SF), a case-control study was conducted. A total of 1023 individuals, including 308 Tibetans, 290 Kazaks and 425 Han, were enrolled in this study, in which cases and controls were 278 and 745, respectively. SF was diagnosed by X-ray absorptiometry. SNPs were genotyped using the Sequenom Mass ARRAY system. The genotypes of ALOX15 rs7220870, rs2664593 and rs1107852 were not associated with the risk of SF. After reconstructing the haplotype of rs7220870 and rs11078528, the risk effect of haplotype CA was found in Han participants aged ≤45 years or with moderate fluoride intake. Diplotype of CC/CC had a protective effect on SF risk in Han participants; whereas, CA/CC diplotype showed a risk effect on SF risk in participants aged ≥65; Our results provide the first evidence of an association between ALOX15 gene polymorphism and SF risk in Han participants.Abbreviation: SF: Skeletal fluorosis; SNP: Single Nucleotide polymorphism.

Expounding on the concerns of indian politicians regarding fluorosis: A qualitative analysis of parliamentary questions on fluorosis over two decades.

Fluorosis is a major public health problem in India affecting nearly 20 states. Despite more than three decades of fluorosis prevention efforts, fluorosis continues to be a widely prevalent disease in India. The debilitating effects of skeletal fluorosis are well documented and pose a serious health risk to people who consume excess fluoride. In order to understand whether fluorosis was being given importance as a public health problem by elected politicians, we analyzed parliamentary questions posed in both the houses of the Indian parliament during the question hour. Thematic analysis revealed three major themes, namely health hazards, fluorosis control, and magnitude of fluorosis. The analysis revealed that politicians have posed questions regarding all the aspects that are necessary for fluorosis control in India. However, we have identified the certain key issues which have to be improved and certain obligations that the Government of India has to fulfill for successful fluorosis mitigation in India.

[Rapamycin activates autophagy by inhibiting mTOR pathway to alleviate early osteoporosis in rats with skeletal fluorosis].

Objective: To investigate the effects of rapamycin target protein (mTOR) pathway and autophagy on bone formation and bone resorption in fluorosis osteoporosis in rats. Methods: In September 2018, a rat model of skeletal fluorosis was established by intragastric administration of fluorine. The experimental animals were divided into control group, 10 mgF(-)/kg group, 20 mgF(-)/kg group, 2 mg/kg rapamycin (RAPA) +10 mgF(-)/kg group and 2 mg/kg RAPA+20 mgF(-)/kg group, 20 per group. The experiment lasted for 3 months. The changes of bone tissue in rats were observed by hematoxylin-eosin (HE) staining. Bone mineral density (BMD) and biomechanical indexes, such as Modulus of elasticity, Stiffness, Maximum stress and Maximum load, were measured by BMD and biomechanical biometer. Serum levels of alkaline phosphatase (ALP) , osteocalcin (BGP) , osteoprotectin (OPG) , type I procollagen amino-terminal peptide (PINP) , tartrate-resistant acid phosphatase (TRACP) and nuclear factor kappa B receptor activator ligand (RANKL) were determined by enzymatic linked immunosorbent assay (ELISA) . Bone tissue phosphorylated mTOR (p-mTOR) , autophagy-related index selective autophagy adaptor protein p62, microtubule associated protein II (LC3-II) , ALP, osteoblastic transcription factor (Osterix) , and RNT Expression of related transcription factor 2 (Runx2) and bone resorption indicator RANKL were detected by Western blotting. Results: Compared with the control group, dental fluorosis in the 10 mgF(-)/kg and 20 mgF(-)/kg groups was significantly increased, periosteum thickness and absorption lacunae appeared, and BGP, OPG, PINP, TRACP and RANKL in serum contents were increased (P<0.05) , BMD, Modulus of elasticity, Stiffness, Maximum stress and Maximum load of bone tissue decreased significantly (P<0.05) , and the expressions of p-mTOR and p62 were decreased (P<0.05) , also the expressions of ALP, Osterix, Runx2 and RANKL were increased (P<0.05) . Compared with 10 mgF(-)/kg and 20 mgF(-)/kg groups, there were no obvious dental fluorosis symptoms in 2 mg/kg RAPA+10 mgF(-)/kg group and 2 mg/kg RAPA+20 mgF(-)/kg group, and serum ALP, BGP and OPG levels were significantly increased (P<0.05) . TRACP and RANKL contents were significantly decreased (P<0.05) . BMD, Modulus of elasticity, Stiffness, Maximum stress and Maximum load were significantly increased (P<0.05) . The levels of p-mTOR, p62 and RANKL in bone tissues were decreased (P<0.05) , and the expressions of LC3-II, LC3-II/LC3-I, ALP, Osterix and Runx2 were increased (P<0.05) . Conclusion: RAPA may activate autophagy by inhibiting mTOR phosphorylation, and inhibit bone resorption while promoting bone formation, thus alleviating early osteoporosis in skeletal fluorosis rats.

Skeletal fluorosis: don't miss the diagnosis!

Skeletal fluorosis is a rare toxic osteopathy characterized by massive bone fixation of fluoride. The disease occurs as an endemic problem in some parts of the world and is the result of prolonged ingestion or rarely by inhalation of high amounts of fluoride. Radiographic presentation is mainly characterized by bone changes with osteocondensation and later ossification of many ligaments and interosseous membranes. Skeletal fluorosis is not clinically obvious and can be confused with other rheumatologic disorders. Its severity lies in the development of skeletal deformities and neurological complications. Management of fluorosis generally focuses on symptom treatment.

A review on the potential sources and health implications of fluoride in groundwater of Sub-Saharan Africa.

Groundwater is a major source of drinking water for millions of people around the world. Over 400 million people in Africa depend solely on it as their main source of water supply. Fluoride is a common contaminant in groundwater. In low concentration (0.5-1.0 mg/L), fluoride is needed by humans for healthy development of bones and teeth, however, a concentration >1.5 mg/L has been linked with several fluorosis and non-fluorosis diseases. Dental and skeletal fluorosis are the major fluorosis diseases commonly reported with the consumption of fluoride-rich water. Although fluoride intake through other pathways such as the drinking of tea and eating of vegetables have been reported, the drinking of fluoride-rich water remains the major pathway of fluoride into humans. Cases of high fluoride levels in groundwater have been reported in almost all the sub-Saharan Africa region but it is more prevalent in East African countries, Sudan and South Africa. Although fluoride is present in surface water mostly in the East African Rift Valley across different countries in East Africa, its significant or high levels are usually associated with groundwater. Geogenic sources such as fluorite, apatite, biotite, amphibole, micas, topaz, cryolite, muscovite and fluorspar have been identified as the major sources of fluoride in groundwater. High fluoride levels have been reported across sub Saharan Africa, with generally higher levels in East Africa resulting from the volcanic activities in the rift system. Dental fluorosis has been reported in many sub-Saharan African countries including South Africa, Tanzania, Uganda, Ethiopia, Kenya, Sudan, Niger, Nigeria, Benin, Ghana and Malawi. Geothermal temperature has been regarded as one of the driving forces for high fluoride levels recorded in groundwater from deep aquifers and geothermal springs. The most affected people with the consumption of fluoride-rich water are the poor with low socioeconomic status who live in rural areas. Some of the proposed alternative sources include rainwater and fog water harvesting and blending of water from various sources. Low-cost and sustainable deflouridation technique remains one of the best ways to treat fluoride contaminated water either at communal level or at the point-of-use.

Aberrant methylation-induced dysfunction of p16 is associated with osteoblast activation caused by fluoride.

Chronic exposure to fluoride continues to be a public health problem worldwide, affecting thousands of people. Fluoride can cause abnormal proliferation and activation of osteoblast and osteoclast, leading to skeletal fluorosis that can cause pain and harm to joints and bones and even lead to permanent disability. Nevertheless, there is no recognized mechanism to explain the bone lesions of fluorosis. In this work, we performed a population study and in vitro experiments to investigate the pathogenic mechanism of skeletal fluorosis in relation to methylation of the promoter of p16. The protein coded by the p16 gene inhibits cdk (cyclin-dependent kinase) 4/cdk6-mediated phosphorylation4 of retinoblastoma gene product and induces cell cycle arrest. The results showed that hypermethylation of p16 and reduced gene expression was evident in peripheral blood mononuclear cells of patients with fluorosis and correlated with the level of fluoride exposure. Studies with cell cultures of osteoblasts revealed in response to sodium fluoride (NaF) treatment, there was an induction of p16 hypermethylation and decreased expression, leading to increased cell proliferation, a longer S-phase of the cell cycle, and development of skeletal fluorosis. Further, the methylation inhibitor, 5-aza-2-deoxycytidine, reversed the p16 hypermethylation and expression in response to NaF. These results reveal a regulatory role of p16 gene methylation on osteoblasts activation during the development of skeletal fluorosis.

FRZB1 rs2242070 polymorphisms is associated with brick tea type skeletal fluorosis in Kazakhs, but not in Tibetans, China.

Skeletal fluorosis is a metabolic bone and joint disease caused by excessive accumulation of fluoride in the bones. Compared with Kazakhs, Tibetans are more likely to develop moderate and severe brick tea type skeletal fluorosis, although they have similar fluoride exposure. Single nucleotide polymorphisms (SNPs) in frizzled-related protein (FRZB) have been associated with osteoarthritis, but their association with the risk of skeletal fluorosis has not been reported. In this paper, we investigated the association of three SNPs (rs7775, rs2242070 and rs9288087) in FRZB1with brick tea type skeletal fluorosis risk in a cross-sectional case-control study conducted in Sinkiang and Qinghai, China. A total of 598 individuals, including 308 Tibetans and 290 Kazakhs, were enrolled in this study, in which cases and controls were 221 and 377, respectively. The skeletal fluorosis was diagnosed according to the Chinese diagnostic criteria of endemic skeletal fluorosis (WS192-2008). The fluoride content in tea water or urine was detected using the fluoride ion electrode. SNPs were assessed using the Sequenom MassARRAY system. Binary logistic regressions found evidence of association with rs2242070 AA genotype in only Kazakh participants [odds ratio (OR) 0.417, 95% CI 0.216-0.807, p = 0.009], but not in Tibetans. When stratified by age, this protective effect of AA genotype in rs2242070 was pronounced in Kazakh participants aged 46-65 (OR 0.321, 95% CI 0.135-0.764, p = 0.010). This protective association with AA genotype in rs2242070 in Kazakhs also appeared to be stronger with tea fluoride intake > 3.5 mg/day (OR 0.396, 95% CI 0.182-0.864, p = 0.020). Our data suggest there might be differential genetic influence on skeletal fluorosis risk in Kazakh and Tibetan participants and that this difference might be modified by tea fluoride intake.

Delayed chance fracture pattern injury in a case of skeletal fluorosis.

PURPOSE: To document a rare complication of a delayed 'chance fracture pattern'-type injury through the proximal end of a pedicle screw construct in the clinical scenario of skeletal fluorosis. METHODS: A 72-year-old man with fluorosis presented following a fall which resulted in a T12-L1 fracture. Investigations revealed an unstable three-column injury, so the patient was treated with surgical stabilisation using pedicle screw fixation from T11 to L2. He presented 1 month following surgery with worsening back pain. Investigations revealed a fracture through T11 in a 'chance fracture pattern' along the pedicle screw tracts at the proximal end of the construct. An extension of fixation was performed proximally to T8 and he made an uneventful recovery showing fusion at 20-month follow-up. RESULTS: Complication of delayed pedicle fractures, in a 'chance fracture pattern' at the ends of a pedicle screw fixation constructs are a rarely reported in the literature. The occurrence of such a complication in a hyperostotic spine associated with fluorosis makes this a unique clinical scenario which is previously unreported to the best of our knowledge. CONCLUSIONS: This report highlights a very rare complication of chance fracture pattern injury in the clinical scenario of fluorosis. A hyperostotic stiff spine, poor quality of bone and extension of pedicle screw tracts to anterior cortex during primary surgery may have resulted in the occurrence of this rare complication.

Chronic excess fluoride uptake contributes to degenerative joint disease (DJD): Evidence from six marsupial species.

One of the manifestations of chronic fluoride toxicosis in mammals is skeletal fluorosis, which can include lesions of degenerative joint disease (DJD). Although DJD lesions have been less commonly studied than bone or dental lesions in relation to the pathology and epidemiology of fluoride toxicosis, there have been multiple independent studies in various species that have concluded that there appears to be an effect. The mechanisms by which fluoride affects the joints are not clear, but our data provide evidence that chronic excess dietary fluoride intake contributes to DJD. Our study is the first to specifically address the association between fluoride exposure and DJD in multiple species of free-ranging mammals. We describe levels of DJD in six marsupial species (Macropus giganteus, Notamacropus rufogriseus, Wallabia bicolor, Phascolarctos cinereus, Trichosurus vulpecula and Pseudocheirus peregrinus) inhabiting high and low fluoride environments. Lesions occurred to varying extents in all species, and lesion distribution varied with biomechanical differences in gait. In addition, we show an association (independent of age) between increasing bone fluoride concentration (as a measure of fluoride exposure) and increasing prevalence of moderate and severe DJD in five species of marsupial, which we propose does not persist at the highest levels of fluoride exposure due to selective survival bias.

Association of Dietary Carotenoids Intake with Skeletal Fluorosis in the Coal-burning Fluorosis Area of Guizhou Province.

OBJECTIVE: To explore whether the intake of dietary carotenoids could protect against skeletal fluorosis in Guizhou province in which coal-burning fluorosis is endemic. METHODS: A case-control study of 196 patients with skeletal fluorosis and 196 age and gender-matched controls was conducted in Zhijin, Guizhou Province. Face-to-face interviews were conducted to assess habitual dietary intake using a 75-item food frequency questionnaire and various covariates with structured questionnaires. Urinary fluoride was measured using an ion-selective electrode method. The genotype of superoxide dismutase 2 (SOD2) rs11968525 was detected by TaqMan method. RESULTS: We observed significant dose-dependent inverse associations of skeletal fluorosis with intake of ß-carotene, lutein/zeaxanthin, lycopene, and total carotenoids (P-trend = 0.002 to 0.018), whereas α-carotene and ß-cryptoxanthin intakes were not found to be related to skeletal fluorosis, after adjustment for potential confounders. The adjusted ORs and 95% CI of skeletal fluorosis for the highest versus lowest quartile were 0.30 (0.10, 0.86) for ß-carotene, 0.23 (0.08, 0.66) for lycopene, 0.26 (0.10, 0.75) for lutein/zeaxanthin and 0.34 (0.14, 0.74) for total carotenoids (all P-trend < 0.05). Stratified analyses showed that the protective effects of lutein/zeaxanthin and total carotenoids on skeletal fluorosis were more evident for individuals with the AG+AA genotypes of SOD2 (rs11968525). CONCLUSION: Increased intakes of ß-carotene, lutein/zeaxanthin, lycopene, and total carotenoids are independently associated with a lower risk of coal-burning skeletal fluorosis. SOD2 (rs11968525) polymorphisms might modify the inverse associations between dietary carotenoids and skeletal fluorosis.

A brief and critical review on hydrofluorosis in diverse species of domestic animals in India.

India is one of the fluoride-endemic countries where the maximum numbers of ground or drinking water sources are naturally fluoridated. In India, a total of 23, out of 36 states and union territories have drinking water contaminated with fluoride in varying concentration. In the present scenario, especially in rural India, besides the surface waters (perennial ponds, dams, rivers, etc.), bore wells and hand pumps are the principal drinking water sources for domestic animals such as cattle (Bos taurus), water buffaloes (Bubalus bubalis), sheep (Ovis aries), goats (Capra hircus), horses (Equus caballus), donkeys (Equus asinus) and dromedary camels (Camelus dromedarius). Out of 23 states, 17 states, namely Andhra Pradesh, Assam, Bihar, Chhattisgarh, Gujarat, Haryana, Jharkhand, Karnataka, Kerala, Madhya Pradesh, Maharashtra, Odisha (Orissa), Punjab, Rajasthan, Telangana, Uttar Pradesh and West Bengal, have fluoride beyond the maximum permissible limit of 1.0 or 1.5 ppm in drinking water. This situation is a great concern for the animal health because fluoride is a slow toxicant and causes chronic diverse serious health hazards or toxic effects. Despite the fact that domestic animals are the basic income sources in rural areas and possess a significant contributory role not only in the agriculture sector but also in the strengthening of economy as well as in sustainable development of the country, research work on chronic fluoride intoxication (hydrofluorosis) due to drinking of fluoridated water in domestic animals rearing in various fluoride-endemic states is not enough as compared to work done in humans. However, some interesting and excellent research works conducted on different aspects of hydrofluorosis in domesticated animals rearing in different states are briefly and critically reviewed in the present communication. Author believes that this review paper not only will be more useful for researchers to do some more advance research work on fluoride-induced toxicosis in different species of animals but will also be helpful in the making of health policy for domestic animals at state and national level for the mitigation of hydrofluorosis in India.