Does Vitamin D Deficiency and Renal Dysfunction Play a Role in the Pathogenesis of Fluorotoxic Metabolic Bone Disease (FMBD)?

Through this study, an Ion Chromatography method has been validated and has been found to have a good correlation with the well-established ISE method. Ion Chromatography is therefore a reliable method in assessment of fluoride levels in the drinking water, but may have a few drawbacks. IC method is known to be expensive and more tedious as it requires chloride and other cations to be extracted from serum and urine samples prior to analysis, which makes the ISE method much easier to perform. The IC method was used to analyse the ground water and drinking water levels of 165 villages in and around the Vellore district, Tamil Nadu. About 46.06% of the villages assessed had water fluoride levels recorded above the Indian standards (<1.00ppm); 19.39% of the villages had water fluoride levels ranging from 1-1.5ppm; 10.91% had levels ranging from 1.5-2 ppm and 12.73% had water fluoride levels ranging from 2.0-3.0 ppm.The Jolarpet taluk of Vellore district has been found to have high levels (0.86-3.56 ppm) of fluoride in drinking water, which makes the people residing in this areaat high risk to develop dental and skeletal fluorosis. Vitamin D deficiency was produced in an experimental group of rats. To assess the changes occurring in bone,in these animals, full body DEXA scan, was usedfor the first time to assess BMDin control and Vitamin D deficient rats. There was a significant decrease in BMD (p<0.05) and BMC (p<0.05) among the vitamin D deficient rats. Thus, Vitamin D deficiency has been shown to play a vital role in bone formation and in maintaining BMC and BMD. It was interesting to note that there was a significant increase in the fat mass (p<0.05) and fat percentage (p<0.01) among the Vitamin D deficient rats. It may be hypothesised that Vitamin D deficiency can lead to an increase in fat mass in individuals. The biochemical parameters of calcium, albumin and alkaline phosphatasewere found to be unchanged in the early stages of Vitamin D deficiency in this rat model. The study found that with increasing levels of water fluoride levels there was a significant increase in BMD (p<0.05). Alkaline Phosphatase, serum and bone fluoride content and Osteocalcin were found to be increased in the Vitamin D deficient rats when compared to the control group rats, as the water fluoride levels increased. On the other hand, increased levels of fluoride was found to have a stimulating and then an inhibitory effect on the activity of the osteoclasts as evidenced by the elevated C terminal telopeptide levels with exposure to moderate fluoride levels and a fall in the levels on exposure to high levels of fluoride . Thus, highlighting that fluoride may affect the osteoblast activity and fluoride deposition in bone while Vitamin D deficiency may accentuate this effect. This could possibly lead to the causation of fluorotoxic metabolic bone disease. Pathological changes of mild bone thickening and increased osteoid in the bone were noticed among five (80%) of the Vitamin D deficient rats exposed to high levels of fluoride. A lesser percentage (40%) two of the rats belonging to the control group exposed to high levels of fluoride showed these same changes in bone. Renal function was assessed by analysing the serum creatinine, urine fluoride and urine Cystatin C which were higher among the rats treated with high levels of fluoride when compared to those treated with low and moderate levels of fluoride. Renal tubular changes may not have been found in all the cases but it was observed that fluoride does play a role in renal damage in selected cases. CONCLUSION: In conclusion, IC is a reliable method of analysing water fluoride levels. Using the IC method for analysis, Jolarpet taluk of Vellore district was found to have high levels of ground water fluoride which may predispose the population to develop dental and skeletal fluorosis. Researcher found that, Vitamin D deficiency affectsBMD,BMC and fat mass in individuals. Fluoride also does have an effect on the osteoblastic activity as well as fluoridedeposition in bone and these effects are accentuated in the presence of Vitamin D deficiency, perhaps leading to the causation of FMBD. Though high fluoride intake is known to deteriorate renal tubular function but it may do so only in selected cases. This paves way for future research to analyse other factors involved in causation of FMBD

Bone turnover markers: Emerging tool in the management of osteoporosis

Bone is a dynamic tissue which undergoes constant remodeling throughout the life span. Bone turnover is balanced with coupling of bone formation and resorption at various rates leading to continuous remodeling of bone. A study of bone turnover markers (BTMs) provides an insight of the dynamics of bone turnover in many metabolic bone disorders. An increase in bone turnover seen with aging and pathological states such as osteoporosis leads to deterioration of bone microarchitecture and thus contributes to an increase in the risk of fracture independent of low bone mineral density (BMD). These microarchitectural alterations affecting the bone quality can be assessed by BTMs and thus may serve as a complementary tool to BMD in the assessment of fracture risk. A systematic search of literature regarding BTMs was carried out using the PubMed database for the purpose of this review. Various reliable, rapid, and cost-effective automated assays of BTMs with good sensitivity are available for the management of osteoporosis. However, BTMs are subjected to various preanalytical and analytical variations necessitating strict sample collection and assays methods along with utilizing ethnicity-based reference standards for different populations. Estimation of fracture risk and monitoring the adherence and response to therapy, which is a challenge in a chronic, asymptomatic disease such as osteoporosis, are the most important applications of measuring BTMs. This review describes the physiology of bone remodeling, various conventional and novel BTMs, and BTM assays and their role in the assessment of fracture risk and monitoring response to treatment with antiresorptive or anabolic agents