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Review Article *Corresponding author Nikhil Gupta, Department of Clinical Immunology & Rheumatology, Christian medical college, India, Tel: Radiology of Skeletal Fluorosis: +91-9873098719; Email: Submitted: 06 June 2016 Accepted: 06 July 2016 A Review Published: 07 July 2016 Nikhil Nair1 and Nikhil Gupta2* Copyright © 2016 Gupta et al. 1Department of Radio-Diagnosis, All India institute of Medical Sciences, India 2Department of Clinical Immunology & Rheumatology, Christian medical college, India OPEN ACCESS

Abstract Keywords • Fluorosis Fluorosis occurs due to excessive fluorine entry into the body. Dental, skeletal • and non-skeletal fluorosis is different types of fluorosis. Endemic skeletal fluorosis • Endemic disease is prevalent in many countries including India. Conventional radiographs and more • recently MRI are helpful in diagnosis of fluorosis which classically reveals a wide and • Skeletal intriguing spectrum of findings. We review the various radiological findings in a case of fluorosis.

INTRODUCTION

22].characteristically involved in fluorosis with the dorsolumbar spine, , and ribs being the most severely afflicted sites [19- Endemic skeletal fluorosis is an entity presenting with an interesting gamut of radiographic appearances. This disease stems from excessive consumption and is prevalent in The earliest sign on a plain radiograph is sand like or granular certain regions of South East Asian countries due to naturally appearance of bone structure owing to bone deposition and occurring high fluoride levels in drinking water. Conventional thickening at the junctions of trabeculae [11]. In the next stage, radiographs and more recently MRI are helpful in diagnosis trabecular thickening is seen followed by trabecular fusion of fluorosis which classically reveals a wide and intriguing appearing as focal round densities in the medullary bone [11]. spectrum of findings ascribed to Osteosclerosis (most common), of the long is also a common finding and [1-5]. reported by many authors [5,17,23]. They also noted that Excessive fluoride consumption results in increased metabolic osteosclerosis in the spine and pelvis was always combined with turnover and impaired collagen synthesis of the bone [6]. The osteopenia of the long bones which was explained as the axial resulting osteo-condensation leading to osteosclerosis, stress skeleton undergoing a different pathologic process from the fractures, ligamentous calcification, and mechanical appendicular skeleton for many years, until late in the natural compressive effects often lead to radiculomyelopathy [7-10]. history of endemic fluorosis. Krishnamachari described severe osteoporosis of the distal femur, proximal tibia and fibula along Clinical diagnosis of fluorosis relies on five criteria which with rarefaction of the metacarpal bones as the most striking include (a) residence in the endemic area for > 10 years; (b) radiologic features of fluorosis [6]. mottled tooth enamel (c) urine fluoride level greaten than 10 mg/I (normal, < 1 .5 mg/I); (d) typical symptoms and findings Osteosclerosis is a common finding in this disorder especially on physical examination and (e) no evidence of other metabolic in lumbosacral spine and pelvis. Some authors even suggest bone disorders found on review of their medical history or on that radiographs of the spine (for osteosclerosis) and forearms physicalRadiology examination of fluorosis [11]. (for periosteal bone formation and interosseous membrane ossification) are accurate enough for the diagnosis of early skeletal fluorosis in children [17,22,24]. However, osteosclerosis alone is Radiological examination is widely considered as the best a nonspecific finding seen in many diverse disorders, including method for diagnosing fluorosis [12-16], especially when metastases, myelofibrosis, Paget’s disease, hemoglobinopathies patients are still in the asymptomatic phase [6,17]. Conventional and among others [1,6]. radiographs and MRI are the currently used methods for Vertebral osteophytosis with soft-tissue calcification and radiological diagnosis of fluorosis. ossification is another common but non specific feature of Conventional radiographic features of fluorosis include fluorosis. This sign can also be seen in spondylitis deformans, increased , trabecular haziness, compact bone diffuse idiopathic skeletal , ankylosing spondylitis, and periosteal thickening and ossification of attachments of psoriasis, acromegaly, neuropathy, and alkaptonunia [1,6]. tendons, ligaments, and muscles [12,13,18]. Axial skeleton is Similarly proliferation at ligament and tendon insertions and Cite this article: Nair N, Gupta N (2016) Radiology of Skeletal Fluorosis: A Review. Ann Orthop Rheumatol 4(2): 1069. Gupta et al. (2016) Email:

Central Bringing Excellence in Open Access REFERENCES are also common but nonspecific findings in fluorosis which can also be seen in diffuse idiopathic skeletal hyperostosis, 1. Lian ZC, Zhang ZO, Zhang WY. Investigation on radiological hyperparathyroidism, X-linked hypophosphatemic osteomalacia, classification of endemic fluorosis. chung Hua Fang She Hsueh Tsa and plasma cell dyscrasia [19]. It is the combination of these 2. Chth 1987:21:40-43 . above findings on conventional radiographs which is diagnostic Teotia M, Teotia SPS, Kunwar KB. Endemic skeletal fluorosis. Arch Dis of fluorosis [1,6,19]. Child. 1971; 46: 686-691 MRI is another useful imaging modality in fluorosis for 3. Jolly SS, Singh BM, Mathun OC, Malhotra KC. Epidemiological, clinical early diagnosis and planning of proper surgical intervention and biochemical study of endemic dental and skeletal fluorosis in in the symptomatic patient as it allows accurate visualization Punjab. BMJ. 1968; 4: 427-429. of extent of soft tissue and spinal cord changes and associated 4. Krishnamachari KAVR. Further observations on the syndrome of abnormalities [25]. endemic genu valgum of South India. Indian J Med Res. 1976; 64: 284- 301. Typical MRI findings include sclerotic/dense bones, ossification of posterior longitudinal ligament and ligamentum 5. Christie DP. The spectrum of radiographic bone changes in children with fluorosis. Radiology. 1980; 136: 85-90. flavum. Stress fractures, spinal canal and neural foramina narrowing caused by osteophytes in addition to possible presence 6. Krishnamachari KA. Skeletal fluorosis in humans: a review of recent of menigocoele can also be seen [10,26,27]. progress in the understanding of the disease. Prog Food Nutr Sci. 1986; 10: 279-314. Osteosclerosis i.e., increased bone density is manifested as 7. Kleerekoper M. Fluoride and the skeleton. Crit Rev Clin Lab Sci. 1996; low signal intensity on both T1 and T2 weighted images [8,28]. 33: 139-161. These typical MRI signal changes along with neural foramina 8. Haettich B, Lebreton C, Prier , Kaplan G. Magnetic resonance imaging narrowing and premature degeneration of vertebrae may be of Fluorosis and stress fractures due to fluoride. Rev Rheum Mal present in many asymptomatic flourotic subjects. Osteoartic. 1991; 58: 803–808.

MRI is superior over other modalities in demonstrating 9. Tamer MN, Kale KorogluB, Arsalan C, Akdogan M, Koroglu M, Cam H, intraspinal ligaments particularly when they are not calcified et al. Osteosclerosis due to endemic fluorosis. Sci Total Environ. 2007; [10]. Ligamentum flavum hypertrophy, ossification/ calcification 373: 43–48. of the posterior longitudinal ligament (PLL) and ligamentum 10. Reddy DR. Neurology of endemic skeletal fluorosis. Neurol India. flavum (LF) are also prominent findings in fluorosis [10,27,29,30]. 2009; 57: 7–12. Pseudomeningocele is a commonly reported association [10]. A 11. Wang Y, Yin Y, Gilula LA, Wilson AJ. Endemic Fluorosis of the Skeleton: novel feature of a high frequency of hemangiomas existing with Radiographic Features in 127 Patients. AJR 1994; 162: 93-9. fluorosis was reported for the first time by Ahmed et al., in 2013 12. Hodge HC, Smith FA. Occupational fluoride exposure. J Occup Med [25]. 1977; 19: 12-39. However it is important to remember that MRI is a costly 13. Moller P, Gudjonsson SV. Massive fluorosis of bones and ligaments. investigation and not feasible for epidemiological studies on Acta Radiologica 1932; 13: 269-294. endemic population which may be the main reason for paucity of 14. Mithal A, Trivedi N, Gupta 5K, Kumar S, Gupta AK. Radiological spec- MRI literature on fluorosis [25]. trum of endemic fluorosis: relationship with calcium intake. Skeletal Radio. 1993; 22: 257-261. The differential diagnosis of altered marrow signals on MRI are not specific to fluorosis and can also be seen in myelofibrosis, 15. Grandjean P. Occupational fluorosis through 50 years: clinical and mastocytosis, lymphoma, osteopetrosis, osteoblastic metastasis, epidemiological experiences. Am J Ind Med 1982; 3: 227-236. and Paget’s disease [25]. In endemic regions of fluorosis, patients 16. Stevens RM. Chronic fluorosis. BMJ 1981; 282: 741-742. with compressive myelopathy secondary to ossification of PLL 17. Teotia SP, Teotia M. Secondary hyperparathyroidism in patients with and/or LF, fluorosis should be considered as a possible etiology. endemic skeletal fluorosis. BMJ 1973; 17: 637-640. MRI may show diffuse low signals on all pulse sequences, and can help in early detection of fluorosis and thus save the patients 18. Xu JC, Wang YZ, Xue DM, Xin SZ, Dai RT, Zhang ZL, et al. X-ray findings and pathological basis of bone fluorosis. Chin Med J (Engl). 1987; 100: from serious manifestations like fluorotic myelopathy which 8-16. require surgical decompression to resolve and fractures [25]. 19. Fisher RL, Medcalf TW, Henderson MC. Endemic fluorosis with spinal Grandjean [15] has suggested that characteristic ligament cord compression. Arch Intern Med 1989; 149: 697-700. calcifications, a history of long-term heavy exposure to fluoride 20. Calenoff L. Osteosclerosis from intentional ingestion of hydro fluoride and high urinary fluoride levels being the most important in the acid. AJR. 1962; 87: 1112-1115. diagnosis of skeletal fluorosis. A history of exposure is essential 21. Singh A, Dass R, Hayreh SS, Jolly SS. Skeletal changes in endemic forCONCLUSION early diagnosis [22]. 22. fluorosis. J Bone Surg. 1962:44: 806-815. Stevenson CA, Watson AR. Fluoride Osteosclerosis. AJR. 1957; 78: 13- Thus to conclude plain radiograph and MRI findings are 18. particularly useful for early and accurate diagnosis of fluorosis, 23. Lian ZC, Wu EH. Osteoporosis: an early radiographic sign of endemic sometimes even in asymptomatic patients. fluorosis. Skeletal Radiol 1986; 15: 350-353. Ann Orthop Rheumatol 4(1): 1069 (2016) 2/3 Gupta et al. (2016) Email:

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24. Singh A, Jolly SS, Bansal BC, Mathur CC. Endemic fluorosis. myelopathy, 20 years after laminectomy: A rare event. Surg Neurol Epidemiological, clinical and biochemical study of chronic fluorine Int. 2011; 2: 11. intoxication in Punjab (India). Medicine (Baltimore) 1963; 42: 229- 28. Reddy DR, Prasad VS, Reddy JJ, Prasad BC. Neuro-radiology of skeletal 246. fluorosis. Ann Acad Med Singapore. 1993; 22: 493-500. 25. Ahmed I, Sohail S, Hussain M, Khan N, Hameed Khan M. MRI features of 29. Wang W, Kong L, Zhao H, Dong R, Li J, Jia Z, et al. Thoracic ossification spinal Fluorosis: Results of an endemic community screening. Pakistan of ligamentum flavum caused by skeletal fluorosis. Eur Spine J. 2007; Journal of Medical Sciences. 2013; 29: 177-180. 16: 1119-1128. 26. Young JWR, Gordon L. text book of radiology and imaging. 7th ed. 30. Muthukumar N. Ossification of the ligamentum flavum as a result of China: Churchill Livingstone; 2003. Metabolic and endocrine disorders fluorosis causing myelopathy: report of two cases. Neurosurgery. affecting bone; 1351–1369. 2005; 56: 622. 27. Kumar P, Gupta A, Sood S, Verma AK. Fluorotic cervical compressive

Cite this article Nair N, Gupta N (2016) Radiology of Skeletal Fluorosis: A Review. Ann Orthop Rheumatol 4(2): 1069.

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