Skeletal fluorosis is a chronic metabolic bone disease caused by the ingestion of large amounts of fluoride through either water or food in geographic areas where high levels of fluoride occur naturally.
Voriconazole is a trifluorinated azole drug that has been purported to cause a diffuse asymmetric periostitis secondary to elevated fluoride levels. Fluoride forms fluorapatite, which stimulates osteoblastic activity and periostitis 7.
Described features include:
- increased bone density: osteosclerosis
- osteopenia or osteoporosis 4,6
- trabecular blurring or haziness
- compact bone thickening
- periosteal bone formation
- ossification of the attachments of tendons, ligaments, and muscles
- interosseous membrane calcification 1
- ossification of the posterior longitudinal ligament 2
Involvement of the axial skeleton is characteristic, and changes are most marked in the spine, pelvis, and ribs.
In early fluorosis, the first changes are bone deposition and thickening at the junctions of trabeculae. This is seen as a sand-like, granular, or particle-like bone structure on radiographs.
In more advanced fluorosis, the trabeculae are more generally thickened because of new bone formation on the trabecular surface. At this stage, radiographs show thickening and condensation of trabeculae, with coarse reticulum or woven bone striations.
If the trabeculae are fused, focal round densities are seen in the medullary bone.
Osteopenia (less common) also may occur in fluorosis, especially in younger patients at an earlier stage 6.
Calcification of the sacrotuberous ligament is considered a characteristic feature.
For diffuse skeletal sclerosis on imaging, consider:
- 1. Mithal A, Trivedi N, Gupta SK et-al. Radiological spectrum of endemic fluorosis: relationship with calcium intake. Skeletal Radiol. 1993;22 (4): 257-61. Pubmed citation
- 2. Boillat MA, Garcia J, Velebit L. Radiological criteria of industrial fluorosis. Skeletal Radiol. 1981;5 (3): 161-5. Pubmed citation
- 3. Kumar H, Boban M, Tiwari M. Skeletal fluorosis causing high cervical myelopathy. J Clin Neurosci. 2009;16 (6): 828-30. doi:10.1016/j.jocn.2008.08.028 - Pubmed citation
- 4. Wang Y, Yin Y, Gilula LA et-al. Endemic fluorosis of the skeleton: radiographic features in 127 patients. AJR Am J Roentgenol. 1994;162 (1): 93-8. AJR Am J Roentgenol (abstract) - Pubmed citation
- 5. Christie DP. The spectrum of radiographic bone changes in children with fluorosis. Radiology. 1980;136 (1): 85-90. Radiology (abstract) - Pubmed citation
- 6. Lian ZC, Wu EH. Osteoporosis-an early radiographic sign of endemic fluorosis. Skeletal Radiol. 1986;15 (5): 350-3. Pubmed citation
- 7. Tan I et.al. Spectrum of Voriconazole-Induced Periostitis With Review of the Differential Diagnosis. (2019) AJR. American journal of roentgenology. doi:10.2214/AJR.18.19991 - Pubmed
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