Skeletal fluorosis secondary to methoxyflurane use for chronic pain

Abstract

Skeletal fluorosis is rare and occurs secondary to chronic high amounts of fluoride consumption, manifesting as diffuse osteosclerosis, skeletal pain, connective tissue calcification, and increased fracture risk. Methoxyflurane is a volatile fluorinated hydrocarbon inhaled analgesic, and the maximum recommended dose is 15 mL (99.9 % w/w) per week. A rodent study found increased skeletal fluoride after methoxyflurane exposure. However, skeletal fluorosis secondary to methoxyflurane use in humans has rarely been reported. We present the case of a 47-year-old female with diffuse osteosclerosis secondary to fluorosis from methoxyflurane use for chronic pain presenting with three years of generalized bony pain and multiple fragility fractures. Lumbar spine bone mineral density was elevated. CT and radiographs demonstrated new-onset marked diffuse osteosclerosis, with calcification of interosseous membranes and ligaments and a bone scan demonstrated grossly increased uptake throughout the skeleton. Biochemistry revealed an elevated alkaline phosphatase and bone turnover markers, mild secondary hyperparathyroidism with vitamin D deficiency and mild renal impairment. Zoledronic acid, prescribed for presumed Paget’s disease, severely exacerbated bony pain. Urinary fluoride was elevated (7.3 mg/L; reference range <3.0 mg/L) and the patient revealed using methoxyflurane 9 mL per week for eight years for chronic pain. A decalcified bone biopsy revealed haphazardly arranged cement lines and osteocytes lacunae and canaliculi, consistent with an osteosclerotic process. Focal subtle basophilic stippling around osteocyte lacunae was suggestive of fluorosis. Although fluorosis is not a histological diagnosis, the presence of compatible histology features was supportive of the diagnosis in this case with clinical-radiological-pathological correlation. Skeletal fluorosis should be considered as a cause of acquired diffuse osteosclerosis. Methoxyflurane should not be recommended for chronic pain. The risk of repeated low-dose exposure to fluoride from methoxyflurane use as analgesia may be greater than expected, and the maximum recommended dose for methoxyflurane may require re-evaluation to minimize skeletal complications.