1 Newcastle Musculoskeletal Research Group, Level 4, Cookson Building, University of Newcastle-upon-Tyne, Framlington Place, NE2 4HH, 2 Department of Rheumatology and 3 Pharmacy, The James Cook University Hospital, Marton Road, Middlesbrough TS4 3BW, UK.
Correspondence to: S. Young-Min, Newcastle Musculoskeletal Research Group, Level 4, Cookson Building, University of Newcastle-upon-Tyne, Framlington Place, NE2 4HH, UK. E-mail: Steven.YoungMin{at}ncl.ac.uk
SIR, A 47-yr-old nursery nurse with a history of chronic asthma and bilateral knee osteoarthritis sustained three low-trauma fractures over a period of 3 yr. After investigation, she was diagnosed with osteoporosis and commenced on weekly alendronate 70 mg. A few hours after her first dose, she noticed pain and swelling of her right knee. This settled spontaneously over the subsequent 3 days. After the second dose of alendronate, her knee symptoms recurred. The pain was severe, she was unable to weight bear and she felt generally unwell. She was seen in the hospital admissions unit, where she was found to have a warm, swollen and tender right knee with restricted movement. She was systemically well, and blood tests including full blood count, bone biochemistry, urate, erythrocyte sedimentation rate and C-reactive protein were normal. The right knee joint was aspirated and fluid sent for culture. She was treated empirically for a septic monoarthritis and transferred to the rheumatology ward. Synovial fluid culture revealed no growth. Two days later, her left knee also began to swell. Both knees were then aspirated and a yellow, turbid fluid drawn from each knee. Polarizing light microscopy revealed intracellular, rhomboid-shaped crystals with weak positive birefringence; findings typical of calcium pyrophosphate dihydrate (CPPD) crystals. Radiographs of the right knee also revealed chondrocalcinosis. Each knee was injected with intra-articular steroid (Adcortyl) and both settled rapidly. Daily alendronate 10 mg was then commenced, as we hoped that this lower-dose preparation would be less likely to trigger pseudogout, but the patient discontinued the treatment after 2 days because of nausea. During the following 6 months, the patient has avoided bisphosphonates and has had no further attacks of pseudogout. We have attempted to treat her osteoporosis with raloxifene, but she had to stop this after developing a rash. She currently remains on calcium and vitamin D supplements and is awaiting funding approval for a trial of parathormone receptor agonist therapy.
The formation and deposition of inorganic pyrophosphate as CPPD crystals is not fully understood [1]. All bisphosphonates are structurally similar to pyrophosphate, and in vitro evidence suggests some effect of bisphosphonates on inorganic pyrophosphate metabolism [2]. However, the precise mechanisms by which bisphosphonates might lead to the deposition of CPPD crystals within synovial fluid is not known and remains speculative.
Two cases of bisphosphonate-induced pseudogout are reported in the literature, in association with cyclical oral etidronate [3] and intravenous pamidronate [4]. This is the first report of acute pseudogout following alendronate therapy, despite its widespread use as a daily preparation. In this case the more novel weekly preparation was used, and it may be that acute pseudogout is more likely to occur with the higher-dose weekly bisphosphonates. As weekly formulations become more popular, it will be of interest to see if further cases of acute pseudogout are reported.
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The authors have declared no conflict of interest.
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