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Parenteral pamidronate is licensed in the United Kingdom for the management of Paget's disease, tumour related hypercalcaemia, and metastatic bone pain, where it can rapidly relieve symptoms.1 It is also widely used for the prevention and treatment of osteoporosis, although this represents unlicensed use of the drug, and there is some evidence that it can be rapidly effective for pain relief in patients with osteoporotic vertebral fractures.2,3 It has been used with some effect for the management of ankylosing spondylitis,4 but the full extent of any analgesic properties of the drug has not been fully explored. These properties became apparent to us quite by chance in the three cases described here.
A 25 year old female nurse with known ankylosing spondylitis was admitted to hospital with worsening back and right buttock pain uncontrolled by regular opiate analgesia and a variety of potent non-steroidal anti-inflammatory drugs. Parenteral methylprednisolone was prescribed, followed by pamidronate 30 mg for “bone protection”. In the event, pamidronate was given but not methylprednisolone, deferred owing to unexplained pyrexia. Shortly after receiving her pamidronate, her intractable pain was so greatly improved that methylprednisolone was declined and she was discharged three days later. The improvement seen has been sustained for over six months. The unexpected analgesic effect of pamidronate in this case led to its use in two subsequent cases.
A 38 year old housewife with chronic low back pain was admitted with a short history of acute back pain and a modestly raised C reactive protein (14 mg/l). Isotope bone scan showed increased uptake in the fifth lumbar intervertebral disc. Magnetic resonance imaging identified abnormal signal from this disc suggestive of discitis. An infective cause was felt to be unlikely: antibiotics were not prescribed, but in view of her persistent symptoms, pamidronate 30 mg was given by intravenous infusion, with sufficient sustained improvement in her acute back pain to allow discharge two days later.
A 33 year old male factory worker with a history of juvenile chronic arthritis since early childhood and spondyloarthropathy was admitted with generalised bone pain despite weekly oral methotrexate, phenylbutazone, and oral analgesia. Intercurrent diarrhoea was investigated but remained unexplained. Parenteral pamidronate 30 mg was given, leading to sustained improvement in his rheumatic pains.
We believe these cases represent the first time that sustained analgesic efficacy has been attributed to a single dose of parenteral pamidronate in acute rheumatic pain not related to osteoporosis or neoplasia. The mechanism whereby pamidronate provides rapid onset sustained pain relief for metastatic bone disease or osteoporotic fractures is unknown. Many of the known effects of bisphosponates on bone structure and cell populations are unlikely to be rapidly analgesic.5 However, it has been suggested that bones have complex sensory innervation, with nociception mediated by neuropeptides including substance P, prostaglandin E2, and calcitonin gene related peptide which may be influenced by bisphosphonates.6 There is no reason to believe that such an analgesic effect would be confined to bone affected by osteoporosis or neoplasm and might well extend to bone pain due to inflammation. In the three cases described many other factors might have led to the apparent response to parenteral pamidronate, including chance. However, the results suggest that the potential role of pamidronate in the control of acute rheumatic pain warrants further evaluation.
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