Mid-Staffordshire General Hospitals, Cannock Chase Hospital, WS11 2XY, UK
SIR, Osteoporotic vertebral fractures are common with increasing age. Although often asymptomatic, they are a cause of disabling back pain that may continue for several weeks. Current treatment available in the acute phase is limited to analgesia and immobilization. Preliminary experience with the use of intravenous pamidronate for pain relief in vertebral fractures secondary to osteoporosis in five patients is reported here.
Five consecutive patients admitted with radiologically confirmed vertebral fractures were treated with intravenous pamidronate at a dose of 15 mg in 250 ml normal saline infused over 30 min daily for 3 days (except cases 4 and 5 who received a first dose of 30 mg).
All patients were female and their ages ranged from 59 to 88 yr. Osteoporosis was documented by bone densitometry and other causes of vertebral fracture were excluded. The severity of fracture on radiography varied from anterior wedge fracture to severe collapse with complete loss of vertebral height. The sites of fracture were limited to thoracic and upper lumbar (T4 to L2) vertebrae. All patients were rendered immobile by pain and had failed to obtain relief from a combination of analgesics including opiates, supplemented in two patients by transcutaneous nerve stimulation. A visual analogue pain scale was completed during the course of their treatment.
Our first patient reported a 15% reduction in pain on day 1 and 45% following the third dose. By day 5 she was able to get out of bed unaided and mobilize slowly with a Zimmer frame. Over the following week her analgesics were gradually reduced with no relapse in pain. Case 2 reported a 50% reduction in pain and on day 6 she was mobilizing independently with the aid of a frame. Opiates were discontinued and she was discharged a week later. Case 3 reported a considerable reduction in pain. With the aid of a rollator frame she started mobilizing on day 5. Prior to discharge analgesics were discontinued and on follow-up mobility had greatly improved with no recurrence of pain. Case 4 was able to get out of bed unaided on day 6 and was mobilizing independently with the aid of a stick. The severity of pain had dropped from 75% at baseline to 55% on movement with no further pain at rest. Analgesics were gradually reduced and she was discharged on diclofenac. Case 5 was pain free at rest and able to dress and wash herself on day 5. Back pain on walking had dropped by 40%. She was discharged on pro re nata diclofenac.
No serious side-effects were seen and significant hypocalcaemia did not occur. Only one patient (case 5) reacted adversely but this did not require discontinuation of pamidronate. Following the first dose she became lethargic, with mild pyrexia (temperature 37.8°C) and developed thrombophlebitis at the infusion site. Symptoms were transient and resolved within 72 h.
The use of biphosphonates in the treatment of osteoporosis is well established [1, 2]. As a group they are potent inhibitors of bone resorption. Among the biphosphonates, pamidronate has also been shown to be effective in reducing skeletal events in multiple myeloma and metastatic cancer [3, 4]. In patients with multiple myeloma pamidronate also significantly reduces bone pain and requirement for analgesia.
In osteoporosis, although the acute back pain from vertebral fracture is self-limiting, it usually persists for several weeks before patients are fully ambulatory. Treatment consists of analgesics and immobilization in the acute stage. Our series of case studies demonstrates the efficacy of intravenous pamidronate in reducing pain of acute vertebral fractures allowing early mobilization and restoration of locomotor function. This is particularly important in older patients where vertebral fractures are most common.
To our knowledge, this is the first report showing the efficacy of intravenous pamidronate in the management of the acute pain of osteoporotic vertebral fractures. The mechanism of action of pamidronate in providing rapid pain relief in this setting is unknown. The speed of onset demonstrated would suggest that a mechanism(s) other than its effect on bone resorption operates. It has been shown that vertebrae have a complex sensory innervation by fibres containing neuropeptides. Of these neuropeptides, substance P and calcitonin gene-related peptide (CGRP) are thought to mediate nociception [5]. CGRP has also been shown to inhibit bone resorption [6]. Whether pamidronate acts via inhibiting these neuropeptides to relieve pain remains speculative at present.
The potential role for intravenous pamidronate in the control of acute pain of osteoporotic vertebral fractures warrants further investigation and a placebo-controlled trial is now needed to confirm its benefit.
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