Objective-To examine the relationship between disease severity and bone density as weli as vertebral fracture risk in patients with ankylosing spondylitis (AS). Methods-Measurements were taken for bone mineral density (BMD) and vertebral fracture rates in 87 patients with AS.

Summary Thirty patients with hypercalcaemia due to malignancy that persisted following rehydration, were treated with a single dose of the bisphosphonate, clodronate. Clodronate (1.5 g) was administered intravenously in 500 ml normal saline over 4 h. Serum and urine biochemistry were measured before and after treatment and the results were compared with data from 15 patients given the recommended regimen 300 mg intravenous clodronate daily for 5 consecutive days.The single infusion induced a rapid and significant fall in serum calcium, apparent at day 3 (P<0.0001) that persisted to the end of follow-up at day 10 (P<0.001). Eighty per cent (24/30) of patients became normocalcaemic. The response was associated with a significant decrease in fasting urinary calcium excretion, and no change in renal function, as judged by serum creatinine. The same dose of clodronate, given as 5 daily infusions, induced a comparable decrease in serum calcium, but was less rapid in onset so that at day 3 the serum calcium was significantly lower with the single infusion (P = 0.02). The calcium lowering effect of both regimens depended on the tumour type.We conclude that the single infusion of 1500 mg clodronate is as effective in reducing serum calcium as the same dose given over 5 days. The single infusion has a more rapid onset of effect, is more convenient than multiple infusions, and has no adverse effect on renal function.

Summary Twenty patients with hypercalcaemia due to malignancy, which persisted following rehydration, were treated with the bisphosphonate, aminohexane bisphosphonate (AHBP), which is structurally similar to pamidronate. The treatment given was a single infusion of 125 mg of AHBP in 500 ml of normal saline infused over 4 h. Serum and urine biochemistry were measured before and after treatment. Acute toxicity was evaluated with particular attention to gastrointestinal symptoms, acute-phase reaction and change in renal function, as judged by serum creatinine. The infusion of AHBP induced a rapid fall apparent by day 3 (P<0.001), with a nadir at day 7. The serum calcium remained lower at days 14 and 28 than at day 0, but the numbers followed up were low (n = 5 and n = 4). In all 20 patients there was a fall in serum calcium after treatment, and in 13 (65%) normocalcaemia was achieved. Failure to respond completely to AHBP appeared to be associated with a renal mechanism of hypercalcaemia. Treatment was associated with a significant decrease in fasting urinary calcium excretion (P<0.05). There was no change in white cell count or renal function following AHBP and only two cases of mild pyrexia after infusion. We conclude that aminohexane bisphosphonate is an effective agent in the treatment of tumour-induced hypercalcaemia, with rapid onset of effect and low toxicity.Hypercalcaemia is a common complication of malignancy, occurring both in patients with solid tumours, particularly carcinoma of the breast and bronchus, and in patients with haematological malignancy. The pathophysiology of the condition varies according to the primary tumour and the presence or absence of focal bone metastases, but in the majority of cases the predominant mechanism is one of increased bone resorption (Bonjour & Rizzoli, 1989). Treatment strategies have therefore focused on the inhibition of bone resorption, and over the past decade the bisphosphonates, specific and potent inhibitors of osteoclastmediated bone resorption, have become the treatment of choice (Coleman & Rubens, 1987;Kanis et al., 1991).The bisphosphonates have in common the central P-C-P structure, but modifications of the side chains alter their biological characteristics, particularly their potency. There are currently three bisphosphonates available for the treatment of tumour-induced hypercalcaemia: 1-hydroxyethylidene-1,1-bisphosphonic acid (HEBP or etidronate), dichloromethylenebisphosphonic acid (Cl2MBP or clodronate) and 3-amino-ihydroxypropylidene-l ,1-bisphosphonic acid (AHPrBP or pamidronate). Pamidronate is the most potent, and research on other experimental compounds suggests that the amino derivatives are particularly active (Shinoda et al., 1983;Rizzoli et al., 1992).However, clinical studies have shown that pamidronate may be associated with a transient acute-phase response which can be manifested as pyrexia or leucopenia Morton et al., 1989). In addition, there are reports of muscle rigors, general malaise, thrombophlebitis and hypocalcaemia, and with the...

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Two methods for diagnosing radiological osteopenia in thoracic (TS) and lumbar (LS) spine radiographs were assessed: a subjective conventional method (A) and a semiquantitative method (B), by comparing them with bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DEXA), in a population of "normal" women aged 45-70 years (n = 818). For both methods there was good intraobserver and interobserver reproducibility. BMDs were significantly lower with increasing radiological osteopenia grades (p < 0.001), and remained lower after adjustment for age and body mass index (p < 0.01). The proportion of subjects with DEXA-defined osteoporosis rose with increasing radiological osteopenia grades for both methods. The worst osteopenia categories identified 29.7-55.3% of women with DEXA-defined osteoporosis, compared with 6.1-11.7% in the "normal" categories. Both methods, however, showed a large degree of overlap of BMDs between the various radiological osteopenia grades. The sensitivity and specificity of method A in diagnosing osteoporosis were 45.3% and 78.4%, respectively, for the TS and 19.0% and 94.3%, respectively, for the LS. For method B the sensitivities and specificities were 8.8% and 96.1%, respectively (TS), and 10.2% and 95.6%, respectively (LS). Although both methods have poor sensitivities, "definite" or "high" grade osteopenia should be an indication for bone densitometry. The high specificities suggest that a "normal" (no osteopenia) X-ray is unlikely to have a significantly low BMD.