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We studied bone biopsies from 26 patients with myelomatosis with apparently normal skeletal metabolism. Quantitative histomorphometric measurements suggested that skeletal disease was progressive despite normocalcaemia and normal urinary excretion rates of calcium and hydroxyproline. When biopsies were divided according to the involvement of marrow by plasma cells, bone resorption — as judged by the eroded surface — increased significantly the greater plasma cell burden. Osteoclasts were frequent with moderate tumour burdens, but there was no further increase in the number of osteoclasts when plasma cell infiltration increased by more than 50% of bone marrow. Contrary to expectation, the numbers of osteoblasts and bone formation rates were increased with bone biopsies with moderate tumour burden, but were markedly lower when plasma cell infiltration occupied more than 50% of bone marrow, due to a decreased functional capacity of osteoblasts. We conclude that skeletal bone disease in myeloma is commonly progressive despite apparently stable bone disease as judged by biochemical measurements. The major mechanism of bone loss in myelomatosis is increased osteoclastic resorption but decreased bone formation contributes to bone loss with heavy plasma cell burdens. Urinary excretion of calcium and hydroxyproline provide insensitive indices of bone resorption in myelomatosis.

Summary Fifty-seven patients with advanced prostate cancer resistant to first-line hormonal therapy were treated with estramustine and additionally randomized for treatment with clodronate or placebo. Clodronate treatment was started with 5 days intravenous administration (300 mg day-') and followed by oral treatment (1.6 g day-1) for 12 months. Skeletal pain relief was only about 10% better in the clodronate than in the placebo group. The results do not support the superiority of combined intravenous and oral treatment with clodronate compared with oral administration only.

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Metacarpal morphometry represents a potentially cheap and widely available non-invasive assessment of skeletal status. In two cross-sectional studies, we compared the performance characteristics of a semiautomated technique (the Teijin Bonalyzer) with an in-house manual measurement, and with measures of skeletal strength at other sites. The metacarpal cortical index (mCI) was measured on hand radiographs of 178 osteoporotic women using both the Teijin Bonalyzer and a digitizing tablet. Measurements on the latter were consistently lower than with the Bonalyzer except for mCI (0.443+/-0.080 vs 0.364+/-0.060, p<0.001), although correlation coefficients between these two methods were highly significant (r = 0.62-0.83, p<0.001). The reproducibility errors of metacarpal bone mineral density (mBMD) were constant (1.1-1.2%) whilst those for mCI showed a marked operator-dependency (2.0-7.9%). In 379 elderly community-dwelling women, Bonalyzer mCI and mBMD showed a significant decline with age (r = -0.30 and -0.27 respectively, p<0.05). Both mCI and mBMD correlated significantly with forearm BMD (r = 0.50 and 0.57 respectively, p<0.001) and hip BMD (r = 0.48 and 0.53 respectively, p<0.001). After adjustment for age and weight, hip BMD demonstrated the best discrimination for prevalent vertebral fractures as judged by the gradient of risk for a 1 SD decrease in measurement (odds ratio (OR) 2.17, 95% CI 1.56-3.01). Similar but smaller gradients of risk were shown by Bonalyzer mCI (OR 1.32, 95% CI 1.00-1.75), mBMD (OR 1.35, 95% CI 1.02-1.78) and forearm BMD (OR 1.39, 95% CI 1.08-1.80). MCI, and in particular mBMD, may be useful assessments of bone mass and fracture risk. In our study, it is comparable to peripheral assessment of skeletal status by forearm densitometry.