Clonal karyotype abnormalities in 124 patients with myelodysplastic syndrome are reviewed. 36% of patients had abnormalities at referral, the most common being 5q-, +8 and lesions of chromosomes 7 and 20. Reduced survival was associated with the presence of either single or multiple clonal abnormalities at referral, abnormalities of chromosome 7 or 8 (either alone or with other lesions) and exclusively abnormal metaphases. The presence of 5q- alone did not appear to affect survival. Sequential studies were carried out in 77 patients of whom 12 showed karyotypic evolution. Reduced survival was observed in patients with an evolving karyotype but appeared to be due almost entirely to evolution in those patients whose initial karyotype was normal. Leukaemic transformation occurred more commonly in patients with an abnormal karyotype, particularly those with multiple abnormalities, and in patients with an evolving karyotype. Although the first appearance of an abnormal karyotype or an apparent evolution are important phenomena, it is probable that in some cases they merely represent expansion of a previously existing clone that has escaped detection. The distinction between true karyotypic evolution or clonal expansion and statistical variations due to small sample size and variability of samples may be difficult but needs to be taken into account in considering clinical significance.

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A computer model of trabecular bone turnover has been developed, based on concepts of Jonathan Reeve [1]. This model predicts changes in bone volume by summing bone resorption and formation over a large number of remodeling sites. Clinical data [histomorphometry and bone mineral content (BMC)] from two clinical studies using an antiresorptive drug (etidronate disodium, EHDP) in postmenopausal osteoporosis were used to test the model. The results for BMC obtained from the EHDP and placebo groups in each study at 60 and 120 weeks were correctly predicted by the model from the histomorphometric data obtained from baseline and week 60 biopsies. The parameter in this model having the greatest influence on predicted changes in bone volume was found by sensitivity analysis to be activation frequency. These results suggest that the contribution of bone turnover to BMC can be predicted solely by considering the cell kinetics of the basic multicellular unit (BMU), and that, in the case of antiresorptive drugs, maximal effects on bone volume may be achieved by pharmacological reduction of activation frequency. The results also suggest that the present model may be useful in predicting in clinical studies the effects of EHDP and similar drugs on bone turnover.

We describe a patient with growth failure and multiple congenital anomalies characteristic of Fanconi anaemia, but without the classical feature of progressive bone marrow hypoplasia. Following treatment with growth hormone for a period of 8 years, he presented with myelodysplastic syndrome and a karyotypically abnormal clone in the bone marrow (47,XY,+8). The diagnosis of Fanconi anaemia was supported by the induction of abnormally high levels of characteristic chromosome aberrations in peripheral lymphocytes following exposure in vitro to the bifunctional alkylating agent mitomycin C. Immune function studies also identified a selective IgA deficiency. The relative importance of interacting constitutional and exogenous factors involved in the development of preleukaemia in this patient is discussed.