In patients with multiple myeloma, despite a major reduction of bone pain achieved with chemotherapy, skeletal disease continues to progress. The effects of clodronate, an inhibitor of osteoclastic bone resorption, are evaluated on the natural history of skeletal disease in patients with newly diagnosed multiple myeloma. Within the framework of the VIth MRC Multiple Myeloma Trial, 536 patients (218 women, 318 men) with recently diagnosed multiple myeloma were randomized to receive either clodronate 1600 mg daily (n=264) or an outwardly identical placebo (n=272) in addition to chemotherapy. Treatment with clodronate was associated with a 50% decrease in the proportion of patients with severe hypercalcaemia (5.1% v 10.1%, P=0.06) and a similar reduction in reported non-vertebral fractures (6.8% v 13.2%, P=0.04). Fewer patients receiving clodronate sustained vertebral fractures after entry to the trial (38% v 55%, P=0.01) and patients also lost less height over 3 years compared to those receiving placebo (2.0 v 3.4 cm, P=0.01). Biochemical indices of bone turnover were significantly lower in patients receiving concomitant clodronate, both at plateau and at disease relapse. The frequencies of back pain and poor performance status were significantly lower at 24 months in clodronate than in placebo-treated patients (10.9% v 19.9%, P=0.05, and 18.3% v 30.5% P=0.03 respectively.) There was no statistically significant difference in survival between the clodronate and placebo treated patients. The study indicates that long-term oral clodronate slows the progression of skeletal disease in multiple myeloma and decreases the associated morbidity. Patients without overt skeletal disease at diagnosis were also found to benefit from clodronate, indicating that this treatment should be initiated as early in the course of the disease as possible.

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Report of the Royal Commission on Price Spreads, reviewed by H. A. Innis J. Wesley Bready, Lord Shaftestbury and Social-indsutrial Progress, reviewed by H. A. Innis W. L. Mackenzie King, Industry and Humanity: A Study in the Principles underlying Industrial Reconstruction, reviewed by H. A. Innis Wm. Aberhart, Social Credit Manual: Social Credit as applied to the Province of Alberta, reviewed by H. A. Innis Research Committee of the League for Social Reconstruction, Social Planning for Canada, reviewed by H. A. Innis J. M. Gibbon, Steel of Empire: The Romantic History of the Canadian Pacific, reviewed by H. A. Innis F. H. Anderson, The Argument of Plato, reviewed by R. D. MacLennan G. M. A. Grube, Plato's Thought, reviewed by R. D. MacLennan Jonathan Swift, The Drapier's Letters of the People of Ireland against receiving Wood's Halfpence, reviewed by Louis A. Landa David Nichol Smith, ed., The Letters of Jonathan Swift to Charles Ford, reviewed by Louis A. Landa Theophile James Meek, Old Akkadian, Sumerian, and Cappadocian Texts from Nuzi, reviewed by Leroy Waterman

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