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In a controlled trial the effects of the osteoclast inhibitor disodium pamidronate were studied over a 6-month period in men with metastatic bone disease from prostate cancer. Using serial biochemical measurement of metabolic bone activity, and complementary subjective and quantitative bone histology, the effects of pamidronate were evaluated in tumour-free and metastatic regions of the skeleton, enabling analysis of the differential mechanisms of bone destruction in this disease. Following treatment, abnormally high markers of bone breakdown fell significantly (fasting urine hydroxyproline/creatinine (OHP): P less than 0.05; fasting urine calcium excretion (CaE): P less than 0.0001), confirming that activated osteoclasts play an integral role in the osteolytic process. Serial histomorphometry of bone from tumour-free areas showed that pamidronate restored abnormal levels of bone erosion to normal in 93% of cases. Suppression of bone destruction was also evident within metastases, although this was incomplete. The results confirm that osteoclast overactivity is responsible for a significant proportion of the accelerated osteolysis seen in both tumour-free and infiltrated bone in patients with prostate cancer. The differential effects in tumour-free and infiltrated bone suggest that the mechanisms of osteoclast activation may differ in metastatic and non-metastatic regions of the skeleton.

A series of 78 patients with metastatic bone disease from prostate cancer underwent iliac crest biopsy, enabling histomorphometric quantification of eroded bone surface and bone volume in both tumour-free and metastatic bone tissue. Eroded surfaces in tumour-free specimens were high in patients with active compared to stable disease but bone volume was maintained in both groups, whilst in bone surrounding micrometastases (n = 8) eroded surfaces were further increased and bone volume reduced. Eroded surfaces within metastases were greater still but were associated with increased bone volume due to replacement of the existing trabecular tissue with abnormal woven bone, giving an overall appearance of sclerosis. These results show that the effect of prostate cancer on bone tissue is complex, involving differential disturbance of bone formation and resorption within metastases, in bone surrounding tumour invasion and in the tumour-free skeleton.

five cases of malakoplakia of the urinary tract are described. It is much more common in middle-aged females (peak incidence in the fifth decade compared with the seventh decade for males) but remains an uncommon condition, although clinically there is a strong association with recurrent urinary tract infection. It causes obstructive stenotic lesions of the ureters or pelviureteric junction, which pose the serious threat. Many cases are associated with non-malakoplakic diseases of other systems which often determine the prognosis. The most commonly used method of treatment was long-term antibiotic therapy; this seemed effective, although controlled trials have not been performed.