Relation between signs and symptoms in Paget's disease of bone

The relation between signs and symptoms of Paget's disease of bone was studied in 180 patients consecutively submitted for treatment. In these patients 826 lesions were identified by scintigraphy. The intensity of scintigraphic uptake was correlated with long-term calcium uptake in bone. The frequency distribution of lesions over the patients was compatible with a 65 per cent chance of local disease once the patient had been exposed to an extraneous agent. The spatial distribution within a skeleton was related to the local density of the osteoclast population. The particular frequency distribution resulted in a log-normal distribution diagram for anatomical spread. Within lesions, increases in numbers of osteoclasts and osteoblasts were proportional and these too had a log-normal distribution. Increases of alkaline phosphatase levels and hydroxyproline excretion were closely related and reflected anatomical spread on the one hand and local activity on the other. They were also closely correlated with overall calcium fluxes. It was shown that alkaline phosphatase is the more sensitive and hydroxyproline the more accurate of the biochemical signs. Maximum values, corresponding to total skeletal disease, were approximately 25 times the upper limit of normal. Equilibrium between bone formation and resorption was not always maintained. There were, indeed, wide variations of urinary calcium, which were significantly related to the difference between bone formation and resorption, but the extracellular calcium homeostasis was generally maintained. This may explain the frequent occurrence of normocalcaemic and hypercalcaemic hyperparathyroidism. The hypercalciuria constitutes an additional risk for urolithiasis in men. The most frequent complaint was pain (86 per cent). Extent of lesions was important, but a major decisive factor was the specific nature of the bone affected. The findings allowed assessment of the relative importance of the various signs, symptoms and locations as criteria of disease severity and as indications for treatment.