Ten patients with severe Paget's disease of bone and serum alkaline phosphatase (sAP) greater than 900 IU/l were treated for six months with the oral diphosphonate APD, (3-amino-1-hydroxypropylidene-1, 1-bisphosphonate). By the end of the treatment period there was a reduction in the log mean urine hydroxyproline (uHP) and the log mean sAP of 92% and 87% respectively. In four patients both sAP and uHP fell to within the normal range and remained normal for at least six months after therapy was stopped. Bone scintigraphy showed a fall in 99mTc-MDP uptake in sites of active Paget's disease in all patients and histomorphometry showed no increase in osteoid. Repair of radiological osteolytic lesions was observed in 6/6 patients and progression of tibial osteolytic wedges was arrested in 5/5 patients and reversed in four. This improvement persisted six months after completion of therapy but further wedge progression occurred in one patient whose urine HP remained elevated. There were no serious effects though five patients complained of nausea. The clinical and biochemical responses to APD were equivalent to those observed in the same patients during a previous six month course of combined therapy with human calcitonin (CT) + EHDP except that there was additional biochemical and radiological evidence of bone healing. This study confirms PAD as an effective treatment of severe Paget's disease of bone.

The effects of therapy on the osteolytic bone lesions of Paget's disease have been assessed from serial bone radiographs. Changes in the rate of progression of lytic "wedge" lesions were measured and alterations in the texture of lytic "blade" lesions were graded on an empirical scale. Useful matching was possible using standard radiographs, although special care was needed to avoid artefacts from suboptimal positioning, magnification and variation in exposure. Serial radiographs were obtained of 57 lytic blade lesions in 54 patients receiving treatment with the bisphosphonate 1-hydroxyethylidene-1, 1-bisphosphonate (EHDP) and of 20 lesions in 20 patients treated with oral or intravenous 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (APD). Treatment with EHDP was associated with a significant deterioration in bone texture in 50% of lytic blade lesions, and with healing in only 20%. Deterioration was accompanied by an increase in local bone pain in 17% of these patients. In contrast, significant healing was observed in 17 of 20 lytic lesions (eight wedge, nine blade) within 6 months of beginning a course of intravenous or oral APD. In four of eight patients the progression of a lytic tibial wedge was arrested and in the remaining four the direction of wedge movement was reversed. In two patients the wedge had almost completely "filled in", making measurement difficult. Bone healing was usually accompanied by pain relief, reduction in skin temperature and rapid suppression of the urine hydroxyproline (uHP) into the normal range. However, in four patients who received intravenous APD, repair of lytic bone lesions was observed despite persisting elevation of uHP. These improvements with APD were sustained at 12 months, although in one patient whose biochemical indices were restored to normal the resorption front showed further progression, despite initial temporary reversal. The trends apparent in these short-term studies were also seen in four patients in whom wedge velocities were measured over periods of 6-10 years. These results confirm that after treatment of Paget's disease, bone healing or deterioration can be accurately assessed from serial standard radiographs. Reproducible matching is best achieved by ensuring that all radiographs are taken by the same radiographer. Minor alterations in radiological bone texture provide an important index of drug effect which is not always apparent from measurement of biochemical and other indices.

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