Treatment of fibrous dysplasia of bone with intravenous pamidronate: long-term effectiveness and evaluation of predictors of response to treatment

Fibrous dysplasia (FD) of bone is a rare but potentially severe bone disease that often entails fractures, deformities, and bone pain. An activating mutation of the α subunit of Gs proteins leads to differentiation abnormalities of the osteoblastic lineage, which are responsible for development of fibrous tissue in the medulla and increased osteoclastic activity. This increased bone resorption has been the rationale to use bisphosphonates in our center since 1988. So, we have analyzed the largest series, so far, of patients treated with the bisphosphonate pamidronate and sought predictors of response to treatment. We have treated 58 patients (41 adults and 17 under 18 years of age) with FD in an open study, using intravenous (IV) pamidronate 180 mg every 6 months and calcium and vitamin D supplements, in combination with oral phosphate and calcitriol in patients with FD who also had renal phosphate wasting. Patients were followed up with biannual visits, for an average 50 months, with pain assessment, annual radiographs of affected bones, measurement of biochemical markers of bone turnover, and annual bone mineral density measurements in the case of affected hips. We found that pain intensity significantly decreased with treatment in the 44 patients who had bone pain at baseline, biochemical markers of bone turnover were significantly reduced, and about 50% of patients had improvement of bone lesions on radiographs, evidenced by filling of osteolytic lesions and/or cortex thickening. Bone mineral density was substantially increased in the 12 patients who had hip FD. There was no significant clinical or biological predictor of positive radiographic response to pamidronate treatment. Long-term treatment with pamidronate was safe, in particular among the 12 patients who were followed up for more than 8 years. Despite the lack of a control group, our results suggest that intravenous pamidronate improves radiological aspect in half of the patients with FD, decreases bone turnover, and may decrease pain intensity.