Pamidronate treatment has been shown to improve outcome in osteogenesis imperfecta (OI); however, factors influencing outcome are unclear. The present study was conducted to evaluate the response to pamidronate therapy with special emphasis on factors influencing outcome. Twenty children with OI treated with pamidronate were evaluated in a prospective, open clinical trial. Pamidronate (9 mg x kg(-1) x yr) was administered intravenously at the age of 4.5 +/- 4.2 years for 2.9 +/- 0.7 years (range, 2-3.8 years). Treatment led to increase in bone mineral density (BMD) Z score by 0.7 +/- 0.3 every year resulting in significant improvement in BMD Z score (from -4.6 +/- 1.1 to -2.5 +/- 1.1, P<0.001). BMD Z score was within the reference range (>-2) in 9 subjects (45%) at the last follow-up as against none at initiation of treatment (P<0.001). Fracture rate decreased significantly during treatment (3.3 +/- 1.4 to 0.8 +/- 0.9, P<0.001) with 8 subjects (40%) having no fracture during the treatment period. Significantly greater proportion (88.2%) of children were able to walk at last follow-up compared with those at initiation of treatment (45.4%). Increase in BMD Z score and final BMD Z score was not influenced by age at initiation of treatment, duration of treatment, or initial BMD Z score. Treatment before infancy (n=7) was associated with higher final subjective score (6.3 +/- 0.5 vs 4.9 +/- 1.5, P=0.03). Our study reiterates the efficacy of pamidronate in OI. The poorer response of our subjects may be related to compromised calcium and vitamin D status.