Intravenous Pamidronate Therapy in Osteogenesis Imperfecta

Abstract

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.

Abnormalities in Tooth Formation after Early Bisphosphonate Treatment in Children with Osteogenesis Imperfecta

“…A substantial body of work has demonstrated the efficacy of these agents in preventing bone fractures, decreasing pain, and increasing the quality of life [ 11 ]. Intravenous, i.v., pamidronate, neridronate, or zoledronate is the treatment of choice for pediatric patients with moderate-to-severe OI, whereas BP treatment for patients with mild forms of OI is still discussed [ 12 – 14 ]. In most previous studies, the average age of children with OI at onset of BP therapy is around 4 years, although there are reports of children who started treatment as early as 2 weeks of age [ 15 ].…”

Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial

“…Bisphosphonates are widely used to increase BMD in children with OI [10][11][12][13], leading to increments in lumbar spine areal BMD (LS-aBMD) [10,14,15]. Adequate intake of calcium and vitamin D is likely to optimize response to bisphosphonate treatments by preventing symptomatic hypocalcemia [13,16] . However, assessment of 315 children with OI found serum 25OHD concentrations were positively correlated with LS-aBMD z-scores [32].…”

Effect of High‐Dose Vitamin D Supplementation on Bone Density in Youth with Osteogenesis Imperfecta: A Randomized Controlled Trial

“…Studies show that bisphosphonates have a higher affinity for trabecular bone compared to cortical bone and their absorption is highest within the spine [55]. The impact of bisphosphonates on BMD z-scores is most significant within the first 2 years of treatment [11,16].…”

“…Bisphosphonates are widely used to increase BMD in children with OI [10][11][12][13], leading to increments in lumbar spine areal BMD (LS-aBMD) [10,14,15]. Adequate intake of calcium and vitamin D is likely to optimize response to bisphosphonate treatments by preventing symptomatic hypocalcemia [13,16] and by optimizing substrate availability for bone mineral accretion [17][18][19]. of young OI patients in North America [24][25][26].…”