Objectives: Intravenous cyclical bisphosphonates are widely used to treat children with moderate to severe osteogenesis imperfecta (OI). They increase bone mineral density (BMD), diminish fracture rates and improve mobility. Bisphosphonates are often discontinued when growth is completed. We aimed to determine if the skeletal gains achieved with bisphosphonates persist after their discontinuation in patients with OI.
Methods: We assessed patients with OI who had started intravenous bisphosphonates (either pamidronate or zoledronate) before 13 years of age, were treated for at least two years and discontinued treatment after completion of growth. Lumbar spine (LS) densitometry by dual-energy x-ray absorptiometry and radius peripheral quantitative tomography were performed at treatment discontinuation (baseline) as well as at two and four years thereafter. Spine radiographs were performed at baseline and four years.
Results: Thirty-one patients (22 females) had performed LS densitometry at baseline, two and four years. Patients had started treatment between ages 0.112.6 years and had stopped 4.715.7 years later, when their age ranged between 13.420.0 years (mean: 16.4 years (SD: 1.8)). Baseline LS areal (a) BMD was lower than in healthy individuals (mean z-score: −1.8 (SD: 1.2) and increased by 3.6% at two years and by 3.6% at four years (P<0.05). Baseline trabecular volumetric (v) BMD was inferior than in healthy individuals (mean z-score: −1.2 (SD: 3.3) and decreased by 9.9% at two years and 18.7% at four years (P<0.05), while baseline cortical vBMD was higher than in healthy individuals (mean z-score: +0.8, SD: 2.1) and increased by 2.9% at two years and 3.8% at four years (P< 0.05). No patient sustained a new vertebral compression fracture at four years of follow-up. The proportion of patients with new long-bone fractures in the two years before treatment discontinuation decreased compared to the last two years of follow-up (42% and 16%, respectively; P<0.05).
Conclusion: In patients with OI, stopping bisphosphonates after completion of growth was not associated with a decline in lumbar spine aBMD nor an increase in fractures at four years. Trabecular density at the radial metaphysis decreased, possibly from disappearance of bisphosphonates-induced metaphyseal transverse lines.
Disclosure: Francis H. Glorieux: Novartis: consulting fees and research grants, Amgen, Ultragenyx and Mereo Biopharma: consulting fees and research grants.
Frank Rauch: PreciThera Inc (study grant).