ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Bone Miner Res. 2019 Dec;34(12):2198–2204.

In brief: In Osteogenesis imperfecta (OI), intravenous (IV) cyclical bisphosphonates are often discontinued after cessation of growth in adolescents. This study showed that, four years after discontinuation of treatment, none of the patients sustained new vertebral compression fractures, and the proportion of individuals with long-bone fractures decreased compared with the two years before cessation of treatment.

Commentary: IV bisphosphonates are used worldwide in OI to increase bone mineral density (BMD) and decrease fracture rates. They are typically given throughout the growing years and are often discontinued when growth is completed.

The benefits of bisphosphonates in growing children are well established and cessation of bisphosphonate treatment in growing children with OI has been associated with poor skeletal outcomes. However, the skeletal outcomes after bisphosphonate discontinuation at final height have not been investigated in detail. This study assessed changes in BMD and fracture incidence during the first 4 years after IV bisphosphonate discontinuation in individuals with OI who had received treatment during skeletal growth and who had discontinued the treatment after achieving final height.

Thirty-one patients (22 females) with OI who had started IV bisphosphonates (either pamidronate or zoledronic acid) before 13 years of age, were treated for at least 2 years (range 4.7–15.7 years), and discontinued treatment after completion of growth, at age range 13.4–20.0 years (mean 16.4 years). At 4 years after treatment discontinuation, lumbar spine areal bone mineral density (BMD) had increased by 4% (P <0.05). Peripheral quantitative computed tomography of the radius showed a decrease in trabecular volumetric BMD at the distal metaphysis of 19% but an increase in cortical volumetric BMD of 4% (P <0.05 for both). None of the patients sustained a new vertebral compression fracture during follow-up. The proportion of patients with new long-bone fractures was higher in the 2 years before treatment discontinuation than in the last 2 years of follow-up (42% and 16%, respectively; P <0.05).

In summary, stopping bisphosphonate therapy after completion of growth is not associated with a decline in bone mass at the lumbar spine or radius shaft, nor an increased number of vertebral compression or long-bone fractures. Decrease in bone mass at the distal radius is likely due to resorption of bisphosphonate-induced metaphyseal transverse lines. There were fewer long-bone fractures in the 4 years after bisphosphonate discontinuation compared with 2 years before discontinuation. Cessation of bisphosphonates after completion of growth is not associate with adverse outcomes.

There were concerns that discontinuing IV bisphosphonates after cessation of growth may adversely impact on the skeleton which is still mineralizing. This study is reassuring and suggests that it is safe to allow a bisphosphonate drug holiday of up to 4 years in most individuals with moderate to severe OI as they become skeletally mature. However, additional studies are required to better define the optimal dose range, dosing interval, duration of treatment and effects on bone mineralization and adverse events during childhood as well as in adults.