A Multicenter Observational Cohort Study to Evaluate the Effects of Bisphosphonate Exposure on Bone Mineral Density and Other Health Outcomes in Osteogenesis Imperfecta

Abstract

Osteogenesis imperfecta (OI) is characterized by low bone mass and bone fragility. Using data from a large cohort of individuals with OI from the Osteogenesis Imperfecta Foundation's linked clinical research centers, we examined the association between exposure to bisphosphonate (BPN) treatment (past or present) and lumbar spine (LS) areal bone mineral density (aBMD), fractures, scoliosis, and mobility. From 466 individuals, we obtained 1394 participant‐age LS aBMD data points. Though all OI subtypes were examined, primary analyses were restricted to type I OI (OI‐1). Using linear regression, we constructed expected OI‐1 LS aBMD‐for‐age curves from the data from individuals who had never received BPN. LS aBMD in those who had been exposed to BPN was then compared with the computed expected aBMD. BPN exposure in preadolescent years (age <14 years) was associated with a LS aBMD that was 9% more than the expected computed values in BPN‐naïve individuals ( p < 0.01); however, such association was not observed across all ages. Exposure to i.v. BPN and treatment duration > 2 years correlated with LS aBMD in preadolescent individuals. BPN exposure also had a significant association with non‐aBMD clinical outcome variables. Logistic regression modeling predicted that with BPN exposure, a 1‐year increase in age would be associated with an 8.2% decrease in fracture probability for preadolescent individuals with OI‐1, compared with no decrease in individuals who had never received any BPN ( p < 0.05). In preadolescent individuals with OI‐1, a 0.1 g/cm 2 increase in LS aBMD was associated with a 10.6% decrease in scoliosis probability, compared with a 46.8% increase in the BPN‐naïve group ( p < 0.01). For the same changes in age and LS aBMD in preadolescent individuals, BPN exposure was also associated with higher mobility scores ( p < 0.01), demonstrating that BPN treatment may be associated with daily function. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

A Multicenter Study of Intramedullary Rodding in Osteogenesis Imperfecta

“…Genotypic information was used to classify patients when available. For participants without a molecular diagnosis, the site principal investigator and project principal investigator were required to be in agreement with regard to the subtype of OI based on specific criteria 1 , 23 - 26 . Data were collected uniformly at each site and the quality was assessed at the data entry point.…”

Bone density, fractures and the associated factors in iranian children and adolescent with Osteogenesis Imperfecta

“…Bisphosphonates not only increase lumbar spine (LS) BMD but also improve bone structures, increase mobility and reduce fracture risk [ 4 , 6 ]. In 2019 Bains et al in a cohort multicenter study on 299 individuals with OI type I (a mild form of disease), revealed that people who were receiving bisphosphonates, BMD and mobility had increased, fracture rate and scoliosis was decreased in comparison with the group who did not took bisphosphonates [ 21 ]. There is no unanimous view as to when bisphosphonate treatment should be initiated for individuals with OI [ 4 ].…”

Management of Endocrine Disease: Osteogenesis imperfecta: an update on clinical features and therapies

“…Bisphosphonates, which act by inhibiting osteoclast activity and bone resorption, are the mainstay of pharmacologic treatment in pediatric patients with OI. Bisphosphonates have been shown to consistently improve bone mineral density in patients with OI (9,49,53) and, to some extent, reduce fracture incidence (9,51). During growth, they have a beneficial effect on reshaping vertebrae that have compression fracture deformities (9,54).…”

“…During growth, they have a beneficial effect on reshaping vertebrae that have compression fracture deformities (9,54). Other than the improvement in bone mass and architecture in growing children, the beneficial effects of bisphosphonates have not been conclusive, although a recent study indicated a positive effect on fracture incidence, scoliosis probability, and mobility in preadolescent patients with OI type I (53). Common side effects include acute phase infusion reaction (most typically during the first infusion) and transient hypocalcemia.…”