Effectiveness of Neridronate in the Management of Bone Loss in Patients with Duchenne Muscular Dystrophy: Results from a Pilot Study

Abstract

Introduction Bone loss is a major issue in patients affected by Duchenne muscular dystrophy (DMD), a rare musculoskeletal disorder, particularly in those treated with glucocorticoids (GCs). We aimed to assess the effectiveness of neridronate in terms of bone mineral density (BMD) changes in this population. Methods We retrospectively reviewed the records of patients affected by DMD receiving GCs referred to our outpatient from 2015 to 2020. All patients were treated with an intramuscular (IM) injection of neridronate (25 mg every month). Bone density was measured at the lumbar spine (LS; L1–L4 tract) using dual-energy x-ray absorptiometry (DXA) (GE Lunar), no more than 4 weeks before (T0) and after 1 year from neridronate treatment (T1). Results Eight boys with DMD were included with a mean age at diagnosis of 4.75 ± 2.81 years. Six of them were non-ambulant and two of them had previous low-trauma fractures (a distal femur fracture and a vertebral compression fracture, respectively). All patients were receiving deflazacort [median duration of therapy 11.5 years (interquartile range 2–25)]. At the DXA evaluation (T0), the mean L1–L4 BMD value was 0.716 ± 0.164 g/cm 2 . Six patients (75%) showed an L1–L4 Z -score height-adjusted of less than − 2. The mean age of neridronate initiation was 18.87 ± 6.81 years. All patients were supplemented with calcium carbonate and vitamin D at baseline. After 12 months of treatment (T1), the mean L1–L4 BMD value was 0.685 ± 0.190 g/cm 2 . Seven patients (87.5%) showed an L1–L4 Z -score of less than − 2. Changes in LS BMD and Z -score were not significant between T0 and T1 in our cohort ( p = 0.674 and p = 0.208, respectively) as well as among non-ambulant patients with DMD without previous fragility fractures. Conclusions In this study, we reported for the first time that neridronate may slow bone loss in GC-treated patients with DMD at 1-year follow-up.

Bisphosphonates in Glucocorticoid-Treated Patients With Duchenne Muscular Dystrophy

“…Looking into descriptive results from included observational cohort studies, Nasomyont et al 18 observed a similar prevalence of thoracic and lumbar vertebral fractures at baseline and each year of follow-up (ranging up to 5 years) in 52 US patients treated with oral alendronate; Sbrocchi et al 21 documented 3 incident vertebral fractures in 2 patients across the 2-year follow-up period (corresponding to a mean incidence rate per person-year of 0.30) in 5 Canadian patients treated with IV pamidronate or zoledronate; and Moretti et al 17 recorded no new fractures during follow-up.…”

“…Individual study samples comprised between 1 and 520 cases, and the age of patients ranged between 5 and 23 years (5 studies did not report minimum and maximum ages). 4 , 13 , 17 , 20 , 22 Two (11%) studies reported results from randomized controlled trials, 24 , 25 8 (42%) from retrospective cohort studies, 4 , 11 , 13 , 17 , 18 , 20 , 21 , 23 5 (26%) from case studies/series, 10 , 14 , 15 , 19 , 27 2 (11%) from prospective cohort studies, 16 , 26 1 (5%) from a case-control trial, 22 and 1 (5%) from an uncontrolled before-and-after trial. 12 …”

“…None of the identified studies were specifically designed and sufficiently powered to detect an effect of bisphosphonates on long bone fracture rates in glucocorticoid-treated patients with DMD. However, 2 RCTs 24 , 25 and 2 uncontrolled observational studies 17 , 21 recorded incident long bone fractures during the bisphosphonate treatment period. In the RCT by Ward et al, 24 involving an international cohort of 34 children with bone fragility and chronic disorders (of whom 38% had DMD and all of whom had with at least 1 dose of glucocorticoid therapy for the treatment of their underlying disease in the 12 months preceding enrollment), the incidence rate per person-year was estimated at 0.17 in patients treated with IV zoledronate and 0.25 in those without IV zoledronate therapy.…”

“…We found 1 study 22 that was designed to evaluate the effects of bisphosphonates on vertebral fractures in glucocorticoid-treated patients with DMD and 2 RCTs 24 , 25 and 4 uncontrolled observational studies 17 , 18 , 21 , 23 recording incident vertebral fractures during bisphosphonate treatment. Specifically, Srinivasan et al 22 conducted a nonrandomized case-control trial of vertebral fracture risk in 51 glucocorticoid-treated UK patients with DMD, of whom 36 received oral risedronate.…”

The Rationale for Using Neridronate in Musculoskeletal Disorders: From Metabolic Bone Diseases to Musculoskeletal Pain

“…The effectiveness of neridronate has been suggested also in patients with Duchenne Muscular Dystrophy (DMD) receiving glucocorticoids (GCs). In this population, 1-year treatment with IM neridronate (25 mg monthly), seems to counteract the BMD loss and to prevent incident fragility fractures [80].…”