Annual Injection of Zoledronic Acid Improves Bone Status in Children with Cerebral Palsy and Rett Syndrome
Osteoporosis is a common complication of cerebral palsy and Rett’s syndrome. It is responsible for multiple fractures, bone pain, and impaired quality of life. In case of Rett’s syndrome, a specific dysfunction of osteoblasts causes bone fragility. We observed the effects of annual zoledronic acid (ZA) infusion in a cohort of children with cerebral palsy and Rett’s syndrome. 27 children under 18 years (19 with cerebral palsy and 8 girls with Rett syndrome confirmed by MCEP2 mutation) were treated with an annual injection of 0.1 mg/kg (max 4 mg) of ZA. Calcium and vitamin D were combined in all patients from the first injection of ZA. Dental examination was performed before treatment. Data were analyzed retrospectively. Bone mineral density was measured at diagnosis and yearly thereafter. Bone mass density (BMD) is decreased in patient with cerebral palsy and RS. One year after injection of ZA, we observe an increase of Lumbar spine BMD from − 2.99 to − 2.14 SD (p < 0.0001) and femoral BMD from − 4.26 to − 3.32 SD (p < 0.001) In the subgroup of patient with Rett syndrome, we also observe an increase from − 3.27 to 2.50 SD (p = 0.018) of Lumbar spine BMD. No fractures have been observed in our cohort since the first infusion. Side effects (flu-like syndrome and hypocalcemia) were more common in younger patients and after the first infusion. No serious complications were noticed. This study confirms the efficacy and the safety of an annual injection of ZA to improve bone status in children with cerebral palsy and Rett syndrome. No severe adverse effects were observed.
The authors would like to thank Mrs. Henrion-Felter for her help to regroup medical records, to Mrs. Saunier for her work on the ethic agreement of the study, and the families for their agreement.
Compliance with Ethical Standards
Conflict of interest
Arnaud Wiedemann, Emeline Renard, Magali Hernandez, Brigitte Dousset, François Brezin, Laetitia Lambert, Georges Weryha, and François Feillet declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
A written information with adverse events related to ZA utilization was given to every parents or legal guardians. Clinical trial has been approved by the Ethical Review Committee of the University Hospital of Nancy and is registered with the CNIL (French Institutional Ethics Committee of Protection and Liberties registration number: R2017-03). All clinical investigations were conducted in accordance to the Declaration of Helsinki.