Annual Injection of Zoledronic Acid Improves Bone Status in Children with Cerebral Palsy and Rett Syndrome

Wiedemann, Arnaud; Renard, E.; Hernandez, Magali; Dousset, B; Brezin, François; Lambert, Laëtitia; Weryha, G.; Feillet, François

doi:10.1007/s00223-018-0505-2

Cited by 13 publications

(6 citation statements)

References 35 publications

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“… 7 While no clear evidence of benefit from the use of bisphosphonates exists, new potential treatment with zoledronic acid in RTT has been recently suggested as it resulted in an increase in bone density and a reduction in the incidence of fractures. 27 …”

Section: Discussionmentioning

confidence: 99%

Phenotypes in adult patients with Rett syndrome: results of a 13-year experience and insights into healthcare transition

et al. 2020

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BackgroundRett syndrome is a complex genetic disorder with age-specific manifestations and over half of the patients surviving into middle age. However, little information about the phenotype of adult individuals with Rett syndrome is available, and mainly relies on questionnaires completed by caregivers. Here, we assess the clinical manifestations and management of adult patients with Rett syndrome and present our experience in transitioning from the paediatric to the adult clinic.MethodsWe analysed the medical records and molecular data of women aged ≥18 years with a diagnosis of classic Rett syndrome and/or pathogenic variants in MECP2, CDKL5 and FOXG1, who were in charge of our clinic.ResultsOf the 50 women with classic Rett syndrome, 94% had epilepsy (26% drug-resistant), 20% showed extrapyramidal signs, 40% sleep problems and 36% behavioural disorders. Eighty-six % patients exhibited gastrointestinal problems; 70% had scoliosis and 90% low bone density. Breathing irregularities were diagnosed in 60%. None of the patients had cardiac issues. CDKL5 patients experienced fewer breathing abnormalities than women with classic Rett syndrome.ConclusionThe delineation of an adult phenotype in Rett syndrome demonstrates the importance of a transitional programme and the need of a dedicated multidisciplinary team to optimise the clinical management of these patients.

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Section: Discussionmentioning

confidence: 99%

Phenotypes in adult patients with Rett syndrome: results of a 13-year experience and insights into healthcare transition

et al. 2020

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“…Absence of severe adverse effects and efficacy of a parenteral third-generation bisphosphonate, i.e., zoledronic acid, have been confirmed in another retrospective evaluation on 19 patients affected by cerebral palsy and 8 RTT children [129]. Some benefits of zoledronic acid over pamidronate include the shorter infusion time and the fact that it can be administered as a single annual injection.…”

Section: Therapeutic Approaches For Bone-related Issues In Rttmentioning

confidence: 79%

“…In addition to the case reports described above, more recently, two other studies conducted an evaluation of the safety and efficacy of bisphosphonate use in larger cohorts of RTT patients [128,129]. In the first retrospective study, a cohort of 20 RTT children, who received pamidronate therapy for 2 years (specifically, on two consecutive days every 3 months), was analyzed for determination of bone mineral density, incidence of fractures, and other biochemical markers [128].…”

Section: Therapeutic Approaches For Bone-related Issues In Rttmentioning

confidence: 99%

“…In the RTT group, one year after injection of zoledronic acid, there was a significant improvement in both lumbar spine and femoral bone mineral density, along with a reduction in the incidence of fractures and pain. The most frequent adverse effects included flu-like symptoms and hypocalcemia, especially in younger patients [129].…”

Section: Therapeutic Approaches For Bone-related Issues In Rttmentioning

confidence: 99%

“…In addition to the above-mentioned pharmacological treatments, there are other nonpharmacological interventions commonly indicated to cope with the well-known risk factors associated with poor bone health in RTT patients, including limited mobility and nutritional deficits [61]. Therefore, adequate dietary calcium intake and serum levels of bone markers, such as calcium and 25-hydroxyvitamin D, are usually monitored in RTT patients and, in case of deficiencies, vitamin D and calcium supplementations are used, as also recommended in the 2016 guidelines for assessment and management of bone health in RTT [30,61,67,129]. Furthermore, physical therapy is another essential intervention for the management of bone health in this disorder [30,132,133].…”

Section: Therapeutic Approaches For Bone-related Issues In Rttmentioning

confidence: 99%

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Altered Bone Status in Rett Syndrome

Pecorelli

Cordone

Schiavone

et al. 2021

Life

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Rett syndrome (RTT) is a monogenic neurodevelopmental disorder primarily caused by mutations in X-linked MECP2 gene, encoding for methyl-CpG binding protein 2 (MeCP2), a multifaceted modulator of gene expression and chromatin organization. Based on the type of mutation, RTT patients exhibit a broad spectrum of clinical phenotypes with various degrees of severity. In addition, as a complex multisystem disease, RTT shows several clinical manifestations ranging from neurological to non-neurological symptoms. The most common non-neurological comorbidities include, among others, orthopedic complications, mainly scoliosis but also early osteopenia/osteoporosis and a high frequency of fractures. A characteristic low bone mineral density dependent on a slow rate of bone formation due to dysfunctional osteoblast activity rather than an increase in bone resorption is at the root of these complications. Evidence from human and animal studies supports the idea that MECP2 mutation could be associated with altered epigenetic regulation of bone-related factors and signaling pathways, including SFRP4/WNT/β-catenin axis and RANKL/RANK/OPG system. More research is needed to better understand the role of MeCP2 in bone homeostasis. Indeed, uncovering the molecular mechanisms underlying RTT bone problems could reveal new potential pharmacological targets for the treatment of these complications that adversely affect the quality of life of RTT patients for whom the only therapeutic approaches currently available include bisphosphonates, dietary supplements, and physical activity.

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