Bone health in cerebral palsy and introduction of a novel therapy

Scheinberg, Morton; Golmia, Ricardo Prado; Sallum, Adriana Maluf Elias; Pippa, Maria Guadalupe Barbosa; Cortada, Aline Pinheiros dos Santos; Silva, Telma Gomes da

doi:10.1590/s1679-45082015ao3321

Cited by 9 publications

(5 citation statements)

References 14 publications

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“…The rapid reversibility of denosumab effects should also be considered in clinical decision-making. Patients with a history of non-adherence may rapidly lose therapeutic effects if doses are missed or given late, and may not be optimal candidates for denosumab [72]. Conversely, reversibility may be an attractive feature in treatment of children with acquired skeletal disorders that carry the potential for full recovery.…”

Section: Safety and Tolerability Of Denosumab In Adults And Childrenmentioning

confidence: 99%

Denosumab: an Emerging Therapy in Pediatric Bone Disorders

Boyce

2017

Curr Osteoporos Rep

106

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Purpose of Review Denosumab is an inhibitor of receptor activator of nuclear factor kappa-B ligand (RANKL), and has emerged as an important novel therapy for skeletal disorders. This article examines the use of denosumab in children. Recent findings Considerable safety and efficacy data exists for denosumab treatment of adults with osteoporosis, bone metastases, and giant cell tumors. Pediatric data is limited; however, evidence suggests denosumab may be beneficial in decreasing bone turnover, increasing bone density, and preventing growth of certain skeletal neoplasms in children. Denosumab’s effect on bone turnover is rapidly reversible after drug discontinuation, representing a key difference from bisphosphonates. Rebound increased bone turnover has led to severe hypercalcemia in several pediatric patients. Summary Denosumab is a promising therapy for pediatric skeletal disorders. At present, safety concerns related to rebounding bone turnover and mineral homeostasis impact use of denosumab in children. Research is needed to determine if and how these effects can be mitigated.

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Section: Safety and Tolerability Of Denosumab In Adults And Childrenmentioning

confidence: 99%

Denosumab: an Emerging Therapy in Pediatric Bone Disorders

Boyce

2017

Curr Osteoporos Rep

106

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“…Children with osteoporosis due to impaired muscle function with cerebral palsy were treated with low doses of 10 mg of Denosumab. A boy with spinal muscular atrophy was treated with a dose of 60 mg [18, 19]. In patients with a localized high turnover osteoporosis and destruction of the skeleton by cystic lesions Denosumab was also used to decrease bone turnover.…”

Section: Discussionmentioning

confidence: 99%

Individualized treatment with denosumab in children with osteogenesis imperfecta – follow up of a trial cohort

Hoyer‐Kuhn

Rehberg

Netzer

et al. 2019

Orphanet J Rare Dis

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Background Osteogenesis imperfecta (OI) is a rare disease leading to hereditary bone fragility. Nearly 90% of cases are caused by mutations in the collagen genes COL1A1/A2 (classical OI) leading to multiple fractures, scoliosis, short stature and nonskeletal findings as blue sclera, hypermobility of joints, bone pain and delayed motor function development. Bisphosphonates are used in most moderate and severely affected patients assuming that an increase of bone mineral density might reduce fractures and bone pain in patients with OI. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. First data from small clinical trials promised a high efficacy of Denosumab in children with OI. Aim of this analysis was a retrospective evaluation of an individualized biomarker-associated treatment regime with Denosumab in 10 children with classical OI which were followed for 1 year after their participation in a pilot trial with Denosumab. Therefore urinary deoxypyridinoline levels were evaluated frequently as an osteoclastic activity marker and depending on that levels Denosumab injections were scheduled individually. Methods Ten patients (age range: 6.16–12.13 years; all participated in the former OI-AK phase 2 trial (NCT01799798)) were included in the follow-up period. Denosumab was administered subcutaneously depending on the individual urinary excretion course of deoxypyridinoline (DPD/Crea) as osteoclastic activity marker with 1 mg/kg body weight. DPD/Crea levels were evaluated before denosumab administration and afterwards. If patients present after an initial decrease after injection with a re-increase up to the DPD/crea level before Denosumab injection next dosage was planned. Changes of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 12 month was evaluated. Safety was assessed by bone metabolism markers and side effect reporting. Results During follow-up mean relative change of lumbar aBMD was − 6.4%. Lumbar spine aBMD z-Scores decreased from − 1.01 ± 2.61 (mean ± SD) to − 1.91 ± 2.12 (p = 0.015). Mobility changed not significantly (GMFM-88 -6.49 ± 8.85% (p = 0.08). No severe side effects occurred. Dose intervals could be extended in the mean from 12 weeks previously to 20.3 weeks. Conclusions On average, it was possible to prolong the intervals between drug administrations and to reduce the total dose about by 25% without a decrease of mobility or change of vertebral shape despite a reduction of lumbar aBMD during 1 year of biomarker-directed Denosumab treatment. Further trials are necessary to balance side effects and highest efficacy in children.

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“…Other cases reported in children include those with osteopetrosis, hypercalcemia (5,10), juvenile Paget disease (JPD) (77), and secondary osteoporosis in children (78,79). Secondary osteoporosis in children mainly includes disuse osteoporosis and glucocorticoid-related osteoporosis.…”

Section: Secondary Osteoporosis and Other Rare Diseasesmentioning

confidence: 99%

“…Huang et al's preliminary study found denosumab to be an effective treatment for low BMD in childhood cancer survivors, although hypocalcemia occurred in 40% of patients (81). Scheinberg et al reported their experience in treating disuse osteoporosis caused by cerebral palsy with denosumab (78). Additionally, Kumaki et al described the first experience of denosumab treatment for glucocorticoid-induced osteoporosis in a patient with DMD (82), with the BMD increasing to some extent.…”

Section: Secondary Osteoporosis and Other Rare Diseasesmentioning

confidence: 99%

Denosumab in pediatric bone disorders and the role of RANKL blockade: a narrative review

Wang¹,

Tang²,

Shi³

et al. 2023

Transl Pediatr

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Background and Objective: Denosumab is a valuable and safe therapy for skeletal disorders in adults and has received regulatory approval to treat osteoporosis and bone metastases. However, denosumab is not licensed for pediatric use due to a lack of high-quality prospective research on children. This study aimed to describe and discuss the benefits and disadvantages of denosumab in treating bone diseases in children and to summarize the current understanding of the role of denosumab therapy in children.Methods: A narrative review was conducted using the literature retrieved from the PubMed, Embase, and Cochrane Library databases.

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Bone health in cerebral palsy and introduction of a novel therapy

Cited by 9 publications

References 14 publications

Denosumab: an Emerging Therapy in Pediatric Bone Disorders

Denosumab: an Emerging Therapy in Pediatric Bone Disorders

Individualized treatment with denosumab in children with osteogenesis imperfecta – follow up of a trial cohort

Denosumab in pediatric bone disorders and the role of RANKL blockade: a narrative review

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