Novel Treatment Options in Childhood Bone Diseases.

BACKGROUND: Several novel treatment options have recently become available in childhood bone diseases. The purpose of this article is to provide an update on some of the therapeutic agents used in the treatment of pediatric osteoporosis, X-linked hypophosphatemic rickets, and achondroplasia (ACH). SUMMARY: Vitamin D3 and Ca supplementation remains the basis of childhood osteoporosis treatment. Bisphosphonate (BP) therapy is the main antiresorptive therapeutic option, while denosumab, a human monoclonal IgG2 antibody with high affinity and specificity for a primary regulator of bone resorption - RANKL, represents a possible alternative. Its potent inhibition of bone resorption and turnover process leads to continuous increase of bone mineral density throughout the treatment also in the pediatric population. With a half-life much shorter than BPs, its effects are rapidly reversible upon discontinuation. Safety and dosing concerns in children remain. Novel treatment options have recently become available in two rare bone diseases. Burosumab, a monoclonal antibody against FGF-23, has been approved for the treatment of children with X-linked hypophosphatemic rickets older than 1 year. It presents an effective, more etiology-based treatment for rickets compared to conventional therapy, without the need for multiple daily oral phosphate supplementation. Its long-term efficacy and safety are currently being investigated. After years of anticipation, a novel treatment option for ACH has become available. C-type natriuretic peptide analog vosoritide effectively increases proportional growth and has a reasonable safety profile in children >2 years. Its effect on other features of the disease and the final height is yet to be determined. Several other treatment options for ACH exploring different therapeutic approaches are currently being investigated. KEY MESSAGES: Denosumab is effective in the treatment of childhood-onset osteoporosis; however, further studies are necessary to determine the optimal treatment protocol. Burosumab is more etiology-based and convenient in comparison to conventional treatment of X-linked hypophospha--temic rickets in children and adults. Vosoritide importantly changes the natural course of achondroplasia, at least in the short term.

Prevalence of Endocrine and Metabolic Comorbidities in a National Cohort of Patients with Craniopharyngioma.

OBJECTIVE: The major part of craniopharyngioma (CP) morbidity is the tumor and/or treatment-related damage, which results in impaired function of the hypothalamic-pituitary axes and metabolic derangements. The aim of the study was to analyze the prevalence of long-term endocrine and metabolic comorbidities in a national cohort of CP patients based on the age at diagnosis and histology criteria. DESIGN: A retrospective-prospective longitudinal cohort analysis. METHODS: Forty-six patients with CP treated from 1979 onwards (19 with childhood-onset disease) in a single university institution were included in our study. Median follow-up from presentation was 12.8 years (interquartile range: 8.3-22.2 years) and comparable between age-at-diagnosis and histological subtype groups. Data on tumor histology were extracted from patients' records and re-evaluated if tissue samples were available (n = 32). RESULTS: Childhood-onset patients presented more frequently with headache, and adult-onset with visual impairment. Prevalence of at least one pituitary axis affected increased from 54% at presentation to 100% at follow-up in childhood-onset and from 41 to 93% in adult-onset CP. Growth hormone deficiency, central diabetes insipidus, and panhypopituitarism were more prevalent in childhood-onset adamantinomatous CP (aCP) and least prevalent in adult-onset papillary CP (pCP). At follow-up, metabolic syndrome (MetS) was diagnosed in 80% of childhood-onset and 68% of adult-onset patients (p = 0.411). In the latter group, it tended to be more frequent in the aCP than pCP subtype (80 vs. 50%, p = 0.110). CONCLUSIONS: Long-term endocrine and metabolic complications are very frequent in childhood- and adult-onset CP patients of both histological subtypes. The prevalence of MetS was higher compared to the largest cohort previously reported.

Advances in the management of craniopharyngioma in children and adults.

Background Childhood and adult-onset craniopharyngioma is a rare embryogenic tumor of the sellar, suprasellar, and parasellar region. Survival rates are high; however, tumor location and treatment sequalae including endocrine deficits, visual impairment, metabolic complications, cognitive and psychosocial deficits can significantly impair patient's quality of life. There is considerable controversy regarding the optimal management of craniopharyngiomas. Subtotal resection of the tumor followed by targeted irradiation to avoid further hypothalamic damage is currently indicated. Novel insights in the tumor's molecular pathology present the possibility for targeted therapy possibly decreasing the rate and severity of treatment-associated morbidity. Conclusions Craniopharyngioma should be seen as a chronic disease. To achieve optimal outcomes a multidisciplinary team of specialized neurosurgeons, neuro-radiologists, neuro-oncologists, pathologists and endocrinologists should be involved in the diagnosis, planning of the surgery, irradiation and long-term follow-up.