Linear growth of children with X-linked hypophosphatemia treated with burosumab: a real-life observational study.

To assess the long-term efficacy of burosumab for pediatric patients with X-linked hypophosphatemia, focusing on linear growth. This multi-center retrospective study included 35 pediatric patients who began treatment with burosumab between January 2018 and January 2021. We collected clinical data, anthropometric measurements, laboratory results, and Rickets Severity Score (RSS), from 2 years prior to treatment initiation and up to 4 years after. Burosumab was initiated at a mean age of 7.5 ± 4.4 years (range 0.6-15.9), with a mean initial dose of 0.8 ± 0.3 mg/kg, which was subsequently increased to 1.1 ± 0.4 mg/kg. The patients were followed for 2.9 ± 1.4 years (range 1-4) after initiating burosumab. Serum phosphorus levels increased from 2.7 ± 0.8 mg/dl at burosumab initiation to 3.4 ± 0.6 mg/dl after 3 months and remained stable (p < 0.001). Total reabsorption of phosphorus increased from 82.0 ± 6.8 to 90.1 ± 5.3% after 12 months of treatment (p = 0.041). The RSS improved from 1.7 ± 1.0 at burosumab initiation to 0.5 ± 0.6 and 0.3 ± 0.6 after 12 and 24 months, respectively (p < 0.001). Both height z-score and weight z-score improved from burosumab initiation to the end of the study: from - 2.07 ± 1.05 to - 1.72 ± 1.04 (p < 0.001) and from - 0.51 ± 1.12 to - 0.11 ± 1.29 (p < 0.001), respectively. Eight children received growth hormone combined with burosumab treatment. Height z-score improved among those who received growth hormone (from - 2.33 ± 1.12 to - 1.94 ± 1.24, p = 0.042) and among those who did not (from - 2.01 ± 1.01 to - 1.66 ± 1.01, p = 0.001). CONCLUSION:  Burosumab treatment in a real-life setting improved phosphate homeostasis and rickets severity and enhanced linear growth. WHAT IS KNOWN: • Compared to conventional therapy, burosumab treatment has been shown to increase serum phosphate levels and reduce the severity of rickets. • The effect of burosumab on growth is still being study. WHAT IS NEW: • Height z-score improved between the start of burosumab treatment and the end of the study (-2.07 ± 1.05 vs. -1.72 ± 1.04, p < 0.001). • Eight children received burosumab combined with growth hormone treatment without side effects during the concomitant treatments.

Optimal 25-OH-Vitamin D Level in Children Derived From Biochemical Parameters.

The aim of the study was to evaluate the bone-optimal pediatric levels of 25-hydroxy-vitamin D (25OHD) by testing the level at which 25OHD optimally effects calcium, phosphorus, and parathyroid hormone levels in a large population-based dataset. This was an observational retrospective "big-data" study. We analyzed 49 935 25OHD tests from children sampled in Clalit Health Services, Jerusalem district between 2009 and 2019. Associated data were available in the following number of samples: corrected calcium; 18 869, phosphorus: 1241, and PTH: 449. We tested correlations between each parameter and 25OHD, adjusting phosphorus levels by age using a "phosphorus index". Pearson's and Spearman's correlation coefficients were calculated to determine the strength of the correlation between 25OHD and each parameter. There was a significant correlation between 25OHD levels and both PTH and calcium but not for the phosphorus index. The level at which increase in 25OHD continued to cause significant alteration was: for PTH up to 100 nmol/l (40 ng/ml), for corrected calcium it increased beyond 100 nmol/l. Increasing levels of 25OHD levels up to at least 100 nmol/l are associated with improvement in parameters known to be associated with increased bone mineralization. Therefore, one should aim for a 25OHD level of 100 nmo/l.

Evidence Refuting the Existence of Autoimmune/Autoinflammatory Syndrome Induced by Adjuvants (ASIA).

Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) was described in 2011. Over time the condition and its triggers have broadened to include several autoimmune disorders, the macrophagic myofasciitis syndrome, the Gulf war syndrome, the sick building syndrome, siliconosis, and the chronic fatigue syndrome. The aluminum-containing adjuvants in the hepatitis B vaccine and the human papillomavirus vaccine in particular have been stated to be the major causes of the disorder. Here, we review the specificity of the diagnostic criteria for ASIA. We also examine relevant human data, pertaining to causation, particularly from patients undergoing allergen-specific immunotherapy (IT). Patients undergoing allergen-specific IT receive 100 to 500 times more injected aluminum over 3 to 5 years, compared with hepatitis B and human papillomavirus vaccine recipients. In a large pharmacoepidemiological study, in contrast to case series of ASIA, patients receiving aluminum-containing allergen IT preparations were shown to have a lower incidence of autoimmune disease. In another clinical trial, there were no increases in exacerbations in a cohort of patients with systemic lupus erythematosus immunized with the hepatitis B vaccine. Current data do not support the causation of ASIA by vaccine adjuvants containing aluminum, which should be of reassurance to patients undergoing routine immunizations as well as to those undergoing allergen-specific IT.