Disease Manifestations and Complications in Dutch X-Linked Hypophosphatemia Patients.

X-linked hypophosphatemia (XLH) is the most common monogenetic cause of chronic hypophosphatemia, characterized by rickets and osteomalacia. Disease manifestations and treatment of XLH patients in the Netherlands are currently unknown. Characteristics of XLH patients participating in the Dutch observational registry for genetic hypophosphatemia and acquired renal phosphate wasting were analyzed. Eighty XLH patients, including 29 children, were included. Genetic testing, performed in 78.8% of patients, showed a PHEX mutation in 96.8%. Median (range) Z-score for height was - 2.5 (- 5.5; 1.0) in adults and - 1.4 (- 3.7; 1.0) in children. Many patients were overweight or obese: 64.3% of adults and 37.0% of children. All children received XLH-related medication e.g., active vitamin D, phosphate supplementation or burosumab, while 8 adults used no medication. Lower age at start of XLH-related treatment was associated with higher height at inclusion. Hearing loss was reported in 6.9% of children and 31.4% of adults. Knee deformities were observed in 75.0% of all patients and osteoarthritis in 51.0% of adult patients. Nephrocalcinosis was observed in 62.1% of children and 33.3% of adults. Earlier start of XLH-related treatment was associated with higher risk of nephrocalcinosis and detection at younger age. Hyperparathyroidism longer than six months was reported in 37.9% of children and 35.3% of adults. This nationwide study confirms the high prevalence of adiposity, hearing loss, bone deformities, osteoarthritis, nephrocalcinosis and hyperparathyroidism in Dutch XLH patients. Early start of XLH-related treatment appears to be beneficial for longitudinal growth but may increase development of nephrocalcinosis.

Bone mineral density and bone metabolism of prepubertal children with asthma after long-term treatment with inhaled corticosteroids.

Little is known about the effect of long-term treatment with inhaled corticosteroids (ICS) on bone mineral density (BMD) in asthmatic children. In the present cross-sectional study BMD, bone metabolism, height, body composition, and bone age were evaluated in 40 prepubertal children (21 boys) with asthma, treated with a moderate to high dose of ICS over a period of 3 to 8 years. Body composition and BMD of the lumbar spine and total body were measured by Dual Energy X-ray Absorptiometry. BMD results were compared with 148 prepubertal healthy children of the same population. Blood samples were taken for the determination of biochemical bone parameters. The asthmatic children had decreased height, lean tissue mass and fat mass, and a delay of bone maturation, indicating growth retardation. ICS-treated asthma was negatively correlated with total body BMD in a multiple regression model with adjustment for age, gender, height and weight (P = 0.01). Duration of ICS therapy correlated negatively with total body BMD when it was added to the model (P = 0.01). Lumbar spine BMD was not affected by ICS in children with ICS-treated asthma. If age of the asthmatic children was replaced by their bone age in the model, no significant correlation was found between ICS-treated asthma and total body or lumbar spine BMD. The biochemical parameters of bone metabolism were within normal limits. In conclusion, children with asthma who have used ICS daily for 3 to 8 years had lower total body BMD than healthy controls. Long-term longitudinal studies are needed to investigate whether these children attain a normal peak bone mass.