Paediatric NF1 patients at risk of low BMD, 25OHD insufficiency

Children with neurofibromatosis type 1 (NF1), an autosomal dominant neurocutaneous disease characterized by multisystemic involvement including bone tissue, tend to have low bone mineral density (BMD) and 25-hydroxyvitamin D (25OHD) inadequacy, particularly at puberty, suggests a Singapore study.

“Quantitative computed tomography (QCT) may be a useful tool to evaluate trabecular and cortical bone separately in NF1 patients,” the researchers said.

In this study, the researchers retrospectively evaluated the data of 52 paediatric NF1 patients (23 female, 29 male) and examined the following: anthropometric measurements; biochemical parameters like total calcium, phosphate, magnesium, alkaline phosphatase, 25OHD, parathyroid hormone, calcitonin, urinary calcium/creatinine ratio; QCT parameters like lumbar trabecular and cortical BMD; trabecular area and cortical thickness. They also compared gender and puberty status of participants.

Of the patients, 25 percent had skeletal deformities and 42.3 percent had 25OHD inadequacy (<20 ng/mL); the frequency of the latter was significantly greater in pubertal/postpubertal than prepubertal patients (61.9 percent vs 29.0 percent; p=0.019). [Singapore Med J 2021;doi:10.11622/smedj.2021052]

Trabecular BMD z-score was <–2.0 in 11.5 percent of patients, and all of those with low BMD were at the pubertal/postpubertal stage. A significant negative correlation was noted between age and trabecular z-score (r, –0.41; p=0.003). Statistically, the mean cortical BMD was similar between the gender and puberty groups, while puberty status, anthropometric z-scores, and biochemical and QCT parameters were comparable between genders (p>0.05).

“Our findings show that the trabecular area increases with age as an indication of axial skeleton growth, but bone mineralization does not, which is worrisome in terms of bone accumulation in paediatric NF1 patients during puberty,” the researchers said.

A study by Rodari and colleagues suggested progressive bone mineralization impairment with age and pubertal development in paediatric NF1 patients (mean age 11.6 years). Therefore, interventions to improve bone accumulation in this population appears essential to prevent NF1-related osteoporosis. [Arch Osteoporos 2018;13:93]

Furthermore, a study by Poyrazoğlu and colleagues showed a significantly positive association between femur BMD and femur z-score. Similarly, the present study found a strong correlation between lumbar trabecular BMD and lumbar z-score. [J Pediatr Endocrinol Metab 2017;30:175-180]

Other factors that may influence vitamin D levels, such as physical activity, daily diet, sunlight exposure, geographical region, weather, and seasonal changes were not examined in this study. The current results also differed from those of previous studies, such that a significant correlation was identified between 25OHD and trabecular z-score. [J Pediatr Endocrinol Metab 2011;24:169-174; Arch Osteoporos 2018;13:93; Clin Biochem 2014;47:560-563]

On the other hand, Stevenson and colleagues found no association between 25OHD and subtotal body BMD z-scores, but they noted a general trend of a positive association between 25OHD levels within the deficient range and BMD z-scores. [J Pediatr Endocrinol Metab 2011;24:169-174]

“Potential explanations for the difference in findings include factors such as race, geographical location, lifestyle, and NF1-related cutaneous and skeletal manifestations,” the researchers said. “Further studies with a larger sample size, which include NF1 individuals with 25OHD deficiency and insufficiency, should investigate the association between low 25OHD levels and the degree of impaired BMD.”

The present study was limited by the following: not having a control group, taking laboratory normal values as reference, including patients from different geographical regions and data from different seasons, not evaluating dietary and physical activity factors, a small sample size; and evaluating only alkaline phosphatase as a bone turnover marker.

“In future, there is a need for larger-size seminal studies that evaluate osteoblastic and osteoclastic activity markers in paediatric NF1 patients using QCT measurements,” the researchers said.