Alkaline phosphatase in pediatric patients with genu varum caused by vitamin D-deficient rickets.

An elevated serum alkaline phosphatase (ALP) level is one of the markers for the presence of rickets in children, but it is also associated with bone formation. However, its role in diagnosing genu varum in pediatric patients with vitamin D-deficient rickets is still unknown. To clarify the role of the serum ALP level in assessing the severity of genu varum, we retrospectively investigated this issue statistically using data on rickets such as serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, ALP, the level of creatinine as the percentage of the median according to age (%Cr), and the metaphyseal diaphyseal angle (MDA) in the lower extremities as an index of the severity of genu varum. A multiple regression analysis revealed that log ALP and %Cr values were negatively associated with MDA values. The former association was also confirmed by a linear mixed model, while iPTH was positively associated with MDA by path model analysis. To elucidate the association of ALP with MDA in the presence of iPTH, we investigated three-dimensional figures by neural network analysis. This indicated the presence of a biphasic association of ALP with MDA: the first phase increases while the second decreases MDA. The latter phenomenon is considered to be associated with the increase in bone formation due to the mechanical stress loaded on the lower extremities. These findings are important and informative for pediatricians to understand the significance of the serum ALP level in pediatric patients with genu varum caused by vitamin D deficiency.

Physiologic Leg Bowing is not a Physiologic Condition but Instead is Associated with Vitamin D Disorders in Toddlers.

When children around 2-year-old show leg bowing without lower-limb radiographic abnormalities for rickets, the leg bowing is classified as "physiologic" genu varum without conducting a blood test. However, it has recently been suggested that toddlers who are diagnosed with physiologic genu varum may in fact have some form of bone metabolic disorder. In this 1:2 case-control study, blood samples were obtained from 33 toddlers with genu varum without radiographic abnormalities for rickets and 66 age- and gender-matched healthy children. Serum alkaline phosphatase (sALP), intact parathyroid hormone (siPTH), 25-hydroxy vitamin D [s25(OH)D], calcium (sCa), and inorganic phosphate (sP) were measured. s25(OH)D of the subjects with genu varum (24.8 ng/ml) were significantly lower than those of the control (33.6 ng/ml) (p < 0.001). The frequency of vitamin D insufficiency/deficiency (< 20 ng/ml) of the subjects with genu varum (39%) was significantly higher than that in the control (14%) (p = 0.004) (odds ratio by vitamin D insufficiency/deficiency: 4.1 [1.5-11.1, p = 0.004]). sCa in subjects with genu varum (10.2 ng/ml) were significantly higher than in control (9.8 ng/ml) (p < 0.001), as were sALP (1057 IU/l) and siPTH (28.4 pg/ml) (740 IU/l and 8.8 pg/ml in control, respectively; p < 0.001). siPTH levels were associated with s25(OH)D levels in subjects with genu varum (r = - 0.57, p < 0.001), while no association was observed in the control (r = 0.11, p = 0.36). Genu varum without radiographic abnormalities of rickets was associated with both vitamin D and bone-metabolic disorders in toddlers, indicating that physiologic genu varum is not a physiologic condition in toddlers.

Association between leg bowing and serum alkaline phosphatase level regardless of the presence of a radiographic growth plate abnormality in pediatric patients with genu varum.

When children around 2 years of age show leg bowing and diseases are ruled out based on radiographic findings without conducting blood tests, they are classified as "physiologic" genu varum. Since whether or not physiologic genu varum is associated with bone metabolism is unclear, this study was conducted to clarify the association between genu varum and bone metabolism in children. Thirty-five pediatric patients with genu varm who visited our out-patient clinic were enrolled. While two of the 35 children had nutritional rickets, showing abnormalities on both blood test (ALP, ≥1000 IU/L; iPTH, >65 pg/mL and 25(OH)D, ≤20 ng/mL) and radiographs (such as cupping, fraying or splaying), five of 35 children showed abnormalities on blood tests but not radiographs. While metaphyseal-diaphyseal angle (MDA) correlated with serum 25-hydroxy vitamin D (r = -0.35, p = 0.04) and magnesium (r = -0.36, p = 0.04), MDA and femorotibial angle (FTA) correlated with alkaline phosphatase (r = 0.43, p = 0.01 and r = 0.51, p = 0.006, respectively). A ridge regression analysis adjusted for age and body mass index indicated that ALP was associated with MDA and FTA. A logistic regression analysis adjusted for age and BMI indicated that higher ALP influenced an MDA >11°, which indicates the risk for the progression of genu varum (odds ratio 1.002, 95% confidence interval 1.0003-1.003, p = 0.021). The higher ALP (+100 IU), the higher risk of an MDA >11° (odds ratio 1.22). In conclusion, genu varum is associated with the alkaline phosphatase level regardless of the presence of radiographic abnormalities in the growth plate in children.

High prevalence of genu varum/valgum in European children with low vitamin D status and insufficient dairy products/calcium intakes.

OBJECTIVE: The prevalence of lower limb deformities physiologically decreases after 5 years of age. It remains high in some tropical and subtropical regions where it has been associated with severe vitamin D deficiency, low calcium/milk intakes, malnutrition, and/or fluoride overexposure. Very little data is available in apparently healthy Caucasian children and adolescents. DESIGN: We evaluated the prevalence of genu varum/valgum and other clinical symptoms, and assessed vitamin D status and markers of calcium metabolism in 226 apparently healthy European full-time boarders (7-16 years) seen during winter-spring and fed a cereal-based diet with little access to meat, milk, and dairy products. A cohort of 71 white children and adolescents hospitalized for acute illness served as age-matched controls. RESULTS: Association studies showed a high prevalence of lower limb deformities (36%) and higher alkaline phosphate activities in the 21% of children and adolescent full-time boarders with serum 25-(OH)D levels ≤ 30 nmol/l, and low serum calcium in the 74% of boarders with 25-(OH)D levels ≤ 50 nmol/l, compared with boarders with higher vitamin D status. No such anomalies were found in the control cohort despite lower serum 25-(OH)D levels. CONCLUSIONS: Low 25-(OH)D levels, at least during winter-spring, combined with additional risk factors such as very low calcium/milk intakes and possibly digestive disorders, are associated with an increased risk of genu varum/valgum in European children and adolescents. Thus, dietary fortification, or supplementation with vitamin D, may be recommended, at least during the winter, to European children and adolescents with either none or insufficient calcium/dairy product intakes.