Abstract
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.
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The authors thank all participating children and parents and all of the medical staffs at the participating institutions for providing the clinical data.
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This study was supported in part by Grant-in-Aid for Scientific Research from the Japanese Society for the Promotion of Science to Y.S. (18K09045) and M.I. (18K09082). This study was also funded in part by a High Technology Research Center Grant and the Program for the Strategic Research Foundation at Private Universities (2014–2019) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).
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Author YS designed the study and prepared the first draft of the paper. MI provided direction about the study method and discussion and brushed up the draft of the paper. Both of them are guarantors. Authors SN, MS and AT contributed extensive data of the control. Author LL was responsible for statistical analysis of the data. SK, TS, KK and MN had responsibility and authority of implementation of this study. All authors revised the paper critically for intellectual content and approved the final version. All authors agree to be accountable for the work and to ensure that any questions relating to the accuracy and integrity of the paper are investigated and properly resolved.
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:All procedures performed in this study involving human participants were in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This study was approved by the Ethics Committee of our University Hospital (Approval Number 18-45), and we obtained written informed consent from the parent(s) of the subjects.
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Sakamoto, Y., Ishijima, M., Nakano, S. et al. Physiologic Leg Bowing is not a Physiologic Condition but Instead is Associated with Vitamin D Disorders in Toddlers. Calcif Tissue Int 106, 95–103 (2020). https://doi.org/10.1007/s00223-019-00619-9
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DOI: https://doi.org/10.1007/s00223-019-00619-9