Physiologic Leg Bowing is not a Physiologic Condition but Instead is Associated with Vitamin D Disorders in Toddlers
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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.
KeywordsPhysiologic leg bowing Genu varum Vitamin D Parathyroid hormone Alkaline phosphatase
The authors thank all participating children and parents and all of the medical staffs at the participating institutions for providing the clinical data.
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.
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).
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
: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.
- 1.Sakamoto Y, Ishijima M, Kinoshita M, Liu L, Suzuki M, Kim SG, Kamata K, Tokita A, Kaneko H, Shimizu T, Kaneko K, Nozawa M (2018) 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. J Bone Miner Metab 36:447–453CrossRefGoogle Scholar
- 3.Tanaka H, Ozono K, Kitanaka S, Tajim T, Hasegawa K, Hujiwara I, Michigami T, Minagawa M, Miyako K (2013) In Clinical guide for the diagnosis of rickets and hypocalcemia due to vitamin D deficiency. Kyoto, p 1Google Scholar
- 6.Kinoshita M, Ishijima M, Kaneko H, Liu L, Nagao M, Sadatsuki R, Hada S, Arita H, Aoki T, Yamanaka M, Nojiri H, Sakamoto Y, Tokita A, Kaneko K (2019) The increase in bone mineral density by bisphosphonate with active vitamin D analog is associated with the serum calcium level within the reference interval in postmenopausal osteoporosis. Mod Rheumatol 29:157–164CrossRefGoogle Scholar
- 8.Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, Michigami T, Tiosano D, Mughal MZ, Makitie O, Ramos-Abad L, Ward L, DiMeglio LA, Atapattu N, Cassinelli H, Braegger C, Pettifor JM, Seth A, Idris HW, Bhatia V, Fu J, Goldberg G, Savendahl L, Khadgawat R, Pludowski P, Maddock J, Hypponen E, Oduwole A, Frew E, Aguiar M, Tulchinsky T, Butler G, Hogler W (2016) Global consensus recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab 101:394–415CrossRefGoogle Scholar
- 22.Bathfield CA, Beighton PH (1978) Blount disease. A review of etiological factors in 110 patients. Clin Orthop Relat Res:29-33Google Scholar