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Published in: Calcified Tissue International 2/2020

01-02-2020 | Rickets | Original Research

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

Authors: Yuko Sakamoto, Muneaki Ishijima, Satoshi Nakano, Mitsuyoshi Suzuki, Lizu Liu, Akifumi Tokita, Sung-Gon Kim, Toshiaki Shimizu, Kazuo Kaneko, Masahiko Nozawa

Published in: Calcified Tissue International | Issue 2/2020

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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.
Literature
1.
go back to reference 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 36:447–453CrossRef 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 36:447–453CrossRef
2.
go back to reference Weiner DS (1981) The natural history of “bow legs” and “knock knees” in childhood. Orthopedics 4:156–160PubMed Weiner DS (1981) The natural history of “bow legs” and “knock knees” in childhood. Orthopedics 4:156–160PubMed
3.
go back to reference 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 1 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 1
4.
go back to reference Nakano S, Suzuki M, Minowa K, Hirai S, Takubo N, Sakamoto Y, Ishijima M, Hoshino E, Tokita A, Shimizu T (2018) Current vitamin D status in healthy Japanese infants and young children. J Nutr Sci Vitaminol (Tokyo) 64:99–105CrossRef Nakano S, Suzuki M, Minowa K, Hirai S, Takubo N, Sakamoto Y, Ishijima M, Hoshino E, Tokita A, Shimizu T (2018) Current vitamin D status in healthy Japanese infants and young children. J Nutr Sci Vitaminol (Tokyo) 64:99–105CrossRef
5.
go back to reference Levine AM, Drennan JC (1982) Physiological bowing and tibia vara. The metaphyseal–diaphyseal angle in the measurement of bowleg deformities. J Bone Jt Surg Am 64:1158–1163CrossRef Levine AM, Drennan JC (1982) Physiological bowing and tibia vara. The metaphyseal–diaphyseal angle in the measurement of bowleg deformities. J Bone Jt Surg Am 64:1158–1163CrossRef
6.
go back to reference 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 29:157–164CrossRef 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 29:157–164CrossRef
7.
go back to reference Akaike H (1974) A new look at the statistical model identification. IEEE Trans Automatic Control AC-19:716–723CrossRef Akaike H (1974) A new look at the statistical model identification. IEEE Trans Automatic Control AC-19:716–723CrossRef
8.
go back to reference 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 101:394–415CrossRef 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 101:394–415CrossRef
9.
go back to reference Chapuy MC, Preziosi P, Maamer M, Arnaud S, Galan P, Hercberg S, Meunier PJ (1997) Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 7:439–443CrossRef Chapuy MC, Preziosi P, Maamer M, Arnaud S, Galan P, Hercberg S, Meunier PJ (1997) Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 7:439–443CrossRef
10.
go back to reference Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS (1998) Hypovitaminosis D in medical inpatients. N Engl J Med 338:777–783CrossRef Thomas MK, Lloyd-Jones DM, Thadhani RI, Shaw AC, Deraska DJ, Kitch BT, Vamvakas EC, Dick IM, Prince RL, Finkelstein JS (1998) Hypovitaminosis D in medical inpatients. N Engl J Med 338:777–783CrossRef
11.
go back to reference Malabanan A, Veronikis IE, Holick MF (1998) Redefining vitamin D insufficiency. Lancet 351:805–806CrossRef Malabanan A, Veronikis IE, Holick MF (1998) Redefining vitamin D insufficiency. Lancet 351:805–806CrossRef
12.
go back to reference Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine Society (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930CrossRef Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine Society (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930CrossRef
13.
go back to reference Sahota O, Mundey MK, San P, Godber IM, Lawson N, Hosking DJ (2004) The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis. Bone 35:312–319CrossRef Sahota O, Mundey MK, San P, Godber IM, Lawson N, Hosking DJ (2004) The relationship between vitamin D and parathyroid hormone: calcium homeostasis, bone turnover, and bone mineral density in postmenopausal women with established osteoporosis. Bone 35:312–319CrossRef
14.
go back to reference Amini Z, Bryant S, Smith C, Singh R, Kumar S (2013) Is the serum vitamin D–parathyroid hormone relationship influenced by obesity in children? Horm Res Paediatr 80:252–256CrossRef Amini Z, Bryant S, Smith C, Singh R, Kumar S (2013) Is the serum vitamin D–parathyroid hormone relationship influenced by obesity in children? Horm Res Paediatr 80:252–256CrossRef
15.
go back to reference Lamberg-Allardt CJ, Outila TA, Karkkainen MU, Rita HJ, Valsta LM (2001) Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe? J Bone Miner Res 16:2066–2073CrossRef Lamberg-Allardt CJ, Outila TA, Karkkainen MU, Rita HJ, Valsta LM (2001) Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe? J Bone Miner Res 16:2066–2073CrossRef
16.
go back to reference Guillemant J, Taupin P, Le HT, Taright N, Allemandou A, Peres G, Guillemant S (1999) Vitamin D status during puberty in French healthy male adolescents. Osteoporos Int 10:222–225CrossRef Guillemant J, Taupin P, Le HT, Taright N, Allemandou A, Peres G, Guillemant S (1999) Vitamin D status during puberty in French healthy male adolescents. Osteoporos Int 10:222–225CrossRef
17.
go back to reference Salenius P, Vankka E (1975) The development of the tibiofemoral angle in children. J Bone Jt Surg Am 57:259–261CrossRef Salenius P, Vankka E (1975) The development of the tibiofemoral angle in children. J Bone Jt Surg Am 57:259–261CrossRef
18.
go back to reference Heath CH, Staheli LT (1993) Normal limits of knee angle in white children—genu varum and genu valgum. J Pediatr Orthop 13:259–262PubMed Heath CH, Staheli LT (1993) Normal limits of knee angle in white children—genu varum and genu valgum. J Pediatr Orthop 13:259–262PubMed
19.
20.
go back to reference Santa Maria C, Cheng Z, Li A, Wang J, Shoback D, Tu CL, Chang W (2016) Interplay between CaSR and PTH1R signaling in skeletal development and osteoanabolism. Semin Cell Dev Biol 49:11–23CrossRef Santa Maria C, Cheng Z, Li A, Wang J, Shoback D, Tu CL, Chang W (2016) Interplay between CaSR and PTH1R signaling in skeletal development and osteoanabolism. Semin Cell Dev Biol 49:11–23CrossRef
21.
go back to reference de Pablos J, Arbeloa-Gutierrez L, Arenas-Miquelez A (2018) Update on treatment of adolescent Blount disease. Curr Opin Pediatr 30:71–77CrossRef de Pablos J, Arbeloa-Gutierrez L, Arenas-Miquelez A (2018) Update on treatment of adolescent Blount disease. Curr Opin Pediatr 30:71–77CrossRef
22.
go back to reference Bathfield CA, Beighton PH (1978) Blount disease. A review of etiological factors in 110 patients. Clin Orthop Relat Res:29-33 Bathfield CA, Beighton PH (1978) Blount disease. A review of etiological factors in 110 patients. Clin Orthop Relat Res:29-33
23.
go back to reference Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72:690–693CrossRef Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72:690–693CrossRef
24.
go back to reference Akazawa Y, Shiohara M, Amano Y, Uchida N, Nakamura S, Minami I, Yasui K, Kurata K, Koike K (2010) The clinical characteristics of vitamin D deficiency in childhood: a systematic literature review of Japanese patients. J Pediatr Endocrinol Metab 23:675–684CrossRef Akazawa Y, Shiohara M, Amano Y, Uchida N, Nakamura S, Minami I, Yasui K, Kurata K, Koike K (2010) The clinical characteristics of vitamin D deficiency in childhood: a systematic literature review of Japanese patients. J Pediatr Endocrinol Metab 23:675–684CrossRef
25.
go back to reference Matsuo K, Mukai T, Suzuki S, Fujieda K (2009) Prevalence and risk factors of vitamin D deficiency rickets in Hokkaido, Japan. Pediatr Int 51:559–562CrossRef Matsuo K, Mukai T, Suzuki S, Fujieda K (2009) Prevalence and risk factors of vitamin D deficiency rickets in Hokkaido, Japan. Pediatr Int 51:559–562CrossRef
26.
go back to reference Yorifuji J, Yorifuji T, Tachibana K, Nagai S, Kawai M, Momoi T, Nagasaka H, Hatayama H, Nakahata T (2008) Craniotabes in normal newborns: the earliest sign of subclinical vitamin D deficiency. J Clin Endocrinol Metab 93:1784–1788CrossRef Yorifuji J, Yorifuji T, Tachibana K, Nagai S, Kawai M, Momoi T, Nagasaka H, Hatayama H, Nakahata T (2008) Craniotabes in normal newborns: the earliest sign of subclinical vitamin D deficiency. J Clin Endocrinol Metab 93:1784–1788CrossRef
27.
go back to reference Kubota T, Kotani T, Miyoshi Y, Santo Y, Hirai H, Namba N, Shima M, Shimizu K, Nakajima S, Ozono K (2006) A spectrum of clinical presentations in seven Japanese patients with vitamin d deficiency. Clin Pediatr Endocrinol 15:23–28CrossRef Kubota T, Kotani T, Miyoshi Y, Santo Y, Hirai H, Namba N, Shima M, Shimizu K, Nakajima S, Ozono K (2006) A spectrum of clinical presentations in seven Japanese patients with vitamin d deficiency. Clin Pediatr Endocrinol 15:23–28CrossRef
Metadata
Title
Physiologic Leg Bowing is not a Physiologic Condition but Instead is Associated with Vitamin D Disorders in Toddlers
Authors
Yuko Sakamoto
Muneaki Ishijima
Satoshi Nakano
Mitsuyoshi Suzuki
Lizu Liu
Akifumi Tokita
Sung-Gon Kim
Toshiaki Shimizu
Kazuo Kaneko
Masahiko Nozawa
Publication date
01-02-2020
Publisher
Springer US
Published in
Calcified Tissue International / Issue 2/2020
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-019-00619-9

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