Estimation of the vitamin D (VD) status of pregnant Japanese women based on food intake and VD synthesis by solar UV-B radiation using a questionnaire and UV-B observations.

Although vitamin D (VD; serum 25 hydroxyvitamin D) deficiency (< 20 ng/mL) is widespread among Japanese women, the VD status among pregnant women is unknown. This study aimed to determine the VD status of pregnant Japanese women during different meteorological seasons and to determine the factors controlling VD status. A total of 309 pregnant Japanese women were recruited at 28 weeks of gestation at the gynecology department of a university hospital in Tokyo between August 2018 and October 2019. Blood samples were collected to measure serum 25(OH)D levels. Two questionnaires were completed: a brief self-administered dietary history questionnaire (BDHQ) and an outdoor exposure history questionnaire to determine skin sunlight exposure and the use of sunscreen. Among the recruited subjects, 268 were included in the statistical analysis. The average VD intake from food was 9.0 µg/day, the average VD synthesis from UV-B was 15.2 µg/day, and the average sum of VD intake and nominal VD synthesis was 24.1 µg/day; this exceeded the recommended 2011 Dietary Reference Intake for the USA and Canada (15.0 µg/day). However, the average serum 25(OH)D level (11.4 ng/mL) was very low, indicating widespread VD deficiency. Serum 25(OH)D and VD synthesis by solar UV-B were significantly correlated only during the high UV-B season. The 25(OH)D level was weakly correlated with the VD intake from food in all seasons. We obtained a statistically significant correlation between serum 25(OH)D level and VD intake from food using the BDHQ. We also obtained a statistically significant correlation between the serum 25(OH)D level and VD synthesis from solar UV-B exposure, especially during the high UV-B season. Our logistic regression analysis model predicted VD deficiency in 88.0% of subjects. Our method might be possible to be used to predict the VD status of pregnant Japanese women, although another validation cohort is needed to verify the ability of the estimation equation.

A case of subacute combined spinal cord degeneration and suspected leukoencephalopathy associated with vitamin B12 deficiency showing improved imaging findings after vitamin B12 administration.

We report a case of subacute combined spinal cord degeneration (SCD) caused by vegetarianism and autoimmune gastritis, which is rarely reported in Japan, and which showed improvement in symptoms and imaging findings after vitamin B12 administration. As delayed treatment can lead to irreversible damage, we suggest that patients with characteristic abnormal signals in the posterior cervical cord should be examined while considering the possibility that SCD may occur even in the absence of a history of gastrectomy or heavy drinking. We also describe the patient's reversible abnormal signals in the cerebral white matter on magnetic resonance imaging, indicative of an early sign of leukoencephalopathy associated with vitamin B12 deficiency. J. Med. Invest. 69 : 299-301, August, 2022.

Clinical and molecular findings in three Japanese patients with N-acetylneuraminic acid synthetase-congenital disorder of glycosylation (NANS-CDG).

We report clinical and molecular findings in three Japanese patients with N-acetylneuraminic acid synthetase-congenital disorder of glycosylation (NANS-CDG). Patient 1 exhibited a unique constellation of clinical features including marked hydrocephalus, spondyloepimetaphyseal dysplasia (SEMD), and thrombocytopenia which is comparable to that of an infant reported by Faye-Peterson et al., whereas patients 2 and 3 showed Camera-Genevieve type SMED with intellectual/developmental disability which is currently known as the sole disease name for NANS-CDG. Molecular studies revealed a maternally inherited likely pathogenic c.207del:p.(Arg69Serfs*57) variant and a paternally derived likely pathogenic c.979_981dup:p.(Ile327dup) variant in patient 1, a homozygous likely pathogenic c.979_981dup:p.(Ile327dup) variant caused by maternal segmental isodisomy involving NANS in patient 2, and a paternally inherited pathogenic c.133-12T>A variant leading to aberrant splicing and a maternally inherited likely pathogenic c.607T>C:p.(Tyr203His) variant in patient 3 (reference mRNA: NM_018946.4). The results, together with previously reported data, imply that (1) NANS plays an important role in postnatal growth and fetal brain development; (2) SMED is recognizable at birth and shows remarkable postnatal evolution; (3) NANS-CDG is associated with low-normal serum sialic acid, obviously elevated urine N-acetylmannosamine, and normal N- and O-glycosylation of serum proteins; and (4) NANS-CDG is divided into Camera-Genevieve type and more severe Faye-Peterson type.

Comparison of the 5-Year Outcomes Between Standard and Short Fit-and-Fill Stems in Japanese Populations.

Background: Fit-and-fill stems are known to have excellent outcomes; however, severe stress shielding has been reported in Japanese populations. Short fit-and-fill stems were modified for Asians; however, there have been no previous reports of its outcome. In this study, we compared the 5-year (mean 68-month) outcomes of 2 fit-and-fill stems with different lengths (standard or short). Material and methods: We reviewed 100 total hip arthroplasties in each standard- or short-stem group. Radiographs were evaluated for femoral morphology, stress shielding, bone remodeling, and fixation. Clinical evaluation was performed using the Japanese Orthopaedic Association (JOA) scores. Results: There was no difference in the degree of stress shielding between the 2 groups. Significant differences were observed in radiolucent lines in zone 4 (P = .005) and cortical hypertrophy in zone 3 (P < .0001) and 5 (P = .048) between the 2 groups. The canal flare index (P < .0003), cortical index (P < .0003), height (P < .0345), and stem size (P < .0081) individually affected stress shielding in the standard-stem group. In contrast, the cortical index (P < .0107) was the only relative factor in the short-stem group. All stems were judged to have bone ingrowth. The JOA score improved significantly (P < .0001); however, there were no significant differences between the 2 groups. Conclusion: The outcomes of both standard and short fit-and-fill stems were favorable. There were no significant differences in the stress shielding or JOA scores. Although there were a few differences in bone remodeling and factors affecting stress shielding, stem length reduction has been achieved without adverse effects with the Japanese femur.

Acetabular cartilage abnormalities in elderly patients with femoral neck fractures.

INTRODUCTION: Both hemiarthroplasty (HA) and total hip arthroplasty (THA) are widely accepted surgical procedures for hip replacement following displaced femoral neck fractures. However, in cases involving an intact joint line before surgery, the choice between HA and THA remains debatable. This study investigated the prevalence of acetabular cartilage and labral abnormalities in elderly patients with femoral neck fractures. METHODS: Thirty-seven patients underwent hip arthroplasty for femoral neck fractures between April 2020 and February 2021. After excluding 4 patients, 33 patients (6 men and 27 women; mean age = 82.2 [range = 67-98] years) with fractures in 12 left and 21 right hips were included. After femoral head removal during arthroplasty, the acetabulum was macroscopically examined for the presence of cartilage and labral lesions. Acetabular cartilage abnormalities were classified as either overall degeneration or partial damage according to the cartilage damage classification system. RESULTS: Acetabular cartilage abnormalities, including overall degeneration or partial damage, were found in all hips (100%). Out of the 33 hips, overall degeneration, partial damage, and labral abnormalities were detected in 32 (96.9%), 16 (48.4%), and 9 (27.2%) hips, respectively. DISCUSSION: In this study, most elderly patients with femoral neck fractures exhibited acetabular cartilage and labral abnormalities, which were already present at the time of surgery. Therefore, surgeons should carefully examine these abnormalities as they may impact postoperative outcomes such as pain and function.

Frequent fractures and sclerotic thick bands on physes related to oral alendronate treatments.

Bisphosphonate treatment has known effects of improving bone mineral density and preventing fractures in children with steroid-induced osteoporosis. However, there have been reports that high-dosage pamidronate therapy induces osteopetrosis in the borders of bones. A 10-year-old boy undergoing long-term treatment with oral alendronate developed frequent fractures throughout adolescence while playing basketball. Radiographs showed osteosclerotic bands on the metaphyses of his long bones and vertebrae, and fractures were evident in the regions surrounding the osteosclerotic lesions: a stress fracture in the fourth metatarsal, anterior limbus vertebra (T12), spondylolysis (L3 and L5), and osteochondritis dissecans of the left lateral femoral condyle. Alendronate had been taken for a period of 6 years when the treatment was discontinued. Approximately 18 months after discontinuation, sclerotic bands remained evident; however, 4 years after discontinuation, sclerotic banding still surrounded the wing of the ilium but appeared diminished in the knees. In children and adolescents who engage in sports activities and are being treated with steroids and bisphosphonates, the possibility of pathological stress fractures should be considered.

Appearance and Frequency of Deep Venous Thrombosis After Total Hip Arthroplasty.

Objectives: Postoperative venous thromboembolism is an important peri-operative complication associated with total hip arthroplasty (THA). In particular, early detection of deep venous thrombosis (DVT) is important for the prevention of pulmonary embolism (PE). However, the methods and timing of examinations for DVT detection differ among the facilities. This study aimed to clarify the time, site, and frequency of DVT after THA. Materials and Methods: Background characteristics including age, sex, body mass index, diagnosis, operation type, operation time, and anesthesia type were investigated in 348 patients who underwent THA at our hospital between April 2017 and April 2019. Blood tests were performed preoperatively and on postoperative days (POD) 0, 1, 3, 7, 14, and 21. Simultaneously, vascular ultrasonography was performed to investigate the time and site of thrombus occurrence before and after the surgery. Results: DVT was observed in 27.2% of the patients on POD 21. The DVT-positive ratio was 9.4% (6/64) in males and 31.3% (89/284) in females. There was a significant difference between the groups (p = 0.0002). Patients in the DVT-positive group were significantly older than those in the DVT-negative group (73.0 ± 7.9 years vs. 63.3 ± 11.2 years, p = 0.0041). DVT mainly occurred in the soleal vein (74.7%). However, there was no significant difference between the operated and non-operated sides. In the DVT-positive group, thrombus occurred in 13.3% of preoperative cases, 20.0% on POD 0, 46.7% on POD 1, 13.3% on POD 3, 6.7% on POD 7, and 0% on POD 14 and 21. Conclusions: Vascular ultrasonography showed that thrombus occurred most frequently in the soleal vein. Thrombus occurred in 66.6% of DVT-positive patients by POD 1, indicating that thrombus appeared very early after surgery. All thrombus cases were formed by POD 7.

A reduced physiological 18F-fluorodeoxyglucose uptake in the brain and liver caused by malignant lymphoma being deprived of the tracer.

Purpose : To investigate whether or not the physiological brain and liver FDG uptake are decreased in patients with highly accelerated glycolysis lesions. Methods : We retrospectively analyzed 51 patients with malignant lymphoma. We compared the FDG uptake in the brain and liver of the patients with that in a control group. In 24 patients with a complete response (CR) or partial response (PR) to treatment, we compared the brain and liver uptake before and after treatment. Results : The maximum standardized uptake value (SUVmax) and total glycolytic volume (TGV) of the brain as well as the SUVmax and mean standardized uptake value (SUVmean) of the liver in malignant lymphoma patients were 13.1 ±â€…2.3, 7386.3 ±â€…1918.4, 3.2 ±â€…0.5, and 2.3 ±â€…0.4, respectively ; in the control group, these values were 14.9 ±â€…2.4, 8566.2 ±â€…1659.5, 3.4 ±â€…0.4, and 2.5 ±â€…0.3, respectively. The SUVmax and TGV of the brain and the SUVmean of the liver in malignant lymphoma patients were significantly lower than the control group. The SUVmax and TGV of the brain after treatment were significantly higher than before treatment. Both the SUVmax and SUVmean of liver after treatment were higher than before treatment, but not significant. Conclusion : A decreased physiological brain and liver FDG uptake is caused by highly accelerated lesion glycolysis. J. Med. Invest. 68 : 181-185, February, 2021.

Total hip arthroplasty with reconstruction of acetabulum through direct anterior approach for metastatic bone disease of acetabulum combined with pathological proximal femoral neck fracture: A case report.

Most surgical treatment options for metastatic acetabular lesions involve variants of total hip arthroplasty (THA). However, these are technically complex reconstructions performed in very frail patients, and previous reports indicate complications such as dislocation, deep infection, aseptic loosening, and intraoperative death. A 73-year-old man presented to the emergency department at our hospital with right hip pain following a fall. He had undergone nephrectomy for the treatment of right kidney cancer at the age of 68 years. Four years after the nephrectomy, multiple lung metastases, pelvic bone metastases, and right femoral head and neck bone metastases were found. A radiograph of the hip joint showed a pathological proximal femoral fracture with a radiolucent lesion of the acetabulum. THA with acetabular reconstruction using a Kerboull-type (KT) plate through the direct anterior approach (DAA) was performed. After removal of the femoral head, curettage of the metastatic acetabular dome lesion was carefully performed under fluoroscopic guidance. After the KT plate was placed, cementation of the metastatic acetabular dome lesion was performed, and an optimally sized polyethylene liner was fixed with cement. A cemented stem was inserted after confirming the hip joint stability. At the 14-month follow-up, he could walk steadily without any complications and his modified Harris hip score was 100. The DAA conserves soft tissue because it is an intermuscular approach. Accordingly, postoperative recovery is fast and thus associated with a low dislocation rate and effective pain reduction. The acetabulum with metastatic disease was reconstructed using a KT plate for hip joint stability. Bone with metastatic disease that appears adequate at the time of THA may become incompetent after a few years. THA with acetabular reconstruction using a KT plate through the DAA was an effective treatment for metastatic bone disease of the acetabulum combined with pathological proximal femoral neck fracture.

Visualization of endogenous nuclear F-actin in mouse embryos reveals abnormal actin assembly after somatic cell nuclear transfer.

Actin in the nucleus, referred to as nuclear actin, is involved in a variety of nuclear events. Nuclear actin is present as a globular (G-actin) and filamentous form (F-actin), and dynamic assembly/disassembly of nuclear actin profoundly affects nuclear functions. However, it is still challenging to observe endogenous nuclear F-actin. Here, we present a condition to visualize endogenous nuclear F-actin of mouse zygotes using different fixation methods. Zygotes fixed with paraformaldehyde and treated with fluorescently conjugated phalloidin show both short and long actin filaments in their pronuclei. Short nuclear actin filaments are characteristic of phalloidin staining, rather than the consequence of severing actin filaments by the fixation process, since long nuclear actin filaments probed with the nuclear actin chromobody are not disassembled into short filaments after fixation with paraformaldehyde. Furthermore, we find that nuclear actin assembly is impaired after somatic cell nuclear transfer (SCNT), suggesting abnormal nucleoskeleton structures in SCNT embryos. Taken together, our presented method for visualizing nuclear F-actin with phalloidin can be used to observe the states of nuclear actin assembly, and revealed improper reprogramming of actin nucleoskeleton structures in cloned mouse embryos.

Correction to: Correlation between functional ability, toe flexor strength, and plantar pressure of hallux valgus in young female adults: a cross-sectional study.

An amendment to this paper has been published and can be accessed via the original article.

Correlation between functional ability, toe flexor strength, and plantar pressure of hallux valgus in young female adults: a cross-sectional study.

BACKGROUND: The prevalence of hallux valgus (HV) increases with age in females. Several studies have investigated the relationship between foot problems, including HV, and falls in older individuals. This study aimed to examine whether HV causes a decline in functional activity in young females and also evaluate the relationship between HV angle, functional activity, toe flexor strength, and plantar pressure. METHODS: We assessed 94 females (mean age, 19.6 ± 1.3 years; mean body mass index, 21.2 ± 2.0 kg/m2) not currently receiving treatment for lower limb disease. HV angle was determined using their footprint. Functional reach (FR) and maximum step length (MSL), toe flexor strength, and plantar pressure were measured. Plantar pressure was measured during walking. We also calculated FR and the pressure in eight regions (first toe, second through fifth toes, first metatarsal, second through fourth metatarsals, fifth metatarsal, midfoot, medial heel, and lateral heel). RESULTS: There were 39 and 55 participants in the HV and no HV groups, respectively. FR and MSL did not differ significantly between the HV and no HV groups. Toe flexor strength was significantly different between the HV and no HV groups (26.69 ± 9.68 vs. 32.19 ± 8.55, respectively) (p = 0.002, ß = 0.206). During walking, plantar pressure was significantly lower in the second through fifth toes in the HV group (p = 0.005, ß = 0.187). During FR, plantar pressure was significantly greater in the first metatarsal in the HV group (p = 0.016, ß = 0.338). HV angle was negatively correlated with toe flexor strength (r = - 0.315, p = 0.002, ß = 0.121) and plantar pressure during walking in the second through fifth toes (r = - 0.362, p < 0.001, ß = 0.047), and positively correlated with plantar pressure during FR in the first metatarsal (r = 0.308, p = 0.002, ß = 0.137). Toe flexor strength was negatively correlated with plantar pressure during FR in the second through fourth metatarsals (r = - 0.318, p = 0.002, ß = 0.115), and there was a positive correlation with MSL (r = 0.330, p = 0.001, ß = 0.092). CONCLUSIONS: This study confirmed that HV reduces toe flexor strength and affects forefoot pressure during walking and FR in young females. Moreover, the toe flexor strength affects MSL. Efforts to prevent the onset and deterioration of HV from a young age might help reduce the risk of falling when older.

Zygotic Nuclear F-Actin Safeguards Embryonic Development.

After fertilization, sperm and oocyte nuclei are rapidly remodeled to form swollen pronuclei (PN) in mammalian zygotes, and the proper formation and function of PN are key to producing totipotent zygotes. However, how mature PN are formed has been unclear. We find that filamentous actin (F-actin) assembles in the PN of mouse zygotes and is required for fully functional PN. The perturbation of nuclear actin dynamics in zygotes results in the misregulation of genes related to genome integrity and abnormal development of mouse embryos. We show that nuclear F-actin ensures DNA damage repair, thus preventing the activation of a zygotic checkpoint. Furthermore, optogenetic control of cofilin nuclear localization reveals the dynamically regulated F-actin nucleoskeleton in zygotes, and its timely disassembly is needed for developmental progression. Nuclear F-actin is a hallmark of totipotent zygotic PN, and the temporal regulation of its polymerized state is necessary for normal embryonic development.

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.

Relationship between foot morphology and toe muscle strength in female university students.

[Purpose] The purpose was to clarify the relationship between foot morphology and toe muscle strength in female university students. [Participants and Methods] Data from 103 female university students (age, 20.4 ± 1.6 years) on height, body weight, pain in the foot and toes, heel height (cm) of shoes worn in everyday life, and the number of times (per week) shoes with heels ≥3 cm were worn were collected. The hallux valgus angle and medial longitudinal arch height ratio of the foot were measured, and toe muscle strength was evaluated according to the strength of the toe flexor and abductor hallucis muscles. [Results] Arch height ratio was significantly lower with hallux valgus angle ≥16°. In the 206 feet, a very weak negative correlation was found between hallux valgus angle and arch height ratio. In 150 feet with hallux valgus angle <16°, a very weak correlation was found between toe flexor strength and arch height ratio. [Conclusion] Body mass index was within the normal range, and the period of wearing high-heeled shoes was short; these factors have no effect on hallux valgus angle. Hallux valgus may be prevented by increasing toe flexor strength to prevent downward movement of the navicular and first cuneiform bones.

Inhibitory Effects of Phenylpropanoid Derivatives from Oenanthe javanica on Antigen-Stimulated Degranulation in RBL-2H3 Cells.

Two diacyldaucic acids (1 and 2), an α,ß-unsaturated γ-lactone-type lignan (3) and its derivatives (4-6), and 12 known compounds were isolated from a traditional East Asian vegetable, Oenanthe javanica. The absolute configuration of 1 was validated by obtaining (+)-osbeckic acid through acid hydrolysis. The absolute configurations of 3-5 were determined by comparing their experimental and computed ECD data. The conclusion was supported by applying the phenylglycine methyl ester method to 3. Compound 6 was obtained as an interconverting mixture of isomers in a 3:1 trans- cis ratio. Several water-soluble components (1, 3, and 6) showed concentration-dependent inhibitory effects on antigen-stimulated degranulation in RBL-2H3 cells without producing any direct cytotoxicity against RBL-2H3 or HeLa cells.

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.

OBJECTIVES: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD). METHODS: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n = 93, Study 2: n = 99) were retrospectively analyzed. RESULTS: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p < .001). A multiple regression analysis among baseline characteristics revealed that serum calcium (sCa: 8.5-10.5 mg/dL) was associated with an increased LS-BMD by treatment (r2: 0.088, p = .02). While average sCa of the patients was 9.2 mg/dL before treatment, it increased time-dependently to 9.6 mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike's information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3 mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3 mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3 mg/dL (0.8%, p = .038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed. CONCLUSION: sCa was associated with an increased LS-BMD by BPs with aVD.

Current Vitamin D Status in Healthy Japanese Infants and Young Children.

This study aimed to characterize serum 25-hydroxyvitamin D (25OH-D) values among Japanese children aged ≤48 mo. The study included 290 healthy infants and young children aged 0-48 mo (males/females=166/124) living in Shizuoka or Tokyo. The subjects were divided into three groups by age (Low Age: 0-5, Middle Age: 6-15, High Age: 16-48 mo). The vitamin D deficient state was defined as 25OH-D <12 ng/mL, the insufficient state as 12-20 ng/mL, and the sufficient state as >20 ng/mL. The seasonal variation of serum 25OH-D levels was also analyzed. The median serum 25OH-D levels in each group were: Low Age (n=50), 19 ng/mL; Middle Age (n=94), 30 ng/mL; and High Age (n=146), 30 ng/mL. The serum 25OH-D level was significantly lower in the Low Age group than in the other groups (p<0.01). Serum 25OH-D levels in summer and autumn (n=149) were significantly higher than in winter and spring (n=141) (33 vs. 25 ng/mL, p<0.01). In the Low Age group, there was a significant difference in serum 25OH-D levels between breast-fed infants (n=26) and formula-fed or mixed-fed infants (n=19) (12 vs. 32 ng/mL, p<0.01). However, there were no significant differences in 25OH-D levels between the two season classifications in either breast-fed or formula-fed and mixed-fed infants. Although clinical symptoms were not available, more than 75% of the breast-fed infants and 14.6% of infants and young children to whom food had been introduced were defined as having a vitamin D deficient or insufficient state. Breastfeeding seems one of the contributing factor to lower serum 25 OH-D levels among infants ≤5 mo of age.

Incidence rate and characteristics of symptomatic vitamin D deficiency in children: a nationwide survey in Japan.

There is concern that vitamin D deficiency is prevalent among children in Japan as well as worldwide. We conducted a nationwide epidemiologic survey of symptomatic vitamin D deficiency to observe its incidence rate among Japanese children. A questionnaire inquiring the number of new patients with vitamin D deficiency rickets and/or hypocalcemia for 3 years was sent to 855 randomly selected hospitals with a pediatrics department in Japan. In this survey, we found that 250 children were diagnosed with symptomatic vitamin D deficiency. The estimated number of patients with symptomatic vitamin D deficiency per year was 183 (95% confidence interval (CI): 145-222). The overall annual incidence rate among children under 15 years of age was 1.1 per 100,000 population (95% CI: 0.9-1.4). The second survey has provided detailed information on 89 patients with symptomatic vitamin D deficiency under 5 years of age in hospitals in the current research group. The nationwide and second surveys estimated the overall annual incidence rate of symptomatic vitamin D deficiency in children under 5 years of age to be 3.5 (2.7-4.2) per 100,000 population. The second survey revealed 83% had bowed legs, 88% had exclusive breastfeeding, 49% had a restricted and/or unbalanced diet and 31% had insufficient sun exposure among the 89 patients. This is the first nationwide survey on definitive clinical vitamin D deficiency in children in Japan. Elucidating the frequency and characteristics of symptomatic vitamin D deficiency among children is useful to develop preventative public health strategies.

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.