Current situation and outcomes of pregnancy in women with Turner syndrome in Japan.

AIM: Reports on pregnancy and delivery in women with Turner syndrome (TS) in Japan are limited to case reports, and the current situation remains unclear. Therefore, this study aimed to clarify the current situation of pregnancy and delivery in women with TS in Japan. METHODS: Our study comprised primary and secondary surveys and we included perinatal centers approved by the Ministry of Health, Labor and Welfare. RESULTS: A total of 24 cases from 19 facilities were reported, and we obtained individual information for 20 cases from 16 facilities. Of these 20 patients, 13 (65%) had become pregnant via oocyte donation. Three of these patients had received oocyte donation in Japan, while the other 10 had received donations in foreign countries. The other seven patients became pregnant with their own oocyte, with spontaneous menarche. Live babies were delivered by 18 patients, while an induced abortion was required at 18 weeks of gestation in one patient and an intrauterine fetal death from an unknown cause was detected at 38 weeks of gestation in another patient. Cesarean section was performed in 14 patients, with the most frequent indication being cephalopelvic disproportion. The rate of implementation of screening for complications related to TS was low, suggesting insufficient cooperation between facilities responsible for TS treatment, infertility and pregnancy and delivery management. CONCLUSION: To improve pregnancy outcomes in women with TS, improved cooperation between facilities and laws regarding oocyte donation in Japan are needed.

25-Hydroxyvitamin D profiles and maternal bone mass during pregnancy and lactation in Japanese women.

Vitamin D deficiency is observed worldwide and represents a health hazard for mothers, infants and elderly persons. We know that many young Japanese women experience vitamin D insufficiency; however, there is a lack of knowledge regarding the serum 25-hydroxyvitamin D [25(OH)D] profile of pregnant Japanese women and of the association between maternal 25(OH)D level and maternal bone mass during pregnancy and lactation. In this longitudinal study, 160 pregnant Japanese women were enrolled; of them, 68 have been followed-up from the first trimester through at least 1 year of breast-feeding. We estimated serum 25(OH)D levels, intact PTH levels, calcaneus quantitative ultrasound (QUS: T score) scores, bone mineral density at the distal one-third of the radius, dietary intakes according to the Food Frequency Questionnaire, and sunlight exposure times. We found that Vitamin D deficiency is prevalent in Japanese women, irrespective of pregnancy or lactation, and our analysis suggested that 25(OH)D levels and BMI in the first trimester were related to the lactating women's bone mass from after delivery to 1 year after delivery.

Comprehensive medical treatment of women with Turner syndrome may improve pregnancy outcomes: A case report.

A 35-year-old primiparous woman was diagnosed with Turner syndrome at the age of 12 yr due to short stature. Her karyotype showed a mosaic pattern [45, X(19)/46, XX(11)]. She had been followed up by the pediatric service. GH was not prescribed because, although she was of relatively short stature, her growth trajectory was reasonable. She was started on estrogen replacement therapy at 15 yr of age and switched to Kaufmann therapy after 1 yr. After transitioning her care to the gynecology service at 20 yr of age, she was screened for complications and Kaufmann therapy was continued. No abnormalities were detected in the pre-pregnancy screening. She conceived by in vitro fertilization and embryo transplantation with oocyte donation. No severe complications occurred during gestation, and she gave birth to a female neonate vaginally at 41 wk and 6 d of gestation. The neonate's birthweight was 3166 g, and her Apgar scores were 8 and 9 at 1 and 5 min, respectively. No severe complications occurred during the postpartum period. Comprehensive medical treatment and appropriate transition from pediatric to adult services may improve the pregnancy outcomes of women with Turner syndrome.

Activated vitamin D3 formulations can be safely used as concomitant medication for prevention of denosumab-induced hypocalcemia in women with postmenopausal osteoporosis.

AIM: Denosumab prevents osteoporosis by potently inhibiting bone resorption, but requires oral therapy with calcium and vitamin D preparations to prevent the side effects of hypocalcemia. Generally, a combination drug containing calcium, natural vitamin D, and magnesium is used. However, if activated vitamin D has been used before the initiation of denosumab therapy, continued use of activated vitamin D is not uncommon. This study aimed to evaluate the combination vitamin D preparation, alfacalcidol, and eldecalcitol on the therapeutic effect on denosumab therapy, the preventive effect on hypocalcemia, and the effect on renal function, to determine the optimal choice of concomitant medication. METHODS: This is a retrospective and single-center study. Among 39 patients who had used denosumab (60 mg dose) for at least 12 months between November 2013 and October 2015, those who used the combination medication concomitantly as the standard treatment, those who used alfacalcidol concomitantly, and those who used eldecalcitol concomitantly were compared. RESULTS: Denosumab therapy markedly increased lumbar spine and femoral neck bone densities at 12 months in the three groups, showing no particular difference in the rate of increase of bone density. The three groups had marked decreases in bone metabolism markers, but had no intergroup differences. No hypocalcemia, hypercalcemia, or obvious renal dysfunction occurred over 12 months. CONCLUSION: This study indicates that the use of activated vitamin D preparations, as concomitant medications with denosumab therapy, is appropriate considering the therapeutic efficacy of denosumab, prevention of hypocalcemia, and influence on renal function.

Eldecalcitol increases bone mass in patients with Turner syndrome who have insufficient bone mass acquisition after estrogen replacement therapy.

Most patients with Turner syndrome (TS) exhibit amenorrhea due to premature ovarian failure. Therefore, estrogen replacement therapy (ERT) is required; however, even after undergoing ERT, it is not rare for bone mass acquisition to be insufficient. This study was conducted in two stages, involving a cross-sectional and a prospective interventional study. We recruited 52 TS patients undergoing ERT due to amenorrhea (categorized into low (LB group; n = 23), and normal (NB group; n = 29) bone mass groups) and 7 TS patients who maintained ovarian function (spontaneous menstrual cycle group (MC group)) as controls. We compared bone associated markers between the three groups (LB, NB, and MC). Furthermore, the LB group had concomitant treatment with eldecalcitol (ELD) and ERT for 12 months. The bone mineral density (BMD) of the lumber spine (L2-4) and the bone metabolism markers were then compared before and after the treatment. The bone metabolism markers were significantly higher in the LB group than the NB and MC groups. Furthermore, with the concomitant use of ELD and ERT in the LB group, BMD increased significantly (pre-treatment 0.710 ± 0.056 g/cm2 vs. 0.736 ± 0.062 g/cm2 after 12 months; p < 0.001). TS patients with insufficient bone mass acquisition even after ERT were characterized by a higher turnover in bone metabolism. Therefore, the concomitant use of ELD was considered an effective adjuvant therapy for increasing bone mass.

Teriparatide and denosumab treatment for pregnancy and lactation-associated osteoporosis with multiple vertebral fractures: A case study.

OBJECTIVE: Pregnancy and lactation-associated osteoporosis (PLO) is a rare disease, which can lead to vertebral fractures in women of reproductive age. No treatment strategy for PLO has been established. Here we report a case of PLO treated with teriparatide followed by denosumab, in which remarkable improvement in bone mineral density (BMD) was achieved. CASE REPORT: A 27-year-old woman experienced severe back pain two weeks after her first delivery. PLO was diagnosed from her low BMD and multiple vertebral compression fractures. She was treated with teriparatide for 6 months, followed by denosumab. After 1 year, her BMD increase from baseline was 16.5% in L2∼4 and her pain had been relieved. CONCLUSION: In addition to weaning, administration of teriparatide followed by denosumab led to remarkable improvement in the patient's symptoms and BMD. Therefore, we regard this method as a promising choice for the treatment of PLO.

Efficacy of estrogen replacement therapy (ERT) on uterine growth and acquisition of bone mass in patients with Turner syndrome.

Estrogen replacement therapy (ERT) is necessary for uterine development and bone mass acquisition in women with Turner syndrome (TS) suffering from ovarian insufficiency. However, adequate ERT regimens have not yet been established. The aim of this study was to evaluate the efficacy of ERT for both uterine development and bone mass acquisition. One hundred TS patients from Yokohama City University Hospital (88 with primary amenorrhea (PA) and 12 patients with spontaneous menstrual cycles (MC)) were enrolled after obtaining consent. Clinical profiles, uterine length (UL) measured by ultrasonic examination, and bone mineral density (BMD) of the lumbar vertebrae (L2-4) assessed by DEXA were evaluated. At the time of the first visit, the ULs of patients in the PA group were significantly shorter than those in the MC group. After receiving ERT, there were no significant differences in UL between patients with PA and MC. Forty-seven patients for whom the ERT initiation age was known were investigated to clarify the influence on BMD. The results showed that the BMD in the late initiation (18 years or older) group at the latest visit (0.770 ± 0.107 g/cm2: n = 16) was significantly lower than that in the early initiation (under 18 years) group (0.858 ± 0.119 g/cm2: n = 21) or the MC group (0.941 ± 0.118 g/cm2: n = 10). No significant differences were seen between the early initiation and MC group. ERT was effective in increasing UL and BMD. However, early initiation of ERT is necessary to increase BMD.