The association between serum vitamin D status and dental caries or molar incisor hypomineralisation in 7-9-year-old Norwegian children: a cross-sectional study.

BACKGROUND: Research focusing on the association between serum vitamin D and oral health outcomes in children, such as dental caries and molar incisor hypomineralisation (MIH), shows inconsistent results. Previous studies have predominantly investigated dental caries and MIH as dichotomized outcomes, which limits the information on their distribution. In addition, the methods used for analysing serum vitamin D have varied. The present study aimed to investigate potential associations between serum vitamin D status measured by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) and the prevalence, as well as the number of teeth, affected by dental caries or MIH among 7-9-year-old Norwegian children. METHODS: The study had a cross-sectional design and included 101 children aged 7-9 years. Serum 25-hydroxyvitamin D (25(OH)D) was measured and included as continuous (per 25 nmol/l) and categorised (insufficient (< 50 nmol/l) and sufficient (≥50 nmol/l)) exposure variables. Adjusted negative binomial hurdle models were used to investigate the potential associations between serum vitamin D and the oral health outcomes (dental caries and MIH) adjusted for sex, age, body mass index, season of blood draw, and mother's educational level. RESULTS: Of the 101 children in the total sample, 27% had insufficient vitamin D levels (< 50 nmol/l). The descriptive analysis indicated that the children with insufficient vitamin D levels had a higher prevalence (33.3%) and a higher number of teeth affected by dental caries (mean (SD) = 0.7 (1.4)), compared to children with sufficient levels of vitamin D (21.6% and mean (SD) = 0.4 (0.8), respectively). The same holds for MIH, with a higher prevalence (38.5%) and a higher number of teeth affected (mean (SD) = 1.2 (2.3)), compared to children with sufficient levels of vitamin D (30.1% and mean (SD) = 0.8 (1.6), respectively). However, in the adjusted hurdle model analysis, neither the prevalence or number of teeth affected by caries or MIH showed statistically significant associations with having insufficient or lower vitamin D levels. CONCLUSIONS: Vitamin D status was not significantly associated with the prevalence and number of teeth affected by caries and MIH among the participating children. Large prospective studies with multiple serum vitamin D measurements and oral examinations throughout childhood are warranted to elucidate the relationship.

Body composition in adults born preterm with very low birth weight.

BACKGROUND: Studies on body composition in preterm very low birth weight (VLBW < 1500 g) survivors are inconsistent and trajectories later in life unknown. We assessed body composition and its change from young to mid-adulthood in VLBW adults. METHODS: We studied 137 VLBW adults and 158 term-born controls from two birth cohorts in Finland and Norway at mean age 36 years. Body composition was assessed by 8-polar bioelectrical impedance. We compared results with dual-energy x-ray absorptiometry measurements at 24 years. RESULTS: In mid-adulthood, VLBW women and men were shorter than controls. Fat percentage (mean difference in women 1.1%; 95% CI, -1.5% to 3.5%, men 0.8%; -2.0% to 3.6%) and BMI were similar. VLBW women had 2.9 (0.9 to 4.8) kg and VLBW men 5.3 (2.7 to 8.1) kg lower lean body mass than controls, mostly attributable to shorter height. Between young and mid-adulthood, both groups gained fat and lean body mass (p for interaction VLBW x age>0.3). CONCLUSION: Compared with term-born controls, VLBW adults had similar body fat percentage but lower lean body mass, largely explained by their shorter height. This could contribute to lower insulin sensitivity and muscular fitness previously found in VLBW survivors and predispose to functional limitations with increasing age. IMPACT: In mid-adulthood, individuals born preterm with very low birth weight had similar body fat percentage but lower lean body mass than those born at term. This was largely explained by their shorter height. First study to report longitudinal assessments of body size and composition from young to mid-adulthood in very low birth weight adults. Lower lean body mass in very low birth weight adults could contribute to lower insulin sensitivity and muscular fitness and lead to earlier functional limitations with increasing age.

Irisin reduces orthodontic tooth movement in rats by promoting the osteogenic potential in the periodontal ligament.

OBJECTIVES: Positive effects of irisin on osteogenic differentiation of periodontal ligament (PDL) cells have been identified previously, this study aims to examine its effect on orthodontic tooth movement (OTM) in vivo. MATERIALS AND METHODS: The maxillary right first molars of male Wistar rats (n = 21) were moved mesially for 14 days, with submucosal injection of two dosages of irisin (0.1 or 1 µg) or phosphate-buffered saline (control) every third day. OTM was recorded by feeler gauge and micro-computed tomography (µCT). Alveolar bone and root volume were analysed using µCT, and plasma irisin levels by ELISA. Histological characteristics of PDL tissues were examined, and the expression of collagen type I, periostin, osteocalcin (OCN), von Willebrand factor (vWF) and fibronectin type III domain-containing protein 5 (FNDC5) in PDL was evaluated by immunofluorescence staining. RESULTS: Repeated 1 µg irisin injections suppressed OTM on days 6, 9, and 12. No significant differences were observed in OTM in the 0.1 µg irisin group, or in bone morphometric parameters, root volume or plasma irisin, compared to control. Resorption lacunae and hyalinization were found at the PDL-bone interface on the compression side in the control, whereas they were scarce after irisin administration. The expression of collagen type I, periostin, OCN, vWF, and FNDC5 in PDL was enhanced by irisin administration. LIMITATIONS: The feeler gauge method may overestimate OTM. CONCLUSIONS: Submucosal irisin injection reduced OTM by enhancing osteogenic potential of PDL, and this effect was more significant on the compression side.

Targeting a therapeutically relevant concentration of alendronate for in vitro studies on osteoblasts.

OBJECTIVE: Bisphosphonates like alendronate mainly exert their effects on osteoclasts. However, osteoblasts are also affected, but exposed to a much lower concentration in vivo than the osteoclasts. Given that the effects are dose-dependent, the intention of the study was to identify a therapeutically relevant concentration of alendronate for in vitro studies on osteoblasts. MATERIALS AND METHODS: Primary human osteoblasts were incubated with alendronate (5, 20 and 100 µM) for 1, 3, 7 and 14 days. Proliferation and viability were assessed, and the effects on cellular growth and function were evaluated by multianalyte profiling of selected proteins in cell culture media using the Luminex 200TM. RESULTS: The viability was not affected by any of the dosages. Exposure to 5 µM alendronate had a neutral effect on osteoblast proliferation, and on secretion of osteogenic and inflammatory markers, while enhancing synthesis of a marker of angiogenesis. 20 µM alendronate induced a decline in proliferation and affected angiogenic and osteogenic biomarkers adversely. 100 µM alendronate reduced proliferation dramatically, and this dosage was excluded from further experiments. CONCLUSION: A concentration of 5 µM alendronate exerted effects on human osteoblasts that may translate to those observed in vivo and could therefore be relevant for in vitro studies.

Gastric Corpus Mucosal Hyperplasia and Neuroendocrine Cell Hyperplasia, but not Spasmolytic Polypeptide-Expressing Metaplasia, Is Prevented by a Gastrin Receptor Antagonist in H+/K+ATPase Beta Subunit Knockout Mice.

Proton pump inhibitor use is associated with an increased risk of gastric cancer, which may be mediated by hypergastrinemia. Spasmolytic polypeptide-expression metaplasia (SPEM) has been proposed as a precursor of gastric cancer. We have examined the effects of the gastrin receptor antagonist netazepide (NTZ) or vehicle on the gastric corpus mucosa of H+/K+ATPase beta subunit knockout (KO) and wild-type (WT) mice. The gastric corpus was evaluated by histopathology, immunohistochemistry (IHC), in situ hybridization (ISH) and whole-genome gene expression analysis, focusing on markers of SPEM and neuroendocrine (NE) cells. KO mice had pronounced hypertrophy, intra- and submucosal cysts and extensive expression of SPEM and NE cell markers in the gastric corpus, but not in the antrum. Numerous SPEM-related genes were upregulated in KO mice compared to WT mice. NTZ reduced hypertrophia, cysts, inflammation and NE hyperplasia. However, NTZ neither affected expression of SPEM markers nor of SPEM-related genes. In conclusion, NTZ prevented mucosal hypertrophy, cyst formation and NE cell hyperplasia but did not affect SPEM. The presence of SPEM seems unrelated to the changes caused by hypergastrinemia in this animal model.

The effect of an exercise program in pregnancy on vitamin D status among healthy, pregnant Norwegian women: a randomized controlled trial.

BACKGROUND: Vitamin D insufficiency is common in pregnant women worldwide. Regular prenatal exercise is considered beneficial for maternal and fetal health. There is a knowledge gap regarding the impact of prenatal exercise on maternal vitamin D levels. The objective of this study was to investigate whether a prenatal exercise program influenced serum levels of total, free and bioavailable 25-hydroxyvitamin D (25(OH)D) and related parameters. This is a post hoc analysis of a randomized controlled trial with gestational diabetes as the primary outcome. METHODS: Healthy, pregnant women from two Norwegian cities (Trondheim and Stavanger) were randomly assigned to a 12-week moderate-intensity exercise program (Borg perceived rating scale 13-14) or standard prenatal care. The intervention group (n = 429) underwent exercise at least three times weekly; one supervised group training and two home based sessions. The controls (n = 426) received standard prenatal care, and exercising was not denied. Training diaries and group training was used to promote compliance and evaluate adherence. Serum levels of 25(OH)D, parathyroid hormone, calcium, phosphate, magnesium and vitamin D-binding protein were measured before (18-22 weeks' gestation) and after the intervention (32-36 weeks' gestation). Free and bioavailable 25(OH)D concentrations were calculated. Regression analysis of covariance (ANCOVA) was applied to assess the effect of the training regime on each substance with pre-intervention levels as covariates. In a second model, we also adjusted for study site and sampling month. Intention-to-treat principle was used. RESULTS: A total of 724 women completed the study. No between-group difference in serum 25(OH)D and related parameters was identified by ANCOVA using baseline serum levels as covariates. The second model revealed a between-group difference in levels of 25(OH)D (1.9, 95% CI 0.0 to 3.8 nmol/L; p = 0.048), free 25(OH)D (0.55, 95% CI 0.10 to 0.99 pmol/L; p = 0.017) and bioavailable 25(OH)D (0.15 95% CI 0.01 to 0.29 nmol/L; p = 0.036). No serious adverse events related to regular exercise were seen. CONCLUSION: This study, a post hoc analysis, indicates that exercise may affect vitamin D status positively, and emphasizes that women with uncomplicated pregnancies should be encouraged to perform regular exercise. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00476567 , registered May 22, 2007.

Prevalence of Sexually Transmitted Infections among Married Women in Rural Nepal.

Introduction: We have previously determined the prevalence of human papillomavirus (HPV) infection among women in rural Nepal. In the current study, we also wanted to examine the prevalence of and risk factors for other sexually transmitted infections (STIs) in the same population. Methods: Population-based study of nonpregnant women ≥ 15 years who were married or had a history of marriage in the past, residing in five rural villages in Nepal. Data on sociodemographic characteristics, reproductive history, and genitourinary symptoms were collected, and a gynecological examination was conducted. Cervical samples were analyzed by real-time PCR for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis and HPV, and a serum sample was analyzed for syphilis, hepatitis B virus (HBV) and HIV infection by serology. Results: Of 2416 eligible women, 62% participated. Trichomoniasis, Chlamydia trachomatis infection, HPV and HBV infection, and syphilis were detected in 5.4%, 0.8%, 14.3%, 0.3%, and 0.2% of the women. None had gonorrhea or HIV infection. Of those with genitourinary symptoms, 6.3% had a curable STI. Vaginal discharge classified as abnormal by gynecological examination, but not self-reported discharge, was significantly associated with laboratory diagnosis of a curable STI. Risk factors for trichomoniasis were reproductive age and high cast/ethnicity. Due to low prevalence, risk factors for other STIs could not be disclosed. Conclusion: We observed high prevalence of HPV infection followed by trichomoniasis, while other STIs were rare among women in rural Nepal. There was no association between genitourinary symptoms and laboratory-confirmed STIs.

Bone mineral density is close to normal for age in long-term lymphoma survivors treated with high-dose therapy with autologous stem cell transplantation.

BACKGROUND: Few studies have assessed bone health in lymphoma survivors treated with high-dose therapy with autologous stem cell transplantation (HDT-ASCT). Therefore, we aimed to assess bone mineral density (BMD) at six different skeletal sites and to investigate associations between clinical factors and BMD in these survivors. MATERIAL AND METHODS: Eligible lymphoma survivors were aged ≥18 years at diagnosis and at HDT-ASCT given between 1987 and 2008. Participants responded to questionnaires, blood samples were drawn, and a dual energy X-ray absorptiometry (DXA) was performed. Mean Z-score was applied for assessment of BMD in relation to age. Prevalence of Z-scores ≥-1, between -1 and -2, and ≤-2 is reported for each measurement site and for the lumbar spine, femoral neck, and hip in combination. Likewise, T-scores were applied to assess the prevalence of normal BMD (≥-1), osteopenia (between -1 and -2.5), and osteoporosis (≤-2.5). RESULTS: We included 228 lymphoma survivors, of whom 62% were males. The median age at survey was 56 years, and median observation time from HDT-ASCT was eight years. Among males, Z-scores were lower at the left femoral neck and higher at the ultra-distal (UD) radius and whole body compared to the Lunar reference database. In females, Z-scores were lower at UD radius and one-third (33%) radius and higher at the whole body. Using a classification based on Z-scores at the lumbar spine, femoral neck, and hip in combination, 25% of males and 16% of females had Z-scores <-1 and >-2, while 8% and 6% had Z-scores ≤-2. According to T-scores, 35% of males and 41% of females had osteopenia, while 8% and 13% had osteoporosis, respectively. CONCLUSION: BMD was close to normal for age in this population of long-term lymphoma survivors treated with HDT-ASCT.

Prevalence of human papillomavirus infection among women in rural Nepal.

INTRODUCTION: In this study we aimed to determine the overall and type-specific prevalence of cervical human papillomavirus (HPV) infection and risk factors for such infection among women in rural Nepal, and to investigate the distribution of HPV infection by cervical cytology. MATERIAL AND METHODS: The study was conducted among women aged ≥15 years in five rural villages within Kavre District in Nepal. Sociodemographic data and information on risk factors for cervical cancer were obtained through an interview, and a cervical specimen was collected for HPV DNA detection and typing using the Anyplex™ ll HPV28 Detection system, and for Papanicolaou test. RESULTS: Among the 1289 women in whom a valid HPV result was obtained the median age was 40 years (range 17-86 years). Overall, the HPV prevalence was 14.4%, 7.9% for high-risk and 6.5% for low-risk HPV types, and was similar between age groups. The five most common HR types were HPV-18 (2.3%), HPV-51 (1.2%), HPV-59 (1.1%), HPV-31 (0.9%), and HPV-16 (0.8%). The prevalence of high-risk types in women with and without abnormal cytology was 8.3 and 7.7%, respectively. HPV infection was associated with current smoking, formal education, and being married to a husband with at least one previous marriage. CONCLUSIONS: This is the first population-based study to report the prevalence of a broad range of HPV types among women from rural Nepal. These data are crucial for development of preventive strategies to reduce cervical cancer burden in the country.

High doses of vitamin C plus E reduce strength training-induced improvements in areal bone mineral density in elderly men.

PURPOSE: Resistance training is beneficial for maintaining bone mass. We aimed to investigate the skeletal effects of high doses of antioxidants [vitamin C + E (α-tocopherol)] supplementation during 12-week supervised strength training in healthy, elderly men METHODS: Design: double-blinded randomized placebo-controlled study. Participants followed a supervised, undulating periodic exercise program with weekly adjusted load: 3 sessions/week and 3-15 repetitions maximum (RM) sets/exercise. The control group (CG, n = 17, 67 ± 5 years) received placebo and the antioxidant group (AO, n = 16, 70 ± 7 years) 1000 mg vitamin C + 235 mg vitamin E, daily. Areal bone mineral density (aBMD) at whole body, lumbar spine (L1-L4), total hip, and femoral neck were measured by dual energy X-ray absorptiometry and muscle strength by 1RM. Serum analyses of bone-related factors and adipokines were performed. RESULTS: In the CG, total hip aBMD increased by 1.0% (CI: 0.3-1.7) versus pretest and lumbar spine aBMD increased by 0.9% (CI: -0.2 to 2.0) compared to the AO. In the CG, there was an increase in serum concentrations of insulin-like growth factor 1 [+27.3% (CI: -0.3 to 54.9)] and leptin [+31.2% (CI: 9.8-52.6)) versus pretest, and a decrease in sclerostin [-9.9% (CI: 4.4-15.3)] versus pretest and versus AO. Serum bone formation markers P1NP and osteocalcin increased in both groups, while the bone resorption marker CTX-1 remained unchanged. CONCLUSION: High doses of antioxidant supplementations may constrain the favorable skeletal benefits of 12 weeks of resistance exercise in healthy elderly men.

Effects of the Histamine 1 Receptor Antagonist Cetirizine on the Osteoporotic Phenotype in H(+) /K(+) ATPase Beta Subunit KO Mice.

Epidemiological studies suggest increased fracture risk in patients using proton pump inhibitors (PPIs). We have previously shown that the H(+) /K(+) ATPase beta subunit knockout (KO) mouse, which is a model of PPI-use, have lower bone mineral density (BMD) and impaired bone quality compared to wild type (WT) mice. Like PPI users, these KO mice display elevated gastric pH and hypergastrinemia, which in turn stimulates gastric histamine release. Previous studies have suggested a negative effect of histamine on bone, thus, we wanted to study whether a histamine 1 receptor (H1R) antagonist could improve bone quality in KO mice. Female KO and WT mice aged 8 weeks received either an H1R antagonist (cetirizine) or polyethylene glycol (PEG) for 6 months. At the end of the study, KO mice displayed elevated plasma histamine levels compared to WT. As demonstrated previously, the KO mice also exhibited lower whole body BMD, reduced mechanical bone strength, and impaired bone quality assessed by µCT. No significant differences, however, were found between the KO groups receiving cetirizine or PEG for any of the measured bone parameters. In vitro gene expression analyses of histamine receptors revealed the presence of H1R and H2R both in osteoblasts and osteoclasts, and H3R in late stage osteoblasts. In conclusion, administration of the H1R antagonist cetirizine in a concentration of 3 mg/kg did not rescue the osteoporotic phenotype in H(+) /K(+) ATPase beta subunit KO mice. It can, however, not be ruled out that histamine may influence bone via other receptors. J. Cell. Biochem. 117: 2089-2096, 2016. © 2016 Wiley Periodicals, Inc.

Impaired skeletal health in patients with chronic atrophic gastritis.

OBJECTIVE: In chronic atrophic gastritis (CAG), destruction of gastric parietal cells causes anacidity and hypergastrinemia. Use of proton pump inhibitors, which also induces gastric anacidity, is associated with increased fracture rates. Our objectives were to study possible differences in bone mineral density (BMD) and bone quality in patients with CAG compared to controls. MATERIAL AND METHODS: We performed a cross-sectional study on 17 CAG patients aged 54 ± 13 years and 41 sex- and age-matched controls. Lumbar and femoral BMD and bone quality assessed by lumbar trabecular bone score (TBS) were measured by DXA, and bone material strength (BMS) by microindentation of the tibia. Serum bone markers (CTX, P1NP, sclerostin, osteocalcin, OPG, RANKL) were analyzed. RESULTS: We found lower lumbar BMD Z-score (-0.324 ± 1.096 versus 0.456 ± 1.262, p = 0.030), as well as a higher frequency of osteoporosis at the lumbar spine (p = 0.046) and osteopenia at total hip (p = 0.019) in patients compared to controls. In a post hoc subgroup analysis, we observed that the differences were confined to the male patients. TBS also tended to be lower in male patients (p = 0.059), while BMS did not differ between the groups. Osteocalcin, sclerostin, OPG, and OPG/RANKL ratio were lower in patients compared to controls, while CTX and P1NP did not differ between the groups. CONCLUSIONS: We observed lower lumbar BMD, increased frequency of osteopenia and osteoporosis in male, but not female patients with CAG. Bone markers suggest a decrease in bone formation and increased bone resorption in CAG patients compared to controls.

Community-Based Health Education has Positive Influence on the Attitude to Cervical Cancer Screening among Women in Rural Nepal.

The main purpose of this study was to assess the knowledge of cervical cancer among women in rural Nepal and explore the feasibility and impact of a community-based awareness program on cervical cancer. Community-based educational meetings on cervical cancer and its prevention were conducted among women's groups in rural Nepal. Through a questionnaire, the women's baseline knowledge of risk factors, symptoms, and perceived risk of cervical cancer were identified. The willingness to participate in cervical cancer screening was compared before and after the educational meeting. The meetings were followed by a cervical cancer screening program. Among the 122 participants at the educational meeting, only 6 % had heard of cervical cancer. Their baseline knowledge of risk factors and symptoms was poor. The proportion of women willing to participate in cervical screening increased from 15.6 to 100 % after attending the educational meeting. All the study subjects participated in the screening program. Additionally, the study participants recruited a further 222 of their peers for screening. Poor knowledge of cervical cancer among women in rural Nepal highlights the urgency of public awareness programs for cervical cancer at a national level. A community-based awareness program can change women's attitude to cervical screening, and women's groups can play a major role in promoting participation in cervical cancer screening programs.

Assessment of body composition in children with cerebral palsy: a cross-sectional study in Norway.

AIM: The assessment of growth and body composition is challenging in children with cerebral palsy (CP). The aim of this study was to compare clinical assessments of body composition with measurements obtained using dual-energy X-ray absorptiometry (DXA) in this population. METHOD: Knee height, weight, and triceps and subscapular skinfold thickness (SFT) were measured in 47 children with CP (age range 8-18y; 18 females, 29 males). Height was estimated from knee height, and used to calculate body mass index (BMI). Using SFT measurements, body fat percentage was calculated by standard ('Slaughter') and CP-modified ('Gurka') equations and compared with results obtained using DXA. RESULTS: Children with severe gross motor function impairments (Gross Motor Function Classification System [GMFCS] level III or IV) exhibited stunted growth and had higher fat percentages and lower lean body mass than children classified in GMFCS level I or II. In 10 children classified as 'thin' according to their BMI (five of whom were assigned thinness grade of 2 or lower), percentage of body fat, as determined by DXA, was normal or high. The Slaughter equations significantly underestimated body fat percentages, whereas the precision of the CP-modified Gurka equations was excellent. INTERPRETATION: In this study, children with CP and severe motor impairments displayed stunted growth, but were not undernourished. Relying solely upon BMIs may be misleading in children with CP. Therefore, clinicians should be encouraged to measure SFT and to calculate body fat percentages using the CP-modified version of the Slaughter equation.

Maximal strength training improves bone mineral density and neuromuscular performance in young adult women.

-Exercise guidelines highlight maximizing bone mass early in life as a strategy to prevent osteoporosis. Which intervention is most effective for this purpose remains unclear. This study investigated the musculoskeletal effects of high acceleration, maximal strength training (MST), in young adult women. Thirty healthy women (22 ± 2 years) were randomly assigned to a training group (TG) and a control group (CG). The TG completed 12 weeks of squat MST, executed at 85-90% of maximal strength 1 repetition maximum (1RM), emphasizing progressive loading and high acceleration in the concentric phase. The CG was encouraged to follow the American College of Sports Medicine's exercise guidelines for skeletal health. Measurements included bone mineral density (BMD) and body composition by dual-energy X-ray absorptiometry, dynamic and isometric rate of force development (RFD), and squat 1RM. Serum levels of type 1 collagen amino-terminal propeptide (P1NP), type 1 collagen C breakdown products (CTX), and sclerostin were analyzed by immunoassays. In the TG, lumbar spine and total hip BMD increased by 2.2 and 1.0%, whereas serum P1NP increased by 26.2%. Dynamic RFD and 1RM improved by 81.7 and 97.7%, and isometric RFD improved by 38% at 100 milliseconds. These improvements were significantly greater than those observed in the CG. Within the CG, dynamic RFD and 1RM increased by 27.2 and 12.9% while no other significant changes occurred. These findings suggest that squat MST may serve as a simple, time-efficient strategy to optimize peak bone mass in early adulthood.

Maximal strength training in postmenopausal women with osteoporosis or osteopenia.

Current guidelines recommend weight-bearing activities, preferably strength training for improving skeletal health in patients with osteoporosis. What type of strength training that is most beneficial for these patients is not established. Maximal strength training (MST) is known to improve 1-repetition maximum (1RM) and rate of force development (RFD), which are considered as important covariables for skeletal health. Squat exercise MST might serve as an effective intervention for patients with low bone mass. We hypothesized that 12 weeks of squat exercise MST would improve 1RM and RFD in postmenopausal women with osteoporosis or osteopenia and that these changes would coincide with improved bone mineral density (BMD) and bone mineral content (BMC), and serum markers of bone metabolism. The participants were randomized to a training group (TG, n = 10) or control group (CG, n = 11). The TG underwent 12 weeks of supervised squat exercise MST, 3 times a week, with emphasis on rapid initiation of the concentric part of the movement. The CG was encouraged to follow current exercise guidelines. Measurements included 1RM, RFD, BMD, BMC, and serum bone metabolism markers; type 1 collagen amino-terminal propeptide (P1NP) and type 1 collagen C breakdown products (CTX). At posttest, 8 participants remained in each group for statistical analyses. The TG improved the 1RM and RFD by 154 and 52%, respectively. Lumbar spine and femoral neck BMC increased by 2.9 and 4.9%. The ratio of serum P1NP/CTX tended to increase (p = 0.09), indicating stimulation of bone formation. In conclusion, squat exercise MST improved 1RM, RFD, and skeletal properties in postmenopausal women with osteopenia or osteoporosis. The MST can be implemented as a simple and effective training method for patients with reduced bone mass.

Osteocyte-Like Cells Differentiated From Primary Osteoblasts in an Artificial Human Bone Tissue Model.

In vitro models of primary human osteocytes embedded in natural mineralized matrix without artificial scaffolds are lacking. We have established cell culture conditions that favored the natural 3D orientation of the bone cells and stimulated the cascade of signaling needed for primary human osteoblasts to differentiate into osteocytes with the characteristically phenotypical dendritic network between cells. Primary human osteoblasts cultured in a 3D rotating bioreactor and incubated with a combination of vitamins A, C, and D for up to 21 days produced osteospheres resembling native bone. Osteocyte-like cells were identified as entrapped, stellate-shaped cells interconnected through canaliculi embedded in a structured, mineralized, collagen matrix. These cells expressed late osteoblast and osteocyte markers such as osteocalcin (OCN), podoplanin (E11), dentin matrix acidic phosphoprotein 1 (DMP1), and sclerostin (SOST). Organized collagen fibrils, observed associated with the cell hydroxyapatite (HAp) crystals, were found throughout the spheroid and in between the collagen fibrils. In addition to osteocyte-like cells, the spheroids consisted of osteoblasts at various differentiation stages surrounded by a rim of cells resembling lining cells. This resemblance to native bone indicates a model system with potential for studying osteocyte-like cell differentiation, cross-talk between bone cells, and the mineralization process in a bonelike structure in vitro without artificial scaffolds. In addition, natural extracellular matrix may allow for the study of tissue-specific biochemical, biophysical, and mechanical properties. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Associations between maternal and offspring glucose metabolism: a 9-year follow-up of a randomised controlled trial.

Introduction: There is increasing evidence that the in utero environment affects the health and disease risk of offspring throughout their lives. The long-term effect of maternal hyperglycaemia on offspring glucose metabolism is of interest in a public health perspective. The aim of this study was to examine the association between in utero exposure to maternal glycaemia and offspring glucose metabolism. Methods: Mother-child pairs were recruited from an RCT to prevent gestational diabetes mellitus where 855 healthy pregnant women were randomised to exercise or standard antenatal care. The original RCT detected no group differences in gestational diabetes mellitus prevalence or insulin resistance. The two groups were analysed as one group in the present study. Maternal glucose levels were assessed after 2-hour 75-gram oral glucose tolerance tests in pregnancy week ~34. Offspring outcomes were evaluated at ~9 years of age and included fasting glucose and homeostatic model assessment of insulin resistance. Multivariable regression models were performed, controlling for potential hereditary and lifestyle confounding factors. Results: Complete data were available for 105 mother-child pairs. The regression analysis showed a positive association between maternal and offspring fasting glucose that was borderline significant (beta=0.18, 95% CI [-0.00027, 0.37], p=0.050). We did not find significant associations between maternal fasting glucose and offspring insulin resistance (beta=0.080, 95% CI [-0.087, 0.25], p=0.34), or between maternal 2-hour glucose and offspring fasting glucose (beta=0.016, 95% CI [-0.038, 0.070], p=0.56) or insulin resistance (beta=0.017, 95% CI [-0.032, 0.065], p=0.49). Conclusions: Assessing a homogeneous group of healthy mother-child pairs, we found a borderline significant positive association between maternal and offspring fasting glucose, which persisted after adjustment for potential hereditary and lifestyle confounding factors. Our findings support other similar studies and highlight that improving the metabolic health of pregnant women, and women in childbearing age, should remain a key public health priority. Clinical trial registration: ClinicalTrials.gov, identifier NCT00476567.

Decreased bone mineral density and reduced bone quality in H(+) /K(+) ATPase beta-subunit deficient mice.

Proton pump inhibitors (PPIs) are widely used against gastroesophageal reflux disease. Recent epidemiological studies suggest that PPI users have an increased risk of fractures, but a causal relationship has been questioned. We have therefore investigated the skeletal phenotype in H(+) /K(+) ATPase beta-subunit knockout (KO) female mice. Skeletal parameters were determined in 6- and 20-month-old KO mice and in wild-type controls (WT). Whole body bone mineral density (BMD) and bone mineral content (BMC) were measured by dual energy X-ray absorptiometry (DXA). Femurs were examined with µCT analyses and break force were examined by a three-point bending test. Plasma levels of gastrin, RANKL, OPG, osteocalcin, leptin, and PTH were analyzed. KO mice had lower whole body BMC at 6 months (0.53 vs. 0.59 g, P = 0.035) and at 20 months (0.49 vs. 0.74 g, P < 0.01) compared to WT as well as lower BMD at 6 months (0.068 vs. 0.072 g/cm(2) , P = 0.026) and 20 months (0.067 vs. 0.077 g/cm(2) , P < 0.01). Mechanical strength was lower in KO mice at the age of 20 months (6.7 vs. 17.9 N, P < 0.01). Cortical thickness at 20 months and trabecular bone volume% at 6 months were significantly reduced in KO mice. Plasma OPG/RANKL ratio and PTH was increased in KO mice compared to controls. H(+) /K(+) ATPase beta subunit KO mice had decreased BMC and BMD, reduced cortical thickness and inferior mechanical bone strength. Whereas the mechanism is uncertain, these findings suggest a causal relationship between long-term PPI use and an increased risk of fractures.

Ten years' experience with centralized surgery of ovarian cancer in one health region in Norway.

BACKGROUND: Better outcome of advanced ovarian cancer after centralized surgery has led to the recommendation for centralized surgery in a Norwegian health region. Whether the practice pattern has changed according to this recommendation has not been examined. OBJECTIVE: The objective of this study was to evaluate the referral practice and treatment of ovarian cancer in a Norwegian health region after the introduction of centralized surgery. METHODS: This was a retrospective, population-based study, including all women undergoing surgery for primary ovarian, tubal, and peritoneal cancer between 2000 and 2005, in Health Region IV of Norway. Clinical data and data regarding treatment and 5-year follow-up were analyzed. RESULTS: In total, 279 cases of ovarian, peritoneal, and tubal cancer were included. Eighty-four percent underwent primary surgery at the teaching hospital and 16% at the nonteaching hospitals. After an immediate rise in the number of cases undergoing primary surgery at the teaching hospital after the introduction of centralization in 1995, the percentage distribution between the teaching and nonteaching hospitals was stable during the study period. The women who underwent surgery at the nonteaching hospitals had a higher percentage of early-stage disease and were at higher risk of reoperation for comprehensive staging. CONCLUSIONS: Centralization of ovarian cancer surgery has been successfully accomplished in a health region in Norway. The referral practice of assumed advanced ovarian cancer cases shows satisfactory compliance with centralization at 10 years after the implementation of centralized surgery.