Using online game-based platforms to improve student performance and engagement in histology teaching.

BACKGROUND: Human morphology is a critical component of dental and medical graduate training. Innovations in basic science teaching methods are needed to keep up with an ever-changing landscape of technology. The purpose of this study was to investigate whether students in a medical and dental histology course would have better grades if they used gaming software Kahoot® and whether gamification effects on learning and enjoyment. METHODS: In an effort to both evoke students' interest and expand their skill retention, an online competition using Kahoot® was implemented for first-year students in 2018 (n = 215) at the University of Eastern Finland. Additionally, closed (160/215) or open-ended (41/215) feedback questions were collected and analyzed. RESULTS: The Kahoot® gamification program was successful and resulted in learning gains. The overall participant satisfaction using Kahoot® was high, with students (124/160) indicating that gamification increased their motivation to learn. The gaming approach seemed to enable the students to overcome individual difficulties (139/160) and to set up collaboration (107/160); furthermore, gamification promoted interest (109/160), and the respondents found the immediate feedback from senior professionals to be positive (146/160). In the open-ended survey, the students (23/41) viewed collaborative team- and gamification-based learning positively. CONCLUSION: This study lends support to the use of gamification in the teaching of histology and may provide a foundation for designing a gamification-integrated curriculum across healthcare disciplines.

Serum 25-Hydroxyvitamin D, Plasma Lipids, and Associated Gene Variants in Prepubertal Children.

Context: The associations of serum 25-hydroxyvitamin D [25(OH)D] with plasma lipids remain controversial in children. Objective: To examine the associations and interactions of 25(OH)D and related gene variants with lipids in children. Design: Cross-sectional. Setting: Kuopio, Finland. Participants: Population sample of 419 prepubertal white children aged 6 to 8 years. Main Outcome Measures: 25(OH)D, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. Results: Serum 25(OH)D was negatively associated with total cholesterol (ß = -0.141, P = 0.004), LDL cholesterol (ß = -0.112, P = 0.023), HDL cholesterol (ß = -0.150, P = 0.002), and triglycerides (ß = -0.104, P = 0.035) adjusted for age and sex. Associations of 25(OH)D with total cholesterol, LDL cholesterol, and HDL cholesterol remained after adjustment for adiposity, physical activity, sedentary behavior, diet, daylight time, and parental education. Children in the highest quartile of 25(OH)D had the lowest total cholesterol (P = 0.022) and LDL cholesterol (P = 0.026) adjusted for age and sex. Cytochrome P450 family 2 subfamily R member 1 (CYP2R1) rs12794714, CYP2R1 rs10741657, and vitamin D binding protein (DBP) rs2282679 were associated with 25(OH)D adjusted for age and sex. CYP2R1 rs12794714 was associated with total cholesterol and LDL cholesterol and C10orf88 rs6599638 with HDL cholesterol adjusted for age, sex, and 25(OH)D. The gene variants did not explain or modify the associations of 25(OH)D with lipids. Conclusions: 25(OH)D was independently and inversely associated with total cholesterol, LDL cholesterol, and HDL cholesterol. CYP2R1 rs12794714, CYP2R1 rs10741657, and DBP rs2282679 were associated with 25(OH)D. CYP2R1 rs12794714 was associated with total cholesterol and LDL cholesterol and chromosome 10 open reading frame 88 (C10orf88) rs6599638 with HDL cholesterol independent of 25(OH)D. None of the gene variants modified the associations of 25(OH)D with lipids. Further studies are needed to detect the mechanisms for the associations of 25(OH)D with lipids.

Body fat mass, lean body mass and associated biomarkers as determinants of bone mineral density in children 6-8years of age - The Physical Activity and Nutrition in Children (PANIC) study.

Lean body mass (LM) has been positively associated with bone mineral density (BMD) in children and adolescents, but the relationship between body fat mass (FM) and BMD remains controversial. Several biomarkers secreted by adipose tissue, skeletal muscle, or bone may affect bone metabolism and BMD. We investigated the associations of LM, FM, and such biomarkers with BMD in children. We studied a population sample of 472 prepubertal Finnish children (227 girls, 245 boys) aged 6-8years. We assessed BMD, LM, and FM using whole-body dual-energy x-ray absorptiometry and analysed several biomarkers from fasting blood samples. We studied the associations of LM, FM, and the biomarkers with BMD of the whole body excluding the head using linear regression analysis. LM (standardized regression coefficient ß=0.708, p<0.001), FM (ß=0.358, p<0.001), and irisin (ß=0.079, p=0.048) were positive correlates for BMD adjusted for age, sex, and height in all children. These associations remained statistically significant after further adjustment for LM or FM. The positive associations of dehydroepiandrosterone sulphate (DHEAS), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), leptin, free leptin index, and high-sensitivity C-reactive protein and the negative association of leptin receptor with BMD were explained by FM. The positive associations of DHEAS and HOMA-IR with BMD were also explained by LM. Serum 25-hydroxyvitamin D was a positive correlate for BMD adjusted for age, sex, and height and after further adjustment for FM but not for LM. LM and FM were positive correlates for BMD also in girls and boys separately. In girls, insulin, HOMA-IR, leptin, and free leptin index were positively and leptin receptor was negatively associated with BMD adjusted for age, height, and LM. After adjustment for age, height, and FM, none of the biomarkers was associated with BMD. In boys, leptin and free leptin index were positively and leptin receptor was negatively associated with BMD adjusted for age, height, and LM. After adjustment for age, height and FM, 25(OH)D was positively and IGF-1 and leptin were negatively associated with BMD. FM strongly modified the association between leptin and BMD. LM but also FM were strong, independent positive correlates for BMD in all children, girls, and boys. Irisin was positively and independently associated with BMD in all children. The associations of other biomarkers with BMD were explained by LM or FM.

Student-focused virtual histology education: Do new scenarios and digital technology matter?

This article was migrated. The article was marked as recommended. Innovative changes have become a critical part of teaching when resources are limited. In this study, we examined whether the student-oriented teaching method, when powered by virtual microscopy, improves histology learning compared to traditional microscope-based studies. Anonymous and voluntary post-course surveys were administered to students and essays were processed for content analysis. Google Analytics was used to obtain accurate Internet usage monitoring for WEBMICROSCOPE®. Using SPSS statistics, the examination scores for 2016 were compared to those of previous year, when the course was taught with a traditional-microscope-based model. The results demonstrated that the new teaching scenario was an effective tool, based on the mean examination scores in 2016 compared to the identical groups in 2015. The survey analysis showed that the students benefited more from using WEBMICROSCOPE® and that they frequently gained access to the Web server when they were not in class. The new scenario helped clarify the concept of histology for most of the students and was generally appreciated during teamwork-based histology classes. Students perceived that the use of the digital technology significantly influenced their confidence in learning the fundamentals of histology. In addition, changing to the new teaching scenario powered by WEBMICROSCOPE® improved the students' motivation to participate in discussions and better understand the concept of Histology between the 2015 and 2016 academic years. Finally, these changes all had a positive impact on the students' attention and satisfaction.

Determinants of serum 25-hydroxyvitamin D concentration in Finnish children: the Physical Activity and Nutrition in Children (PANIC) study.

We studied vitamin D intake, serum 25-hydroxyvitamin D (S-25(OH)D) concentration, determinants of S-25(OH)D and risk factors for S-25(OH)D <50 nmol/l in a population sample of Finnish children. We studied 184 girls and 190 boys aged 6-8 years, analysed S-25(OH)D by chemiluminescence immunoassay and assessed diet quality using 4-d food records and other lifestyle factors by questionnaires. We analysed the determinants of S-25(OH)D using linear regression and risk factors for S-25(OH)D <50 nmol/l using logistic regression. Mean dietary intake of vitamin D was 5·9 (sd 2·1) µg/d. Altogether, 40·8 % of children used no vitamin D supplements. Of all children, 82·4 % did not meet the recommended total vitamin D intake of 10 µg/d. Milk fortified with vitamin D was the main dietary source of vitamin D, providing 48·7 % of daily intake. S-25(OH)D was <50 nmol/l in 19·5 % of children. Consumption of milk products was the main determinant of S-25(OH)D in all children (standardised regression coefficient ß=0·262; P<0·001), girls (ß=0·214; P=0·009) and boys (ß=0·257; P=0·003) in multivariable models. Vitamin D intake from supplements (ß=0·171; P=0·035) and age (ß=-0·198; P=0·015) were associated with S-25(OH)D in girls. Children who drank ≥450 g/d of milk, spent ≥2·2 h/d in physical activity, had ≥13·1 h/d of daylight time or were examined in autumn had reduced risk for S-25(OH)D <50 nmol/l. Insufficient vitamin D intake was common among Finnish children, one-fifth of whom had S-25(OH)D <50 nmol/l. More attention should be paid to the sufficient intake of vitamin D from food and supplements, especially among children who do not use fortified milk products.

Nonuniform temperature rise in in vitro osteoblast ultrasound exposures with associated bioeffect.

There is a growing interest to use ultrasound to stimulate cellular material in vitro conditions for the treatment of musculoskeletal disorders. However, the beneficial effect resulting from ultrasound exposure is not accurately specified. Many in vitro ultrasound setups are very vulnerable to temperature elevation due to sound absorption, sound reflections, and inadequate heat transfer. The objective of this study is to show that temperature variations capable of modifying biological results may exist in common in vitro exposure system. Human osteoblastic MG-63 cells plated on a 24-well cell plate were treated with pulsed ultrasound in 37 °C water bath (10 min, frequency = 1.035 MHz, burst length = 200 µs, pulse repetition frequency = 1 kHz, duty cycle = 0.2, temporal-average acoustic power = 2 W, and peak pressure = 670-730 kPa) and the activation of heat-dependent canonical Wnt cell signaling was measured. The ultrasound-induced temperature rise was measured with thermocouples and infrared imaging. Chamber-to-chamber comparison showed substantial temperature variation (41.6 °C versus 49.1 °C) among the different chambers. The chamber walls were the most susceptible to heating. The variations in the chamber temperatures correlated to variations in the cell signaling levels (1.3-fold versus 11.5-fold increase). These observations underline the need for system-specific temperature measurements during in vitro exposures.

Ultrasound-induced activation of Wnt signaling in human MG-63 osteoblastic cells.

The benefit from an ultrasound (US) exposure for fracture healing has been clearly shown. However, the molecular mechanisms behind this effect are not fully known. Recently, the canonical Wnt signaling pathway has been recognized as one of the essential regulators of osteoblastogenesis and bone mass, and thereby considered crucial for bone health. Mechanical loading and fluid shear stress have been reported to activate the canonical Wnt signaling pathway in bone cells, but previous reports on the effects of therapeutic US on Wnt signaling in general or in bone, in particular, have not been published yet. Therefore, activation of Wnt signaling pathway was assayed in human osteoblastic cells, and indeed, this pathway was found to be activated in MG-63 cells through the phosphoinositol 3-kinase/Akt (PI3K/Akt) and mTOR cascades following a single 10 min US exposure (2 W, 1.035 MHz). In addition to the reporter assay results, the Wnt pathway activation was also observed as nuclear localization of beta-catenin. Wnt activation showed also temperature dependence at elevated temperatures, and the expression of canonical Wnt ligands was induced under the thermal exposures. However, existence of a specific, non-thermal US component was evident as well, perhaps evidence of a potential dual action of therapeutic US on bone. Neither US nor heat exposures affected cell viability in our experiments. In summary, this is the first study to report that Wnt signaling cascade, important for osteoblast function and bone health, is one of the pathways activated by therapeutic US as well as by hyperthermia in human osteoblastic cells. Our results provide evidence for the potential molecular mechanisms behind the beneficial effects of US on fracture healing. Combinations of US, heat, and possible pharmacological treatment could provide useful flexibility for clinical cases in treating various bone disorders.

Dioxins interfere with differentiation of osteoblasts and osteoclasts.

We have previously shown that the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects bone growth, modelling and mechanical strength in vivo. In this study, we utilized differentiation of bone marrow stem cells to osteoblasts and osteoclasts as a model system to study the effects of TCDD on bones. Stem cells were isolated from bone marrow of femurs and tibias of rats and mice. Progress of osteoblastic differentiation was monitored by measuring mRNA expression levels of differentiation markers from control and TCDD-treated cells using quantitative RT-PCR. TCDD significantly and dose-dependently decreased the mRNA levels of RUNX2, alkaline phosphatase and osteocalcin. Also the activity of alkaline phosphatase was significantly inhibited in both rat and mice cells. In the case of osteoclasts, TCDD decreased the number of TRACP+ multinucleated cells, with corresponding decreases in the number of F-actin rings and the area of resorption. Studies in AHR-knockout mice indicated that TCDD has no effect on the expression of osteoblastic differentiation markers suggesting that TCDD mediates its effects by AHR. Both osteoblastic and osteoclastic effects took place at very low doses of TCDD, as in most cases 100 fM TCDD was enough to significantly affect the differentiation markers. Therefore, differentiation of osteoblasts and osteoclasts from bone marrow stem cells seems to be a very sensitive target for TCDD. Disrupting effects in osteoblastic cells, in addition to disturbed osteoclastogenesis, may thus play a role in adverse effects on bone quality in TCDD exposed animals.

Calreticulin mediated glucocorticoid receptor export is involved in beta-catenin translocation and Wnt signalling inhibition in human osteoblastic cells.

Wnt signalling pathway is a multicomponent cascade involving interaction of several proteins and found to be important for development and function of various cells and tissues. There is increasing evidence that the Wnt/beta-catenin pathway constitutes also one of the essential molecular mechanisms controlling the metabolic aspects of osteoblastic cells. However, in bone, glucocorticoids (GCs) have been reported to weaken Wnt signalling. Therefore, the aim of this study was to characterize the mechanisms behind the cross-talk of these two signalling pathways in human osteoblastic cells. Based on our findings, liganded glucocorticoid receptor (GR) modulated Wnt signalling pathway by decreasing beta-catenin's nuclear accumulation and increasing its relocalization to cell membranes rather than affecting its degradation in human osteoblastic cells. The region of GR responsible for this inhibitory effect located into an area, which harbours the DNA binding as well as nuclear export domains. In further studies, a chaperone protein calreticulin (CRT), known to bind the DNA binding domain of GR and regulate receptor export, was found to be involved in the GR-mediated downregulation of Wnt signalling: GR mutants containing incomplete CRT binding sites were not able to translocate beta-catenin to cell surface. In addition, the inhibitory effect of GCs on endogenous Wnt target gene, cyclin D1, was abolished, when the expression of CRT was attenuated by the RNAi technique. Furthermore, GR and beta-catenin were shown to exist in the same immunocomplex, while interaction between CRT and beta-catenin was observed only in the presence of GR as a mediator molecule. In addition, the GR mutant lacking CRT binding ability impaired the complex formation between beta-catenin and CRT. Together with GR, beta-catenin could thus be co-transported from the nucleus in a CRT-dependent way. These observations represent a novel mechanism for GCs to downregulate Wnt signalling pathway in human osteoblastic cells. Knowledge of these molecular mechanisms is important for understanding the network of multiple signalling cascades in bone environment. Functional Wnt signalling pathway is a prerequisite for proper osteoblastogenesis, and this modulative cross-talk between the steroid pathway and Wnt cascade could therefore explain some of the two-edged effects of GCs on osteoblastic differentiation and function.

Genome-wide microarray analysis of MG-63 osteoblastic cells exposed to ultrasound.

It is well documented that low intensity pulsed ultrasound can be clinically used to accelerate bone fracture healing. Additionally, in vitro studies have shown that ultrasound can, for instance, increase mineralization, collagen production and alkaline phosphatase activity in osteoblasts. Despite the extensive research on the subject, the exact mechanism of ultrasound effect on bone cell gene regulation has not yet been deduced. In this study, we made an effort to reveal the features of genome-wide transcriptional response of osteoblast-type cells to ultrasound. MG-63 osteoblastic cell transcriptome was analyzed with whole genome microarray either 6 or 24 h after 30 min long exposure to 1.035 MHz pulsed ultrasound with three different acoustic pressures. Special attention was paid to the experimental design to minimize thermal effects and unwanted reflections of ultrasound. Microarray analysis suggested that ultrasound affects the genes involved with cellular membranes, and regulation of transcription as well. Several plasma membrane solute carriers were also regulated by ultrasound. It also changed the transcript level of several transcription factors belonging to the zinc finger proteins. However, ultrasound did not clearly promote genes involved with osteoblast differentiation.

Wnt and steroid pathways control glutamate signalling by regulating glutamine synthetase activity in osteoblastic cells.

Glutamate signalling has recently been found functional also outside the central nervous system, especially in bone. Glutamate is converted to glutamine by glutamine synthetase (GS), which is therefore able to regulate intracellular concentrations of glutamate. We previously characterized the induction of GS expression by glucocorticoids (GCs) in human osteoblast-like cells. Besides this observation, the mechanisms controlling GS in bone are unknown. Therefore, the aim of our present study was to investigate further the regulation of GS in osteoblastic cells. We observed that vitamin D inhibited basal and, even more efficiently, GC-stimulated GS activity by affecting both the mRNA and protein levels of the enzyme in human MG-63 osteoblast-like cells. In osteoblasts derived from rat bone marrow stem cells (rMSCs), GS activity was induced accordingly by the osteogenic culture conditions including GCs. Also in these primary cells, vitamin D clearly inhibited GS activity. In addition, the canonical Wnt signalling pathway was characterized as a negative regulator of GS activity. All these changes in GS activity were reflected on the intracellular glutamate concentration. Our results provide novel evidence that GS activity and expression are regulated by several different signalling pathways in osteoblastic cells. Therefore, GS is a strategic enzyme in controlling glutamate concentration in bone environment: GCs decreased the amount of this signalling molecule while vitamin D and Wnt signalling pathway increased it. Interestingly, GS activity and expression declined rapidly when the rMSC derived osteoblasts began to mineralize. Due to its downregulation during osteoblast mineralization, GS could be held as a marker for osteoblast development. Further supporting this, GS activity was stimulated and intracellular glutamate concentration maintained by the N-methyl-d-aspartate (NMDA) type glutamate receptor antagonist MK801, which inhibited osteogenic differentiation of the rMSCs. GS, a novel target for both steroidal and Wnt pathways in bone, might be a central player in the regulation of osteoblastogenesis and/or intercellular signal transmission. Therefore, the proper understanding of the interplay of these three signalling cascades, i.e., steroidal, Wnt, and glutamate signalling, gives vital information on how bone cells communicate together aiming to keep bone healthy.

Estrogen receptor alpha polymorphism modifies the association between childhood exercise and bone mass: follow-up study.

This follow-up study confirms our previous findings that the ER-alpha PvuII polymorphism (Pp) modulates the association between exercise and bone mass. The differences in bone properties of girls with consistently low physical activity (LLPA) and consistently high physical activity (HHPA) were evident only in those bearing the heterozygote ER-alpha genotype (Pp). In particular, areal bone mineral density of the total femur, bone mineral content and areal bone mineral density of the femoral neck, and bone mineral content and cortical thickness of the tibia shaft were significantly (p < .05) lower in the Pp girls with LLPA than in their HHPA counterparts. These findings might partly explain the genetic basis of human variation associated with exercise training.

Estrogen receptor alpha genotype confers interindividual variability of response to estrogen and testosterone in mesenchymal-stem-cell-derived osteoblasts.

Hormone replacement therapy is effectively used to prevent postmenopausal bone loss. Variation in response to the therapy is, however, frequently seen. In addition, the direct effects of sex steroids on isolated human bone marrow stromal cells have been reported to vary depending on the donor, but the biological mechanisms are not understood. The aim of this study was to investigate the effects of 17beta-estradiol (E2) and testosterone in human-bone-marrow-derived mesenchymal stem cell (MSC) cultures from both female and male donors of various ages. The osteoblast differentiation capacity and activity of the MSCs were quantified in vitro by measuring alkaline phosphatase activity and calcium deposition. We show here that also the osteoblast responses of MSCs to sex hormones vary widely depending on the donor. When the results from all donors were analyzed together, treatment with E2 increased calcium deposition significantly by MSCs of both sexes but ALP activity only in the male MSCs. Testosterone had no effect on ALP activity nor calcium deposition in either sex. To further characterize the individual variation, we investigated estrogen receptor alpha PvuII restriction site polymorphism with PCR. Restriction fragment-length polymorphism was assigned as P or non-P, P signifying the absence of the restriction site. Our results indicate that higher basal osteoblast differentiation capacity of MSCs is associated with the presence of the P allele in females, whereas higher response to sex steroids treatment is associated with the non-P allele. These results could help explain the contradictory effects of E2 on osteoblasts in vitro and might also provide new insights to understanding the differences in responses to hormone replacement therapy.

Proteomic analysis of cartilage- and bone-associated samples.

The skeleton of the human body is built of cartilage and bone, which are tissues that contain extensive amounts of extracellular matrix (ECM). In bone, inorganic mineral hydroxyapatite forms 50-70% of the whole weight of the tissue. Although the organic matrix of bone consists of numerous proteins, 90% of it is composed of type I collagen. In cartilage, ECM forms a major fraction of the tissue, type II collagen and aggrecans being the most abundant macromolecules. It is obvious that the high content of ECM components causes analytical problems in the proteomic analysis of cartilage and bone, analogous to those in the analysis of low-abundance proteins present in serum. The massive contents of carbohydrates present in cartilage proteoglycans, and hydroxyapatite in bone, further complicate the situation. However, the development of proteomic tools makes them more and more tempting also for research of musculoskeletal tissues. Application of proteomic techniques to the research of chondrocytes, osteoblasts, osteocytes, and osteoclasts in cell cultures can immediately benefit from the present knowledge. Here we make an overview to previous proteomic research of cartilage- and bone-associated samples and evaluate the future prospects of applying proteomic techniques to investigate key events, such as cellular signal transduction, in cartilage- and bone-derived cells.

COL1A1 Sp1 polymorphism associates with bone density in early puberty.

Optimal acquisition of bone mass in puberty is a key determinant of the lifetime risk of osteoporosis and has a strong genetic basis. We investigated the relationship between the COL1A1 Sp1 polymorphism and BMD in early puberty, and how the genotypes relate to bone size and geometry as well as bone turnover and material properties in 247 10- to 13-year-old girls. Bone properties were measured using DXA, pQCT, and ultrasound. Also, serum P1NP, OC, B-ALP, and TRACP 5b were assessed. Our results showed that girls with the TT genotype had significantly lower BMC and BMD of the total body, lumbar spine, and proximal femur, as well as BUA at the calcaneus, than those with the GT and GG genotype. They also had significantly lower B-ALP, as well as P1NP/TRACP 5b and (OC + B-ALP)/TRACP 5b, compared to the others. These findings indicate that the COL1A1 polymorphism is associated with low bone properties in early puberty and suggest a possible physiological effect on collagen metabolism and bone turnover. This information may contribute to the identification of children at risk for suboptimal acquisition of peak bone mass and may ultimately be of value in the planning of early preventive strategies for osteoporosis.

Effects of calcium, dairy product, and vitamin D supplementation on bone mass accrual and body composition in 10-12-y-old girls: a 2-y randomized trial.

BACKGROUND: Little is known about the relative effectiveness of calcium supplementation from food or pills with or without vitamin D supplementation for bone mass accrual during the rapid growth period. OBJECTIVE: The purpose was to examine the effects of both food-based and pill supplements of calcium and vitamin D on bone mass and body composition in girls aged 10-12 y. DESIGN: This placebo-controlled intervention trial randomly assigned 195 healthy girls at Tanner stage I-II, aged 10-12 y, with dietary calcium intakes <900 mg/d to 1 of 4 groups: calcium (1000 mg) + vitamin D3 (200 IU), calcium (1000 mg), cheese (1000 mg calcium), and placebo. Primary outcomes were bone indexes of the hip, spine, and whole body by dual-energy X-ray absorptiometry and of the radius and tibia by peripheral quantitative computed tomography. RESULTS: With the use of intention-to-treat or efficacy analysis, calcium supplementation with cheese resulted in a higher percentage change in cortical thickness of the tibia than did placebo, calcium, or calcium + vitamin D treatment (P = 0.01, 0.038, and 0.004, respectively) and in higher whole-body bone mineral density than did placebo treatment (P = 0.044) when compliance was >50%. With the use of a hierarchical linear model with random effects to control for growth velocity, these differences disappeared. CONCLUSIONS: Increasing calcium intake by consuming cheese appears to be more beneficial for cortical bone mass accrual than the consumption of tablets containing a similar amount of calcium. Diverse patterns of growth velocity may mask the efficacy of supplementation in a short-term trial of children transiting through puberty.

Bone mineral density, body height, and vitamin D receptor gene polymorphism in middle-aged men.

BACKGROUND: Polymorphisms of the vitamin D receptor (VDR) gene have been suggested to account for some of the genetic variation in bone mass. However, the relationship has been controversial. It has been suggested that environmental factors such as physical activity may be one of the many reasons for this controversy.AIM. We investigated the possible interactions of VDR gene polymorphisms and low to moderate intensity exercise on bone mineral density (BMD) in a four-year controlled, randomized intervention trial in 140 middle-aged Finnish men. METHOD: The TaqI, FokI, and ApaI restriction fragment length polymorphism (RFLP)-markers of the VDR gene were evaluated. BMDs of the lumbar spine (L2-L4), femoral neck, and total proximal femur were measured with dual-energy X-ray absorptiometry (DXA). In addition, the relations of the VDR gene polymorphism with bone turnover markers (serum tartrate-resistant acid phosphatase (TRAP) 5b activity and serum osteocalcin concentration) were evaluated. RESULTS: At the randomization, the subjects with the VDR TaqI Tt or tt genotype had a greater body height than the subjects with TT genotype (P=0.001). In addition, the association of VDR TaqI polymorphism with femoral BMD was found. The Tt or tt genotype associated with higher femoral neck values than the TT genotype (P=0.003) at randomization. After adjusting the femoral neck for body height, the association remained (P=0.021). We did not find any association between VDR gene polymorphism and bone turnover markers or any interactions of VDR gene polymorphisms and exercise on BMD. CONCLUSIONS: The TaqI polymorphism may be associated with body height and femoral neck BMD values. The present findings also suggest that the VDR polymorphisms do not modify the effect of regular aerobic exercise on BMD. However, more randomized controlled exercise trials are needed to investigate the role of exercise intensity on VDR gene polymorphisms, and the role of VDR gene polymorphisms on BMD.

The COMT val158met polymorphism is associated with early pubertal development, height and cortical bone mass in girls.

Estrogens are involved in accretion of bone mass during puberty. Catechol-O-Methyltransferase (COMT) is involved in the degradation of estrogens. In this cross-sectional study we investigated associations between the COMT val158met polymorphism, which results in a 60-75% difference in enzyme activity between the val (high activity = H) and the met (low activity = L) variant, and skeletal phenotypes in 246 healthy pre/early pubertal girls. Girls with COMT(LL) were 5.4 cm taller than COMT(HH) girls. Dual x-ray absorptiometry showed higher values of bone mineral content (BMC), and larger areas of total body, femur and spine in COMT(LL). Cortical BMC, measured by peripheral quantitative computerized tomography in the tibia, was 9.8% higher in COMT(LL) compared with COMT(HH). This was due to a larger cortical cross sectional area while the cortical volumetric bone mineral density was not associated with COMT genotype. COMT(LL) girls had higher serum levels of free estradiol and insulin like growth factor. Regression models indicated that COMT genotype exerted effects on skeletal growth mainly via a regulation of free estradiol, resulting in an affected pubertal development (Tanner staging). We propose that the COMT(LL) genotype results in higher free estradiol levels and earlier pubertal development, leading to an increased skeletal growth in pre/early pubertal girls. Possible consequences for the adult skeleton however can be determined only after cessation of growth.

Association between exercise and pubertal BMD is modulated by estrogen receptor alpha genotype.

UNLABELLED: Genetic and environmental factors contribute to bone mass, but the ways they interact remain poorly understood. This study of 245 pre- and early pubertal girls found that the PvuII polymorphism in the ER-alpha gene modulates the effect of exercise on BMD at loaded bone sites. INTRODUCTION: Impaired achievement of bone mass at puberty is an important risk factor for the development of osteoporosis in later life. Genetic, as well as environmental, factors contribute to bone mass, but the ways they interact with each other remain poorly understood. MATERIALS AND METHODS: We investigated the interaction between a PvuII polymorphism at the ER-alpha gene and physical activity (PA) on the modulation of bone mass and geometry in 245 10- to 13-year-old pre- and early pubertal Finnish girls. Level of PA was assessed using a questionnaire. Bone properties were measured using DXA and pQCT. The analyses were controlled for the effects of Tanner stage and body size index. RESULTS: Girls with heterozygote ER-alpha genotype (Pp) and high PA had significantly higher bone mass and BMD, as well as thicker cortex, at loaded bone sites than their low-PA counterparts. No differences were found in bone properties of the distal radius, which is not a weight-bearing bone. Bone properties did not differ in either homozygote groups (PP and pp) regardless of the PA level. CONCLUSIONS: These findings suggest that the PvuII polymorphism in the ER-alpha gene may modulate the effect of exercise on BMD at loaded bone sites. The heterozygotes may benefit most from the effect of exercise, whereas neither of the homozygote groups received any significant improvement from high PA. Furthermore, high PA may hide the genetic influence on bone. Indeed, it seems that one may compensate one's less favorable Pp genotype by increasing leisure PA at early puberty.