Maternal vitamin D status in pregnancy and molar incisor hypomineralisation and hypomineralised second primary molars in the offspring at 7-9 years of age: a longitudinal study.

PURPOSE: The study aimed to investigate associations between maternal vitamin D status during pregnancy and molar incisor hypomineralisation (MIH) and hypomineralised second primary molars (HSPM) among children. METHODS: The study had a longitudinal design using prospectively collected data from 176 mother and child pairs. Mothers were initially recruited in a randomised controlled trial to assess a pregnancy exercise programme. Along with the 7-year follow-up, we invited the children to a dental examination. The exposure variable was maternal serum 25-hydroxyvitamin D in gestational weeks 18-22 and 32-36, categorised as insufficient (< 50 nmol/l) and sufficient (≥ 50 nmol/l). Negative binomial hurdle models were used to analyse potential associations between the exposure variables and MIH or HSPM. The models were adjusted for potential confounders. RESULTS: Among the children (7-9 years old), 32% and 22% had at least one tooth with MIH or HSPM, respectively. A significant association was found between insufficient maternal vitamin D measured in gestational weeks 18-22 and the number of affected teeth among those with MIH at 7-9 years (adjusted RR = 1.82, 95% CI 1.13-2.93). CONCLUSION: Considering any limitations of the present study, it has been shown that insufficient maternal serum vitamin D at mid-pregnancy was associated with a higher number of affected teeth among the offspring with MIH at 7-9 years of age. Further prospective studies are needed to investigate whether this finding is replicable and to clarify the role of maternal vitamin D status during pregnancy and MIH, as well as HSPM, in children.

Vitamin D and stress urinary incontinence in pregnancy: a cross-sectional study.

OBJECTIVE: To assess the association between levels of vitamin D and urinary incontinence (UI) in pregnancy. DESIGN: A cross-sectional study. Secondary analysis of a randomised controlled trial. SETTING: Two university hospitals in Norway. POPULATION: A total of 851 healthy, pregnant women >18 years in gestational weeks 18-22 with a singleton live fetus. METHODS: Data on UI were collected from a questionnaire at inclusion and serum analysis of 25-hydroxy vitamin D (25(OH)D) was performed. Univariable and multivariable logistic regression analyses were applied to study associations between exposure and outcomes. MAIN OUTCOME MEASURES: Prevalence of self-reported UI, stress (SUI) and urge (UUI) or mixed UI. RESULTS: In total, 230/851 (27%) of the participants were vitamin D insufficient (25(OH)D <50 nmol/l) and 42% reported to have any UI. Women with 25(OH)D <50 nmol/l were more likely to report any UI (P = 0.03) and SUI (P < 0.01) compared with women with 25(OH)D ≥50 nmol/l. In a univariable logistic regression analysis, serum levels of 25(OH)D <50 nmol/l was associated with increased risk of any UI (odds ratio [OR] 1.5 with 95% CI 1.0-2.1), SUI only (OR 1.7, 95% CI 1.2-2.4), but not mixed UI or UUI only (OR 0.8, 95% CI 0.5-1.5). In a multivariable logistic regression model, serum levels of 25(OH)D <50 nmol/l were associated with a higher risk of experiencing SUI only (OR 1.5, 95% CI 1.1-2.2). CONCLUSIONS: Serum 25(OH)D <50 nmol/l was associated with increased risk of any UI, and SUI in particular. TWEETABLE ABSTRACT: Low levels of vitamin D are associated with increased risk of urinary incontinence in pregnancy.

Skeletal effects of plyometric exercise and metformin in ovariectomized rats.

Estrogen deficiency causes bone loss and skeletal muscle dysfunction, and attenuates the musculoskeletal effects of exercise. The anti-diabetic drug metformin has been suggested to promote beneficial skeletal effects. To explore whether metformin can improve musculoskeletal training response during estrogen deficiency, we investigated the skeletal effects of plyometric exercise and metformin, in an ovarectomized (OVX) rat model of osteoporosis. Female Sprague Dawley rats, 12 weeks of age, rats were allocated to a sham-operated group (Sham), and four OVX groups; metformin (OVX-Met), exercise (OVX-Ex), combined metformin and exercise (OVX-MetEx) and a control group (OVX-Ctr), n = 12/group. Dual X-ray absorptiometry, micro computed tomography, fracture toughness testing, histomorphometry and plasma analyses were performed to explore skeletal effects. All intervention groups exhibited a higher gain in femoral bone mineral density (BMD) than OVX-Ctr (p < .01). The combined intervention also resulted in a higher gain in femoral and spine BMD compared to OVX-Met (p < .01). Both exercise groups displayed improved microarchitecture, including both cortical and trabecular parameters (p < .05). This was most evident in the OVX-MetEx group where several indices were at sham level or superior to OVX-Ctr (p < .05). The OVX-MetEx group also exhibited an enhanced toughening effect compared to the other OVX groups (p < .05). The beneficial skeletal effects seemed to be mediated by inhibition of bone resorption and stimulation of bone formation. The training response (i.e. jumping height) was also greater in the metformin treated rats compared to OVX-Ex (p < .01), indicating a performance-enhancing effect of metformin. Both exercise groups displayed higher lean mass than OVX-Ctr (p < .05). In conclusion, the combination of plyometric exercise and metformin improved trabecular microarchitecture and bone material properties relative to OVX controls. However, no additive effect of the combined intervention was observed compared to exercise alone.

Maximal strength training improves musculoskeletal health in amphetamine users in clinical treatment.

Amphetamine use leads to impaired skeletal health and elevated risk of osteoporosis. In the current study, we document that maximal strength training (MST), as a part of clinical treatment, works as a countermeasure, improving muscle force generating capacity, body composition, and skeletal health at sites particularly prone to osteoporotic fractures. INTRODUCTION: Amphetamine users have attenuated musculoskeletal health. MST with heavy loads, few repetitions, and emphasis on maximal mobilization in the concentric phase may increase muscle force generating capacity and skeletal health. This study investigated if MST-induced improvements in force generating capacity improved bone mineral density (BMD), trabecular bone score, and body composition in amphetamine users participating in 3-months clinical treatment. METHODS: Of 40 randomized patients, 23 completed the study: 11 in the supervised training group (TG; 8 men, 3 women, 34 ± 10 years) and 12 in the control group (CG; 9 men, 3 women, 32 ± 8 years). The TG performed hack-squat MST three times a week for 12 weeks with an intensity of ~90% of one repetition maximum (1RM). Both groups attended conventional clinical treatment. Pre-training and post-training, we assessed hack-squat 1RM and rate of force development (RFD), BMD, body composition and trabecular bone score by dual X-ray absorptiometry, and serum bone metabolism markers. RESULTS: MST induced increases in 1RM (70%) and RFD (86%), and resulted in BMD improvements at lumbar spine (3.6%) and total hip (2.4%); all improvements were different from CG (p < 0.05). Both the 1RM and RFD increases were associated with BMD improvements (lumbar spine: r = 0.73 (1RM), r = 0.60 (RFD); total hip: r = 0.61 (1RM); all p < 0.05). No differences were observed in trabecular bone score or bone metabolism markers. CONCLUSIONS: MST improved force generating capacity and skeletal health at sites prone to bone loss in amphetamine users, and advocate that MST should be implemented as a clinical strategy to restore the patients' musculoskeletal health.

Impaired skeletal health and neuromuscular function among amphetamine users in clinical treatment.

SUMMARY: This study examined musculoskeletal health in amphetamine users, compared with healthy age-matched controls. We show that amphetamine users have reduced bone mass at several skeletal sites and attenuated maximal muscle strength and force development capacity in the lower extremities. INTRODUCTION: Amphetamine use may cause poor bone quality and elevated risk of osteoporosis. The purpose of this study was to investigate whether amphetamine users exhibit reduced regional and whole body bone mineral density (BMD), altered bone metabolism, and how muscle function may relate to the patient groups' skeletal health. METHODS: We assessed hip, lumbar spine and whole body BMD, and trabecular bone score (TBS) by dual x-ray absorptiometry (DXA), and bone metabolism markers in serum and maximal strength and force development capacity in 36 amphetamine users (25 men, 30 ± 7 years; 11 women 35 ± 10 years) and in 37 healthy controls (23 men, 31 ± 9 years; 14 women, 35 ± 7 years). RESULTS: Whole body BMD was lower in amphetamine users (8% in males and 7% females, p < 0.01), as were BMD at the total hip and sub-regions of the hip (9-11% in men and 10-11 % in women, p < 0.05). Male users had 4% lower TBS (p < 0.05) and higher serum level of type 1 collagen amino-terminal propeptide (p < 0.01). This coincided with reduced lower extremity maximal strength of 30% (males, p < 0.001) and 25% (females, p < 0.05) and 27% slower muscular force development in males compared to controls (p < 0.01). CONCLUSIONS: These findings demonstrate that amphetamine users suffer from a generalized reduction in bone mass, which was associated with attenuated maximal muscle strength and force development capacity in the lower extremities.

Effects of the peroxisome proliferator-activated receptor (PPAR)-δ agonist GW501516 on bone and muscle in ovariectomized rats.

Estrogen deficiency promotes bone loss and skeletal muscle dysfunction. Peroxisome proliferator-activated receptors (PPARs) have 3 subtypes (α, δ, and γ). PPARγ agonists induce bone loss, whereas PPARα agonists increase bone mass. Although PPARδ agonists are known to influence skeletal muscle metabolism, the skeletal effects are unsettled. This study investigated the musculoskeletal effects of the PPARδ agonist GW501516 in ovariectomized (OVX) rats. Female Sprague Dawley rats, 12 weeks of age, were allocated to a sham-operated group and 3 OVX groups; high-dose GW501516 (OVX-GW5), low-dose GW501516 (OVX-GW1), and a control group (OVX-CTR), respectively (n = 12 per group). Animals received GW501516 or vehicle (methylcellulose) daily for 4 months by gavage. Bone mineral density (BMD) was assessed by dual x-ray absorptiometry at the femur, spine, and whole body. Bone microarchitecture at the proximal tibia was assessed by microcomputed tomography, and dynamic histomorphometry was performed. Quadriceps muscle morphology and the relative expression of mitochondrial proteins were analyzed. Bone metabolism markers and metabolic markers were measured in plasma. After 4 months, the OVX-GW5 group displayed lower femoral BMD than OVX-CTR. Trabecular separation was higher in the GW-treated groups, compared with OVX-CTR. The OVX-GW5 group also exhibited lower cortical area fraction and a higher structure model index than OVX-CTR. These effects coincided with impaired bone formation in both GW groups. The OVX-GW5 group displayed elevated triglyceride levels and reduced adiponectin levels, whereas no effects on muscle morphology or mitochondrial gene expression appeared. In summary, the PPARδ agonist GW501516 negatively affected bone properties in OVX rats, whereas no effects were detected in skeletal muscle.

Adipocytes express a functional system for serotonin synthesis, reuptake and receptor activation.

AIMS: Serotonergic pathways in the central nervous system (CNS) are activated in the regulation of food intake and body weight. We hypothesized that adipocytes, like other cells of mesenchymal origin, possess serotonin receptors and thus could be regulated by peripherally circulating serotonin. METHODS: In vivo studies: four Sprague-Dawley rats were given daily serotonin (5HT) injections subcutaneously (s.c., 25 mg/kg) for 5 days; four controls received saline. In a long-term study, 12 rats were given serotonin s.c. for 4 months, 10 controls received saline. Body weight was registered throughout the studies, and visceral adipose tissue and plasma were collected and analysed. Adipocytes were isolated from normal rat visceral abdominal adipose tissue and analysed for the expression of serotonin receptors, the serotonin transporter (5HTT/SERT), activation of serotonin synthesis (tryptophan hydroxylase 1, Tph1) and secretion and serotonin-induced leptin regulation by RT-PCR and protein analyses. RESULTS: Hyperserotoninergic rats had significantly lower body weight (-7.4 and -6.8%) and plasma leptin levels (-44 and -38%) than controls, after both short- and long-term serotonin treatment, respectively, whereas plasma ghrelin levels were unaffected. Compared to controls, serotonin induced a 40-fold upregulation of 5HTT mRNA in visceral adipose tissue after 5 days of treatment. In vitro experiments showed that adipocytes express serotonin receptors, Tph1 and 5HTT, synthesize and secrete serotonin and that serotonin regulates leptin in mature adipocytes. CONCLUSIONS: These findings show that serotonin may regulate adipocyte function in a direct manner via the blood circulation and/or paracrine and autocrine mechanisms, and not only indirectly via the CNS as previously assumed.

Serotonin and fluoxetine modulate bone cell function in vitro.

Recent studies have proposed a role for serotonin and its transporter in regulation of bone cell function. In the present study, we examined the in vitro effects of serotonin and the serotonin transporter inhibitor fluoxetine "Prozac" on osteoblasts and osteoclasts. Human mononuclear cells were differentiated into osteoclasts in the presence of serotonin or fluoxetine. Both compounds affected the total number of differentiated osteoclasts as well as bone resorption in a bell-shaped manner. RT-PCR on the human osteoclasts demonstrated several serotonin receptors, the serotonin transporter, and the rate-limiting enzyme in serotonin synthesis, tryptophan hydroxylase 1 (Tph1). Tph1 expression was also found in murine osteoblasts and osteoclasts, indicating an ability to produce serotonin. In murine pre-osteoclasts (RAW264.7), serotonin as well as fluoxetine affected proliferation and NFkappaB activity in a biphasic manner. Proliferation of human mesenchymal stem cells (MSC) and primary osteoblasts (NHO), and 5-HT2A receptor expression was enhanced by serotonin. Fluoxetine stimulated proliferation of MSC and murine preosteoblasts (MC3T3-E1) in nM concentrations, microM concentrations were inhibitory. The effect of fluoxetine seemed direct, probably through 5-HT2 receptors. Serotonin-induced proliferation of MC3T3-E1 cells was inhibited by the PKC inhibitor (GF109203) and was also markedly reduced when antagonists of the serotonin receptors 5-HT2B/C or 5-HT2A/C were added. Serotonin increased osteoprotegerin (OPG) and decreased receptor activator of NF-kappaB ligand (RANKL) secretion from osteoblasts, suggesting a role in osteoblast-induced inhibition of osteoclast differentiation, whereas fluoxetine had the opposite effect. This study further describes possible mechanisms by which serotonin and the serotonin transporter can affect bone cell function.