Fluctuation of bone turnover markers’ levels in samples of gingival crevicular fluid after orthodontic stimulus: a systematic review

Background The aim of the present study was to provide an overview of gingival crevicular fluid (GCF) bone turnover markers (BTMs) concerning the physiology of orthodontic tooth movement (OTM) and assess their potential contributions to regulating bone remodeling, that could prove useful in designing future approaches to modulating orthodontic tooth movement. Methods Multiple electronic databases (MEDLINE/PubMed, Ovid MEDLINE, Ovid Embase, LILACS, and Cochrane Library) were searched up to October 1st, 2020. Randomized controlled trials (RCTs), controlled clinical trials, observational studies of prospective and retrospective designs, and cross-sectional studies reporting on levels of BTMs in GCF were eligible for inclusion. The quality of the included RCTs was assessed per the revised Cochrane risk of bias tool for randomized trials (RoB 2.0), whereas the risk of bias of the included cohort studies was assessed using the Risk Of Bias In Non-randomized Studies of Interventions tool. Results Five RCTs, 9 prospective cohort studies, and 1 cross-sectional study fulfilled the inclusion criteria. The risk of bias was deemed as high for the RCTs and 4 of the prospective studies and moderate for the rest of the studies. The following biomarkers for bone formation were assessed: bone alcaline phosphatase (BALP), alcaline phosphatase (ALP), and osteocalcin (OC). For bone resorption, the following BTMs were assessed: deoxypyridinoline (DPD) and pyridinoline (PYD), N-terminal telopeptide (NTX), osteopontin (OPN), and tartrate-resistant acid phosphatase (TRAP). The follow-up period ranged mainly from baseline to 45 days, although one study had an expanded follow-up period of up to 16 months. The results of the included studies comparing different BTMs were heterogeneous and qualitatively reported. Conclusions Current evidence continues to support the potential for BTMs to provide clinically useful information particularly for adjusting or standardizing the orthodontic stimulus. The present systematic review has retrieved studies of high, overall, risk of bias, and has unveiled a substantial clinical and methodological heterogeneity among included studies. Further data of the relationships between the clinical assays and the physiological or pre-analytical factors contributing to variability in BTMs’ concentrations are required. Systematic review registration CRD42020212056.

Structural Changes in Trabecular Bone, Cortical Bone and Hyaline Cartilage as Well as Disturbances in Bone Metabolism and Mineralization in an Animal Model of Secondary Osteoporosis in Clostridium perfringens Infection

There is no information regarding whether changes in the microbiological balance of the gastrointestinal tract as a result of an infection with Clostridium perfringens influence the development of metabolic bone disorders. The experiment was carried out on male broiler chickens divided into two groups: control (n = 10) and experimental (n = 10). The experimental animals were infected with Clostridium perfringens between 17 and 20 days of age. The animals were euthanized at 42 days of age. The structural parameters of the trabecular bone, cortical bone, and hyaline cartilage as well as the mineralization of the bone were determined. The metabolism of the skeletal system was assessed by determining the levels of bone turnover markers, hormones, and minerals in the blood serum. The results confirm that the disturbed composition of the gastrointestinal microflora has an impact on the mineralization and metabolism of bone tissue, leading to the structural changes in cortical bone, trabecular bone, and hyaline cartilage. On the basis of the obtained results, it can be concluded that changes in the microenvironment of the gastrointestinal tract by infection with C. perfringens may have an impact on the earlier development of osteoporosis.

Hemoglobin A1c Threshold for Reduction in Bone Turnover in Men With Type 2 Diabetes Mellitus

BackgroundEmerging data suggest that type 2 diabetes mellitus (T2D) is associated with an increased risk for fractures despite relatively normal or increased bone mineral density (BMD). Although the mechanism for bone fragility in T2D patients is multifactorial, whether glycemic control is important in generating this impairment in bone metabolism remains unclear. The purpose of our study is to identify a hemoglobin A1c (A1c) threshold level by which reduction in bone turnover begins in men with T2D.MethodA cross-sectional analysis of baseline data was obtained from 217 men, ages 35–65, regardless of the presence or absence of hypogonadism or T2D, who participated in 2 clinical trials. The following data were obtained: A1c by HPLC, testosterone and estradiol by LC/MS, bone turnover markers Osteocalcin [OC], C-terminal telopeptide [CTx], and sclerostin by ELISA, and BMD by DXA. Patients were grouped into 4 categories based of A1c (group I: <6%, group II: 6.0–6.4%, group III: 6.5–6.9%, and group IV: ≥7%). Threshold models were fit to the data using nonlinear regression and group comparisons among the different A1c categories performed by ANOVA.ResultsThreshold model and nonlinear regression showed an A1c cut-off of 7.0, among all choices of A1cs, yields the least sum of squared errors. A comparison of bone turnover markers revealed relatively lower OC (p = 0.002) and CTx (p = 0.0002) in group IV (A1c ≥7%), compared to the other groups. An analysis of men with T2D (n = 94) showed relatively lower OC (p=0.001) and CTx (p=0.002) in those with A1c ≥7% compared to those with <7%, respectively. The significance between groups persisted even after adjusting for medications and duration of diabetes.ConclusionAn analysis across our entire study population showed a breakpoint A1c level of 7% or greater is associated with lower bone turnover. Also in men with T2D, an A1c ≥7% is associated with low bone turnover.

Nutrient Intake and Status in Adults Consuming Plant-Based Diets Compared to Meat-Eaters: A Systematic Review

Health authorities increasingly recommend a more plant-based diet, rich in fruits, vegetables, pulses, whole grains and nuts, low in red meat and moderate in dairy, eggs, poultry and fish which will be beneficial for both health and the environment. A systematic review of observational and intervention studies published between 2000 and January 2020 was conducted to assess nutrient intake and status in adult populations consuming plant-based diets (mainly vegetarian and vegan) with that of meat-eaters. Mean intake of nutrients were calculated and benchmarked to dietary reference values. For micronutrient status, mean concentrations of biomarkers were calculated and compared across diet groups. A total of 141 studies were included, mostly from Europe, South/East Asia, and North America. Protein intake was lower in people following plant-based diets compared to meat-eaters, but well within recommended intake levels. While fiber, polyunsaturated fatty acids (PUFA), folate, vitamin C, E and magnesium intake was higher, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake was lower in vegetarians and vegans as compared to meat-eaters. Intake and status of vitamin B12, vitamin D, iron, zinc, iodine, calcium and bone turnover markers were generally lower in plant-based dietary patterns compared to meat-eaters. Vegans had the lowest vitamin B12, calcium and iodine intake, and also lower iodine status and lower bone mineral density. Meat-eaters were at risk of inadequate intakes of fiber, PUFA, α-linolenic acid (ALA), folate, vitamin D, E, calcium and magnesium. There were nutrient inadequacies across all dietary patterns, including vegan, vegetarian and meat-based diets. As plant-based diets are generally better for health and the environment, public health strategies should facilitate the transition to a balanced diet with more diverse nutrient-dense plant foods through consumer education, food fortification and possibly supplementation.

Exploring the Effects of Greek Yogurt Supplementation and Exercise Training on Serum Lithium and Its Relationship With Musculoskeletal Outcomes in Men

Dairy products can act as a dietary source of lithium (Li), and a recent study in university-aged males demonstrated that Greek yogurt (GY) supplementation augmented gains in fat free mass, strength and bone formation after 12 weeks of resistance exercise training compared to carbohydrate (CHO) pudding supplementation. Here, we performed secondary analyses to explore whether GY would alter serum Li levels and whether changes in serum Li would associate with changes in body composition, strength, and bone turnover markers. Results show that the GY group maintained serum Li levels after exercise training, whereas the CHO group did not. Maintaining/elevating serum Li levels was also associated with greater gains in strength and reductions in bone resorption. However, controlling for other dietary factors in GY such as protein and calcium weakened these associations. Thus, future studies should assess the causative role, if any, of dietary Li alone on strength and bone resorption in humans.

PTHR1 Genetic Polymorphisms Are Associated with Osteoporosis among Postmenopausal Arab Women

The parathyroid hormone 1 receptor (PTHR1) plays a crucial role in calcium homeostasis and bone metabolism. However, its genetic role in regulating bone turnover markers (BTMs) in postmenopausal osteoporosis (PMO) remains unclear. Herein, we explored parathyroid hormone (PTH) and PTHR gene variant susceptibility to osteoporosis and their association with various circulating BTM and inflammatory markers in postmenopausal women of Arab ethnicity. In total, 600 postmenopausal Arab women (300-PMO and 300-control) were genotyped for selected SNPs in PTH (rs1459015, rs307253, rs6054, rs307247, rs10500783 and rs10500784), PTHR1 (rs6442037, rs1138518, and rs724449 SNPs) and PTHR2 (rs9288393, rs10497900, and rs897083). Anthropometrics, BTMs, and inflammatory markers were measured. Bone mineral density (BMD) was measured at the lumbar spine L1–L4 and the femoral neck using dual-energy X-ray absorptiometry (DXA). PTHR1 rs1138518 genotype C/T was found to be a significant risk factor for PMO ( OR = 1.49 , 95% CI 1.0-2.1, P = 0.03 ). The genotypes C/T and T/T of PTHR1 rs1138518 were associated with 25-hydroxy-vitamin D (25(OH)D) regulation. In the PMO group, carriers of the C/T genotype had significantly lower 25(OH)D levels than carriers of the same genotypes in the control group (59.9 (36.7-92.4) nmol/l and 66.4 (43.5-87.8) nmol/l, respectively; P = 0.048 ]. Our study concludes that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and 25(OH)D regulation in Arab women with PMO.

Prebiotic to Improve Calcium Absorption in Postmenopausal Women After Gastric Bypass: A Randomized Controlled Trial

Context The adverse skeletal effects of Roux-en-Y gastric bypass (RYGB) are partly caused by intestinal calcium absorption decline. Prebiotics, such as soluble corn fiber (SCF), augment colonic calcium absorption in healthy individuals. Objective We tested the effects of SCF on fractional calcium absorption (FCA), biochemical parameters, and the fecal microbiome in a post-RYGB population. Design, Setting, Participants : Randomized, double-blind, placebo-controlled trial of 20 postmenopausal women with history of RYGB mean 5 years prior. Intervention 2-month course of 20 g/day SCF or maltodextrin placebo orally. Main Outcomes Between-group difference in absolute change in FCA (primary outcome) was measured with a gold-standard dual stable isotope method. Other measures included tolerability, adherence, serum calciotropic hormones and bone turnover markers, and fecal microbial composition via 16S rRNA gene sequencing. Results Mean FCA ±SD at baseline was low at 5.5±5.1%. Comparing SCF to placebo, there was no between-group difference in mean (95% CI) change in FCA (+3.4 [-6.7,+13.6]%), nor in calciotropic hormones or bone turnover markers. The SCF group had a wider variation in FCA change than placebo (SD 13.4% vs. 7.0%). Those with greater change in microbial composition following SCF treatment had greater increase in FCA (r 2=0.72,p=0.05). SCF adherence was high, and GI symptoms similar between groups. Conclusions No between-group differences were observed in changes in FCA or calciotropic hormones, but wide confidence intervals suggest a variable impact of SCF that may be due to the degree of gut microbiome alteration. Daily SCF consumption was well-tolerated. Larger and longer-term studies are warranted.

Differences in femur geometry and bone markers in atypical femur fractures and the general population

This study aimed to identify differences in femur geometry between patients with subtrochanteric/shaft atypical femur fractures (AFFs) and the general population, and to evaluate the biomechanical factors related to femoral bowing in AFFs. We retrospectively reviewed 46 patients. Data on age, and history and duration of bisphosphonate use were evaluated. Femur computed tomography images were reconstructed into a 3D model, which was analyzed with a geometry analysis program to obtain the femur length, femur width and length, and femoral bowing. Patients were divided into two groups according to fracture location: the subtrochanteric and shaft AFF groups. We compared all parameters between groups, and also between each group and a general population of 300 women ≥ 60 years. Thirty-five patients had a history of bisphosphonate use (average duration, 6.1 years; range, 0.8–20 years). There was no statistical difference in bone turnover markers between the two groups. The shaft AFF group had a lower radius of curvature (ROC) (P = 0.001), lower bone mineral density (BMD, T score) (P = 0.020), and lower calcium (P = 0.016). However, other parameters and rate of bisphosphonate use were not significantly different. There were no significant differences in the parameters of the subtrochanter AFF group and the general population, but the shaft AFF group demonstrated a wider femur width (P < 0.001), longer anteroposterior length (P = 0.001), and lower ROC (P < 0.001) than the general population. Femoral bowing and width increased in shaft AFFs, but similar to subtrochanter AFFs compared to the general population. Our results highlight the biomechanical factors of femur geometry in AFFs.