Bone Outcomes Research Articles

Healthy eating index and bone health markers in adults with metabolically healthy and unhealthy obese phenotypes.

The Healthy Eating Index (HEI) estimates the diet quality, and low HEI scores are associated with adverse bone outcomes. However, the relationship between HEI scores and bone health in individuals who are obese but otherwise healthy or obese with comorbidities remains unclear. We aimed to evaluate the association of HEI scores with bone mineral density (BMD), bone regulating hormones and bone turnover markers in individuals with metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) phenotypes. This was a cross-sectional analysis of 122 adults who were overweight or obese. A questionnaire was completed to obtain demographic data. Body composition and BMD were assessed by a Dual Energy X-Ray Absorptiometry (DXA) exam. The HEI scores and dietary components were calculated using a 24-h dietary recall. Blood samples were collected for the analysis of serum 25-hydroxyvitamin D (s25OHD), total osteocalcin (OC), parathyroid hormone (PTH), and C-terminal telopeptide (CTx) concentrations. The MHO and MUO phenotypes were classified according to the absence or presence of metabolic abnormalities. The sample mean age was 37.91 ± 12.66 years, 50.8% were men, mean body mass index (BMI) was 30.01 ± 4.63 kg/m2, and 45.9% were classified as the MUO phenotype. The mean HEI scores were 54.42 ± 16.25 and 61.48% had low-diet quality. HEI scores were positively associated with s25OHD in the MUO phenotype group (β = 0.194, 95%CI = 0.038-0.350, p = 0.016). Certain dietary score components, such as fruits, seafood and plant protein, added sugars, whole grains, and fatty acids were also associated with bone health markers. However, HEI scores were not associated with BMD measures, neither with other bone regulating hormones and turnover markers. There was a positive association between HEI scores and s25OHD in adults who were overweight or obese with MUO phenotype. Additionally, the adequate consumption of specific food groups may benefit bone mass and metabolism. These results emphasize the importance of lifestyle interventions encouraging healthy eating habits to prevent s25OHD deficiency, poor bone health, and cardiometabolic complications.

Comparative analysis of bone outcomes between quantitative ultrasound and dual-energy x-ray absorptiometry from the UK Biobank cohort

SummaryThis large cohort study investigated reliability and validity of heel ultrasound to estimate bone mineral density in adults. Reliability calculated between left and right heels was relatively poor and so was criterion validity assessed relative to dual-energy X-ray absorptiometry. Heel ultrasound should be used cautiously when estimating bone mineral density.IntroductionCalcaneal quantitative ultrasound (QUS) may be used as a safe, low cost, and portable means to estimate bone mineral density (BMD) in large cohorts. The purpose of this study was to quantify the reliability and validity of QUS in comparison to dual-energy X-ray absorptiometry (DXA), which is the reference method for BMD measurement and diagnoses of osteopenia and osteoporosis.MethodsBone outcomes measured on the large UK Biobank cohort were used. The reliability of QUS estimated BMD was quantified by comparing values obtained from the left and right heel measured in the same session. Criterion validity was assessed through agreement between QUS and DXA, quantifying correlations, and sensitivity and specificity of osteopenia and osteoporosis diagnoses.ResultsReliability calculations were made using data from over 216,000 participants demonstrating similar QUS BMD values between left and right heels in the absolute scale (Sd of difference for men: 0.12 and 0.07 g·cm−2). However, when expressed in relative scales, including concordance of quartiles, reliability was poor. Agreement between QUS and DXA was quantified using data from 5042 participants. Low to modest correlations (r = 0.29 to 0.44) were obtained between multiple QUS variables and DXA BMD, with sensitivity identified as very poor (0.05 to 0.23) for osteoporosis, and poor (0.37 to 0.62) for osteopenia diagnoses.ConclusionsThe findings of this large comparative analysis identify that whilst calcaneal QUS has the potential to produce reliable absolute BMD measurements and demonstrate modest associations with DXA BMD measures, use of that information to make relative statements about participants in the context of the larger population or to appropriately diagnose osteopenia or osteoporosis may be severely limited.

Thermoneutral housing does not rescue olanzapine-induced trabecular bone loss in C57BL/6J female mice

Antipsychotic drugs are prescribed to a wide range of individuals to treat mental health conditions including schizophrenia. However, antipsychotic drugs cause bone loss and increase fracture risk. We previously found that the atypical antipsychotic (AA) drug risperidone causes bone loss through multiple pharmacological mechanisms, including activation of the sympathetic nervous system in mice treated with clinically relevant doses. However, bone loss was dependent upon housing temperature, which modulates sympathetic activity. Another AA drug, olanzapine, has substantial metabolic side effects, including weight gain and insulin resistance, but it is unknown whether bone and metabolic outcomes of olanzapine are also dependent upon housing temperature in mice. We therefore treated eight week-old female mice with vehicle or olanzapine for four weeks, housed at either room temperature (23 °C) or thermoneutrality (28–30 °C), which has previously been shown to be positive for bone. Olanzapine caused significant trabecular bone loss (−13% BV/TV), likely through increased RANKL-dependent osteoclast resorption, which was not suppressed by thermoneutral housing. Additionally, olanzapine inhibited cortical bone expansion at thermoneutrality, but did not alter cortical bone expansion at room temperature. Olanzapine also increased markers of thermogenesis within brown and inguinal adipose depots independent of housing temperature. Overall, olanzapine causes trabecular bone loss and inhibits the positive effect of thermoneutral housing on bone. Understanding how housing temperature modulates the impact of AA drugs on bone is important for future pre-clinical studies, as well as for the prescription of AA drugs, particularly to older adults and adolescents who are most vulnerable to the effects on bone.

Guided Bone Regeneration Effects on Bone Quantity and Outcomes of Dental Implants in Patients With Insufficient Bone Support: A Single-Center Observational Study.

Background Guided bone regeneration (GBR)is used to influence on stabilization of dental implants in patients with insufficient bone quantity and anatomical problems.But many studies using GBR resulted in divergent results according to the efficiency of new bone quantity formation and implant survival. This research aimed to study the effects of GBR on the increase of bone quantity and short-term stabilization of dental implants in patients with insufficient bone support. Methodology The study included 26 patientsthat underwent the procedure for 40 dental implants from September 2020 to September 2021. In each case, the vertical bone support was intraoperatively measured, through the MEDIDENT Italia paradontal millimetric probe (Medident Italia, Carpi, Italy). The vertical bone defect was considered when the mean vertical depth between the abutment junction and the marginal bone wasgreater than 1mm up to 8mm. In the group with the presence of the vertical bone defect, GBR technique was used duringthe procedure of dental implantsrealized with synthetic bone graft, resorbable membrane, and platelet-rich fibrin (PRF), and the group was considered the study (GBR) group. The group of patients with no vertical bone defects(less than 1mm) and no need for any GBR technique usewas considered the control (no-GBR) group. The bone support was evaluated again intraoperatively after six months in both groups when the healing abutmentswere positioned. The vertical bone defect for each group in baseline and after six months is presented as mean±SD and compared using a t-test. A t-test for Equality of Means was used to calculate the mean depth difference (MDD) between baseline and six months values in each group (GBR and no-GBR) and also between both groups. P-value ≤ 0.05 is considered statistically significant. Results Overall 40 dental implants were placed, 20 of them were included in the GBR group and 20 in the no-GBR group. In the GBR group, a statistically significant greater mean vertical bone defect in baseline (day 1), compared to the no-GBR group was found (-4.46±2.76 vs -0.27±0.22; MDD = -4.19 [-5.44 to -2.94] p<0.001). At six months of follow-up in the GBR group, a new bone around the implant was formed, presenting a significantly lower bone defect compared to the baseline measure (-0.39±0.43 vs -4.46±2.76; MDD = -4.07 mm [-5.37 to -2.78]p<0.001). In six months, no statistically significant difference between GBR and no-GBR group in bone support was found (-0.39±0.43 vs -0.27±0.22; MDD = -0.19 [-0.40 to -0.03] p=0.10). In each group, only one implant failure was observed. Conclusions The use of GBR showed an important reduction of vertical depth defect between healing abutment and marginal bone predisposing similarshort-term stability and survival of dental implants. The use of GBR techniques could be essential in the stabilization of dental implants in patients with insufficient bone support.

Body composition phenotypes and bone health in young adults: A cluster analysis

Lean mass is considered the best predictor of bone mass, as it is an excellent marker of bone mechanical stimulation, and changes in lean mass are highly correlated with bone outcomes in young adults. The aim of this study was to use cluster analysis to examine phenotype categories of body composition assessed by lean and fat mass in young adults and to assess how these body composition categories are associated with bone health outcomes. Cluster cross-sectional analyses of data from 719 young adults (526 women) aged 18-30 years from Cuenca and Toledo, Spain, were conducted. Lean mass index (lean mass (kg)/height (m)2), fat mass index (fat mass (kg)/height (m)2), bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed by dual-energy X-ray absorptiometry. A cluster analysis of lean mass and fat mass index z scores resulted in a classification of a five-category cluster solution that could be interpreted according to the body composition phenotypes of individuals as follows: high adiposity-high lean mass (n=98), average adiposity-high lean mass (n=113), high adiposity-average lean mass (n=213), low adiposity-average lean mass (n=142), and average adiposity-low lean mass (n=153). ANCOVA models showed that individuals in clusters with a higher lean mass had significantly better bone health (z score: 0.764, se: 0.090) than their peers in other cluster categories (z score:-0.529, se: 0.074) after controlling for sex, age, and cardiorespiratory fitness (p<0.05). Additionally, subjects belonging to the categories with a similar average lean mass index but with high or low-adiposity levels (z score: 0.289, se: 0.111; z score: 0.086, se: 0.076) showed better bone outcomes when the fat mass index was higher (p<0.05). This study confirms the validity of a body composition model using a cluster analysis to classify young adults according to their lean mass and fat mass indices. In addition, this model reinforces the main role of lean mass on bone health in this population and that in phenotypes with high-average lean mass, factors associated with fat mass may also have a positive effect on bone status.

Leveraging mice with diverse microbial exposures for advances in osteoimmunology.

The skeletal and immune systems are intricately intertwined within the bone marrow microenvironment, a field of study termed osteoimmunology. Osteoimmune interactions are key players in bone homeostasis and remodeling. Despite the critical role of the immune system in bone health, virtually all animal research in osteoimmunology, and more broadly bone biology, relies on organisms with naïve immune systems. Drawing on insights from osteoimmunology, evolutionary anthropology, and immunology, this perspective proposes the use of a novel translational model: the dirty mouse. Dirty mice, characterized by diverse exposures to commensal and pathogenic microbes, have mature immune systems comparable to adult humans, while the naïve immune system of specific-pathogen free mice is akin to a neonate. Investigation into the dirty mouse model will likely yield important insights in our understanding of bone diseases and disorders. A high benefit of this model is expected for diseases known to have a connection between overactivation of the immune system and negative bone outcomes, including aging and osteoporosis, rheumatoid arthritis, HIV/AIDS, obesity and diabetes, bone marrow metastases, and bone cancers.

Association between a Calcium-to-Magnesium Ratio and Osteoporosis among Puerto Rican Adults

BackgroundThe ratio of calcium-to-magnesium intake (Ca:Mg) may be important for bone due to their competitive absorption. The Ca:Mg ratio has been related to health outcomes, but few studies have related it to bone. ObjectivesThe purpose of this analysis was to examine associations between the Ca:Mg intake with bone mineral density (BMD) and osteoporosis among Puerto Rican adults. MethodsAdults, aged 47–79 y, from the Boston Puerto Rican Osteoporosis Study, with complete BMD and dietary data (n = 955) were included. BMD was assessed with dual-energy X-ray absorptiometry and diet by a food frequency questionnaire. Calcium and magnesium intakes from food were energy adjusted, and the Ca:Mg was calculated. Adjusted linear and logistic regression models were utilized for testing associations between Ca:Mg and bone outcomes. ResultsCalcium intake was greater in the highest compared with lowest tertile, whereas magnesium intake was similar across tertiles. Mean BMD at hip sites was higher in the middle, compared with the lowest, tertile. Higher odds of osteoporosis were observed for the highest and lowest tertiles, compared with the middle tertile, after adjustment (T3 compared with T2 OR: 2.79; 95% CI: 1.47, 5.3; T1 compared with T2 OR: 2.01; 95% CI: 1.03, 3.92). Repeated analyses without supplement users (n = 432) led to stronger differences and ORs, but lost significance for some comparisons. ConclusionsDietary calcium and magnesium are important for bone, perhaps not independently. The Ca:Mg intake ratio appeared most protective within a range of 2.2–3.2, suggesting that a balance of these nutrients may be considered in recommendations for osteoporosis..

Clinical Features and Outcomes of Enterococcal Bone and Joint Infections and Factors Associated with Treatment Failure over a 13-Year Period in a French Teaching Hospital.

Enterococcal bone and joint infections (BJIs) are reported to have poor outcomes, but there are conflicting results. This study aimed to describe the clinical characteristics and outcomes of patients with enterococcal BJI and to assess the factors associated with treatment failure. We conducted a retrospective cohort study at Nimes University Hospital from January 2007 to December 2020. The factors associated with treatment failure were assessed using a Cox model. We included 90 consecutive adult patients, 11 with native BJIs, 40 with prosthetic joint infections and 39 with orthopedic implant-associated infections. Two-thirds of patients had local signs of infection, but few (9%) had fever. Most BJIs were caused by Enterococcus faecalis (n = 82, 91%) and were polymicrobial (n = 75, 83%). The treatment failure rate was 39%, and treatment failure was associated with coinfection with Staphylococcus epidermidis (adjusted hazard ratio = 3.04, confidence interval at 95% [1.31-7.07], p = 0.01) and with the presence of local signs of inflammation at the time of diagnosis (aHR = 2.39, CI 95% [1.22-4.69], p = 0.01). Our results confirm the poor prognosis of enterococcal BJIs, prompting clinicians to carefully monitor for local signs of infection and to optimize the medical-surgical management in case of coinfections, especially with S. epidermidis.

A STUDY OF MANAGEMENT OF NON UNION BONES BY AUTOLOGUS BONE MARROW INJECTION.

Background : Non union is a serious complication of fracture and has multiple causes of which most common cause is lack of osteoconductive mediators, osteogenic cells and adequate vascularity. As most of the nonunion fractures are treated by open bone graft. we conducted a study on 30 patients with non union fracture treated by autologous bone marrow injection. As autologous bone marrow injections containing mesenchymal stem cells (MSC) increases the osteogenic potential of these non-union sites and can obtain healing of these non-union site. Material and Methods: A total 50 patients with non-union,33 were male and 17 were female,15 were femur nonunion,21 were tibia nonunion,6 were humerus nonunion, 5 were radius nonunion, 3 were ulna nonunion. Study conducted on these patients and were treated with autologous bone marrow injection at the fracture site under regional anaesthesia in supine position. patients were evaluated at pre operative and post operative follow up period with serial radiography at 6 weeks,12 weeks, 6 months and 9 months. average duration of treatment was 9months and outcome was evaluated with ASAMI scoring system. Union occurred in 82% patients. out of 50, 31 (64%) patients outc Results: ome was excellent, followed by 5 (10%) had good outcome, 5 (10%) had fair and 9(18%) had poor long bone and functional outcomes. Manageme Conclusion: nt of nonunion bones by autologous bone marrow injection provides an effective and reliable alternative to open bone grafting. Thus,it is observed that with an adequate amount of autologous bone marrow injection, union can be achieved in non union of bones

Bad to the Bone: Emerging Approaches to Aggressive Bone Sarcomas.

Bone sarcomas are rare heterogeneous tumors that affect patients of all ages including children, adolescent young adults, and older adults. They include many aggressive subtypes and patient groups with poor outcomes, poor access to clinical trials, and lack of defined standard therapeutic strategies. Conventional chondrosarcoma remains a surgical disease, with no defined role for cytotoxic therapy and no approved targeted systemic therapies. Here, we discuss promising novel targets and strategies undergoing evaluation in clinical trials. Multiagent chemotherapy has greatly improved outcomes for patients with Ewing sarcoma (ES) and osteosarcoma, but management of those with high-risk or recurrent disease remains challenging and controversial. We describe the impact of international collaborative trials, such as the rEECur study, that aim to define optimal treatment strategies for those with recurrent, refractory ES, and evidence for high-dose chemotherapy with stem-cell support. We also discuss current and emerging strategies for other small round cell sarcomas, such as CIC-rearranged, BCOR-rearranged tumors, and the evaluation of emerging novel therapeutics and trial designs that may offer a new paradigm to improve survival in these aggressive tumors with notoriously bad (to the bone) outcomes.

Adolescent Bone Advantages 3Years After Resistance Training Trial.

We assessed maintenance of skeletal advantages 3years after completion of a 2-year, school-based, controlled exercise trial in adolescent girls. Middle-school girls participated in a resistance training program embedded in physical education classes. Effort groups (low-effort group [LO] and high-effort group [HI]) were identified; the control group (CON) participated in standard physical education at a separate school. Baseline and follow-up (FU) assessments at 6, 18, and 54 (FU3) months included densitometry, anthropometry, and questionnaires assessing physical maturity and nonintervention organized physical activity. Linear mixed effects models were fit to evaluate bone outcomes across all FU time points for CON versus LO/HI. Sixty-eight girls (23 CON/25 HI/20 LO) were 11.6 (0.3)years at baseline. Bone parameters did not differ at baseline, except femoral neck bone mineral density (LO < HI/CON, P < .05). Forty-seven participants provided FU3 assessment: 17 CON/16 HI/14 LO. After adjusting for height, gynecologic age, baseline bone, and organized physical activity, bone gains across all time points were greater for HI versus CON for legs bone mineral content, femoral neck bone mineral content/bone mineral density, and third lumbar vertebra bone mineral content/bone mineral density (P ≤ .05). At FU3, bone values were greater for HI versus CON at subhead, legs, femoral neck, and third lumbar vertebra (P < .03). Adolescent girls who exerted high effort in a school-based resistance training program demonstrated significant skeletal benefits 3years after program completion.

Radiographic Outcomes of Titanium Augment vs Bone Graft in Lateral Column Lengthening for Adult-Acquired Flatfoot Deformity.

Lateral column lengthening (LCL) is a surgical procedure used to manage forefoot abduction and, in theory, also increases the longitudinal arch by plantarflexion of the first ray through tensioning the peroneus longus for patients with stage IIB adult acquired flatfoot deformity (AAFD). This procedure utilizes an opening wedge osteotomy of the calcaneus, which is then filled with autograft, allograft, or a porous metal wedge. The primary aim of this study was to compare the radiographic outcomes of these different bone substitutes following LCL for stage IIB AAFD. We conducted a retrospective review of all patients who underwent LCL from October 2008 until October 2018. Preoperative weightbearing radiographs, initial postoperative radiographs, and 1-year weightbearing radiographs were reviewed. The following radiographic measurements were recorded: incongruency angle, talonavicular coverage angle (TNCA), talar-first metatarsal angle (T-1MT), and calcaneal pitch. A total of 44 patients were included in our study. The mean age of the cohort was 54 (range, 18-74). The study cohort was divided into 2 groups. There were 17 (38.7%) patients who received a titanium metal wedge and 27 (61.5%) that received autograft or allograft. Patients that underwent LCL with the autograft/allograft group were significantly older (59 vs 47 years old, P = .006). Patients who underwent LCL with a titanium wedge had a significantly higher preoperative talonavicular angle (32 vs 27 degrees, P = .013). There were no significant differences in postoperative TNCA, incongruency angle, or calcaneal pitch at 6 months or 1 year. At 6 months and 1 year, no radiographic differences were found between autograft/allograft bone substitutes vs titanium wedge in LCL. Level III, retrospective cohort study.

A comprehensive molecular profiling approach reveals metabolic alterations that steer bone tissue regeneration

Bone regeneration after fracture is a complex process with high and dynamic energy demands. The impact of metabolism on bone healing progression and outcome, however, is so far understudied. Our comprehensive molecular profiling reveals that central metabolic pathways, such as glycolysis and the citric acid cycle, are differentially activated between rats with successful or compromised bone regeneration (young versus aged female Sprague-Dawley rats) early in the inflammatory phase of bone healing. We also found that the citric acid cycle intermediate succinate mediates individual cellular responses and plays a central role in successful bone healing. Succinate induces IL-1β in macrophages, enhances vessel formation, increases mesenchymal stromal cell migration, and potentiates osteogenic differentiation and matrix formation in vitro. Taken together, metabolites—here particularly succinate—are shown to play central roles as signaling molecules during the onset of healing and in steering bone tissue regeneration.

Intermittent fasting and bone health: a bone of contention?

Intermittent fasting (IF) is a promising strategy for weight loss and improving metabolic health, but its effects on bone health are less clear. This review aims to summarise and critically evaluate the preclinical and clinical evidence on IF regimens (the 5:2 diet, alternate-day fasting (ADF) and time-restricted eating (TRE)/time-restricted feeding and bone health outcomes. Animal studies have utilised IF alongside other dietary practices known to elicit detrimental effects on bone health and/or in models mimicking specific conditions; thus, findings from these studies are difficult to apply to humans. While limited in scope, observational studies suggest a link between some IF practices (e.g. breakfast omission) and compromised bone health, although lack of control for confounding factors makes these data difficult to interpret. Interventional studies suggest that TRE regimens practised up to 6 months do not adversely affect bone outcomes and may even slightly protect against bone loss during modest weight loss (< 5 % of baseline body weight). Most studies on ADF have shown no adverse effects on bone outcomes, while no studies on the ‘5–2’ diet have reported bone outcomes. Available interventional studies are limited by their short duration, small and diverse population samples, assessment of total body bone mass exclusively (by dual-energy X-ray absorptiometry) and inadequate control of factors that may affect bone outcomes, making the interpretation of existing data challenging. Further research is required to better characterise bone responses to various IF approaches using well-controlled protocols of sufficient duration, adequately powered to assess changes in bone outcomes and designed to include clinically relevant bone assessments.

The Influence of Accelerometer Epoch Length on Associations of Physical Activity Intensity and Volume with Bone Outcomes.

Two accelerometer metrics (intensity-gradient and average-acceleration) can be used to determine the relative contributions of physical activity (PA) volume and intensity for health, but it is unknown whether epoch length influences the associations detected. This is important when considering bone health, as bone is particularly responsive to high intensity PA, which may be underestimated by longer epochs. This study aimed to assess the associations between average-acceleration, a proxy measure of PA volume, and intensity-gradient, reflective of PA intensity distribution, from PA data from 1-s to 60-s epochs at age 17 to 23 years with bone outcomes at age 23 years. This is a secondary analysis of 220 participants (124 females) from the Iowa Bone Development Study, a longitudinal study of bone health from childhood to early adulthood. Accelerometer-assessed PA data, captured at age 17 to 23 years, were summarised over 1-s, 5-s, 15-s, 30-s, and 60-s epochs, to generate average-acceleration and intensity-gradient from each epoch length, averaged across ages. Regression analysed associations between mutually adjusted average-acceleration and intensity-gradient with dual-energy X-ray absorptiometry assessed total-body-less-head (TBLH) bone mineral content (BMC), spine areal bone mineral density (aBMD), hip aBMD, and femoral neck cross-sectional area and section modulus at age 23 years. Intensity-gradient was positively associated with TBLH BMC in females, with spine aBMD in males, and with hip aBMD and geometry in both sexes, when a 1 to 5-s epoch was used. Average-acceleration was positively associated with TBLH BMC, spine aBMD and hip aBMD in males, generally when the adjustment for intensity-gradient was from > 1-s epochs. Intensity and volume were important for bone outcomes in both sexes and males, respectively. A 1 to 5-s epoch length was most appropriate to assess the mutually adjusted associations of intensity-gradient and average-acceleration with bone outcomes in young adults.

Impact of urinary calcium excretion on kidney, bone, and cardiovascular systems in patients with bone biopsy proven osteoporosis: a longitudinal long-term follow-up study.

Hypercalciuria is common in patients with osteoporosis. However, the long-term effect of urinary calcium excretion (UCaE) on patients' health is not well-examined. The current study aims to assess the impact of UCaE on kidney, bone, and cardiovascular outcomes in patients with bone biopsy proven osteoporosis. Longitudinal study of all patients with osteoporosis who underwent bone biopsy and 24-h urine collection between 2008 and 2015 in the University of Kentucky. DXA scans, serum markers, kidney function, and cardiovascular events were recorded until last clinic visit in 2021. Exclusion criteria were secondary osteoporosis or conditions that might substantially impact UCaE. The significant results in univariate analysis were confirmed in multi-variable regression models involving clinically important covariates that might impact patients' outcomes. Study included 230 patients with mean follow-up of 7.2 ± 2.9 years. The mean age was 61 years, and the mean eGFR at baseline was 85 ± 19 ml/min/1.73 m2. Low bone turnover (LBT) was present in 57% and high bone turnover (HBT) in 43% of patients. Hypercalciuria was found in one-third of patients with no difference between LTB and HTB. UCaE correlated positively with eGFR but did not affect the rate of eGFR decline over time. Higher UCaE predicted kidney stones development. We observed U-shaped effect of UCaE on bone health. Hypercalciuria predicted loss of BMD at all sites, but also hypocalciuria was associated with higher loss in total hip BMD. Upper limb fractures were the most observed fractures, and their incidence was higher in patients with hyper- or hypo-calciuria. Lower UCaE independently predicted development of major adverse cardiac events (MACE) and cardiovascular disease (CVD). UCaE correlated with eGFR but it did not affect the change of eGFR over time. Patients with normal UCaE had lower incidence of upper limb fractures and less reduction in BMD. Low UCaE predicted MACE and CVD.

Comprehensive Associations between Acidosis and the Skeleton in Patients with Kidney Disease.

Renal osteodystrophy (ROD) contributes substantially to morbidity in CKD, including increased fracture risk. Metabolic acidosis (MA) contributes to the development of ROD, but an up-to-date skeletal phenotype in CKD-associated acidosis has not been described. We comprehensively studied associations between acidosis and bone in patients with CKD using advanced methods to image the skeleton and analyze bone-tissue, along with biochemical testing. Cross-sectionally, acidosis was associated with higher markers of bone remodeling and female-specific impairments in cortical and trabecular bone quality. Prospectively, acidosis was associated with cortical expansion and trabecular microarchitectural deterioration. At the bone-tissue level, acidosis was associated with deficits in bone mineral content. Future work investigating acidosis correction on bone quality is warranted. Renal osteodystrophy is a state of impaired bone quality and strength. Metabolic acidosis (MA) is associated with alterations in bone quality including remodeling, microarchitecture, and mineralization. No studies in patients with CKD have provided a comprehensive multimodal skeletal phenotype of MA. We aim to describe the structure and makeup of bone in patients with MA in the setting of CKD using biochemistry, noninvasive imaging, and histomorphometry. The retrospective cross-sectional analyses included 180 patients with CKD. MA was defined as bicarbonate ≤22 mEq/L. We evaluated circulating bone turnover markers and skeletal imaging with dual energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subset of 54 participants had follow-up. We assessed associations between baseline and change in bicarbonate with change in bone outcomes. Histomorphometry, microCT, and quantitative backscatter electron microscopy assessed bone biopsy outcomes in 22 participants. The mean age was 68±10 years, 54% of participants were male, and 55% were White. At baseline, acidotic subjects had higher markers of bone turnover, lower areal bone mineral density at the radius by dual energy x-ray absorptiometry, and lower cortical and trabecular volumetric bone mineral density and impaired trabecular microarchitecture. Over time, acidosis was associated with opposing cortical and trabecular effects: cortical expansion but trabecular deterioration. Bone-tissue analyses showed reduced tissue mineral density with increased heterogeneity of calcium distribution in acidotic participants. MA is associated with multiple impairments in bone quality. Future work should examine whether correction of acidosis improves bone quality and strength in patients with CKD.

Associations Between Inflammatory Mediators and Bone Outcomes in Postmenopausal Women: A Cross-Sectional Analysis of Baseline Data from the Prune Study.

Hypoestrogenism triggers increased production of inflammatory mediators, which contribute to bone loss during postmenopausal osteoporosis. This study aimed to investigate the association between circulating inflammatory markers and bone outcomes in postmenopausal women. We conducted a cross-sectional, secondary analysis of baseline data from participants who completed a 12-month randomized controlled trial, The Prune Study (NCT02822378), which included healthy postmenopausal women (n=183, 55-75 years old) with bone mineral density (BMD) T-score between 0.0 and -3.0 at any site. BMD was measured using dual-energy X-ray absorptiometry, and bone geometry and strength were measured using peripheral quantitative computed tomography. Blood was collected at baseline to measure (1) serum biomarkers of bone turnover, including procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide and (2) inflammatory markers, including serum high-sensitivity C-reactive protein (hs-CRP) and plasma pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, and monocyte chemoattractant protein (MCP)-1, using enzyme-linked immunosorbent assay. The associations between bone and inflammatory outcomes at baseline were analyzed using correlation and regression analyses. Serum hs-CRP negatively correlated with P1NP (r=-0.197, p=0.042). Plasma IL-1β, IL-6, IL-8, and TNF-α negatively correlated with trabecular bone score at the lumbar spine (all p<0.05). In normal-weight women, plasma IL-1β, IL-6, and IL-8 negatively correlated (p<0.05) with trabecular and cortical bone area, content, and density at various sites in the tibia and radius. Serum hs-CRP positively predicted lumbar spine BMD (β=0.078, p=0.028). Plasma IL-6 negatively predicted BMD at the total body (β=-0.131, p=0.027) and lumbar spine (β=-0.151, p=0.036), whereas plasma TNF-α negatively predicted total hip BMD (β=-0.114, p=0.028). At baseline, inflammatory markers were inversely associated with various estimates of bone density, geometry, and strength in postmenopausal women. These findings suggest that inflammatory markers may be an important mediator for postmenopausal bone loss.

Zebrafish Tric-b is required for skeletal development and bone cells differentiation.

Trimeric intracellular potassium channels TRIC-A and -B are endoplasmic reticulum (ER) integral membrane proteins, involved in the regulation of calcium release mediated by ryanodine (RyRs) and inositol 1,4,5-trisphosphate (IP3Rs) receptors, respectively. While TRIC-A is mainly expressed in excitable cells, TRIC-B is ubiquitously distributed at moderate level. TRIC-B deficiency causes a dysregulation of calcium flux from the ER, which impacts on multiple collagen specific chaperones and modifying enzymatic activity, leading to a rare form of osteogenesis imperfecta (OI Type XIV). The relevance of TRIC-B on cell homeostasis and the molecular mechanism behind the disease are still unknown. In this study, we exploited zebrafish to elucidate the role of TRIC-B in skeletal tissue. We demonstrated, for the first time, that tmem38a and tmem38b genes encoding Tric-a and -b, respectively are expressed at early developmental stages in zebrafish, but only the latter has a maternal expression. Two zebrafish mutants for tmem38b were generated by CRISPR/Cas9, one carrying an out of frame mutation introducing a premature stop codon (tmem38b-/- ) and one with an in frame deletion that removes the highly conserved KEV domain (tmem38bΔ120-7/Δ120-7 ). In both models collagen type I is under-modified and partially intracellularly retained in the endoplasmic reticulum, as described in individuals affected by OI type XIV. Tmem38b-/- showed a mild skeletal phenotype at the late larval and juvenile stages of development whereas tmem38bΔ120-7/Δ120-7 bone outcome was limited to a reduced vertebral length at 21 dpf. A caudal fin regeneration study pointed towards impaired activity of osteoblasts and osteoclasts associated with mineralization impairment. Our data support the requirement of Tric-b during early development and for bone cell differentiation.

Influence of using collagen on the soft and hard tissue outcomes of immediate dental implant placement: A systematic review and meta-analysis

ObjectiveTo compare the effects of bone grafting materials, collagen-infused grafting materials, and no grafting materials on the soft and hard tissue outcomes when an immediate implant is placed. Materials and MethodsIn addition to hand searching, electronic searches were performed in Pubmed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL). Only RCTs were included in our review. The Cochrane ROB 2.0 tool was used to assess the risk of bias (ROB). Two subgroups were used to evaluate implant failure rate, buccal bone resorption, soft tissue thickness, and esthetic scores. In the meta-analysis, both the fixed-effects model and the random-effects model were employed. Result7 RCTs were selected after screening 580 studies, and 205 patients were included in the review, with 279 implants. Two RCTs were at low bias of risk, three were at moderate bias, and two were deemed at high risk of bias. The failure rate (95% CI: 0.17 to 11.84) and soft tissue thickness were not significantly different between collagen with bone grafting materials and without bone grafting materials. On the basis of the failure rate and buccal bone thickness, there was no significant difference between collagen with bone grafting materials and bone grafting materials. While we found collagen with bone grafting materials could have a significant advantage on the buccal bone thickness (MD: −0.43,95% CI −0.72 to −0.41) and esthetic outcome (MD: −1.23,95% CI −1.90 to −0.55). ConclusionIn the statement of immediate implant implantation, the thickness of the buccal bone and esthetic outcomes did significantly benefit from bone grafting materials with collagen inserted in the “jumping gap”.