Chronic melatonin treatment improves obesity by inducing uncoupling of skeletal muscle SERCA-SLN mediated by CaMKII/AMPK/PGC1α pathway and mitochondrial biogenesis in female and male Zücker diabetic fatty rats.

Melatonin acute treatment limits obesity of young Zücker diabetic fatty (ZDF) rats by non-shivering thermogenesis (NST). We recently showed melatonin chronically increases the oxidative status of vastus lateralis (VL) in both obese and lean adult male animals. The identification of VL skeletal muscle-based NST by uncoupling of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA)- sarcolipin (SLN) prompted us to investigate whether melatonin is a SERCA-SLN calcium futile cycle uncoupling and mitochondrial biogenesis enhancer. Obese ZDF rats and lean littermates (ZL) of both sexes were subdivided into two subgroups: control (C) and 12 weeks orally melatonin treated (M) (10 mg/kg/day). Compared to the control groups, melatonin decreased the body weight gain and visceral fat in ZDF rats of both sexes. Melatonin treatment in both sex obese rats restored the VL muscle skin temperature and sensitized the thermogenic effect of acute cold exposure. Moreover, melatonin not only raised SLN protein levels in the VL of obese and lean rats of both sexes; also, the SERCA activity. Melatonin treatment increased the SERCA2 expression in obese and lean rats (both sexes), with no effects on SERCA1 expression. Melatonin increased the expression of thermogenic genes and proteins (PGC1-α, PPARγ, and NRF1). Furthermore, melatonin treatment enhanced the expression ratio of P-CaMKII/CaMKII and P-AMPK/AMPK. In addition, it rose mitochondrial biogenesis. These results provided the initial evidence that chronic oral melatonin treatment triggers the CaMKII/AMPK/PGC1α axis by upregulating SERCA2-SLN-mediated NST in ZDF diabetic rats of both sexes. This may further contribute to the body weight control and metabolic benefits of melatonin.

A Cluster Analysis of Oral and Cognitive Health Indicators: An Exploratory Study on Cholinergic Activity as the Link.

INTRODUCTION: Poor oral health has been suggested as a risk factor for cognitive decline. Yet, biologically plausible mechanisms explaining this relationship remain unknown. OBJECTIVES: We aimed (1) to identify oral and cognitive health clustering patterns among middle-aged to elderly Canadians and (2) to investigate the extent to which these patterns could be explained by bone mineral density (BMD), a proxy measure of the cholinergic neurons' activity. METHODS: This cross-sectional study used baseline data from the Comprehensive cohort of the Canadian Longitudinal Study of Aging (CLSA). Oral health was assessed by a self-report questionnaire, and 7 task-based instruments measured cognitive health. We identified oral and cognitive health clusters, our outcome variables, using latent class analysis. Two sets of multivariate logistic regression and 95% confidence intervals were used to investigate whether BMD explains the odds of membership in a certain oral and cognitive health group. The final models were adjusted for socioeconomic, health, and lifestyle factors. RESULTS: Our study sample (N = 25,444: 13,035 males, 12,409 females) was grouped into 5 and 4 clusters based on the oral health status and performance on the cognitive tasks, respectively. After adjusting for all potential covariates, increase in BMD was not associated with higher odds of membership in classes with better oral health (odds ratio [OR] = 1.58 [95% confidence interval {CI}: 0.85-2.92]) and cognitive health (OR = 1.61 [95% CI: 1-2.6]) compared with the groups with the least favorable oral and cognitive health status, respectively. CONCLUSION: Middle-aged and elderly Canadians show different oral and cognitive health profiles, based on their denture-wearing status and performance on cognitive tests. No evidence could be found to support BMD in place of cholinergic neurons' activity as the common explanatory factor behind the association between oral health and cognitive health. KNOWLEDGE TRANSFER STATEMENT: This study is probably the first of its kind to shed light on the cholinergic system as a potential pathway influencing oral and cognitive health. Our findings may support the notion that any potential association between poor oral health and cognitive health might be explained by common contributors, helping clinicians to find the common risk factors for both conditions.

Artificial Intelligence and Ethics in Dentistry: A Scoping Review.

Dentistry increasingly integrates artificial intelligence (AI) to help improve the current state of clinical dental practice. However, this revolutionary technological field raises various complex ethical challenges. The objective of this systematic scoping review is to document the current uses of AI in dentistry and the ethical concerns or challenges they imply. Three health care databases (MEDLINE [PubMed], SciVerse Scopus, and Cochrane Library) and 2 computer science databases (ArXiv, IEEE Xplore) were searched. After identifying 1,553 records, the documents were filtered, and a full-text screening was performed. In total, 178 studies were retained and analyzed by 8 researchers specialized in dentistry, AI, and ethics. The team used Covidence for data extraction and Dedoose for the identification of ethics-related information. PRISMA guidelines were followed. Among the included studies, 130 (73.0%) studies were published after 2016, and 93 (52.2%) were published in journals specialized in computer sciences. The technologies used were neural learning techniques for 75 (42.1%), traditional learning techniques for 76 (42.7%), or a combination of several technologies for 20 (11.2%). Overall, 7 countries contributed to 109 (61.2%) studies. A total of 53 different applications of AI in dentistry were identified, involving most dental specialties. The use of initial data sets for internal validation was reported in 152 (85.4%) studies. Forty-five ethical issues (related to the use AI in dentistry) were reported in 22 (12.4%) studies around 6 principles: prudence (10 times), equity (8), privacy (8), responsibility (6), democratic participation (4), and solidarity (4). The ratio of studies mentioning AI-related ethical issues has remained similar in the past years, showing that there is no increasing interest in the field of dentistry on this topic. This study confirms the growing presence of AI in dentistry and highlights a current lack of information on the ethical challenges surrounding its use. In addition, the scarcity of studies sharing their code could prevent future replications. The authors formulate recommendations to contribute to a more responsible use of AI technologies in dentistry.

Platelet Concentrate Treatments for Temporomandibular Disorders: A Systematic Review and Meta-analysis.

OBJECTIVES: This systematic review compared platelet concentrates (PCs) versus hyaluronic acid (HA) or saline/Ringer's solution injections as treatments of temporomandibular osteoarthritis and disc displacement in terms of pain and maximum mouth opening (MMO). METHODS: PubMed, Cochrane, and Scopus were searched up to March 6, 2020. Inclusion criteria were randomized clinical trials (RCTs). Exclusion criteria were case series, observational studies, animal studies, and reviews. The Effective Public Health Practice Project (EPHPP) quality assessment tool was used to assess the risk of bias in the included studies. The weighted mean difference was used to compare the results. RESULTS: Nine RCTs were included with a total of 407 patients. The numbers of joints treated were 262, 112, and 112 in the PC, HA, and saline groups, respectively. The quality of studies was rated as strong in 4 studies, moderate in 4 studies, and weak in 1 study. The meta-analysis revealed that PCs decreased pain visual analogue scale (VAS) scores compared to HA by an average of -1.11 (CI, -1.62 to -0.60; P < 0.0001) and -0.57 (CI, -1.55 to 0.41; P = 0.26) at 3 and 12 mo follow-up respectively. Also, the average decrease in pain scores with PC compared to saline was -1.33 (CI, -2.61 to -0.06; P = 0.04), -2.07 (CI, -3.46 to -0.69; P = 0.003), and -2.71 (CI, -4.69 to -0.72; P = 0.008) at 3, 6, and 12 mo, respectively. Regarding MMO measurements, PC was comparable to HA, but it was significantly better than saline after 3 and 6 mo [2.9 mm (CI,1.47 to 4.3; P < 0.0001), and 1.69 mm (CI, 0.13 to 3.25; P = 0.03) respectively]. CONCLUSION: PC reduces pain VAS scores compared to HA during the first 3 m after treatment, and when compared to saline, it reduces pain and increases MMO for longer durations. However, due to differences between groups regarding PC preparation protocols and study heterogeneity, further standardized RCTs are required. KNOWLEDGE TRANSFER STATEMENT: This study provides researchers and clinicians with quantitative and qualitative analyses of the current evidence regarding the clinical outcomes of platelet concentrate injections in the treatment of temporomandibular joint osteoarthritis and disc displacement in terms of pain control and maximum mouth opening.

Age related changes in the bone microstructure in patients with femoral neck fractures.

BACKGROUND: The risk of femoral neck fracture progressively increases with age. However, the reasons behind this consistent increase in the fracture risk can't be completely justified by the decrease in the bone mineral density. The objective of this study was to analyze the correlation between various bone structural features and age. STUDY DESIGN & METHODS: A total of 29 consecutive patients who suffered an intracapsular hip fracture and underwent joint replacement surgery between May 2012 and March 2013 were included in this study. A 2 cm × 1 cm Ø cylindrical trabecular bone sample was collected from the femoral heads and preserved in formaldehyde. Bone mineral density (BMD), microarchitecture, organic content and crystallography were analyzed using a Dual-energy X-ray absorptiometry scan, micro-CT scan, and high resolution magic-angle-spinning-nuclear magnetic resonance (MAS-NMR), respectively. Statistical correlations were made using Spearman´s or Pearson´s correlation tests depending on the distribution of the continuous variables. RESULTS: The mean patient age was 79.83 ± 9.31 years. A moderate negative correlation was observed between age and the hydrogen content in bone (1H), which is an indirect estimate to quantify the organic matrix (r = -0.512, p = 0.005). No correlations were observed between BMD, trabecular number, trabecular thickness, phosphorous content, apatite crystal size, and age (r = 0.06, p = 0.755; r = -0.008, p = 0.967; r = -0.046, p = 0.812; r = -0.152, p = 0.430, respectively). A weak positive correlation was observed between Charlson´s comorbidity index (CCI) and c-axis of the hydroxiapatite (HA) crystals (r = -0.400, p = 0.035). CONCLUSION: The femoral head relative protein content progressively decreases with age. BMD was not correlated with other structural bone parameters and age. Patients with higher comorbidity scores had larger HA crystals. The present results suggest that the progressive increase in the hip fracture risk in elderly patients could be partially explained by the lower bone protein content in this age group.

Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery.

Postoperative pain relief is crucial for full recovery. With the ongoing opioid epidemic and the insufficient effect of acetaminophen on severe pain; non-steroidal anti-inflammatory drugs (NSAIDs) are heavily used to alleviate this pain. However, NSAIDs are known to inhibit postoperative healing of connective tissues by inhibiting prostaglandin signaling. Pain intensity, inflammatory mediators associated with wound healing and the pharmacological action of NSAIDs vary throughout the day due to the circadian rhythm regulated by the clock genes. According to this rhythm, most of wound healing mediators and connective tissue formation occurs during the resting phase, while pain, inflammation and tissue resorption occur during the active period of the day. Here we show, in a murine tibia fracture surgical model, that NSAIDs are most effective in managing postoperative pain, healing and recovery when drug administration is limited to the active phase of the circadian rhythm. Limiting NSAID treatment to the active phase of the circadian rhythm resulted in overexpression of circadian clock genes, such as Period 2 (Per2) at the healing callus, and increased serum levels of anti-inflammatory cytokines interleukin-13 (IL-13), interleukin-4 (IL-4) and vascular endothelial growth factor. By contrast, NSAID administration during the resting phase resulted in severe bone healing impairment.

Correction to: Acetylcholinesterase inhibitors and the risk of osteoporotic fractures: nested case-control study.

Please find below the correction for the paragraph under the Heading "Materials and methods - Regulatory approval".

Genotype and malocclusion in patients with osteogenesis imperfecta.

OBJECTS: To investigate the relationship between genotype and severity of malocclusion in osteogenesis imperfecta (OI). SETTING AND SAMPLE POPULATION: A total of 49 patients participated in this cross-sectional study (age range: 5-19 years; 28 females; diagnoses: OI type I, N = 7; OI type III, N = 11; OI type IV, N = 27; OI type V, N = 2; OI type VI, N = 2). MATERIALS AND METHODS: Sequence analysis of COL1A1/COL1A2 and other OI-related genes was compared to the Peer Assessment Rating (PAR), an index reflecting the severity of malocclusion. RESULTS: The mutation spectrum was as follows: COL1A1, N = 22; COL1A2, N = 22, IFITM5, N = 2; SERPINF1, N = 2; no mutation detected, N = 1). Compared to patients with COL1A1 mutations, patients with COL1A2 mutations had significantly higher scores for total PAR, anterior cross-bite, anterior open bite and anteroposterior buccal occlusion. Males with COL1A2 mutations had significantly higher total PAR scores than females (median 36 vs 30, P = .047, Mann-Whitney test). Exploratory correlation between age and buccal vertical occlusion was noted in patients with COL1A2 mutations (Spearman correlation: r = .46, P = .03, power = .50). Two patients with OI type V (caused by IFITM5 mutations) had total PAR scores of 44 and 21. Both patients scored high for "segment." Patients with OI type VI (due to SERPINF1 mutations) scored similar to OI type V for "centreline." Considerable difference was observed in the total PAR score between the 2 patients with OI type VI. They had total PAR of 43 and 2. CONCLUSION: Type of disease-causing mutation affects the severity of malocclusion in individuals with OI.

Surface modification of CoCr alloys by electrochemical reduction of diazonium salts.

Tailoring the surface chemistry of CoCr alloys is of tremendous interest in many biomedical applications. In this work, we show that CoCr can be modified by diazonium electrografting provided the surface is not homogeneously covered with an oxide layer. Cyclic voltammetry (CV) and X-ray photoelectron spectroscopy (XPS) show the electrografting of a poly(aminophenylene) (PAP) layer on CoCr when treated at a reductive potential (CoCr-0.5 V), whereas no PAP film was formed on CoCrOCP and CoCr1 V, treated at open circuit and anodic potentials respectively. Based on XPS results, we attributed the electrografting to the formation of carbide bonds between PAP and the inhomogeneous thin oxide layer of CoCr-0.5 V. We then show an example of application of PAP coatings on CoCr and prove that the presence of a PAP coating on CoCr-0.5 V results in a 5-fold increase of the adherence of poly methyl methacrylate (PMMA) to PAP-coated CoCr compared to uncoated samples; this is of prime significance to improving the long-term stability of dental prostheses. These findings support the importance of reducing the oxide layer for effective functionalization of metal oxides with aryl diazonium salts and suggest a promising surface modification approach for biomedical applications.

Acetylcholinesterase inhibitors and the risk of osteoporotic fractures: nested case-control study.

The objective of this study was to analyze the effect of acetylcholinesterase inhibitors (AChEIs) on the risk of osteoporotic fractures in Alzheimer patients. A nested case-control study was conducted on 1190 cases and 4760 controls. The use of AChEIs was found to decrease the risk of osteoporotic fractures in these patients. INTRODUCTION: The objective of this study is to estimate the extent to which the use of AChEIs is associated with a reduction in the risk of osteoporotic fractures. METHODS: A nested case-control study was conducted using data from the UK Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database (1998-2013). The study cohort consisted of Alzheimer's Disease (AD) patients aged ≥ 65 years with no previous history of osteoporotic fractures at cohort baseline. Cases were individuals who suffered an osteoporotic fracture during the study period, whereas controls were subject who did not experience any osteoporotic fractures during the same period. Controls were drawn from the population time at risk while being matched to the cases in respect to age, sex, up-to-standard follow-up in the CPRD, calendar time, and duration of AD (control-to-case ratio: 4-to-1). Information on the use of AChEIs and the relevant potential confounders was ascertained from the CPRD database for all the cases and controls. RESULTS: We identified 1190 cases and 4760 controls. Compared to non-users, any use of AChEIs prior to the fracture was associated with a reduction in the fracture risk [adjusted odds ratio (OR) 0.80 (confidence interval (CI) 95%, 0.70-0.91)]. The use of AChEIs corresponding to a proportion of days covered of 0.8-1.0 was associated with a lower osteoporotic fracture risk compared to non-use [adjusted OR 0.76 (CI 95%, 0.66-0.87)]. CONCLUSIONS: In this study using large primary care databases, the use and treatment adherence to AChEIs were associated with a decreased risk of osteoporotic fractures in elderly AD patients.

Effect of acetylcholinesterase inhibitors on post-surgical complications and mortality following a hip fracture: a cohort study.

There is increasing evidence suggesting that the use of acetylcholinesterase inhibitors may have beneficial effects on bone. Data on the potential post-surgical effects of these medications on orthopedic interventions are very limited. This study was designed to determine whether the use of acetylcholinesterase inhibitors is associated with a decrease in post-surgical mortality and complications in hip fracture patients with Alzheimer's disease. To accomplish this objective, a retrospective cohort study was performed using data from the Clinical Practice Research Database, UK. The study included 532 Alzheimer's disease patients of age 65 years and older, who sustained a hip fracture between 1998 and 2012. During the follow-up period, 34% of the patients died (n=182), 22% sustained a second hip fracture (n=118) and 5% (n=29) required reintervention. The users of acetylcholinesterase inhibitors had a 56% reduction in all-cause mortality (HR= 0.44, 95% CI 0.30-0.63) and a 41% reduction in second hip fracture incidence during a year of post-surgical follow-up (HR= 0.59, 95% CI 0.38-0.94) after adjusting for potential confounders. Our results show that acetylcholinesterase inhibitors may have the potential to reduce all-cause mortality and the risk of suffering a second hip fracture during the first year after surgery.

Osseointegration Pharmacology.

The process of osseointegration around dental implants is similar to the biological events occurring during bone repair and fracture healing. Therefore, bone metabolic activity plays a crucial role on the success of osseointegration, and dysregulation of bone metabolism can have a negative impact on bone healing and implant osseointegration. Accordingly, it could be hypothesized that drugs interfering with healing and bone metabolism could affect osseointegration and implant survival. Looking into the relationship between pharmacology, osseointegration, and dental implants, drugs can open the door for new pharmacological innovations to improve implant success and avoid unnecessary complications, and it is also of special interest because most implant patients are elder adults who are often polymedicated. In this commentary, we discuss the discoveries made by us as well as by other researchers regarding the effect of several drugs on bone, osseointegration, and implant survival. Of particular interest is the growing evidence showing that commonly used drugs such as nonsteroidal anti-inflammatories, serotonin reuptake inhibitors, and proton pump inhibitors could lead to implant failure.

Failure of single-unit restorations on root filled posterior teeth: a systematic review.

This systematic review investigated the failure rate of conventional single-unit restorations in root filled posterior permanent teeth. Two reviewers independently applied eligibility criteria, extracted data and assessed the quality of the evidence of each included study according to the Cochrane Collaboration's procedures for randomized control trials (RCTs) and the STROBE criteria for observational studies. The MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Oral Health Group Trials Register and CENTRAL (via Cochrane Library) databases were searched electronically (January 1993 to week 1, February 2015). This was complemented by an additional hand search of selected journals and the references of relevant studies. Clinical studies published on root filled single-unit restorative treatments with a mean follow-up period of at least 3 years were selected. The outcome measured was clinical or radiological failure. Overall, the four RCTs and the single observational study included were of low and high quality, respectively. Therefore, a meta-analysis was not possible. The pooled mean failure rates were reported according to the type of treatment and remaining coronal tooth structure. The current evidence suggested that the failure rates of the treatments may depend on the amount of remaining tooth structure and type of treatment. Post-retained crowns were associated with the most favourable outcome in teeth with one to two remaining coronal tooth wall(s), whereas post-free crowns were superior when greater tooth structure was available. Restorations in teeth without ferrules had such a high rate of failure that other treatment options should be considered.

Evidence-based dentistry for planning restorative treatments: barriers and potential solutions.

INTRODUCTION: Evidence-based dentistry (EBD) can help provide the best treatment option for every patient, however, its implementation in restorative dentistry is very limited. OBJECTIVE: This study aimed at assessing the barriers preventing the implementation of EBD among dental undergraduate and graduate students in Montreal, and explore possible solutions to overcome these barriers. MATERIALS AND METHODS: A cross-sectional survey was conducted by means of a paper format self-administrated questionnaire distributed among dental students. The survey assessed the barriers and potential solutions for implementation of an evidence-based practice. RESULTS: Sixty-one students completed the questionnaire. Forty-one percent of respondents found evidence-based literature to be the most reliable source of information for restorative treatment planning, however, only 16% used it. They considered that finding reliable information was difficult and they sometimes encountered conflicting information when consulting different sources. Dental students had positive attitudes towards the need for better access to evidence-based literature to assist learning and decision making in restorative treatment planning and to improve treatment outcomes. Even for dentists trained in EBD, online searching takes too much time, and even though it can provide information of better quality than personal intuition, it might not be enough to identify the best available evidence. CONCLUSIONS: Even though dental students are aware of the importance of EBD in restorative dentistry they rarely apply the concept, mainly due to time constraints. For this reason, implementation of EBD would probably require faster access to evidence-based knowledge.

Craniofacial and Dental Defects in the Col1a1Jrt/+ Mouse Model of Osteogenesis Imperfecta.

Certain mutations in the COL1A1 and COL1A2 genes produce clinical symptoms of both osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) that include abnormal craniofacial growth, dental malocclusion, and dentinogenesis imperfecta. A mouse model (Col1a1(Jrt)/+) was recently developed that had a skeletal phenotype and other features consistent with moderate-to-severe OI and also with EDS. The craniofacial phenotype of 4- and 20-wk-old Col1a1(Jrt)/+ mice and wild-type littermates was assessed by micro-computed tomography (µCT) and morphometry. Teeth and the periodontal ligament compartment were analyzed by µCT, light microscopy/histomorphometry, and electron microscopy. Over time, at 20 wk, Col1a1(Jrt)/+ mice developed smaller heads, a shortened anterior cranial base, class III occlusion, and a mandibular side shift with shorter morphology in the masticatory region (maxilla and mandible). Col1a1(Jrt)/+ mice also had changes in the periodontal compartment and abnormalities in the dentin matrix and mineralization. These findings validate Col1a1(Jrt)/+ mice as a model for OI and EDS in humans.

Selective serotonin reuptake inhibitors and the risk of osseointegrated implant failure: a cohort study.

Selective serotonin reuptake inhibitors (SSRIs), the most widely used drugs for the treatment of depression, have been reported to reduce bone formation and increase the risk of bone fracture. Since osseointegration is influenced by bone metabolism, this study aimed to investigate the association between SSRIs and the risk of failures in osseointegrated implants. This retrospective cohort study was conducted on patients treated with dental implants from January 2007 to January 2013. A total of 916 dental implants in 490 patients (94 implants on 51 patients using SSRIs) were used to estimate the risk of failure associated with the use of SSRIs. Data analysis involved Cox proportional hazards, generalized estimating equation models, multilevel mixed effects parametric survival analysis, and Kaplan-Meier analysis. After 3 to 67 mo of follow-up, 38 dental implants failed and 784 succeeded in the nonusers group, while 10 failed and 84 succeeded in the SSRI-users group. The main limitation of this retrospective study was that drug compliance dose and treatment period could not be acquired from the files of the patients. The primary outcome was that compared with nonusers of SSRIs, SSRI usage was associated with an increased risk of dental implants failure (hazard ratio, 6.28; 95% confidence interval, 1.25-31.61; p = .03). The failure rates were 4.6% for SSRI nonusers and 10.6% for SSRI users. The secondary outcomes were that small implant diameters (≤4 mm; p = .02) and smoking habits (p = .01) also seemed to be associated with higher risk of implant failure. Our findings indicate that treatment with SSRIs is associated with an increased failure risk of osseointegrated implants, which might suggest a careful surgical treatment planning for SSRI users.

Acetylcholinesterase inhibitors and healing of hip fracture in Alzheimer's disease patients: a retrospective cohort study.

OBJECTIVES: This study was designed to assess effects of cholinergic stimulation using acetylcholinesterase inhibitors (AChEIs), a group of drugs that stimulate cholinergic receptors and are used to treat Alzheimer's disease (AD), on healing of hip fractures. METHODS: A retrospective cohort study was performed using 46-female AD patients, aged above 75 years, who sustained hip fractures. Study analyses included the first 6-months after hip fracture fixation procedure. Presence of AChEIs was used as predictor variable. Other variables that could affect study outcomes: age, body mass index (BMI), mental state or type of hip fracture, were also included. Radiographic union at fracture site (Hammer index), bone quality (Singh index) and fracture healing complications were recorded as study outcomes. The collected data was analyzed by student's-t, Mann-Whitney-U and chi-square tests. RESULTS: No significant differences in age, BMI, mental state or type of hip fracture were observed between AChEIs-users and nonusers. However, AChEIs-users had better radiographic union at the fracture site (relative risk (RR),2.7; 95%confidence interval (CI),0.9-7.8), better bone quality (RR,2.0; 95%CI,1.2-3.3) and fewer healing complications (RR,0.8; 95%CI,0.7-1.0) than nonusers. CONCLUSION: In elderly female patients with AD, the use of AChEIs might be associated with an enhanced fracture healing and minimized complications.

Cholinergic regulation of bone.

Bone remodeling is regulated by the two branches of the autonomic nervous system: the adrenergic and the cholinergic branches. Adrenergic activity favors bone loss, whereas cholinergic activity has been recently shown to favor bone mass accrual. In vitro studies have reported that cholinergic activity induces proliferation and differentiation of bone cells. In vivo studies have shown that the inhibition of cholinergic activity favors bone loss, whereas its stimulation favors bone mass accrual. Clinical studies have shown that bone density is associated with the function of many cholinergic-regulated tissues such as the hypothalamus, salivary glands, lacrimal glands and langerhans cells, suggesting a common mechanism of control. Altogether, these observations and linked findings are of great significance since they improve our understanding of bone physiology. These discoveries have been successfully used recently to investigate new promising therapies for bone diseases based on cholinergic stimulation. Here, we review the current understanding of the cholinergic activity and its association with bone health.