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.

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".

Sleep-Disordered Breathing Is Associated with Reduced Mandibular Cortical Width in Children.

INTRODUCTION: Evidence from the adult population suggests that sleep-disordered breathing (SDB) (i.e., obstructive sleep apnea [OSA]) is negatively associated with bone mineral density. Whether a similar association exists in children with SDB has not been investigated. Using the mandibular cortical width (MCW) as a proxy for skeletal bone density, we investigated if children at risk of SDB or diagnosed with OSA have a reduced mandibular cortical width compared to children without SDB. METHODS: Two retrospective cross-sectional studies were performed. The first study included comparison of MCW between 24 children with polysomnographically (PSG) diagnosed OSA and 72 age- and sex-matched control children. The second study included a cohort of children in which SDB was suggested by the Pediatric Sleep Questionnaire (PSQ) ( n = 101). MCW was measured from panoramic radiographs. RESULTS: Multiple-predictors regression analysis from the first study indicated that in children with a severe form of SDB, as induced by OSA severity, there was a negative association with MCW (ß = -0.290, P = 0.049). Moreover, PSG-diagnosed OSA children had thinner MCW (2.9. ± 0.6mm) compared to healthy children (3.5 ± 0.6 mm; P = 0.002). These findings were further supported by the second study illustrating that PSQ total scores were negatively associated with MCW (ß = -0.391, P < 0.001). CONCLUSIONS: Findings suggest that children at risk for or diagnosed with SDB exhibit reduced mandibular cortical width that purportedly may reflect alterations in bone homeostasis. KNOWLEDGE TRANSFER STATEMENT: We report that sleep-disordered breathing (including its severe form, obstructive sleep apnea) in children is associated with reduced mandibular cortical width. This association might be a direct consequence of reduced bone health to sleep-disordered breathing or a reflection that reduced bone formation underlies the development of sleep-disordered breathing. Our findings suggest that mandibular cortical width can be used as an adjunct diagnostic parameter for the diagnosis of sleep-disordered breathing.

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.

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.

Association between sleep apnea and low bone mass in adults: a systematic review and meta-analysis.

We performed a systematic review of the literature to assess the association between sleep apnea and bone metabolism diseases including osteoporosis in adult population. Results from clinical trials suggest that the association between sleep apnea and low bone mass in adults is possible. INTRODUCTION: This study aimed to synthesize existing evidence on the potential association between sleep apnea and low bone mass in adults. METHODS: Electronic searches of five databases were performed. The inclusion criteria consisted of studies in humans that assessed potential associations between sleep apnea and bone metabolic diseases in an adult population. For diagnosis of sleep apnea overnight polysomnography, home polygraphy, or validated records from healthcare databases were considered. Reduced bone density, osteoporosis, serum/urinary levels for markers of bone formation and resorption, or risk of fractures caused without history of trauma were considered indicators of low bone mass. A random-effects model meta-analysis was applied when possible. RESULTS: Of the 963 relevant references, 12 studies met our inclusion criteria and were assessed to be of medium to low bias. Nine out of 12 studies reported an association between sleep apnea and low bone mass (increased bone resorption markers, reduced bone density, and higher risk of osteoporosis). Two studies did not report a significant association, whereas one study reported an increase of bone density in sleep apnea patients compared to non-sleep apnea patients. Meta-analysis of 2 studies (n = 112,258 patients) showed that sleep apnea was a significant risk factor for osteoporosis (odds ratio (OR), 1.92; 95%CI, 1.24 to 2.97; I2 = 66%); females only had an OR of 2.56 (95% CI, 1.96 to 3.34; I2 = 0%) while the OR in males was 2.03 (95% CI, 1.24 to 3.35; I2 = 38%). CONCLUSIONS: An association between sleep apnea and low bone mass in adults is plausible, but supporting evidence has a risk of bias and is inconsistent.

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.

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.

Local regulation of tooth mineralization by sphingomyelin phosphodiesterase 3.

Sphingomyelin phosphodiesterase 3 (Smpd3) encodes a membrane-bound enzyme that cleaves sphingomyelin to generate several bioactive metabolites. A recessive mutation called fragilitas ossium (fro) in the Smpd3 gene leads to impaired mineralization of bone and tooth extracellular matrix (ECM) in fro/fro mice. In teeth from fro/fro mice at various neonatal ages, radiography and light and electron microscopy showed delayed mantle dentin mineralization and a consequent delay in enamel formation as compared with that in control +/fro mice. These tooth abnormalities progressively improved with time. Immunohistochemistry showed expression of SMPD3 by dentin-forming odontoblasts. SMPD3 deficiency, however, did not affect the differentiation of these cells, as shown by osterix and dentin sialophosphoprotein expression. Using a transgenic mouse rescue model (fro/fro; Col1a1-Smpd3) in which Smpd3 expression is driven by a murine Col1a1 promoter fragment active in osteoblasts and odontoblasts, we demonstrate a complete correction of the tooth mineralization delays. In conclusion, analysis of these data demonstrates that Smpd3 expression in odontoblasts is required for tooth mineralization.