Aims. Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD. Methods. A total of 3,321 independent loci of gut microbiota were used to calculate the individual polygenic risk score (PRS) for 114 gut microbiota-related traits. The individual genotype data were obtained from UK Biobank cohort. Linear regressions were then conducted to evaluate the possible association of gut microbiota with L1-L4 BMD (n = 4,070), total BMD (n = 4,056), and femur total BMD (n = 4,054), respectively. PLINK 2.0 was used to detect the single-nucleotide polymorphism (SNP) × gut microbiota interaction effect on the risks of L1-L4 BMD, total BMD, and femur total BMD, respectively. Results. We detected five, three, and seven candidate gut microbiota-related traits for L1-L4 BMD, total BMD, and femur BMD, respectively, such as genus Dialister (p = 0.004) for L1-L4 BMD, and genus Eisenbergiella (p = 0.046) for total BMD. We also detected two common gut microbiota-related traits shared by L1-L4 BMD, total BMD, and femur total BMD, including genus Escherichia Shigella and genus Lactococcus. Interaction analysis of BMD detected several genes that interacted with gut microbiota, such as phospholipase D1 (PLD1) and endomucin (EMCN) interacting with genus Dialister in total BMD, and COL12A1 and Discs Large MAGUK Scaffold Protein 2 (DLG2) interacting with genus Lactococcus in femur BMD. Conclusion. Our results suggest associations between gut microbiota and BMD, which will be helpful to further explore the regulation mechanism and intervention gut microbiota of BMD. Cite this article: Bone Joint Res 2021;10(11):734–741

Objectives. The goal of this study is to investigate the relation between indicators of osteoporosis (i.e., bone mineral density (BMD), and Cortical Index (CI)) and the complexity of a fracture of the proximal humerus as a result of a low-energy trauma. Methods. A retrospective chart review of 168 patients (mean age 67.2 years, range 51 to 88.7) with a fracture of the proximal humerus between 2007 and 2011, whose BMD was assessed at the Fracture Liaison Service with Dual Energy X-ray Absorptiometry (DXA) measurements of the hip, femoral neck (FN) and/or lumbar spine (LS), and whose CI and complexity of fracture were assessed on plain anteroposterior radiographs of the proximal humerus. Results. No significant differences were found between simple and complex fractures of the proximal humerus in the BMD of the hip, FN or LS (all p > 0.3) or in the CI (p = 0.14). Only the body mass index was significantly higher in patients with a complex fracture compared with those with a simple fracture (26.9 vs 25.2; p = 0.05). Conclusion. There was no difference in BMD of the hip, FN, LS or CI of the proximal humerus in simple compared with complex fractures of the proximal humerus after a low-energy trauma. Factors other than the BMD and CI, for example body mass index, may play a more important role in the complexity of this fracture. Cite this article: J.W.A.M. den Teuling, B.S. Pauwels, L. Janssen, C.E. Wyers, H. M. J. Janzing, J.P.W. van den Bergh, J. W. Morrenhof. The Influence of bone mineral density and cortical index on the complexity of fractures of the proximal humerus. Bone Joint Res 2017;6:584–589. DOI: 10.1302/2046-3758.610.BJR-2017-0080

Aims. Osteoporosis and abnormal bone metabolism may prove to be significant factors influencing the outcome of arthroplasty surgery, predisposing to complications of aseptic loosening and peri-prosthetic fracture. We aimed to investigate baseline bone mineral density (BMD) and bone turnover in patients about to undergo arthroplasty of the hip and knee. Methods. We prospectively measured bone mineral density of the hip and lumbar spine using dual-energy X-ray absorptiometry (DEXA) scans in a cohort of 194 patients awaiting hip or knee arthroplasty. We also assessed bone turnover using urinary deoxypyridinoline (DPD), a type I collagen crosslink, normalised to creatinine. Results. The prevalence of DEXA proven hip osteoporosis (T-score ≤ -2.5) among hip and knee arthroplasty patients was found to be low at 2.8% (4 of 143). Spinal osteoporosis prevalence was higher at 6.9% (12 of 175). Sixty patients (42% (60 of 143)) had osteopenia or osteoporosis of either the hip or spine. The mean T-score for the hip was -0.34 (. sd. 1.23), which is within normal limits, and the mean hip Z-score was positive at 0.87 (. sd. 1.17), signifying higher-than-average BMD for age. The median urinary DPD/creatinine was raised in both female patients at 8.1 (interquartile range (IQR) 6.6 to 9.9) and male patients at 6.2 (IQR 4.8 to 7.5). Conclusions. Our results indicate hip and knee arthroplasty patients have higher BMD of the hip and spine compared with an age-matched general population, and a lower prevalence of osteoporosis. However, untreated osteoporotic patients are undergoing arthroplasty, which may negatively impact their outcome. Raised DPD levels suggest abnormal bone turnover, requiring further investigation. Cite this article: Bone Joint Res 2014;3:14–19

Purpose. The purpose of this study was to evaluate periprosthetic bone mineral density (BMD) changes around a cementless short tapered-wedge stem and determine correlations between BMD changes and various clinical factors, including daily activity, after total hip arthroplasty (THA) with a short tapered-wedge stem. Methods. The study included 65 patients (65 joints) who underwent THA with a TriLock stem. At baseline, and 6, 12, and 24 months postoperatively, BMDs of the seven Gruen zones were evaluated using dual-energy X-ray absorptiometry. Correlations were determined between BMD changes and clinical factors, including the Harris hip score, body mass index, University of California at Los Angeles (UCLA) activity rating score, age at surgery, and initial lumbar BMD. Results. Minimal BMD changes were noted in the distal femur (Gruen zones 3, 4, and 5). However, significant BMD loss was noted in zone 7 at each time point. BMD loss was also noted in zone 1 at 6 and 12 months postoperatively, but BMD recovered after 18 months. Significant positive correlations were noted between BMD changes and the UCLA activity rating score in zones 1, 6, and 7. Additionally, negative correlations were noted between BMD changes and initial spine BMD in zones 2 and 3. Table legends. Table 1 Background of the patients. Table 2 Bone mineral density changes (%) at 6, 12, and 24 months postoperatively in the seven Gruen zones. Columns represent mean ± standard deviation. ※indicates P < 0.05 compared with baseline bone mineral density. Table 3 Correlations between periprosthetic bone mineral density changes and clinical factors (the Harris hip score, body mass index, University of California at Los Angeles activity rating score, age at surgery, and initial lumbar bone mineral density) in the seven Gruen zones at 24 months postoperatively. Correlation coefficients and P-values are presented. Boldface indicates P < 0.05. Conclusion. Periprosthetic BMD was maintained in the proximal femur, especially Gruen zone 1, with a short tapered stem. Daily activity may reflect improvements in periprosthetic bone quality after THA with a short tapered stem; however, this stem is not recommended in patients with low bone quality. To view tables, please contact authors directly

There is limited literature available looking into circumstances surrounding the development of stress fracture of the medial and lateral malleoli after ankle replacement. We present the preliminary results of a prospective study examining the effect of ankle replacement upon local bone mineral density and the phenomenon of stress shielding. We aimed to assess the effect of ankle replacement loading of the medial and lateral malleoli, by analysing the Bone Mineral Density (BMD) of the medial and lateral malleoli before and after Mobility total ankle replacement. Ten consecutive patients undergoing Mobility total ankle replacement for osteoarthritis had pre-operative bone densitometry scans of the ankle, repeated at 6 months after surgery. The bone mineral density of a 2 cm square area within the medial malleolus and lateral malleolus was measured. The pre-operative and postoperative bone densitometry scans were compared. The relation between the alignment of the tibial component and the bone mineral density of the malleoli was also analysed. The mean preoperative BMD within the medial malleolus improved from 0.57g/cm2 to mean 6 months postoperative BMD of 0.62g/cm2. The mean preoperative BMD within the lateral malleolus decreased from 0.39g/cm2 to a mean 6 months postoperative of 0.33g/cm2. The mean alignment of the tibial component was 88.50 varus (range 850 varus to 940 valgus). However, there was no correlation between the alignment of the tibial component and the bone mineral density on the medial malleolus (r = 0.09, p = 0.865). The absence of stress shielding around the medial malleolus indicates that ankle replacements implanted within the accepted limits for implant alignment, load the medial malleolus. However, there was stress shielding over the lateral malleolus resulting in decreased BMD in the lateral malleolus

Aims. The distal radius is a major site of osteoporotic bone loss resulting in a high risk of fragility fracture. This study evaluated the capability of a cortical index (CI) at the distal radius to predict the local bone mineral density (BMD). Methods. A total of 54 human cadaver forearms (ten singles, 22 pairs) (19 to 90 years) were systematically assessed by clinical radiograph (XR), dual-energy X-ray absorptiometry (DXA), CT, as well as high-resolution peripheral quantitative CT (HR-pQCT). Cortical bone thickness (CBT) of the distal radius was measured on XR and CT scans, and two cortical indices mean average (CBTavg) and gauge (CBTg) were determined. These cortical indices were compared to the BMD of the distal radius determined by DXA (areal BMD (aBMD)) and HR-pQCT (volumetric BMD (vBMD)). Pearson correlation coefficient (r) and intraclass correlation coefficient (ICC) were used to compare the results and degree of reliability. Results. The CBT could accurately be determined on XRs and highly correlated to those determined on CT scans (r = 0.87 to 0.93). The CBTavg index of the XRs significantly correlated with the BMD measured by DXA (r = 0.78) and HR-pQCT (r = 0.63), as did the CBTg index with the DXA (r = 0.55) and HR-pQCT (r = 0.64) (all p < 0.001). A high correlation of the BMD and CBT was observed between paired specimens (r = 0.79 to 0.96). The intra- and inter-rater reliability was excellent (ICC 0.79 to 0.92). Conclusion. The cortical index (CBTavg) at the distal radius shows a close correlation to the local BMD. It thus can serve as an initial screening tool to estimate the local bone quality if quantitative BMD measurements are unavailable, and enhance decision-making in acute settings on fracture management or further osteoporosis screening. Cite this article: Bone Joint Res 2021;10(12):820–829

Aims. Assessment of bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) is a well-established clinical technique, but it is not available in the acute trauma setting. Thus, it cannot provide a preoperative estimation of BMD to help guide the technique of fracture fixation. Alternative methods that have been suggested for assessing BMD include: 1) cortical measures, such as cortical ratios and combined cortical scores; and 2) aluminium grading systems from preoperative digital radiographs. However, limited research has been performed in this area to validate the different methods. The aim of this study was to investigate the evaluation of BMD from digital radiographs by comparing various methods against DXA scanning. Methods. A total of 54 patients with distal radial fractures were included in the study. Each underwent posteroanterior (PA) and lateral radiographs of the injured wrist with an aluminium step wedge. Overall 27 patients underwent routine DXA scanning of the hip and lumbar spine, with 13 undergoing additional DXA scanning of the uninjured forearm. Analysis of radiographs was performed on ImageJ and Matlab with calculations of cortical measures, cortical indices, combined cortical scores, and aluminium equivalent grading. Results. Cortical measures showed varying correlations with the forearm DXA results (range: Pearson correlation coefficient (r) = 0.343 (p = 0.251) to r = 0.521 (p = 0.068)), with none showing statistically significant correlations. Aluminium equivalent grading showed statistically significant correlations with the forearm DXA of the corresponding region of interest (p < 0.017). Conclusion. Cortical measures, cortical indices, and combined cortical scores did not show a statistically significant correlation to forearm DXA measures. Aluminium-equivalent is an easily applicable method for estimation of BMD from digital radiographs in the preoperative setting. Cite this article: Bone Joint Res 2021;10(12):830–839

To analyze the effect of tooth extraction site preservation on bone mineral density 6 months after surgery. From 2020 to 2021, two adjacent teeth (37, 38) of the same patient were extracted at the same time, and then 37 were selected for site preservation, implanted with Bio-oss bone powder, covered with double Bio-gide membrane, reduce tension and sutured. After 6 months of self-healing, 38 was taken CBCT, and the gray value measurement tool in the software was used to measure the bone mineral density of 37 bone graft areas and 38 extraction sockets. Bone density was high in the center of the bone graft area after the extraction site, and the density decreased in the adjacent alveolar socket, but the gray value was still higher than 38 for natural healing. Extraction site surgery can improve bone mass and quality at the extraction site. It is good for implanting

Introduction: Osteoporosis is one of the major diseases worldwide, affecting millions of elderly people, with severe economical and medical consequences. The most commonly used method for the determination of decreased bone quality is the assessment of Bone Mineral Density, measured by dual X-ray absorptiometry (DXA). However DXA is quantitative and not qualitative index of the bone structure. The purpose of this study was to correlate the bone mineral density measured by DXA with the mechanical properties of the femoral neck. Materials and Methods: Bone mineral density of the proximal femur of 30 patients (27 women, 3 men) undergoing total hip displacement was estimated by DXA. The average age of these patients was 63.7 years. Patients with sort femoral neck or previous surgeries in proximal femur were excluded from the study. After hip replacement bone samples (femoral head and neck) were frozen and stored at −60 °C. A plane bone slice with 6mm thickness was sawed of femoral neck using a double cutting saw. The exact specimen dimensions were measured using a sliding calliper with high accuracy. All bone specimens were destructively tested on a material testing machine, in order to determine the material properties (Young’s modulus and yield stress) of the samples. The maximum available compression load was 100 kN with a load rate of 10 kN/min. The operational parameters and experimental data were fully controlled and handled by a graphical software package. Finally all data were evaluated and statistically analyzed. Results: A strong linear correlation of bone mineral density (T-score) with maximum failure load of samples was noted (R2=0.852). No significant differences in Young’s modulus values, was found between bone samples. Conclusions: Bone mineral density measured by DXA, although has limitations, remain a strong predictor of bone strength in the femoral neck region

Introduction: There is limited literature available looking into circumstances surrounding the development of stress fracture of the medial and lateral malleoli after ankle replacement. We present the preliminary results of a prospective study examining the effect of ankle replacement upon local bone mineral density and the phenomenon of stress shielding. Aim: To assess the effect of ankle replacement loading of the medial and lateral malleoli, by analysing the BMD of the medial and lateral malleoli before and after Mobility total ankle replacement. Methodology: Ten consecutive patients undergoing Mobility total ankle replacement for osteoarthritis had pre-operative bone densitometry scans of the ankle, repeated at 6 months after surgery. The bone mineral density of a 2 cm square area within the medial malleolus and lateral malleolus was measured. The pre-operative and post-operative bone densitometry scans were compared. The relation between the alignment of the tibial component and the bone mineral density of the malleoli was also analysed. Results: The mean preoperative BMD within the medial malleolus improved from 0.57g/cm2 to mean 6 months postoperative BMD of 0.62g/cm2. The mean preoperative BMD within the lateral malleolus decreased from 0.39g/cm2 to a mean 6 months postoperative BMD of 0.33g/cm2. The mean alignment of the tibial component was 88.50 varus (range 850 varus to 940 valgus). However, there was no correlation between the alignment of the tibial component and the bone mineral density on the medial malleolus (r = 0.09, p = 0.865). Conclusion: The absence of stress shielding around the medial malleolus indicates that ankle replacements implanted within the accepted limits for implant alignment, load the medial malleolus. However, there was stress shielding over the lateral malleolus resulting in decreased BMD in the lateral malleolus

Introduction: There is limited literature looking into the circumstances surrounding the development of stress fractures of the medial and lateral malleoli after ankle replacement. We present the preliminary results of a prospective study examining the effect of total ankle replacement (TAR) upon local bone mineral density (BMD) and the phenomenon of stress shielding. Aim: To assess the effect of TAR loading othe medial and lateral malleoli, by analysing the BMD of the medial and lateral malleoli before and after Mobility TAR. Methodology: Ten consecutive patients undergoing Mobility total ankle replacement for osteoarthritis had pre-operative bone densitometry scans of the ankle, repeated at 6 and 12 months after surgery. The bone mineral density of a 2 cm square area within the medial and lateral malleoli was measured. The pre-operative and post-operative bone densitometry scans were compared. The relation between the alignment of the tibial component and the bone mineral density of the malleoli was also analysed. Results: The mean preoperative BMD within the medial malleolus increased from a mean of 0.57g/cm2 to 0.58g/cm2 at six months and 0.60g/cm2 at 12 months postoperatively. The mean preoperative BMD within the lateral malleolus decreased from 0.39g/cm2 to 0.34g/cm2 at six months postoperatively. However the BMD over the lateral malleolus increased to 0.356g/cm2 at 12 months. The mean alignment of the tibial component was 88.50 varus (range 850 varus to 940 valgus). There was no correlation between the alignment of the tibial component and the bone mineral density on the medial malleolus (r = 0.09, p = 0.865). Conclusion: The absence of stress shielding around the medial malleolus indicates that ankle replacements implanted within the accepted limits for implant alignment, load the medial malleolus. However, there was stress shielding over the lateral malleolus resulting in decreased BMD in the lateral malleolus

Varus deformity is found in 90% of patients with knee OA. Axis deviation of lower extremity influences joint biomechanics and produce alteration in bone mineral density. Structure and density of subchondral bone of the knee was previously examined by X-ray. Densitometry gives us a new method of bone mineral content measurement in the interesting regions of the skeleton. The aim of this study was the assessment of effect of varus deformity on bone mineral density in tibial epiphysis. Bone mineral densities (BMD) were estimated in 46 patients at a mean age of 62 years (15 to 78) who were operated on in Department of Orthopaedics. All of them represented osteoarthritis of the knee with varus deviation. BMD of the proximal tibia was evaluated on the Lunar DPX-IQ densitometer and analyzed in three regions of interest: medial, lateral and central. Lower extremity axis deviation was measured using the Metrecom devise (Faro). Results were compared to a control group of 20 patients without osteoarthritis of the knee and without deviation of lower extremity axis. Increased BMD was found on the overweighed compartment of the knee in comparison to the underweight one. These differences were not observed in the control group. We developed a coefficient, which is the ratio of BMD in the overweighed compartment compared to BMD in underweight one. In our patients the mean value of this coefficient was 3.3, and it ranged from 1,2 to 24,5 (SD 5,7). Significant correlation between varus axis deviation of the lower extremity and increased BMD coefficient was found

Background. Reduced bone mineral density is recognised as a risk factor for hip fractures and fragility fractures in general. Vitamin D is important in maintaining healthy bone mineral levels and can therefore affect risk of hip fracture. We investigated the correlation between vitamin D levels and bone mineral density, as well as fracture type, in neck of femur fractures and also assessed the relationship of vitamin D and social deprivation. Method. We included all patients admitted to our department, with a neck of femur fracture over one year (October 2013 to October 2014). We analysed vitamin D levels for all patients during admission and compared these to bone mineral density scores, based on DEXA scan results; hip fracture type & comminution, based on admission radiographs; and levels of social deprivation, based on the patient's address. Results. In total 360 patients were admitted over the study period, with a neck of femur fracture, of which 298 had vitamin D assessed and 76 had DEXA scans. Of these cohorts, 71% were found to be vitamin D deficient and 7% had osteoporosis. No significant correlation was found between vitamin D scores and bone density, or with level of vitamin D deficiency and fracture type or comminution. A significant correlation was however identified, between low vitamin D levels and decreasing levels of social deprivation (R=0.11, p=0.04). Conclusion. No relationship was identified between vitamin D levels and hip fracture type, suggesting that vitamin D cannot be used to predict patients at risk of more comminuted fractures. Although no relationship was also identified for bone mineral density and vitamin D, this may be because the sample size of DEXA scans was relatively small. Interestingly the relationship between vitamin D and social deprivation was the reverse of what was expected and suggests that affluent individuals may be at greater risk of low vitamin D

Femoral stem design affects periprosthetic bone mineral density (BMD), which may impact long term survival of cementless implants in total hip arthroplasty (THA). The aim of this study was to examine proximal femoral BMD in three morphologically different uncemented femoral stems designs to investigate whether one particular design resulted in improved preservation of BMDMethods: 119 patients were randomised to receive either a proximally coated dual taper wedge stem, a proximally coated anatomic stem or a fully coated collarless triple tapered stem. All surgeries were performed via the posterior approach with mobilization on the day of surgery. Dual energy x-ray absorptiometry scans (Lunar iDXA, GE Healthcare, Madison, WI) assessed BMD across the seven Gruen zones pre-operatively, and post-operatively at 6-weeks, 1-year, and 2-years and compared to the unoperated contralateral femur as a control. Patient reported outcome measures of pain, function and health were also included at these corresponding follow-ups. BMD increased in zones one (2.5%), two (17.1%), three (13.0%), five (10%) and six (17.9%) for all stems. Greater preservation of BMD was measured on the lateral cortex (zone 2) for both the dual taper wedge and anatomic stems (p = 0.019). The dual taper wedge stem also demonstrated preservation of BMD in the medial calcar (zone 7) whilst the anatomic and triple taper stem declined in this region, however this was not statistically significant (p = 0.059). BMD decreased on average by 2.1% inthe mid-diaphysis region, distal to the stem tip (zone 4) for all implants. All stems performed equivalently at final follow-up in all patient reported outcome measures. This study demonstrated maintenance of femoral BMD in three different cementless femoral stem designs, with all achieving excellent improvements in patient reported outcomes. There was no significant stress shielding observed, however longer follow-up is required to elucidate the impact of this finding on implant survivorship

Aims. To examine the relationship of sex steroid hormones with osteopenia in a nationally representative sample of men in the USA. Methods. Data on bone mineral density (BMD), serum sex hormones, dairy consumption, smoking status, and body composition were available for 806 adult male participants of the cross-sectional National Health and Nutrition Examination Survey (NHANES, 1999-2004). We estimated associations between quartiles of total and estimated free oestradiol (E2) and testosterone (T) and osteopenia (defined as 1 to 2.5 SD below the mean BMD for healthy 20- to 29-year-old men) by applying sampling weights and using multivariate-adjusted logistic regression. We then estimated the association between serum hormone concentrations and osteopenia by percentage of body fat, frequency of dairy intake, cigarette smoking status, age, and race/ethnicity. Results. Men in the lowest quartile of total E2 concentrations (< 21.52 pg/ml) had greater odds of osteopenia compared with men in the highest quartile (odds ratio (OR) 2.29, 95% confidence interval (CI) 1.11 to 4.73; p-trend = 0.030). Total and free T were not associated with osteopenia. Low total E2 concentrations were associated with greater odds of osteopenia among non-daily dairy consumers (p-trend = 0.046), current or former smokers (p-trend = 0.032), and younger men (p-trend = 0.031). No differences were observed by race/ethnicity and obesity. Conclusion. In this nationally representative study of the USA, men with lower total E2 were more likely to have osteopenia, which was particularly evident among younger men, men with less-than-daily dairy consumption, and current or former smokers. Cite this article:Bone Joint Res. 2020;9(3):139–145

Femoral stem design affects periprosthetic bone mineral density (BMD), which may impact long term survival of cementless implants in total hip arthroplasty (THA). The aim of this study was to examine proximal femoral BMD in three morphologically different uncemented femoral stems designs to investigate whether one particular design resulted in improved preservation of BMD. 119 patients were randomized to receive either a proximally coated dual taper wedge stem, a proximally coated anatomic stem or a fully coated collarless triple tapered stem. Dual energy x-ray absorptiometry scans (Lunar iDXA, GE Healthcare, Madison, WI) assessed BMD across the seven Gruen zones pre-operatively, and post-operatively at 6-weeks, 1-year, and 2-years comparing the unoperated contralateral femur as a control. BMD increased in zones one (2.5%), two (17.1%), three (13.0%), five (10%) and six (17.9%) for all stems. Greater preservation of BMD was measured on the lateral cortex (zone 2) for both the dual taper wedge and anatomic stems (p = 0.019). The dual taper wedge stem also demonstrated preservation of BMD in the medial calcar (zone 7) whilst the anatomic and triple taper stem declined in this region, however this was not statistically significant (p = 0.059). BMD decreased on average by 2.1% in the mid-diaphysis region, distal to the stem tip (zone 4) for all implants. All stems performed equivalently at final follow-up in all patient reported outcome measures. Implant design was shown to impact BMD changes. All stems preserved bone at the metaphyseal level in early follow-up, which theoretically indicates favorable implant fixation. There was no significant stress shielding observed, however longer follow-up is required to elucidate the impact of this finding on implant survivorship

Objectives. Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data. Method. We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients’ BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05. Results. We identified multiple gene sets associated with BMD in one or more regions, including relevant known biological gene sets such as the Reactome Circadian Clock (GSEA p-value = 1.0 × 10. -4. for LS and 2.7 × 10. -2. for femoral necks BMD in eQTLs-based GSEA) and insulin-like growth factor receptor binding (GSEA p-value = 5.0 × 10. -4. for femoral necks and 2.6 × 10. -2. for lumbar spines BMD in meQTLs-based GSEA). Conclusion. Our results provided novel clues for subsequent functional analysis of bone metabolism, and illustrated the benefit of integrating eQTLs and meQTLs data into pathway association analysis for genetic studies of complex human diseases. Cite this article: W. Wang, S. Huang, W. Hou, Y. Liu, Q. Fan, A. He, Y. Wen, J. Hao, X. Guo, F. Zhang. Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density. Bone Joint Res 2017;6:572–576

To prevent bone loss, OPG/RANK/RANKL signalling pathway is a key in keeping the balance between the action of osteoblasts and osteoclasts. Aim of this study is to assess the influence of long-term nicotine exposure on bone mineral density (BMD) scores, RANKL and OPG levels of plasma and RANKL and OPG immunoreactivities of tissue in rats. In this study, totally 36 Swiss Albino rats (70±10 g) were used in three groups. Whereas normal drinking water was given for the control group (n:12), 0.4 mg/kg/day and 6.0 mg/kg/day nicotine was added to drinking water for low-dose nicotine (LDN) group (n:12) and high-dose nicotine (HDN) group (n:12), respectively for 12 months. At the end of 12. th. month, BMD scores were measured via X-ray absorptiometry and then bone turnover was assessed via measuring both RANKL, OPG levels in plasma and RANKL, OPG immunoreactivities in tail vertebrae of all rats. Lumbar spine and femoral regions BMD scores of the control group and the nicotine groups were not significantly difference. In HDN group, OPG levels of plasma were found significantly higher when compared with the control and LDN groups (p=0.001) unlike RANKL levels of plasma. RANKL and OPG immunoreactivities of tissue were found significantly lower in both LDN and HDN groups (p<0.001, p=0.004, respectively) in comparison to control group. No correlation was found between plasma levels and tissue immunoreactivities of RANKL and OPG. As a result, this study indicates that nicotine is not primarily responsible for the decline of BMD frequently seen in smokers

To investigate whether children with fractures have a low bone mineral density, 109 children (46 female and 63 male) aged 10.5 ± 2.9 years (range 5–16) sustaining either a single fracture (n=60 patients) or multiple fractures (n=49 patients) had Bone Mineral Density measurements [BMD] (Hologic QDR4500A) of L2 to L4. The Z score {(Patient’s BMD – mean aged related BMD)/ standard deviation of that age group)} was calculated using two previously published data from Shropshire children and American children. A z score of zero indicates that the patients’ BMD is exactly on the mean. The proportion above and below zero and was compared using the binomial theorem. Comparison of frequencies between the groups was undertaken using the Chi 2 test. In a scatter plot of z score against age, low z scores were frequent in girls under 8yrs using both reference data. In this group BMD z score was more likely to be below zero (p< 0.05). A low z score was more frequent in boys less than 8 years using American reference data but not Shropshire data. Girls and boys above 8 years did not show any evidence of low BMD. There was no difference in the frequency of low BMD in patients with multiple compared with single fracture. Girls and possibly boys below 8 years who have sustained a fracture show evidence of low BMD. Boys at any age and girls over 8 years did not show any evidence of having low bone density. Further work is needed to establish whether this risk continues into later life. Multiple fractures do not appear to confer additional risk of low bone density

Introduction. There is no published series described change in bone mineral density (BMD) after ankle replacement. We present the results of a prospective study examining the effect of total ankle replacement (TAR) upon local bone mineral density (BMD). Aim. To design a method and assess the effect of TAR loading on local ankle bones, by analysing the BMD of different area around ankle before and after Mobility TAR. Methods. 23 patients undergoing Mobility ankle arthroplasty for osteoarthritis had preoperative bone densitometry scans of the ankle, repeated at 1 and 2 years after surgery. BMD of 2 cm. 2. areas around ankle were measured. Pre- and postoperative data were compared. Results: Mean BMD within the lateral malleolus decreased significantly from 0.5g/cm. 2. to 0.42g/cm. 2. (17%, P > 0.01), at 1 & 2 years postoperatively. Mean BMD within medial malleolus decreased slightly from 0.67g/cm. 2. to 0.64 g/cm. 2. at the same period. However BMD at medial side metaphysic of tibia increased by 7%. There was little increase in BMD in tibia just proximal to implant and at talus. Discussion and Conclusion. Absence of stress shielding around distal tibia, just proximal to tibial component and talus indicates that ankle replacements implanted within the accepted limits for implant alignment, load distal tibia and talus. However, there was stress shielding over the lateral malleolus resulting in decreased BMD in lateral malleolus. Increase BMD at tibial metaphysis, proximal to medial malleolus indicates an increase in mechanical stress which may explain occasional postoperative stress fracture of medial malleolus or medial side ankle pain