Cementless total knee replacement (TKR) is at the present date a controversial topic. Aim of the study was to compare the effect on tibial periprosthetic bone mineral density (BMD) between different implant materials and designs. During the two-year period between January 2005 and December 2006, we analysed data of 45 patients who underwent consecutively cementless TKR (49 implants) at our Institution for primary osteoarthritis. Data was divided in 2 groups: A) 26 implants with tantalium tibial component (Zimmer NexGen Trabecular Metal. TM. Monoblock); B) 23 implants with porous titanium tibial component (Lima MultiGen. TM. ). Data was comparable per sex, age, BMI, post-op alignment, post-op KSS > 75, absence of major post-op complications. Standard AP x-rays were taken 4 months post-op and 8 years post-op. In order to quantify the reduction of BDM, we determined using ImageJ (an open source software) the Mean Grey Value (MGV) of a specific area on the 4 months- and 8 yrs-postop AP x-rays. Group A and Group B had an average MGV variation of, respectively, 11.79% and 10.51%; there was no statistically significant difference between the two groups. Reduction of BMD in a TKR is known to be a biomechanical response to load and it is conditioned by the alignment of the components and their design. Our study shows that the different materials (porous titanium vs. tantalium), in relation to the different implant design, have a similar effect on the surrounding bone. The overall results show a valid osseointegration in both group of patients

Resurfacing THA is claimed to transfer stress naturally to the femur neck and preserve proximal femoral bone mass postoperatively. DXA is an established method in estimating BMD around a standard THA, but due to the anteversion of the femur neck, rotation could affect the size of the neck-regions and thereby the BMD measurements around a RTHA. To our knowledge, this is the first study to analyze the effects of hip rotation on BMD in the femoral neck around a RTHA.

We scanned the femoral neck of 15 patients twice in each position of 15° inward, 0° and 15° outward rotation, and analyzed BMD in a single and a six-region model. CVs were calculated for BMD in the same position as well as between different positions.

For double measurements in the same position we found mean CVs of 3.1% (range 2.5% – 3.7%) and 4.6% (range 2.2% – 8.6%) in the one- and six-region models, respectively. When the 15° outward position was excluded, the CVs decreased to 2.8% and 4.0%. With rotation, the mean CVs rose to 5.4% (range 3.2%–7.2%) and 11.8% (range 2.7% – 36.3%). This effect was most pronounced in the 6-region model, predominantly in the lateral and distal parts of the femoral neck, where the change was significantly different from the fixated position. For the single-region model 15° rotation could be allowed without compromising the precision.

We conclude that rotation adversely affects the precision of BMD measurements around a RTHA, but in the single-region model smaller rotations can be allowed.

With the hip fixated the six-region model produces low CVs, acceptable for longitudinal studies. For maximal topographical detail we prefer the six-region model and recommend that future longitudinal DXA studies, including RTHA, be performed standardised, Preferably, with the hip in the neutral or internal rotation.

Introduction: Bone resorption in the proximal femur is commonly seen after cementless total hip arthroplasty (THA). One of the main determinants of bone remodeling seems to be prosthesis design. With DXA, the amount of bone mass after THA can be precisely determined. We evaluated the BMD behavior of two different ultra-short implants with proximal load transfer, in order to study how a design can affect femoral bone remodeling. The rationale behind these designs is the experimental evidence that loading the medial and the lateral flare effectively preserves in time metaphyseal bone stock. Moreover, biomechanical tests have confirmed that this kind of stress distribution allows to remove the diaphyseal portion of the stem.

Methods: A total of 33 patients operated with a cementless femoral implant were included in this study. Two slightly different designs were tested: Type 1 (Stanmore Orthopaedics), featuring an extremely short distal stem (n=10), and Type 2 (DePuy International Ltd), where distal stem was virtually absent (n=23). All implants were customized based on pre-operative CT data. The main features of these implants were the ultra-short stem and the large lateral flare. The rationale was to preserve bone stock and gain a more physiologic load transfer to the proximal femur thus preventing stress-shielding. DXA examination was performed on all patients 3 years after THA. Due to the peculiar design, a specific protocol of analysis with five regions of interest (ROI) was developed: ROI1 (greater trochanter), ROI2 and ROI4 (respectively lateral and medial of the ultra-short stem), ROI3 (below the tip) and ROI5 (calcar). The same protocol was applied to the non-operated contralateral femur and percentage contralateral BMD was calculated with the following formula: (BMD of operated hip/BMD of contralateral hip)×100. A standard DXA of contralateral hip and lumbar spine was also performed to evaluate the skeletal bone mineralization.

Results: No differences were found in the anthropometric data and sex between the two groups. Age was found lower (p=0.001) in Type 2. BMD of lumbar spine and contralateral femur from standard DXA were not different in the two groups. BMD was higher in Type 2 in ROI4 and ROI5 (p< 0.001). The calculated percentage contralateral BMD was higher in Type 2 in ROI2 (p=0.009), ROI4 (p< 0.001) and ROI5 (p=0.01).

Conclusions: This study confirms that progressive shortening of femoral stem produces a more proximal loading, which effectively preserves in time metaphyseal bone stock and increases periprosthetic BMD in the medial ROIs. The increased BMD in periprosthetic lateral and medial proximal regions in the operated hip respect to the contralateral femur seems to be due not only to the increased weight-bearing, but also to the specific ultra-short stem design.

Aims: The purpose of this study was to investigate interactions of vitamin D receptor gene (VDR) polymorphisms and regular physical exercise on BMD in a four-year randomized, controlled intervention trial in Finnish middle-aged men. Methods: The TaqI, FokI, and ApaI RFLP-markers of the VDR gene were evaluated. BMDs of the lumbar spine (L2–L4), femoral neck, and total proximal femur were measured with a dual-energy X-ray absorptiometry (DXA). Results: In the entire study group, the subjects with the VDR gene TaqI Tt or tt genotype had a greater body height and higher femoral neck BMD values than the TT subjects (p=0.001, p=0.003, respectively). After adjustment the femoral neck BMD for body height, the association remained (p=0.021). There was no difference in BMD values between the reference and exercise groups during intervention. Conclusions: We suggest that the VDR gene TaqI polymorphism may be affecting bone mass through an influence on body growth. The present findings also suggest that the VDR polymorphisms do not modify the effect of regular aerobic exercise on BMD.

Aims. The association of auraptene (AUR), a 7-geranyloxycoumarin, on osteoporosis and its potential pathway was predicted by network pharmacology and confirmed in experimental osteoporotic mice. Methods. The network of AUR was constructed and a potential pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) terms enrichment. Female ovariectomized (OVX) Institute of Cancer Research mice were intraperitoneally injected with 0.01, 0.1, and 1 mM AUR for four weeks. The bone mineral density (BMD) level was measured by dual-energy X-ray absorptiometry. The bone microstructure was determined by histomorphological changes in the femora. In addition, biochemical analysis of the serum and assessment of the messenger RNA (mRNA) levels of osteoclastic markers were performed. Results. In total, 65.93% of the genes of the AUR network matched with osteoporosis-related genes. Osteoclast differentiation was predicted to be a potential pathway of AUR in osteoporosis. Based on the network pharmacology, the BMD and bone mineral content levels were significantly (p < 0.05) increased in the whole body, femur, tibia, and lumbar spine by AUR. AUR normalized the bone microstructure and the serum alkaline phosphatase (ALP), bone-specific alkaline phosphatase (bALP), osteocalcin, and calcium in comparison with the OVX group. In addition, AUR treatment reduced TRAP-positive osteoclasts and receptor activator of nuclear factor kappa-B ligand (RANKL). +. nuclear factor of activated T cells 1 (NFATc1). +. expression in the femoral body. Moreover, the expressions of initiators for osteoclastic resorption and bone matrix degradation were significantly (p < 0.05) regulated by AUR in the lumbar spine of the osteoporotic mice. Conclusion. AUR ameliorated bone loss by downregulating the RANKL/NFATc1 pathway, resulting in improvement of osteoporosis. In conclusion, AUR might be an ameliorative cure that alleviates bone loss in osteoporosis via inhibition of osteoclastic activity. Cite this article: Bone Joint Res 2022;11(5):304–316

Aims. This study aimed to develop and validate a fully automated system that quantifies proximal femoral bone mineral density (BMD) from CT images. Methods. The study analyzed 978 pairs of hip CT and dual-energy X-ray absorptiometry (DXA) measurements of the proximal femur (DXA-BMD) collected from three institutions. From the CT images, the femur and a calibration phantom were automatically segmented using previously trained deep-learning models. The Hounsfield units of each voxel were converted into density (mg/cm. 3. ). Then, a deep-learning model trained by manual landmark selection of 315 cases was developed to select the landmarks at the proximal femur to rotate the CT volume to the neutral position. Finally, the CT volume of the femur was projected onto the coronal plane, and the areal BMD of the proximal femur (CT-aBMD) was quantified. CT-aBMD correlated to DXA-BMD, and a receiver operating characteristic (ROC) analysis quantified the accuracy in diagnosing osteoporosis. Results. CT-aBMD was successfully measured in 976/978 hips (99.8%). A significant correlation was found between CT-aBMD and DXA-BMD (r = 0.941; p < 0.001). In the ROC analysis, the area under the curve to diagnose osteoporosis was 0.976. The diagnostic sensitivity and specificity were 88.9% and 96%, respectively, with the cutoff set at 0.625 g/cm. 2. . Conclusion. Accurate DXA-BMD measurements and diagnosis of osteoporosis were performed from CT images using the system developed herein. As the models are open-source, clinicians can use the proposed system to screen osteoporosis and determine the surgical strategy for hip surgery. Cite this article: Bone Joint Res 2023;12(9):590–597

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. Osteoporosis can determine surgical strategy for total hip arthroplasty (THA), and perioperative fracture risk. The aims of this study were to use hip CT to measure femoral bone mineral density (BMD) using CT X-ray absorptiometry (CTXA), determine if systematic evaluation of preoperative femoral BMD with CTXA would improve identification of osteopenia and osteoporosis compared with available preoperative dual-energy X-ray absorptiometry (DXA) analysis, and determine if improved recognition of low BMD would affect the use of cemented stem fixation. Methods. Retrospective chart review of a single-surgeon database identified 78 patients with CTXA performed prior to robotic-assisted THA (raTHA) (Group 1). Group 1 was age- and sex-matched to 78 raTHAs that had a preoperative hip CT but did not have CTXA analysis (Group 2). Clinical demographics, femoral fixation method, CTXA, and DXA data were recorded. Demographic data were similar for both groups. Results. Preoperative femoral BMD was available for 100% of Group 1 patients (CTXA) and 43.6% of Group 2 patients (DXA). CTXA analysis for all Group 1 patients preoperatively identified 13 osteopenic and eight osteoporotic patients for whom there were no available preoperative DXA data. Cemented stem fixation was used with higher frequency in Group 1 versus Group 2 (28.2% vs 14.3%, respectively; p = 0.030), and in all cases where osteoporosis was diagnosed, irrespective of technique (DXA or CTXA). Conclusion. Preoperative hip CT scans which are routinely obtained prior to raTHA can determine bone health, and thus guide femoral fixation strategy. Systematic preoperative evaluation with CTXA resulted in increased recognition of osteopenia and osteoporosis, and contributed to increased use of cemented femoral fixation compared with routine clinical care; in this small study, however, it did not impact short-term periprosthetic fracture risk. Cite this article: Bone Joint J 2023;105-B(3):254–260

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

Aims. The aim of this study was to compare the pattern of initial fixation and changes in periprosthetic bone mineral density (BMD) between patients who underwent total hip arthroplasty (THA) using a traditional fully hydroxyapatite (HA)-coated stem (T-HA group) and those with a newly introduced fully HA-coated stem (N-HA group). Methods. The study included 36 patients with T-HA stems and 30 with N-HA stems. Dual-energy X-ray absorptiometry was used to measure the change in periprosthetic BMD, one and two years postoperatively. The 3D contact between the stem and femoral cortical bone was evaluated using a density-mapping system, and clinical assessment, including patient-reported outcome measurements, was recorded. Results. There were significantly larger contact areas in Gruen zones 3, 5, and 6 in the N-HA group than in the T-HA group. At two years postoperatively, there was a significant decrease in BMD around the proximal-medial femur (zone 6) in the N-HA group and a significant increase in the T-HA group. BMD changes in both groups correlated with BMI or preoperative lumbar BMD rather than with the extent of contact with the femoral cortical bone. Conclusion. The N-HA-coated stem showed a significantly larger contact area, indicating a distal fixation pattern, compared with the traditional fully HA-coated stem. The T-HA-coated stem showed better preservation of periprosthetic BMD, two years postoperatively. Surgeons should consider these patterns of fixation and differences in BMD when selecting fully HA-coated stems for THA, to improve the long-term outcomes. Cite this article: Bone Joint J 2024;106-B(6):548–554

Aims. Mechanical stimulation is a key factor in the development and healing of tendon-bone insertion. Treadmill training is an important rehabilitation treatment. This study aims to investigate the benefits of treadmill training initiated on postoperative day 7 for tendon-bone insertion healing. Methods. A tendon-bone insertion injury healing model was established in 92 C57BL/6 male mice. All mice were divided into control and training groups by random digital table method. The control group mice had full free activity in the cage, and the training group mice started the treadmill training on postoperative day 7. The quality of tendon-bone insertion healing was evaluated by histology, immunohistochemistry, reverse transcription quantitative polymerase chain reaction, Western blotting, micro-CT, micro-MRI, open field tests, and CatWalk gait and biomechanical assessments. Results. Our results showed a significantly higher tendon-bone insertion histomorphological score in the training group, and the messenger RNA and protein expression levels of type II collagen (COL2A1), SOX9, and type X collagen (COL10A1) were significantly elevated. Additionally, tendon-bone insertion resulted in less scar hyperplasia after treadmill training, the bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly improved, and the force required to induce failure became stronger in the training group. Functionally, the motor ability, limb stride length, and stride frequency of mice with tendon-bone insertion injuries were significantly improved in the training group compared with the control group. Conclusion. Treadmill training initiated on postoperative day 7 is beneficial to tendon-bone insertion healing, promoting biomechanical strength and motor function. Our findings are expected to guide clinical rehabilitation training programmes. Cite this article: Bone Joint Res 2023;12(5):339–351

Aims. One of the main causes of tibial revision surgery for total knee arthroplasty is aseptic loosening. Therefore, stable fixation between the tibial component and the cement, and between the tibial component and the bone, is essential. A factor that could influence the implant stability is the implant design, with its different variations. In an existing implant system, the tibial component was modified by adding cement pockets. The aim of this experimental in vitro study was to investigate whether additional cement pockets on the underside of the tibial component could improve implant stability. The relative motion between implant and bone, the maximum pull-out force, the tibial cement mantle, and a possible path from the bone marrow to the metal-cement interface were determined. Methods. A tibial component with (group S: Attune S+) and without (group A: Attune) additional cement pockets was implanted in 15 fresh-frozen human leg pairs. The relative motion was determined under dynamic loading (extension-flexion 20° to 50°, load-level 1,200 to 2,100 N) with subsequent determination of the maximum pull-out force. In addition, the cement mantle was analyzed radiologically for possible defects, the tibia base cement adhesion, and preoperative bone mineral density (BMD). Results. The BMD showed no statistically significant difference between both groups. Group A showed for all load levels significantly higher maximum relative motion compared to group S for 20° and 50° flexion. Group S improved the maximum failure load significantly compared to group A without additional cement pockets. Group S showed a significantly increased cement adhesion compared to group A. The cement penetration and cement mantle defect analysis showed no significant differences between both groups. Conclusion. From a biomechanical point of view, the additional cement pockets of the component have improved the fixation performance of the implant. Cite this article: Bone Joint Res 2022;11(4):229–238

Aims. To analyze the short-term outcome of two types of total wrist arthroplasty (TWA) in terms of wrist function, migration, and periprosthetic bone behaviour. Methods. A total of 40 patients suffering from non-rheumatoid wrist arthritis were enrolled in a randomized controlled trial comparing the ReMotion and Motec TWAs. Patient-rated and functional outcomes, radiological changes, blood metal ion levels, migration measured by model-based radiostereometric analysis (RSA), bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA), complications, loosening, and revision rates at two years were compared. Results. Patient-Rated Wrist and Hand Evaluation (PRWHE) scores, abbreviated version of the Disabilities of the Arm, Shoulder and Hand questionnaire (QuickDASH) scores, and pain improved similarly and significantly in both groups. Wrist motion improved significantly in the Motec group only, and forearm rotation in the ReMotion group only. Cobalt (Co) and chromium (Cr) blood ion levels were significantly higher in the metal-on-metal (MoM) Motec group than in the metal-on-polyethylene (MoP) ReMotion group. Mean total translation was 0.65 mm (95% confidence interval (CI) 0.26 to 1.12) and 0.27 mm (95% CI 0.14 to 0.47) for the ReMotion carpal and radial components, and 0.32 mm (95% CI 0.22 to 0.45) and 0.26 mm (95% CI 0.20 to 0.34) for the Motec metacarpal and radial components, respectively. Apart from dorsal and volar tilts, which were significantly higher for the radial ReMotion than for the Motec component, no significant differences in absolute migration occurred. BMD around the radial components never returned to baseline. Almost one-third of patients required reoperation due to complications. Two ReMotion implants were revised to Motec TWAs due to carpal component loosening, and three Motec MoM articulations were revised to metal-on-polyether ether ketone due to painful synovitis. Conclusion. Both implants provided matched function and were stable at short-term follow-up, but with a high complication rate. This procedure should be restricted to specialist centres undertaking prospective analysis until its role is clarified. Cite this article: Bone Joint J 2022;104-B(10):1132–1141

Aims. The aim of this study was to compare the mid-term patient-reported outcome, bone remodelling, and migration of a short stem (Collum Femoris Preserving; CFP) with a conventional uncemented stem (Corail). Methods. Of 81 patients who were initially enrolled, 71 were available at five years’ follow-up. The outcomes at two years have previously been reported. The primary outcome measure was the clinical result assessed using the Oxford Hip Score (OHS). Secondary outcomes were the migration of the stem, measured using radiostereometric analysis (RSA), change of bone mineral density (BMD) around the stem, the development of radiolucent lines, and additional patient-reported outcome measures (PROMs). Results. There were no statistically significant differences between the groups regarding PROMs (median OHS (CFP 45 (interquartile range (IQR) 35 to 48); Corail 45 (IQR 40 to 48); p = 0.568). RSA showed stable stems in both groups, with little or no further subsidence between two and five years. Resorption of the femoral neck was evident in nine patients in the CFP group and in none of the 15 Corail stems with a collar that could be studied. Dual X-ray absorbiometry showed a significantly higher loss of BMD in the proximal Gruen zones in the CFP group (mean changes in BMD: Gruen zone 1, CFP -9.5 (95% confidence interval (CI) -14.8 to -4.2), Corail 1.0 (95% CI 3.4 to 5.4); Gruen zone 7, CFP -23.0 (95% CI -29.4 to -16.6), Corail -7.2 (95% CI -15.9 to 1.4). Two CFP stems were revised before two years’ follow-up due to loosening, and one Corail stem was revised after two years due to chronic infection. Conclusion. The CFP stem has a similar clinical outcome and subsidence pattern when compared with the Corail stem. More pronounced proximal stress-shielding was seen with the CFP stem, suggesting diaphyseal fixation, and questioning its femoral neck-sparing properties in the long term. Cite this article: Bone Joint J 2022;104-B(5):581–588

Aims. Low-energy distal radius fractures (DRFs) are the most common upper arm fractures correlated with bone fragility. Vitamin D deficiency is an important risk factor associated with DRFs. However, the relationship between DRF severity and vitamin D deficiency is not elucidated. Therefore, this study aimed to identify the correlation between DRF severity and serum 25-hydroxyvitamin-D level, which is an indicator of vitamin D deficiency. Methods. This multicentre retrospective observational study enrolled 122 female patients aged over 45 years with DRFs with extension deformity. DRF severity was assessed by three independent examiners using 3D CT. Moreover, it was categorized based on the AO classification, and the degree of articular and volar cortex comminution was evaluated. Articular comminution was defined as an articular fragment involving three or more fragments, and volar cortex comminution as a fracture in the volar cortex of the distal fragment. Serum 25-hydroxyvitamin-D level, bone metabolic markers, and bone mineral density (BMD) at the lumbar spine, hip, and wrist were evaluated six months after injury. According to DRF severity, serum 25-hydroxyvitamin-D level, parameters correlated with bone metabolism, and BMD was compared. Results. The articular comminuted group (n = 28) had a significantly lower median serum 25-hydroxyvitamin-D level than the non-comminuted group (n = 94; 13.4 ng/ml (interquartile range (IQR) 9.8 to 17.3) vs 16.2 ng/ml (IQR 12.5 to 20.4); p = 0.005). The AO classification and volar cortex comminution were not correlated with the serum 25-hydroxyvitamin-D level. Bone metabolic markers and BMD did not significantly differ in terms of DRF severities. Conclusion. Articular comminuted DRF, referred to as AO C3 fracture, is significantly associated with low serum 25-hydroxyvitamin-D levels. Therefore, vitamin D. 3. supplementation for vitamin D deficiency might prevent articular comminuted DRFs. Nevertheless, further studies must be conducted to validate the results of the current study. Cite this article: Bone Jt Open 2022;3(3):261–267

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Previous studies have suggested that selenium as a trace element is involved in bone health, but findings related to the specific effect of selenium on bone health remain inconclusive. Thus, we performed a meta-analysis by including all the relevant studies to elucidate the association between selenium status (dietary intake or serum selenium) and bone health indicators (bone mineral density (BMD), osteoporosis (OP), or fracture).

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This study investigated the effects of β-caryophyllene (BCP) on protecting bone from vitamin D deficiency in mice fed on a diet either lacking (D-) or containing (D+) vitamin D.

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This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night.

Aims. This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model. Methods. The study included 538 joints that underwent primary THA. The patients were divided into groups using unsupervised time series clustering for five-year BMD loss of Gruen zone 7 postoperatively, and a machine-learning model to predict the BMD loss was developed. Additionally, the predictor for BMD loss was extracted using SHapley Additive exPlanations (SHAP). The patient-specific efficacy of bisphosphonate, which is the most important categorical predictor for BMD loss, was examined by calculating the change in predictive probability when hypothetically switching between the inclusion and exclusion of bisphosphonate. Results. Time series clustering allowed us to divide the patients into two groups, and the predictive factors were identified including patient- and operation-related factors. The area under the receiver operating characteristic (ROC) curve (AUC) for the BMD loss prediction averaged 0.734. Virtual administration of bisphosphonate showed on average 14% efficacy in preventing BMD loss of zone 7. Additionally, stem types and preoperative triglyceride (TG), creatinine (Cr), estimated glomerular filtration rate (eGFR), and creatine kinase (CK) showed significant association with the estimated patient-specific efficacy of bisphosphonate. Conclusion. Periprosthetic BMD loss after THA is predictable based on patient- and operation-related factors, and optimal prescription of bisphosphonate based on the prediction may prevent BMD loss. Cite this article: Bone Joint Res 2024;13(4):184–192

Aims. Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD. Methods. We conducted an integrative analysis of BMD genome-wide association study (GWAS) and regulatory single nucleotide polymorphism (rSNP) annotation information. Firstly, the discovery GWAS dataset and replication GWAS dataset were integrated with rSNP annotation database to obtain BMD associated SNP regulatory elements and SNP regulatory element-target gene (E-G) pairs, respectively. Then, the common genes were further subjected to HumanNet v2 to explore the biological effects. Results. Through discovery and replication integrative analysis for BMD GWAS and rSNP annotation database, we identified 36 common BMD-associated genes for BMD irrespective of regulatory elements, such as FAM3C (p. discovery GWAS. = 1.21 × 10. -25. , p. replication GWAS. = 1.80 × 10. -12. ), CCDC170 (p. discovery GWAS. = 1.23 × 10. -11. , p. replication GWAS. = 3.22 × 10. -9. ), and SOX6 (p. discovery GWAS. = 4.41 × 10. -15. , p. replication GWAS. = 6.57 × 10. -14. ). Then, for the 36 common target genes, multiple gene ontology (GO) terms were detected for BMD such as positive regulation of cartilage development (p = 9.27 × 10. -3. ) and positive regulation of chondrocyte differentiation (p = 9.27 × 10. -3. ). Conclusion. We explored the potential roles of rSNP in the genetic mechanisms of BMD and identified multiple candidate genes. Our study results support the implication of regulatory genetic variants in the development of OP. Cite this article: Bone Joint Res 2023;12(2):147–154

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Osteoporosis is common in total hip arthroplasty (THA) patients. It plays a substantial factor in the surgery’s outcome, and previous studies have revealed that pharmacological treatment for osteoporosis influences implant survival rate. The purpose of this study was to examine the prevalence of and treatment rates for osteoporosis prior to THA, and to explore differences in osteoporosis-related biomarkers between patients treated and untreated for osteoporosis.

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

Aims. Uncemented metal acetabular components show good osseointegration, but material stiffness causes stress shielding and retroacetabular bone loss. Cemented monoblock polyethylene components load more physiologically; however, the cement bone interface can suffer fibrous encapsulation and loosening. It was hypothesized that an uncemented titanium-sintered monoblock polyethylene component may offer the optimum combination of osseointegration and anatomical loading. Methods. A total of 38 patients were prospectively enrolled and received an uncemented monoblock polyethylene acetabular (pressfit) component. This single cohort was then retrospectively compared with previously reported randomized cohorts of cemented monoblock (cemented) and trabecular metal (trabecular) acetabular implants. The primary outcome measure was periprosthetic bone density using dual-energy x-ray absorptiometry over two years. Secondary outcomes included radiological and clinical analysis. Results. Although there were differences in the number of males and females in each group, no significant sex bias was noted (p = 0.080). Furthermore, there was no significant difference in age (p = 0.910) or baseline lumbar bone mineral density (BMD) (p = 0.998) found between any of the groups (pressfit, cemented, or trabecular). The pressfit implant initially behaved like the trabecular component with an immediate fall in BMD in the inferior and medial regions, with preserved BMD laterally, suggesting lateral rim loading. However, the pressfit component subsequently showed a reversal in BMD medially with recovery back towards baseline, and a continued rise in lateral BMD. This would suggest that the pressfit component begins to reload the medial bone over time, more akin to the cemented component. Analysis of postoperative radiographs revealed no pressfit component subsidence or movement up to two years postoperatively (100% interobserver reliability). Medial defects seen immediately postoperatively in five cases had completely resolved by two years in four patients. Conclusion. Initially, the uncemented monoblock component behaved similarly to the rigid trabecular metal component with lateral rim loading; however, over two years this changed to more closely resemble the loading pattern of a cemented polyethylene component with increasing medial pelvic loading. This indicates that the uncemented monoblock acetabular component may result in optimized fixation and preservation of retroacetabular bone stock. Cite this article: Bone Joint J 2021;103-B(5):872–880

Aims. Osteoarthritis (OA) is a disabling joint disorder and mechanical loading is an important pathogenesis. This study aims to investigate the benefits of less mechanical loading created by intermittent tail suspension for knee OA. Methods. A post-traumatic OA model was established in 20 rats (12 weeks old, male). Ten rats were treated with less mechanical loading through intermittent tail suspension, while another ten rats were treated with normal mechanical loading. Cartilage damage was determined by gross appearance, Safranin O/Fast Green staining, and immunohistochemistry examinations. Subchondral bone changes were analyzed by micro-CT and tartrate-resistant acid phosphatase (TRAP) staining, and serum inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA). Results. Our radiographs showed that joint space was significantly enlarged in rats with less mechanical loading. Moreover, cartilage destruction was attenuated in the less mechanical loading group with lower histological damage scores, and lower expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5, matrix metalloproteinase (MMP)-3, and MMP-13. In addition, subchondral bone abnormal changes were ameliorated in OA rats with less mechanical loading, as reduced bone mineral density (BMD), bone volume/tissue volume (BV/TV), and number of osteophytes and osteoclasts in the subchondral bone were observed. Finally, the level of serum inflammatory cytokines was significantly downregulated in the less mechanical loading group compared with the normal mechanical loading group, as well as the expression of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), caspase-1, and interleukin 1β (IL-1β) in the cartilage. Conclusion. Less mechanical loading alleviates cartilage destruction, subchondral bone changes, and secondary inflammation in OA joints. This study provides fundamental insights into the benefit of non-weight loading rest for patients with OA. Cite this article: Bone Joint Res 2020;9(10):731–741

Objectives. MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture. Methods. Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined. Results. MicroRNA-186 was predicted to regulate SMAD6. Furthermore, SMAD6 was verified as a target gene of miR-186. Overexpressed miR-186 and SMAD6 silencing resulted in increased callus formation, BMD and BV/TV, as well as maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. In addition, the mRNA and protein levels of SMAD6 were decreased, while BMP-2 and BMP-7 levels were elevated in response to upregulated miR-186 and SMAD6 silencing. Conclusion. In conclusion, the study indicated that miR-186 could activate the BMP signalling pathway to promote fracture healing by inhibiting SMAD6 in a mouse model of femoral fracture. Cite this article: Bone Joint Res 2019;8:550–562

Aims. The aim of this prospective cohort study was to evaluate the early migration of the TriFit cementless proximally coated tapered femoral stem using radiostereometric analysis (RSA). Methods. A total of 21 patients (eight men and 13 women) undergoing primary total hip arthroplasty (THA) for osteoarthritis of the hip were recruited in this study and followed up for two years. Two patients were lost to follow-up. All patients received a TriFit stem and Trinity Cup with a vitamin E-infused highly cross-linked ultra-high molecular weight polyethylene liner. Radiographs for RSA were taken postoperatively and then at three, 12, and 24 months. Oxford Hip Score (OHS), EuroQol five-dimension questionnaire (EQ-5D), and adverse events were reported. Results. At two years, the mean subsidence of the head and tip for the TriFit stem was 0.38 mm (SD 0.32) and 0.52 mm (SD 0.36), respectively. The total migration of the head and tip was 0.55 mm (SD 0.32) and 0.71 mm (SD 0.38), respectively. There were no statistically significant differences between the three to 12 months' migration (p = 0.105) and 12 to 24 months' migration (p = 0.694). The OHS and EQ-5D showed significant improvements at two years. Conclusion. The results of this study suggest that the TriFit femoral stem achieves initial stability and is likely to be stable in the mid and long term. A long-term outcome study is required to assess late mechanisms of failure and the effects of bone mineral density (BMD) related changes. Cite this article: Bone Joint J 2021;103-B(4):644–649

Objectives. Researchers continue to seek easier ways to evaluate the quality of bone and screen for osteoporosis and osteopenia. Until recently, radiographic images of various parts of the body, except the distal femur, have been reappraised in the light of dual-energy X-ray absorptiometry (DXA) findings. The incidence of osteoporotic fractures around the knee joint in the elderly continues to increase. The aim of this study was to propose two new radiographic parameters of the distal femur for the assessment of bone quality. Methods. Anteroposterior radiographs of the knee and bone mineral density (BMD) and T-scores from DXA scans of 361 healthy patients were prospectively analyzed. The mean cortical bone thickness (CBTavg) and the distal femoral cortex index (DFCI) were the two parameters that were proposed and measured. Intra- and interobserver reliabilities were assessed. Correlations between the BMD and T-score and these parameters were investigated and their value in the diagnosis of osteoporosis and osteopenia was evaluated. Results. The DFCI, as a ratio, had higher reliability than the CBTavg. Both showed significant correlation with BMD and T-score. When compared with DFCI, CBTavg showed better correlation and was better for predicting osteoporosis and osteopenia. Conclusion. The CBTavg and DFCI are simple and reliable screening tools for the prediction of osteoporosis and osteopenia. The CBTavg is more accurate but the DFCI is easier to use in clinical practice. Cite this article: Q-F. He, H. Sun, L-Y. Shu, Y. Zhu, X-T. Xie, Y. Zhan, C-F. Luo. Radiographic predictors for bone mineral loss: Cortical thickness and index of the distal femur. Bone Joint Res 2018;7:468–475. DOI: 10.1302/2046-3758.77.BJR-2017-0332.R1

Aims. The effect of the gut microbiota (GM) and its metabolite on bone health is termed the gut-bone axis. Multiple studies have elucidated the mechanisms but findings vary greatly. A systematic review was performed to analyze current animal models and explore the effect of GM on bone. Methods. Literature search was performed on PubMed and Embase databases. Information on the types and strains of animals, induction of osteoporosis, intervention strategies, determination of GM, assessment on bone mineral density (BMD) and bone quality, and key findings were extracted. Results. A total of 30 studies were included, of which six studies used rats and 24 studies used mice. Osteoporosis or bone loss was induced in 14 studies. Interventions included ten with probiotics, three with prebiotics, nine with antibiotics, two with short-chain fatty acid (SCFA), six with vitamins and proteins, two with traditional Chinese medicine (TCM), and one with neuropeptide Y1R antagonist. In general, probiotics, prebiotics, nutritional interventions, and TCM were found to reverse the GM dysbiosis and rescue bone loss. Conclusion. Despite the positive therapeutic effect of probiotics, prebiotics, and nutritional or pharmaceutical interventions on osteoporosis, there is still a critical knowledge gap regarding the role of GM in rescuing bone loss and its related pathways. Cite this article: Bone Joint Res 2021;10(1):51–59

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

Aims. Dual mobility (DM) implants have been shown to reduce the dislocation rate after total hip arthroplasty (THA), but there remain concerns about the use of cobalt chrome liners inserted into titanium shells. The aim of this study was to assess the clinical outcomes, metal ion levels, and periprosthetic femoral bone mineral density (BMD) at mid-term follow-up in young, active patients receiving a modular DM THA. Methods. This was a prospective study involving patients aged < 65 years, with a BMI of < 35 kg/m. 2. , and University of California, Los Angeles activity score of > 6 who underwent primary THA with a modular cobalt chrome acetabular liner, highly cross-linked polyethylene mobile bearing, and a cementless titanium femoral stem. Patient-reported outcome measures, whole blood metal ion levels (μg/l), and periprosthetic femoral BMD were measured at baseline and at one, two, and five years postoperatively. The results two years postoperatively for this cohort have been previously reported. Results. A total of 43 patients were enrolled. At minimum follow-up of five years, 23 (53.4%) returned for clinical and radiological review, 25 (58.1%) had metal ion analysis performed, 19 (44.2%) underwent dual energy x-ray absorptiometry scans, and 25 (58%) completed a pain-drawing questionnaire. The mean modified Harris Hip Scores improved significantly from 54.8 (SD 19) preoperatively to 93.08 (SD 10.5) five years postoperatively (p < 0.001). One patient was revised for aseptic acetabular loosening. The mean cobalt levels increased from 0.065 μg/l (SD 0.03) to 0.08 (SD 0.05) and the mean titanium levels increased from 0.35 (SD 0.13) to 0.78 (SD 0.29). The femoral BMD ratio decreased in Gruen Zone 1 (91.9%) at five years postoperatively compared with the baseline scores at six weeks potoperatively. The femoral BMD ratio was maintained in Gruen zones 2 to 7. Conclusion. The use of a modular DM component and a cementless, tapered femoral stem shows excellent mid-term survivorship with minimal concerns for corrosion and metal ion release in a cohort of young, active patients undergoing primary THA. Cite this article: Bone Joint J 2021;103-B(7 Supple B):73–77

Aims. Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process. Methods. Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone. Results. Enhanced matrix catabolism, increased apoptosis of chondrocytes in cartilage, and overexpressed JAK2/STAT3 and p-JAK2/p-STAT3 were observed in cartilage in this model. All of these changes were prevented by PTH (1-34) treatment, with no significant difference between the low-dose and high-dose groups. Micro-CT analysis indicated that bone mineral density (BMD), bone volume/trabecular volume (BV/TV), and trabecular thickness (Tb.Th) levels were significantly lower in the OA group than those in the Sham, PTH 10 μg, and PTH 40 μg groups, but these parameters were significantly higher in the PTH 40 μg group than in the PTH 10 μg group. Conclusion. Intermittent administration of PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a dose-dependent manner on the latter in a collagenase-induced OA mouse model, which may be involved in regulating the JAK2/STAT3 signalling pathway. Cite this article: Bone Joint Res 2020;9(10):675–688

Aims. Idiopathic scoliosis is the most common spinal deformity in adolescents and children. The aetiology of the disease remains unknown. Previous studies have shown a lower bone mineral density in individuals with idiopathic scoliosis, which may contribute to the causation. The aim of the present study was to compare bone health in adolescents with idiopathic scoliosis with controls. Methods. We included 78 adolescents with idiopathic scoliosis (57 female patients) at a mean age of 13.7 years (8.5 to 19.6) and 52 age- and sex-matched healthy controls (39 female patients) at a mean age of 13.8 years (9.1 to 17.6). Mean skeletal age, estimated according to the Tanner-Whitehouse 3 system (TW3), was 13.4 years (7.4 to 17.8) for those with idiopathic scoliosis, and 13.1 years (7.4 to 16.5) for the controls. Mean Cobb angle for those with idiopathic scoliosis was 29° (SD 11°). All individuals were scanned with dual energy x-ray absorptiometry (DXA) and peripheral quantitative CT (pQCT) of the left radius and tibia to assess bone density. Statistical analyses were performed with independent-samples t-test, the Mann-Whitney U test, and the chi-squared test. Results. Compared with controls, adolescents with idiopathic scoliosis had mean lower DXA values in the left femoral neck (0.94 g/cm. 2. (SD 0.14) vs 1.00 g/cm. 2. (SD 0.15)), left total hip (0.94 g/cm. 2. (SD 0.14) vs 1.01 g/cm. 2. (SD 0.17)), L1 to L4 (0.99 g/cm. 2. (SD 0.15) vs 1.06 g/cm. 2. (SD 0.17)) and distal radius (0.35 g/cm. 2. (SD 0.07) vs 0.39 g/cm. 2. (SD 0.08; all p ≤ 0.024), but not in the mid-radius (0.72 g/cm. 2. vs 0.74 g/cm. 2. ; p = 0.198, independent t-test) and total body less head (1,559 g (SD 380) vs 1,649 g (SD 492; p = 0.0.247, independent t-test). Compared with controls, adolescents with idiopathic scoliosis had lower trabecular volume bone mineral density (BMD) on pQCT in the distal radius (184.7 mg/cm. 3. (SD 40.0) vs 201.7 mg/cm. 3. (SD 46.8); p = 0.029), but not in other parts of the radius or the tibia (p ≥ 0.062, Mann-Whitney U test). Conclusion. In the present study, idiopathic scoliosis patients seemed to have lower BMD at central skeletal sites and less evident differences at peripheral skeletal sites when compared with controls. Cite this article: Bone Joint J 2020;102-B(2):268–272

To evaluate the effects of 6 and 18 months of abaloparatide (ABL) compared with placebo (PBO) on bone mineral density (BMD) in the acetabular regions of postmenopausal women with osteoporosis (OP). Acetabular bone loss, as may occur in OP, increases risk of acetabular fragility fractures. a. In total hip arthroplasty (THA), low acetabular BMD adversely affects primary stability, osseointegration, and migration of acetabular cups. c. ABL is an osteoanabolic agent for the treatment of men and postmenopausal women with OP at high risk for fracture. Effects of ABL on acetabular BMD are unknown. Hip DXA scans were obtained at baseline, 6, and 18 months from a random subgroup of postmenopausal women (aged 49–86 y) from the phase 3 ACTIVE trial randomized to either ABL 80 µg/d or PBO (n=250/group). Anatomical landmarks were identified in each DXA scan to virtually place a hemispherical shell model of an acetabular cup and define regions of interest corresponding to DeLee & Charnley zones 1 (R1), 2 (R2), and 3 (R3). BMD changes compared to baseline were calculated for each zone. Statistical P values were based on a repeated mixed measures model. BMD in all zones were similar at baseline in the ABL and PBO groups. BMD significantly increased in the ABL group at 6 and 18 months compared with PBO (all P<0.0001 vs PBO). BMD in the PBO group was relatively stable over time. ABL treatment resulted in rapid and progressive increases in BMD of all 3 acetabular zones. Increasing acetabular BMD has the potential to improve acetabular strength, which may reduce risk of acetabular fragility fractures. In bone health optimization prior to THA, increased acetabular BMD via ABL may provide better primary stability and longevity of acetabular cups in postmenopausal women with OP

Femoroacetabular impingement (FAI) results from a morphological deformity of the hip and is associated with osteoarthritis (OA). Increased bone mineral density (BMD) is observed in the antero-superior acetabulum rim where impingement occurs. It is hypothesized that the repeated abnormal contact leads to damage of the cartilage layer, but could also cause a bone remodelling response according to Wolff's Law. Thus the goal of this study was to assess the relationship between bone metabolic activity measured by PET and BMD measured in CT scans. Five participants with asymptomatic cam deformity, three patients with uni-lateral symptomatic cam FAI and three healthy controls were scanned in a 3T PET-MRI scanner following injection with [18F]NaF. Bone remodelling activity was quantified with Standard Uptake Values (SUVs). SUVmax was analyzed in the antero-superior acetabular rim, femoral head and head-neck junction. In these same regions, BMD was calculated from CT scans using the calibration phantom included in the scan. The relationship between SUVmax and BMD from corresponding regions was assessed using the coefficient of determination (R. 2. ) from linear regression. High bone activity was seen in the cam deformity and acetabular rim. SUVmax was negatively correlated with BMD in the antero-superior region of the acetabulum (R. 2. =0.30, p=0.08). SUVmax was positively correlated with BMD in the antero-superior head-neck junction of the femur (R. 2. =0.359, p=0.067). Correlations were weak in other regions. Elevated bone turnover was seen in patients with a cam deformity but the relationship to BMD was moderate. This study demonstrates a pathomechanism of hip degeneration associated with FAI deformities, consistent with Wolff's law and the proposed mechanical cause of hip degeneration in FAI. [18F]-NaF PET SUV may be a biomarker of degeneration, especially in early stages of degeneration, when joint preservation surgery is likely to be the most successful

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

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

Odontoid fracture of the second cervical vertebra (C2) is the most common spinal fracture type in elderly patients. However, very little is known about the biomechanical fracture mechanisms, but could play a role in fracture prevention and treatment. This study aimed to investigate the biomechanical competence and fracture characteristics of the odontoid process. A total of 42 human C2 specimens (14 female and 28 male, 71.5 ± 6.5 years) were scanned via quantitative computed tomography, divided in 6 groups (n = 7) and subjected to combined quasi-static loading at a rate of 0.1 mm/s until fracturing at inclinations of −15°, 0° and 15° in sagittal plane, and −50° and 0° in transverse plane. Bone mineral density (BMD), specimen height, fusion state of the ossification centers, stiffness, yield load, ultimate load, and fracture type according to Anderson and d'Alonzo were assessed. While the lowest values for stiffness, yield, and ultimate load were observed at load inclination of 15° in sagittal plane, no statistically significant differences could be observed among the six groups (p = 0.235, p = 0.646, and p = 0.505, respectively). Evaluating specimens with only clearly distinguishable fusion of the ossification centers (n = 26) reveled even less differences among the groups for all mechanical parameters. BMD was positively correlated with yield load (R² = 0.350, p < 0.001), and ultimate load (R² = 0.955, p < 0.001), but not with stiffness (p = 0.070). Type III was the most common fracture type (23.5%). These biomechanical outcomes indicate that load direction plays a subordinate role in traumatic fractures of the odontoid process in contrast to BMD which is a strong determinant of stiffness and strength. Thus, odontoid fractures appear to result from an interaction between load magnitude and bone quality

We have developed a novel technique to analyse bone, using imaging mass cytometry (IMC) without the constraints of using immunofluorescent histochemistry. IMC can measure the expression of over 40 proteins simultaneously, without autofluorescence. We analysed mitochondrial respiratory chain (RC) protein deficiencies in human bone which are thought to contribute to osteoporosis with increasing age. Osteoporosis is characterised by reduced bone mineral density (BMD) and fragility fractures. Humans accumulate mitochondrial mutations and RC deficiency with age and this has been linked to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of 30 onwards, coincidently the age BMD begins to decline. Mitochondria contain their own genome which accumulates somatic variants at around 10 times the rate of nuclear DNA. Once these mutations exceed a threshold, RC deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model expresses a proof-reading deficient version of PolgA, a mtDNA polymerase. These mice accumulate mutations 3-5 times higher than wild-type mice showing enhanced levels of age-related osteoporosis and RC deficiency in osteoblasts. Bone samples were analysed from young and old patients, developing a protocol and analysis framework for IMC in bone tissue sections to analyse osteoblasts in-situ for RC deficiency. Samples from the femoral neck of 10 older healthy volunteers aged 40 – 85 were compared with samples from young patients aged 1-19. We have identified RC complex I defect in osteoblasts from 6 of the older volunteers, complex II defects in 2 of the older volunteers, complex IV defect in just 1 older volunteer, and complex V defect in 4 of the older volunteers. These observations are consistent with the PolgD257A/D257A mouse-model and suggest that RC deficiency, due to age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis

Quantitative ultrasound (QUS) is a promising tool to estimate bone structure characteristics and predict fragile fracture. The aim of this pilot cross-sectional study was to evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragile fractures retrospectively in postmenopausal women. Methods. RF signal and speed of sound (SOS) were obtained using an axial transmission QUS at one‐third distal radius for 246 postmenopausal women. Based on the involved RF signal, we conducted a MResNet, which combines multi-channel training with original ResNet, to classify the high risk of fragility fractures patients from all subjects. The bone mineral density (BMD) at lumber, hip and femoral neck acquired with DXA was recorded on the same day. The fracture history of all subjects in adulthood were collected. To assess the ability of the different methods in the discrimination of fragile fracture, the odds ratios (OR) calculated using binomial logistic regression analysis and the area under the receiver operator characteristic curves (AUC) were analyzed. Results. Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was discriminant for all fragile fractures (OR = 2.64; AUC = 0.74), for Vertebral fracture (OR = 3.02; AUC = 0.77), for non-vertebral fracture (OR = 2.01; AUC = 0.69). MResNet showed comparable performance to that of BMD of hip and lumbar with all types of fractures, and significantly better performance than SOS all types of fractures. Conclusions. the MResNet model based on the ultrasonic RF signal can significantly improve the ability of QUS device to recognize previous fragile fractures. Moreover, the performance of the proposed model modified by age, weight, and height is further optimized. These results open perspectives to evaluate the risk of fragile fracture applying a deep learning model to analyze ultrasonic RF signal

Stand-alone anterior lumbar interbody fusion (ALIF) provides the opportunity to avoid supplemental posterior fixation. This may reduce morbidity and complication rate, which is of special interest in patients with reduced bone mineral density (BMD). This study aims to assess immediate biomechanical stability and radiographic outcome of a stand-alone ALIF device with integrated screws in specimens of low BMD. Eight human cadaveric spines (L4-sacrum) were instrumented with SynFix-LR™ (DePuy Synthes) at L5/S1. Quantitative computed tomography was used to measure BMD of L5 in AMIRA. Threshold values proposed by the American Society of Radiology 80 and 120 mg CaHa/mL were used to differentiate between Osteoporosis, Osteopenia, and normal BMD. Segmental lordosis, anterior and posterior disc height were analysed on pre- and postoperative radiographs (Fig 1). Specimens were tested intact and following instrumentation using a flexibility protocol consisting of three loading cycles to ±7.5 Nm in flexion-extension, lateral bending, and axial rotation. The ranges of motion (ROM) of the index level were assessed using an optoelectronic system. BMD ranged 58–181mg CaHA/mL. Comparison of pre- and postoperative radiographs revealed significant increase of L5/S1 segmental lordosis (mean 14.6°, SD 5.1, p < 0.001) and anterior disc height (mean 5.8mm, SD 1.8, p < 0.001), but not posterior disc height. ROM of 6 specimens was reduced compared to the intact state. Two specimens showed destructive failure in extension. Mean decrease was most distinct in axial rotation up to 83% followed by flexion-extension. ALIF device with integrated screws at L5/S1 significantly increases segmental lordosis and anterior disc height without correlation to BMD. Primary stability in the immediate postoperative situation is mostly warranted in axial rotation. The risk of failure might be increased in extension for some patients with reduced lumbar BMD, therefore additional posterior stabilization could be considered. For any figures or tables, please contact the authors directly

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

Objectives. In total hip arthroplasty (THA), the cementless, tapered-wedge stem design contributes to achieving initial stability and providing optimal load transfer in the proximal femur. However, loading conditions on the femur following THA are also influenced by femoral structure. Therefore, we determined the effects of tapered-wedge stems on the load distribution of the femur using subject-specific finite element models of femurs with various canal shapes. Patients and Methods. We studied 20 femurs, including seven champagne flute-type femurs, five stovepipe-type femurs, and eight intermediate-type femurs, in patients who had undergone cementless THA using the Accolade TMZF stem at our institution. Subject–specific finite element (FE) models of pre- and post-operative femurs with stems were constructed and used to perform FE analyses (FEAs) to simulate single-leg stance. FEA predictions were compared with changes in bone mineral density (BMD) measured for each patient during the first post-operative year. Results. Stovepipe models implanted with large-size stems had significantly lower equivalent stress on the proximal-medial area of the femur compared with champagne-flute and intermediate models, with a significant loss of BMD in the corresponding area at one year post-operatively. Conclusions. The stovepipe femurs required a large-size stem to obtain an optimal fit of the stem. The FEA result and post-operative BMD change of the femur suggest that the combination of a large-size Accolade TMZF stem and stovepipe femur may be associated with proximal stress shielding. Cite this article: M. Oba, Y. Inaba, N. Kobayashi, H. Ike, T. Tezuka, T. Saito. Effect of femoral canal shape on mechanical stress distribution and adaptive bone remodelling around a cementless tapered-wedge stem. Bone Joint Res 2016;5:362–369. DOI: 10.1302/2046-3758.59.2000525

Nuclear factor erythroid 2–related factor 2 (Nrf2) is a crucial transcription factor to maintain cellular redox homeostasis, but is also affecting bone metabolism. As the association between Nrf2 and osteoporosis in elderly females is not fully elucidated, our aim was to shed light on the potential contribution of Nrf2 to the development of age-dependent osteoporosis using a mouse model. Female wild-type (WT, n=18) and Nrf2-knockout (KO, n=12) mice were sacrificed at different ages (12 weeks=young mature adult, and 90 weeks=old), morphological cortical and trabecular properties of femoral bone analyzed by micro-computed tomography (µCT), and compared to histochemistry. Mechanical properties were derived from quasi-static compression tests and digital image correlation (DIC) used to analyze full-field strain distribution. Bone resorbing cells and aromatase expression by osteocytes were evaluated immunohistochemically and empty osteocyte lacunae counted in cortical bone. Wilcoxon rank sum test was used for data comparison and differences considered statistically significant at p<0.05. When compared to old WT mice, old Nrf2-KO mice revealed a significantly reduced trabecular bone mineral density (BMD), cortical thickness (Ct.Th), cortical area (Ct.Ar), and cortical bone fraction (Ct.Ar/Tt.Ar). Surprisingly, these parameters were not different in skeletally mature young adult mice. Metaphyseal trabeculae were thin but present in all old WT mice, while no trabecular bone was detectable in 60% of old KO mice. Occurrence of empty osteocyte lacunae did not differ between both groups, but a significantly higher number of osteoclast-like cells and fewer aromatase-positive osteocytes were found in old KO mice. Furthermore, female Nrf2-KO mice showed an age-dependently reduced fracture resilience when compared to age-matched WT mice. Our results confirmed lower bone quantity and quality as well as an increased number of bone resorbing cells in old female Nrf2-KO mice. Additionally, aromatase expression in osteocytes of old Nrf2-KO mice was compromised, which may indicate a chronic lack of estrogen in bones of old Nrf2-deficient mice. Thus, chronic Nrf2 loss seems to contribute to age-dependent progression of female osteoporosis

Objectives. Osteoporosis is a metabolic disease resulting in progressive loss of bone mass as measured by bone mineral density (BMD). Physical exercise has a positive effect on increasing or maintaining BMD in postmenopausal women. The contribution of exercise to the regulation of osteogenesis in osteoblasts remains unclear. We therefore investigated the effect of exercise on osteoblasts in ovariectomized mice. Methods. We compared the activity of differentially expressed genes of osteoblasts in ovariectomized mice that undertook exercise (OVX+T) with those that did not (OVX), using microarray and bioinformatics. Results. Many inflammatory pathways were significantly downregulated in the osteoblasts after exercise. Meanwhile, IBSP and SLc13A5 gene expressions were upregulated in the OVX+T group. Furthermore, in in vitro assay, IBSP and SLc13A5 mRNAs were also upregulated during the osteogenic differentiation of MC3T3-E1 and 7F2 cells. Conclusion. These findings suggest that exercise may not only reduce the inflammatory environment in ovariectomized mice, indirectly suppressing the overactivated osteoclasts, but may also directly activate osteogenesis-related genes in osteoblasts. Exercise may thus prevent the bone loss caused by oestrogen deficiency through mediating the imbalance between the bone resorptive activity of osteoclasts and the bone formation activity of osteoblasts. Cite this article: W-B. Hsu, W-H. Hsu, J-S. Hung, W-J. Shen, R. W-W. Hsu. Transcriptome analysis of osteoblasts in an ovariectomized mouse model in response to physical exercise. Bone Joint Res 2018;7:601–608. DOI: 10.1302/2046-3758.711.BJR-2018-0075.R2

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

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

Objective. In ex vivo hip fracture studies femoral pairs are split to create two comparable test groups. When more than two groups are required, or if paired femurs cannot be obtained, group allocation according to bone mineral density (BMD) is sometimes performed. In this statistical experiment we explore how this affects experimental results and sample size considerations. Methods. In a hip fracture experiment, nine pairs of human cadaver femurs were tested in a paired study design. The femurs were then re-matched according to BMD, creating two new test groups. Intra-pair variance and paired correlations in fixation stability were calculated. A hypothetical power analysis was then performed to explore the required sample size for the two types of group allocation. . Results. The standard deviation (. sd. ) of the mean paired difference in fixation stability increased from 2 mm in donor pairs to 5 mm in BMD-matched pairs. Intra-pair correlation was 0.953 (Pearson’s r) in donor pairs and non-significant at -0.134 (Pearson’s r) in BMD-matched pairs. Required sample size to achieve a statistical power of 0.8 increased from ten pairs using donor pairs to 54 pairs using BMD-matched pairs. Conclusion. BMD cannot be used to create comparable test groups unless sample size is increased substantially and paired statistics are no longer valid. Cite this article: Bone Joint Res 2014;3:317–20

Total Hip Replacement (THR) is one of the most successful operations in all of medicine, however surgeons just rely on their experience and expertise when choosing between cemented or cementless stem, without having any quantitative guidelines. The aim of this project is to provide clinicians with some tools to support in their decision making. A novel method based on bone mineral density (BMD) measurements and assessments was developed 1) to estimate the periprosthetic fracture risk (FR) while press-fitting cementless stem; 2) to evaluate post-operative bone remodeling in terms of BMD changes after primary THR. Data for 5 out of over 70 patients (already involved in a previous study. 1. ) that underwent primary THA in Iceland were selected for developing novel methods to assess intra-operative FR and bone mineral density (BMD) changes after the operation. For each patient three CT images were acquired (Philips Brilliance 64 Spiral-CT, 120 kVp, slice thickness: 1 mm, slice increment: 0.5 mm): pre-op, 24 hours and 1 year post-operative. Pre-op CT scan was used to create 3D finite element model (Materialise Mimics) of the proximal femur. The material properties were assigned based on Hounsfield Units. Different strategies were analyzed for simulating the press-fitting operation, developing what has already been done in prior study. 1. In the finite element simulation (Ansys Workbench), a pressure (related to the implant hammering force of 9.25 kN. 2. ) was applied around the femur's hollow for the stem and the distribution of maximum principal elastic strain over the bone was calculated. Assuming a critical failure value. 3. of 7300 με, the percentage of fractured elements was calculated (i.e. FR). Post 24 hours and Post 1 year CT images were co-registrated and compared (Materialise Mimics) in order to assess BMD changes. Successively, volumes of bone lost and bone gained were calculated and represented in a 3D model. Age and gender should not be taken as unique indicators to choose between implants typologies, since also three dimensional BMD distribution along with volume of cortical bone influence the risk of periprosthetic fractures. Highest FR values were experienced in the calcar-femorale zone and in similar location on the posterior side. BMD loss volume fractions after 1 year were usually higher than BMD gain ones. Consistently with prior studies. 4. , BMD loss was mainly concentrated around the proximal end (lesser trochanter area, outer bone). If present, BMD gain occurred at the distal end (below stem's tip) or proximally (lesser trochanter area, interface contact with the stem). The use of clinical data for BMD assessments serves as an important tool to develop a quantitative method which will support surgeons in their decisions, guiding them to the optimal implant for the patient. Knowing the risk of fracture if choosing a cementless stem and being aware of how the bone will remodel around the stem in one year's time can eventually lead to reduction in revisions and increased quality of life for the patient. Further work will target analysis of a larger cohort of patients and validate FE models

Objectives. Our primary aim was to describe migration of the Exeter stem with a 32 mm head on highly crosslinked polyethylene and whether this is influenced by age. Our secondary aims were to assess functional outcome, satisfaction, activity, and bone mineral density (BMD) according to age. Patients and Methods. A prospective cohort study was conducted. Patients were recruited into three age groups: less than 65 years (n = 65), 65 to 74 years (n = 68), and 75 years and older (n = 67). There were 200 patients enrolled in the study, of whom 115 were female and 85 were male, with a mean age of 69.9 years (sd 9.5, 42 to 92). They were assessed preoperatively, and at three, 12 and, 24 months postoperatively. Stem migration was assessed using Einzel-Bild-Röntgen-Analyse (EBRA). Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), Hip Disability and Osteoarthritis Outcome Score (HOOS), EuroQol-5 domains questionnaire (EQ-5D), short form-36 questionnaire (SF-36,) and patient satisfaction were used to assess outcome. The Lower Extremity Activity Scale (LEAS), Timed Up and Go (TUG) test, and activPAL monitor (energy expelled, time lying/standing/walking and step count) were used to assess activity. The BMD was assessed in Gruen and Charnley zones. Results. Mean varus/valgus tilt was -0.77⁰ and axial subsidence was -1.20 mm. No significant difference was observed between age groups (p ⩾ 0.07). There was no difference according to age group for postoperative WOMAC (p ⩾ 0.11), HHS (p ⩾ 0.06), HOOS (p ⩾ 0.46), EQ-5D (p ⩾ 0.38), patient satisfaction (p ⩾ 0.05), or activPAL (p ⩾ 0.06). Patients 75 years and older had a worse SF-36 physical function (p = 0.01) and physical role (p = 0.03), LEAS score (p < 0.001), a shorter TUG (p = 0.01), and a lower BMD in Charnley zone 1 (p = 0.02). Conclusion. Exeter stem migration is within normal limits and is not influenced by age group. Functional outcome, patient satisfaction, activity level, and periprosthetic BMD are similar across all age groups. Cite this article: N. D. Clement, M. Bardgett, K. Merrie, S. Furtado, R. Bowman, D. J. Langton, D. J. Deehan, J. Holland. Cemented Exeter total hip arthroplasty with a 32 mm head on highly crosslinked polyethylene: Does age influence functional outcome, satisfaction, activity, stem migration, and periprosthetic bone mineral density? Bone Joint Res 2019;8:275–287. DOI: 10.1302/2046-3758.86.BJR-2018-0300.R1