Pamidronate [3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD)] was the first nitrogen-containing bisphosphonate (N-BP) investigated in clinical studies. In contrast to other clinically used bisphosphonates, pamidronate was discovered and its properties were initially studied in an Academic Institution. On the occasion of the 50th Anniversary of the first publications on the biological effects of bisphosphonates, I review in this article the contribution of Leiden investigators to the development of pamidronate that led to the recognition of the significance of the Nitrogen atom in the side chain of bisphosphonates for their action on bone resorption and to the formulation of principles for the use of N-BPs in the management of patients with different skeletal disorders.

Extracellular pyrophosphate (ePPi) was first identified as a key endogenous inhibitor of mineralisation in the 1960's by Fleisch and colleagues. The main source of ePPi seems to be extracellular ATP which is continually released from cells in a controlled way. ATP is rapidly broken down by enzymes including ecto-nucleotide pyrophosphatase/phosphodiesterases to produce ePPi. The major function of ePPi is to directly inhibit hydroxyapatite formation and growth meaning that this simple molecule acts as the body's own “water softener”. However, studies have also shown that ePPi can influence gene expression and regulate its own production and breakdown. This review will summarise our current knowledge of ePPi metabolism and how it acts to prevent pathological soft tissue calcification and regulate physiological bone mineralisation.

Inactivating mutations of the ENPP1 gene are associated with generalized arterial calcification of infancy (GACI) and less often autosomal‐recessive hypophosphatemic rickets type 2 (ARHR2). We aimed to investigate the spectrum of phenotypes in a family with monoallelic and biallelic mutations of ENPP1 after identification through whole exome sequencing of a 54‐year‐old female with biallelic mutation of ENPP1, c.323G > T; p.Cys108Phe and c.1441C > T; p.Arg481Trp. Including the proband, 2 subjects had biallelic mutations, 5 had monoallelic mutations, and 2 had no mutation of ENPP1. The maternal mutation, a known pathogenic variant associated with GACI, was found in 3 subjects with monoallelic mutations, while the paternal mutation, which was not previously reported, was present in 2 subjects with monoallelic mutations. Both subjects with biallelic mutations had bowing of bilateral femurs, periarticular mineral deposition, normocalcemic primary hyperparathyroidism with multigland parathyroidectomy, increased carotid intima‐media thickness, and enthesopathy was also noted in one subject. Intact FGF23 was elevated in both subjects with biallelic mutations, while C‐terminal FGF23 was only elevated in one and PPi was reduced in one. Subjects with monoallelic mutations did not have periarticular calcifications or bone deformities. To conclude, patients with biallelic GACI causing mutations can survive well into adulthood, and despite the same biallelic ENPP1 pathogenic variants, clinical and biochemical manifestations can significantly differ, and include enthesopathy and primary hyperparathyroidism, which have not been previously described. Although carriers of monoallelic ENPP1 variants appear unaffected by classic disease manifestations, there may be subtle biochemical and clinical findings that warrant further investigation. © 2019 American Society for Bone and Mineral Research.

The spatial heterogeneity in trabecular bone density within the vertebral centrum is associated with vertebral strength and could explain why volumetric bone mineral density (vBMD) exhibits low sensitivity in identifying fracture risk. This study evaluated whether the heterogeneity and spatial distribution of trabecular vBMD are associated with prevalent vertebral fracture. We examined the volumetric quantitative computed tomography (QCT) scans of the L3 vertebra in 148 participants in the Framingham Heart Study Multidetector CT study. Of these individuals, 37 were identified as cases of prevalent fracture, and 111 were controls, matched on sex and age with three controls per case. vBMD was calculated within 5‐mm contiguous cubic regions of the centrum. Two measures of heterogeneity were calculated: (i) interquartile range (IQR); and (ii) quartile coefficient of variation (QCV). Ratios in the spatial distributions of the trabecular vBMD were also calculated: anterior/posterior, central/outer, superior/mid‐transverse, and inferior/mid‐transverse. Heterogeneity and spatial distributions were compared between cases and controls using Wilcoxon rank sum tests and t tests and tested for association with prevalent fractures with conditional logistic regressions independent of integral vBMD. Prevalent fracture cases had lower mean ± SD integral vBMD (134 ± 38 versus165 ± 42 mg/cm3, p < .001), higher QCV (0.22 ± 0.13 versus 0.17 ± 0.09, p = .003), and lower anterior/posterior rBMD (0.65 ± 0.13 versus 0.78 ± 0.16, p < .001) than controls. QCV was positively associated with increased odds of prevalent fracture (OR 1.61; 95% CI, 1.04 to 2.49; p = .034), but this association was not independent of integral vBMD (p = .598). Increased anterior/posterior trabecular vBMD ratio was associated with decreased odds of prevalent fracture independent of integral vBMD (OR 0.38; 95% CI, 0.20 to 0.71; p = .003). In conclusion, increased trabecular vBMD in the anterior versus posterior centrum, but not trabecular vBMD heterogeneity, was associated with decreased risk of prevalent fracture independent of integral vBMD. Regional measurements of trabecular vBMD could aid in determining the risk and underlying mechanisms of vertebral fracture. © 2019 American Society for Bone and Mineral Research.

Exposure of humans and animals to microgravity in spaceflight results in various deleterious effects on bone health. In addition to microgravity, the hypomagnetic field (HyMF) is also an extreme environment in space, such as on the Moon and Mars; magnetic intensity is far weaker than the geomagnetic field (GMF) on Earth. Recently, we showed that HyMF promoted additional bone loss in hindlimb unloading–induced bone loss, and the underlying mechanism probably involved an increase of body iron storage. Numerous studies have indicated that bone loss induced by mechanical unloading can be largely restored after skeletal reloading in GMF conditions. However, it is unknown whether this bone deficit can return to a healthy state under HyMF condition. Therefore, the purpose of this study is to examine the effects of HyMF on the recovery of microgravity‐induced bone loss, and illustrates the changes of body iron storage in this process. Our results showed that there was lower bone mineral content (BMC) in the HyMF reloading group compared to the GMF reloading group. Reloaded mice in the HyMF condition had a worse microstructure of femur than in the GMF condition. Femoral mechanical properties, including elastic modulus, stiffness, and ultimate stress, were poorer and toughness was higher in the HyMF group compared with the GMF group. Simultaneously, more iron content in serum, the tibia, liver, and spleen was found under HyMF reloading than GMF reloading. The iron chelator deferoxamine mesylate (DFO) decreased the iron content in the bone, liver, and spleen, and significantly relieved unloading‐induced bone loss under HyMF reloading. These results showed that HyMF inhibits the recovery of microgravity‐induced bone loss, probably by suppressing the elevated iron levels’ return to physiological level. © 2019 American Society for Bone and Mineral Research.

Multiple myeloma is caused by abnormal plasma cells that accumulate in the bone marrow and interact with resident cells of the bone microenvironment to drive disease progression and development of an osteolytic bone disease. Bone marrow adipocytes (BMAds) are emerging as having important endocrine functions that can support myeloma cell growth and survival. However, how BMAds respond to infiltrating tumor cells remains poorly understood. Using the C57BL/KaLwRij murine model of myeloma, bone marrow adiposity was found to be increased in early stage myeloma with BMAds localizing along the tumor‐bone interface at later stages of disease. Myeloma cells were found to uptake BMAd‐derived lipids in vitro and in vivo, although lipid uptake was not associated with the ability of BMAds to promote myeloma cell growth and survival. However, BMAd‐derived factors were found to increase myeloma cell migration, viability, and the evasion of apoptosis. BMAds are a major source of adiponectin, which is known to be myeloma‐suppressive. Myeloma cells were found to downregulate adiponectin specifically in a model of BMAds but not in white adipocytes. The ability of myeloma cells to downregulate adiponectin was dependent at least in part on TNF‐α. Collectively our data support the link between increased bone marrow adiposity and myeloma progression. By demonstrating how TNF‐α downregulates BMAd‐derived adiponectin, we reveal a new mechanism by which myeloma cells alter the bone microenvironment to support disease progression. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Although use of cellular bone allografts (CBA) in orthopedic surgery has become increasingly common, little information is available regarding their short-term clinical performance. In these two case reports of two-stage hip arthroplasties, ViviGen Formable CBA (V-CBA) was used in stage one to fill voids left by previous metal implants. The two patients had distinctly different health profiles, but each of them had previous metal implants due to a hip fracture. In the otherwise healthy 49-year-old male patient, the total hip arthroplasty (THA) was performed 7 weeks after nail removal and V-CBA backfill. In the 64-year-old female patient with Type 1 diabetes and severe osteoporosis, stage 2 was performed after 12 weeks. At the time of THA for each patient, bone containing some V-CBA was removed to accommodate the hip implant. The explants were histologically analyzed for bone matrix, mineralization, and neovascularization. Histological staining showed substantial new bone formation and neovascularization in both explants albeit at different levels of maturity. Although limited, these results suggest that V-CBA may facilitate new bone formation in healthy as well as in metabolically challenged patients. V, case report

Stress shielding after total hip arthroplasty (THA) can induce bone mineral density (BMD) loss around the femoral implant. Several studies using drug have described methods to prevent BMD loss around implants following THA. Switching from teriparatide to alendronate was reported to increase lumbar BMD; on the other hands, it is unclear whether switching from teriparatide to alendronate is effective around the implant. The aim of this study is that changes in BMD is compared in patients switched from teriparatide to alendronate, in patients treated with alendronate alone, and in control patients without medication after total hip arthroplasty. Patients were randomized into three groups, those switched to alendronate after teriparatide (switch: n = 17), those receiving continuous alendronate (ALD: n = 15), and control untreated patients (control: n = 16) and followed up for 2 years after THA. Baseline periprosthetic BMD was measured by dual-energy X-ray absorptiometry (DEXA) 1 week after THA, followed by subsequent measurements at 1 and 2 years postoperatively. Lumbar BMD was also evaluated at preoperatively, 1 and 2 years postoperatively. Two years after surgery, BMD (%) at zone 1 was significantly higher in the switch group than in the control group (P = 0.02). BMD (%) at zone 7 was significantly higher in the switch and ALD groups than in the control group (P = 0.01, P = 0.03). Lumbar BMD (%) anterior-posterior (AP) side was significantly higher in the switch group than in the ALD and control groups 2 years after surgery. On the other hand, lumbar BMD (%) lateral side was significantly higher in the switch and ALD groups than control group 2 years after surgery. Switching therapy had a significant effect on BMD of the lumbar spine and zones 1 and 7 at 2 years postoperatively. At zone 1 in particular, it was found to be more effective than ALD alone. UMIN, registry number UMIN000016158. Registered 8 January 2015

The purpose of this study is to discuss the surgical strategy, technical feasibility, and clinical efficacy of coronal shear fractures of the distal humerus using the anti-sliding plate technique. Fifty-two patients (35 males and 17 females) were treated with the anti-sliding plate technique in our hospital from January 2012 to January 2017. The average age of the patients was 40.4 years. They were classified according to the Dubberley classification system and treated with the anti-sliding plate technique. The long-term functional scores represented by the Mayo Elbow Performance Index and complications were evaluated. Fractures were classified as follows: 11 type-IA, 5 type-IB, 16 type-IIA, 4 type-IIB, 13 type-IIIA, and 3 type-IIIB according to the Dubberley classification system. All patients were treated with open reduction and internal fixation by the extensile lateral approach and completed a clinical and radiographic follow-up (average, 17.6 months). The average Mayo elbow performance score was 90.6 points, with 36 excellent, 11 good, and 5 fair results. The average range of movement of the elbow joint was 3° (0–15°) for extension and 136° (90–150°) for flexion. The anti-sliding plate technique follows basic AO principles and neutralizes the shearing force combined with lag screws and/or Kirschner wires after the anatomic reduction of the fracture. It allows for the stable internal fixation of the fracture, which is critical for early mobilization and a good functional outcome. Level IV, Case Series, Treatment Study

Intertrochanteric femoral fractures are prevalent among the elderly, and usually demands surgical treatments. Proximal femoral nail antirotation Asian version (PFNA-II) is widely used for intertrochanteric fracture treatment. The computer-assisted preoperative planning (CAPP) system has the potential to reduce the difficulty of PFNA-II in the treatment of intertrochanteric fractures. The aim of the study was to investigate and compare the learning curves of PFNA-II treatment with CAPP and conventional preoperational planning methods for intertrochanteric femoral fractures. A total of 125 patients with intertrochanteric fracture who were treated with PFNA-II between March 2012 and June 2015 were retrospectively analyzed. Patients who underwent surgery with CAPP procedure by a junior surgeon were regarded as group A (n = 53); patients who underwent the conventional surgery by another junior surgeon were regarded as group B (n = 72). Each group was divided into three subgroups (case 1–20, case 21–40, case 41–53 or case 41–72). The average operation time of group A was 45.00(42.00, 50.00) minutes, and in group B was 55.00 (50.00, 60.00) minutes (P < 0.01). Average radiation frequency and blood loss were 13.02 ± 2.32, 160.00 (140.00, 170.00) ml and 20.92 ± 3.27, 250.00 (195.00, 279.50) ml, respectively, with significant differences (P < 0.01). The learning curve of the surgical procedure in group A was steeper than that in group B. There were no significant differences in patient reported outcomes, hospital stay and complication rate between the two groups. Significant differences were observed between group A and B in Harris score at last follow-up in the AO/OTA type 31-A2 intertrochanteric fracture (P < 0.05). Compared with conventional preoperative planning methods, CAPP system significantly reduced operation time, radiation frequency and blood loss, thus reshaped the learning curve of PFNA-II treatment with lower learning difficulty. researchregistry4770. Registered 25 March 2019.

Reverse shoulder arthroplasty (RSA) is a common treatment for proximal humeral fractures. (PHF) in the elderly. This study evaluates the functional outcome and the influence of. tuberosity healing (TH) following RSA with 135° humeral inclination and a neutral glenosphere without lateralization for PHFs. In this retrospective case series, all patients with an acute PHF treated with primary RSA with 135° humeral inclination and a standard glenosphere without lateralization during a four-year period were followed up. Constant score (CS), patient satisfaction (subjective shoulder value (SSV)), TH and glenoid notching were analyzed. 38 patients with a mean age of 77 ± 8 years were available for follow-up at 34 ± 5 months. The mean adjusted CS was 61 ± 9 points. TH of the greater tuberosity (GT) was 82% and resulted in significantly improved abduction (117° vs. 81°; P < 0.001), forward flexion (139° vs. 99°; p < 0.001), external rotation (28° vs. 10°; p = 0.002), CS (65 vs. 41 points; p < 0.001) and patient satisfaction (SSV 79% vs. 48%; p < 0.001). TH of the LT was 87% without affecting internal rotation or overall outcome. The complication- and revision rate was 5%; implant survival was 100%. Scapular notching occurred in 3 (8%) cases (all grade 1). RSA with 135° humeral inclination and a standard glenosphere for PHF leads to good functional outcome in combination with a high rate of TH and a low rate of scapular notching. The short-term revision rate is low and the results are predictable and continuous. TH is associated with improved ROM, patient satisfaction and functional outcome.

Chronic widespread pain (CWP) has a negative impact on health status, but results have varied regarding gender-related differences and reported health status. The aim was to study the impact of CWP on health status in women and men aged 35–54 years in a sample of the general population. The aim was further to investigate lifestyle-related predictors of better health status in those with CWP in a 12- and 21-year perspective. A general population cohort study including 975 participants aged 35–54 years, with a 12- and 21-year follow-up. CWP was measured with a pain mannequin, and the questionnaire included questions on lifestyles factors with SF-36 for measurement of health status. Differences in health status were analysed with independent samples t-test and health predictors with logistic regression analysis. The prevalence of CWP was higher in women at all time points, but health status was reduced in both women and men with CWP (p < 0.001) with no gender differences of clinical relevance. At the 12-year follow-up, a higher proportion of women than men had developed CWP (OR 2.04; CI 1.27–3.26), and at the 21-year follow-up, a higher proportion of men had recovered from CWP (OR 3.79; CI 1.00–14.33). In those reporting CWP at baseline, a better SF-36 health status (Physical Functioning, Vitality or Mental Health) at the 12-year follow-up was predicted by male gender, having personal support, being a former smoker, and having no sleeping problems. In the 21-year follow-up, predictors of better health were male gender, a weekly intake of alcohol, and having no sleeping problems. Women and men with CWP have the same worsening of health status, but men recover from CWP to a greater extent in the long-term. Being male, having social support, being a former smoker, and having no sleeping problems were associated with better health status in those with CWP.

Cam and pincer-type morphologies can cause femoroacetabular impingement syndrome (FAI) and can be measured on plain radiographs using the alpha angle and the center edge angle. As an addition to plain radiographs and to assess femoroacetabular impingement, it is possible to visualize the interplay of the acetabular and femoral morphology by means of dynamic three-dimensional simulation of hip joint. Therefore, the objective of this study is to compare alpha angles and center edge angles on plain radiographs with the dynamic computerized tomography (CT) analysis in patients with complaints of femoroacetabular impingement. All patients from our prospective cohort from 2012 to 2015 who underwent radiographs and a dynamic CT analysis for FAI were selected. Cam type morphologies were measured with the alpha angle and pincer type morphologies with lateral center-edge angle on radiographs and with CT analysis. The dynamic CT analysis also calculated position and size of impingement of femur and acetabulum. Intra-operative assessment was used to confirm impingement. Sensitivity, specificity and predictive values were calculated compared with respect to the intra-operative assessment. A total of 127 patients were included. 90 cam morphologies and 45 pincer morphologies were identified intra-operatively. The sensitivity and specificity for cam morphology measured with radiographs was 84 and 72% compared to 90 and 43% with three dimensional dynamic analyses. The sensitivity and specificity for pincer morphology measured with radiographs was 82 and 39% compared to 84 and 51% with three dimensional dynamic analyses. Diagnostic accuracy is comparable in three-dimensional dynamic analysis of CT scans and radiographs representing FAI caused by cam or pincer type morphology. IV

Abstract Purpose Patients with Hirayama disease (HD) present with a larger range of neck flexion and show signs of cervical spine instability. Cervical spine stability largely relies on cervical spine muscles. The purpose of this study was to compare the cross-sectional areas (CSAs) of cervical spine muscles between patients with HD and healthy controls, providing some insights into whether there is cervical spine muscle weakness and incongruence in HD patients. Methods In this retrospective study, cervical spine muscles CSAs of 44 HD patients, as well as that of 44 age- and sex-matched healthy counterparts, were measured on the T2-weighted axial MR images. The ratios of cervical spine muscles CSA to the corresponding vertebral body areas, defined as R-CSAs, and the flexor/extensor CSA ratios were computed and compared between two groups. Results Compared with healthy counterparts, R-CSAs of total cervical spine muscles, total extensors, superficial extensors, and deep flexors were significantly lower in HD patients. HD patients also demonstrated a significantly greater superficial flexor/superficial extensor CSA ratio than the healthy counterparts, indicating a mismatch between superficial flexors CSA and superficial extensors CSA in HD patients. Conclusions In this pioneering study, HD patients had decreased size in most cervical spine muscles and a mismatch between CSAs of superficial flexor and that of superficial extensors. These results indicate generalized weakness and incongruence of cervical spine muscles, which may predispose cervical spine of HD patients to a less stable situation. Graphic abstract These slides can be retrieved under Electronic Supplementary Material.

Distal radius and ulna (DRU) classification scheme has been proposed for predicting skeletal maturity in patients with idiopathic scoliosis (IS). However, the utilization of DRU classification scheme in the assessment of growth peak and curve progression in IS was still inconclusive. This study aimed to correlate the distal radius and ulna stages with several indicators for growth potential and to evaluate the predictive value of DRU system for curve progression in braced female IS patients.

Background Patients with chronic kidney disease (CKD) are at high risk for fracture. The ability of bone mineral density (BMD) to predict fractures in CKD patients has been inconsistent. Other measures such as trabecular bone score (TBS) and impact microindentation (IMI) may be more useful in this group. This study aimed to determine if TBS or IMI values differed between men with and without CKD and examine associations between prior fracture, TBS and IMI values. Methods Men (n = 343, age 33–96 yr) from the Geelong Osteoporosis Study were included. Femoral neck (FNBMD) and lumbar spine BMD (LSBMD) were measured using DXA (Lunar ProdigyPro). TBS was determined from lumbar spine scans (TBS iNsight software Version 2.2). IMI values (bone material strength index; BMSi) were measured using an OsteoProbe. CKD was defined as an eGFR<60 mL/min/1.73m2 (n = 53). Prior low trauma fractures (n = 37) were ascertained from radiological reports. Associations were examined using binary logistic regression, adjusting for potential confounders. Interaction terms were tested in all models. Results Men with CKD tended to have a higher likelihood of prior fracture (adjusted OR 2.27, 95%CI 1.02–5.01). Higher BMSi was associated with a lower likelihood of prior fracture (adjusted OR for 1SD increase: 0.70; 95%CI 0.51–0.97). This association was sustained after adjustment for FNBMD (OR 0.68; 95%CI 0.49–0.96) or LSBMD (OR 0.69; 95%CI 0.49–0.95). No interaction was detected between BMSi and CKD (p = 0.898). No associations were detected between FNBMD, LSBMD or TBS and prior fracture in either population and there were no interactions with CKD for FNBMD, LSBMD or TBS. Conclusions BMSi was associated with prior fracture in men with and without CKD, however, FNBMD, LSBMD and TBS were not. Lack of an interaction term suggests that BMSi performed similarly in identifying the likelihood of prior fracture, regardless of CKD status. IMI may have clinical utility for assessing fracture risk in patients with CKD.

This study aimed to explore the effect of the treatment through autologous fibula graft and hollow needle fixation to treat femoral head cutting after dynamic hip screw (DHS) fixation. A total of 41 patients were admitted to the department of orthopedic trauma and received DHS fixation. Preoperative and postoperative harris score of hip function, limb shortening length and collodiaphysial angle between operation group (n = 11) and non-operation group (n = 13) were compared. There was no difference between the two groups before surgery (P > 0.05). There was a difference between the preoperative and postoperative in the operation group (P < 0.05). The excellent and good rate of the hip function score in patients 6 months after the operation was 55.6%. In the operation group, the hip function score increased after surgery (P < 0.001). Except for two groups of patients before operation, there was a difference in the limb shortening length and collodiaphysial angle between the operation group and non-operation group in other time points after surgery (P < 0.001). The application of the autogenous fibula graft and hollow nail fixation was effective in treating femoral head cutting after DHS fixation, and patients’ subjective evaluation and objective indicators’ outcomes of follow up were satisfactory, which was worthy of clinical application.

Limb salvage for bone sarcoma around the knee in skeletally immature children is challenging because of interference on two critical growth plates in the lower limb. This retrospective study aims to evaluate long-term outcomes and influence on growth of the lower limb of the cemented extendible endoprostheses. Forty-five children with bone sarcoma around the knee, who underwent custom-made extendible endoprosthesis replacements, were included in this study. The average follow-up was 10.1 years. Survival, prosthetic-related complications and revision, functional outcomes, and influence on growth by prosthesis implantation were recorded. The 5-year disease-free survival and overall survival are 54.9% and 72.7%, and the 5-year prosthesis survival rate is 59.4%. The prosthesis was extended 4.2 cm in average. Limb length discrepancies of 20 patients were within 2 cm, and growth inhibition of proximal tibial epiphysis by passive implant insertion was observed. Aseptic loosening in 7 patients was the most significant complication. The Musculoskeletal Tumor Society score at last visit was 83.2%. The use of custom-made extendible endoprosthesis provided good functional results for children with bone tumor around the knee. Further improvement of the prosthesis design and operation technique will help to decrease complication and gain better limb function.

Approximately 300 mg of calcium a day is provided into infants to maintain the physical development of infants, and 5 to 10% bone loss occurs in women during breastfeeding. Hip fractures are considered the most serious type of osteoporotic fracture. We performed this meta-analysis to investigate the association between breastfeeding and osteoporotic hip fractures. PubMed and Embase were searched until May 1, 2019, for studies evaluating the relationship between breastfeeding and osteoporotic hip fracture in women. The quality of the included studies was evaluated by the methodological index for non-randomized studies (MINORS). For the dose-response meta-analysis, we used the “generalized least squares for trend estimation” method proposed by Greenland and Longnecker to take into account the correlation with the log RR estimates across the duration of breastfeeding. Seven studies were moderate or high quality, enrolling a total of 103,898 subjects. The pooled outcomes suggested that breastfeeding can decrease the incidence of osteoporotic hip fracture (RR = 0.64 (95% CI 0.43, 0.95), P = 0.027). Dose-response analysis demonstrated that the incidence of osteoporotic hip fracture decreased with the increase of breastfeeding time. The RR and 95% CI for 3 months, 6 months, 12 months, and 24 months were RR = 0.93, 95% CI 0.88, 0.98; RR = 0.87, 95% CI 0.79, 0.96; RR = 0.79, 95% CI 0.67, 0.92; and RR = 0.76, 95% CI 0.59, 0.98, respectively, whereas no significant relationship was found between them when the duration of breastfeeding time was more than 25 months. Our meta-analysis demonstrated that the incidence of osteoporotic hip fracture decreased with the extension of breastfeeding time. However, there is no significant relationship between them when the duration of breastfeeding time was more than 25 months.

Human adipose-derived Mesenchymal stem cells (HADMSCs) have proven their efficacy in treating osteoarthritis (OA), in earlier preclinical and clinical studies. As the tissue repairers are under the control of mechanical and biochemical signals, improving regeneration outcomes using such signals has of late been the focus of attention. Among mechanical stimuli, low-intensity pulsed ultrasound (LIPUS) has recently shown promise both in vitro and in vivo. This study will investigate the potential of LIPUS in enhancing the regeneration process of an osteoarthritic knee joint. This study involves a prospective, randomized, placebo-controlled, and single-blind trial based on the SPIRIT guidelines, and aims to recruit 96 patients initially diagnosed with knee osteoarthritis, following American College of Rheumatology criteria. Patients will be randomized in a 1:1:1 ratio to receive Intraarticular HADMSCs injection with LIPUS, Intraarticular HADMSCs injection with shame LIPUS, or Normal saline with LIPUS. The primary outcome is Western Ontario and McMaster Universities Index of OA (WOMAC) score, while the secondary outcomes will be other knee structural changes, and lower limb muscle strength such as the knee cartilage thickness measured by MRI. Blinded assessments will be performed at baseline (1 month prior to treatment), 1 month, 3 months, and 6 months following the interventions. This trial will be the first clinical study to comprehensively investigate the safety and efficacy of LIPUS on stem cell therapy in OA patients. The results may provide evidence of the effectiveness of LIPUS in improving stem cell therapy and deliver valuable information for the design of subsequent trials. This study had been prospectively registered with the Chinese Clinical Trials Registry. registration number: ChiCTR1900025907 at September 14, 2019.

Nonunion of femur fractures is a devastating disabling complication which is rare in children. The purpose of this study was to report the outcomes of treating infected femur nonunions in children by the Ilizarov fixator in one stage.

The purpose of this study was to investigate the subjective recovery from pregnancy-related pelvic girdle pain (PGP) during the first 6 weeks after delivery and to detect possible risk factors for a poor recovery.

Objective Abdominal obesity and type 2 diabetes are associated with insulin resistance and low bone turnover along with an increased fracture risk. The mode of action is poorly understood. The bone resorption marker, C-terminal telopeptide type 1 collagen (CTX), and to a lesser extent, the bone formation marker, Procollagen type 1 N-terminal propeptide (P1NP) appear to be inhibited by food consumption. The link between food consumption, insulin resistance and bone turnover remains to be clarified. Primarily we aimed to compare the postprandial CTX, P1NP and PTH responses by two frequently applied methods in assessing metabolic health; oral glucose tolerance test (OGTT) and mixed meal tolerance test. Secondly, we explored the effect of insulin resistance on bone marker responses. Methods We enrolled 64 subjects with abdominal obesity. Following 10 h of fasting, subjects initially underwent a standard OGTT (300 kcal) and approximately one week later a mixed meal tolerance test (1130 kcal). Circulating CTX, P1NP and PTH were assessed on both days at time = 0, after 30 min and after 90 min for comparison of the two interventions. We analyzed glucose and insulin levels for the assessment of insulin resistance. Additionally, we measured plasma calcium levels along with the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide 2 (GLP-2) in an attempt to identify possible mediators of the postprandial bone response. Results CTX, P1NP and PTH were suppressed by OGTT and the mixed meal; the latter induced a more pronounced suppression after 90 min. Calcium levels were similar between OGTT and meal. GIP and GLP-2 levels increased after both interventions, although only the meal induced a sustained increase after 90 min. Fasting P1NP was inversely associated with insulin resistance. The meal-induced suppression of P1NP (but not CTX or PTH) was inversely associated with level of insulin resistance. Conclusion The acute postprandial suppression of bone turnover markers is extended after ingestion of a mixed meal compared to an OGTT. The response appears to be independent of gender and prompted by a reduction in PTH. The study additionally indicates a possible link between the development of insulin resistance and low bone turnover — which may be of key essence in the development of the fragile bone structure and increased fracture risk demonstrated in subjects with abdominal obesity and T2D.

The acetabular index (AI) is the most commonly used parameter for diagnosing hip dysplasia. Pelvic malposition can result in misinterpretation of AI measurement especially in younger children. We aimed to investigate the correlation between pelvic orientation and acetabular index (AI) by using digital reconstructed radiographs (DRRs) and identify reliable parameters predictive of pelvic orientation on plain radiographs. We retrospectively identified 33 children (52 hips) who received dual source CT examinations. Virtual pelvic models were reconstructed after scanning. After orientating in the standard neutral position, the models were rotated and tilted around corresponding axes. DRRs were generated at every 3° during the process. The acetabular index, the horizontal diameter (Dh) and vertical diameter (Dv) of bilateral obturator foramina, the vertical distance (h) between upper border of pubic symphysis, and Hilgenreiner’s line were measured on each DRR by two independent observers. Rotation index (Rr = right Dh/left Dh), tilt index (Rt = h/Dv), intra-observer error, and inter-observer error of AI were calculated. For tilt and rotation up to 12.0°, AI increased with anterior tilt and decreased with posterior tilt. And for rotation, it increased on the side toward which the pelvis rotated and decreased on the opposite side. AI varied dramatically if angulation exceeded 6.0°. Malposition below this limit demonstrated the intra- and inter-observer errors were ± 2.0° and ± 3.0° respectively and caused no significant effect on AI measurement. For children up to age 6 years, an acceptable pelvic plain radiograph can be determined when Rt is approximately between 0.9 and 1.4 and Rr between 0.7 and 1.5. For the first time, we have identified parameters derived from a group of subjects which can predict this degree of malposition. The parameters obturator diameters (Dh), obturator height (Dv), and distance (h) between symphysis and Hilgengreiner’s line can be feasibly measured on X-ray and employed in clinical practice to assess the acceptability of the pediatric pelvic radiograph prior to measurement of the AI.

Spinal surgery performed entirely with minimally invasive surgery is referred to as circumferential MIS (cMIS). However, cMIS still has a limited sagittal correction capability for adult spinal deformity (ASD) with a marked sagittal deformity. We investigated the effectiveness of cMIS using oblique lateral interbody fusion (OLIF) and percutaneous posterior spine fixation in correcting marked sagittal deformity. This study retrospectively evaluated 23 patients with ASD with marked sagittal deformity who underwent cMIS using OLIF without osteotomy and were followed-up for at least 24 months (whole group). The whole group was divided into the following two groups according to the type of interbody fusion at L5–S1: the OLIF51 group (n = 13) underwent OLIF at L1–L5 and L5–S1 and the TLIF51 group (n = 10) underwent OLIF at L1–L5 and transforaminal lumbar interbody fusion (TLIF) at L5–S1. Sagittal vertebral axis (SVA; 125.7 vs. 29.5 mm, p < 0.001), lumbar lordosis (LL; 18.2° vs. 51.7°, p < 0.001), and pelvic incidence-LL mismatch (PI-LL, 35.5° vs. 5.3°) significantly improved postoperatively in the whole group. The OLIF51 group showed significantly higher postoperative LL than the TLIF51 group (55.5° vs. 46.9°, p < 0.001). OLIF yielded a significantly greater disc angle at L5–S1 than did TLIF (18.4° vs. 6.9°, p < 0.001). Proximal junctional kyphosis occurred significantly earlier in the OLIF51 group than in the TLIF51 group (8.6 vs. 26.3 months, p < 0.001). Successful sagittal correction in ASD patients with marked sagittal deformity was achieved with cMIS using OLIF. OLIF at L5–S1 showed a synergistic effect in sagittal deformity correction by cMIS.

There is some limited evidence for the presence of viruses in herniated disc material including a previous case series that claimed to provide “unequivocal evidence of the presence of herpes virus DNA in intervertebral disc specimens of patients with lumbar disc herniation suggesting the potential role of herpes viruses as a contributing factor to the pathogenesis of degenerative disc disease”. This study has not been replicated. The objective of our study was to determine if viruses were present in herniated disc fragments in participants with a prior history of back pain. We recruited fifteen participants with a history of prior low-back pain prior to undergoing disc herniation surgery in the lumbar spine. Harvested disc samples were subject to next generation sequencing for detection of both RNA and DNA viral pathogens. Additionally, samples were analysed by a broadly reactive PCR targeting herpesviral DNA. Ethics approval was granted by the Human Research Ethics Committees of both Murdoch University, and St John of God Hospital, Western Australia. Of the fifteen research participants, 8 were female. Mean age was 49.4 years (SD 14.5 yrs) with a range of 24–70 years. All participants had prior back pain with mean time since first ever attack being 8.8 years (SD 8.8 yrs). No samples contained significant DNA sequences relating to known human viral agents. Inconsequential retroviral sequences were commonly found and were a mixture of putative animal and human retroviral protein coding segments. All samples were negative for herpesvirus DNA when analysed by pan-herpesvirus PCR. This study found no viral pathogens in any intervertebral disc fragments of patients who had previous back pain and underwent discectomy for disc herniation and thus it is unlikely that viruses are associated with disc herniation, however given the contradiction between key studies enhanced replication of this experiment is recommended.

Osteotomies in the cervical spine are technically challenging. The purpose of this study was to evaluate the feasibility of the modified pedicle subtraction osteotomy (PSO) technique at C7 to be used for the treatment of cervicothoracic kyphosis secondary to ankylosing spondylitis. A total of 120 cervical spine computed tomography (CT) scans (of 82 male and 38 female patients) were evaluated. The scans were taken parallel to the middle sagittal plane and the sagittal plane intersecting the pedicles. Simulated osteotomy was performed by setting the apex of the wedge osteotomy at different points, and morphologic measurements were obtained. Seven patients with cervicothoracic kyphosis who underwent a modified PSO at C7 between May 2009 and June 2015 were retrospectively evaluated. The mean follow up was 32.9 months (range 21–54 months). Preoperative and postoperative chin-brow vertical angle (CBVA), sagittal vertical axis (SVA) and sagittal Cobb angle of the cervical region were reviewed. The outcomes were analyzed through various measures, which included the 36-Item Short Form Health Survey (SF-36) and a visual analog scale for neck pain. In this morphometric study, a modified PSO was performed on 87 patients (59 male and 28 female) with a reasonable ratio of 72.5%. In the case series, radiographic parameters and health-related quality-of-life measures were found to show significant postoperative improvement in all patients. No major complications occurred, and no implant failures were noted until the latest follow up. The modified PSO is a safe and valid alternative to the classic PSO, allowing for excellent correction of cervical kyphosis and improvement in health-related quality-of-life measures.

Total knee arthroplasty is a common procedure with generally good results. However, there are still patients who are dissatisfied without known explanation. Satisfaction and dissatisfaction have previously been captured by quantitative designs, but there is a lack of qualitative studies regarding these patients’ experiences. Qualitative knowledge might be useful in creating strategies to decrease the dissatisfaction rate. Of the 348 patients who responded to a letter asking if they were satisfied or dissatisfied with their surgery, 61 (18%) reported discontent. After excluding patients with documented complications and those who declined to participate, semi-structured interviews were conducted with 44 patients. The interviews were analyzed according to qualitative content analysis. The purpose was to describe patients’ experiences of discontentment 1 year after total knee arthroplasty. The patients experienced unfulfilled expectations and needs regarding unresolved and new problems, limited independence, and lacking of relational supports. They were bothered by pain and stiffness, and worried that changes were complications as a result of surgery. They described inability to perform daily activities and valued activities. They also felt a lack of relational supports, and a lack of respect and continuity, support from health care, and information adapted to their needs. Patient expectation seems to be the major contributing factor in patient discontentment after knee replacement surgery. This qualitative study sheds light on the on the meaning of unfulfilled expectations, in contrast to previous quantitative studies. The elements of unfulfilled expectations need to be dealt with both on the individual staff level and on the organizational level. For instance, increased continuity of healthcare staff and facilities may help to improve patient satisfaction after surgery.

There is no available literature for comparison on muscle atrophy between the “stand-alone” oblique lateral interbody fusion (OLIF) and regular OLIF (i.e., combined with percutaneous pedicle screws fixation (PPSF) in patients with spondylolisthesis). This study aimed to identify changes in back muscle atrophy between the two surgeries. This was a retrospective cohort study of patients who underwent OLIF or OLIF+PPSF at Beijing Jishuitan Hospital and Shanghai ChangZheng Hospital between 07/2014 and 10/2017. Computed tomography (CT) was used to measure functional cross-sectional area (FCSA) and fat infiltration percentage (FIP) of the multifidus and erector spinae before and 24 months after surgery. There were no differences in FCSA and FIP between OLIF (n = 32) and OLIF+PPSF (n = 41) groups before surgery. In the OLIF group, the multifidus and erector spinae FCSA and FIP did not change at 24 months (FCSA: multifidus: from 8.59 ± 1.76 to 9.39 ± 1.74 cm2, P = 0.072; erector spinae: from 13.32 ± 1.59 to 13.55 ± 1.31 cm2, P = 0.533) (FIP: multifidus: from 15.91 ± 5.30% to 14.38 ± 3.21%, P = 0.721; erector spinae: from 11.63 ± 3.05% to 11.22 ± 3.12%, P = 0.578). In the OLIF+PPSF group, the multifidus and erector spinae FCSA decreased (multifidus: from 7.72 ± 2.69 to 5.67 ± 1.71 cm2, P < 0.001; erector spinae: from 12.60 ± 2.04 to 10.15 ± 1.82 cm2, P < 0.001), while the FIP increased (multifidus: from 16.13 ± 7.01% to 49.38 ± 20.54%, P < 0.001; erector spinae: from 11.93 ± 3.22% to 22.60 ± 4.99%, P < 0.001). The differences of FCSA and FIP between the two groups at 24 months were significant (all P < 0.001). The patients in the standalone OLIF group had better VAS back pain, and JOA scores than the patients in the OLIF combined group (all P < 0.05) at 1 week and 3 months after surgery. There were two cases (4.9%) of adjacent segment degeneration in the OLIF combined group, while there was no case in the OLIF alone group. Standalone OLIF had better clinical outcomes at 1 week and 3 months than OLIF+PPSF in patients with spondylolisthesis. OLIF may not result in paraspinal muscle atrophy at 24 months after surgery.

In highly active older individuals, end-stage ankle osteoarthritis has traditionally been treated using tibiotalar arthrodesis, which provides considerable pain relief. However, there is a loss of ankle joint movement and a risk of future arthrosis in the adjacent joints. Distraction arthroplasty is a simple method that allows joint cartilage repair; however, the results are currently mixed, with some reports showing improved pain scores and others showing no improvement. Distal tibial osteotomy (DTO) without fibular osteotomy is a type of joint preservation surgery that has garnered attention in recent years. However, to our knowledge, there are no reports on DTO with joint distraction using a circular external fixator. Therefore, the purpose of this study was to examine the effect of DTO with joint distraction using a circular external fixator for treating ankle osteoarthritis. A total of 21 patients with medial ankle arthritis were examined. Arthroscopic synovectomy and a microfracture procedure were performed, followed by angled osteotomy and correction of the distal tibia; the ankle joint was then stabilized after its condition improved. An external fixator was used in all patients, and joint distraction of approximately 5.8 mm was performed. All patients were allowed full weight-bearing walking immediately after surgery. The anteroposterior and lateral mortise angle during weight-bearing, talar tilt angle, and anterior translation of the talus on ankle stress radiography were improved significantly (P < 0.05). Signal changes on magnetic resonance imaging also improved in all patients. Visual analog scale and American Orthopedic Foot & Ankle Society scores improved significantly (P < 0.05), and no severe complications were observed. DTO with joint distraction may be useful as a joint-preserving surgery for medial ankle osteoarthritis in older patients with high levels of physical activity. Level IV, retrospective case series.

To clarify the risk factors for subsidence of titanium mesh cage (TMC) following single-level anterior cervical corpectomy and fusion (ACCF) to reduce subsidence. The present retrospective cohort study included 73 consecutive patients who underwent single-level ACCF. Patients were divided into subsidence (n = 31) and non-subsidence groups (n = 42). Medical records and radiological parameters such as age, sex, operation level, segmental angle (SA), cervical sagittal angle (CSA), height of anterior (HAE) and posterior endplate (HPE), ratio of anterior (RAE) and posterior endplate (RPE), the alignment of TMC, the global cervical Hounsfield Units (HU) were analyzed. Clinical results were evaluated using the Japanese Orthopedic Association (JOA) scoring system and the Visual Analog Scale (VAS). Subsidence occurred in 31 of 73 (42.5%) patients. Comparison between the groups showed significant differences in the value of RAE, the alignment of TMC and the global cervical HU value (p < 0.001, p = 0.002, p < 0.001). In multivariate logistic regression analysis, RAE > 1.18 (OR = 6.116, 95%CI = 1.613–23.192, p = 0.008), alignment of TMC > 3° (OR = 5.355, 95%CI = 1.474–19.454, p = 0.011) and the global cervical HU value< 333 (OR = 11.238, 95%CI = 2.844–44.413, p = 0.001) were independently associated with subsidence. Linear regression analysis revealed that RAE is significantly positive related to the extent of subsidence (r = − 0.502, p = 0.006). Our findings suggest that the value of RAE more than 1.18, alignment of TMC and poor bone mineral density are the risk factors for subsidence. TMC subsidence does not negatively affect the clinical outcomes after operation. Avoiding over expansion of intervertebral height, optimizing placing of TMC and initiation of anti-osteoporosis treatments 6 months prior to surgery might help surgeons to reduce subsidence after ACCF.

Human cadaveric study has indicated that the metacarpal head (MCH) is intracapsular in location. We hypothesized that exposure to the intra-articular inflammatory milieu in psoriatic arthritis (PsA) will lead to bone loss in the MCH.

Abstract Summary There is controversy over whether African Americans have higher vitamin D requirements than recommended by the Institute of Medicine. We previously reported that maintaining serum 25(OH)D above 30 ng/mL does not prevent age-related bone loss. Herein, we report that bone strength is also unaffected by maintaining this level in this population. Introduction The role of vitamin D in bone strength has not been investigated in the African American (AA) population. Methods A 3-year randomized controlled trial was designed to examine the effect of vitamin D supplementation on physical performance, bone loss, and bone strength in healthy older AA women. A total of 260 postmenopausal AA women, ages ≥ 60 years were randomized to a vitamin D3 or placebo arm. Vitamin D3 dose was adjusted to maintain serum 25OHD > 30 ng/mL. Bone mineral density, femoral axis length, and femoral neck (FN) width were measured by dual-energy X-ray absorptiometry. Composite indices of FN strength [compression strength index (CSI), bending strength index (BSI), and impact strength index (ISI)] were computed. Results The mean age of participants was 68.2 ± 4.9 years. Baseline characteristics between groups were similar. The average dose of vitamin D3 was 3490 ± 1465 IU/day in the active group. The mean serum 25OHD was 46.8 ± 1.2 ng/mL versus 20.7 ± 1.1 ng/mL in the active versus placebo group. Serum 25OHD did not correlate with any composite indices. The longitudinal differences observed in FN width, CSI, BSI, and ISI in both groups were not statistically significant (all p values > 0.05). Further, there was no group × time interaction effect for any of the composite indices (all p values > 0.05). Conclusion Maintaining serum 25OHD > 30 ng/mL (75 nmol/L) does not affect bone strength in older AA women. There is no evidence to support vitamin D intake greater than the recommended RDA by the Institute of Medicine in this population for bone strength.

Abstract Purpose Chlorhexidine showers prior to shoulder arthroplasty are commonly recommended by surgeons to lower the risk of periprosthetic infection; however, the effectiveness of these washes in eliminating bacteria from the skin of the shoulder has not been thoroughly evaluated. The objective of this study was to determine the degree to which pre-operative chlorhexidine washes effectively eliminate bacteria from the epidermal skin surface and from the dermis freshly incised during shoulder arthroplasty. Methods Around 66 patients undergoing primary shoulder arthroplasty were instructed to shower with chlorhexidine before surgery. Each patient had three skin swabs: (1) the epidermis at a pre-operative clinic appointment, (2) the epidermis at surgery after home chlorhexidine showers but prior to skin preparation, and (3) the dermis after incision of the prepared skin. The bacterial loads of Cutibacterium and other bacterial types from each swab were compared to determine whether the showers were effective in altering the bacterial loads. Results Chlorhexidine washes were effective in reducing the skin load of other bacterial species (p < 0.005), but they did not decrease the skin load of Cutibacterium (p = 0.585). Conclusions Pre-operative skin showers with chlorhexidine were not effective in reducing the load of Cutibacterium on the skin of patients having shoulder arthroplasty. Since Cutibacterium is responsible for the highest percentage of shoulder periprosthetic infections, research is needed to identify more effective means of removing these bacteria from the surgical field.

Unfortunately, the following reference was missed out in the original publication.

DHS is characterized by chin-on-chest deformity and devastatingly impedes activities of daily living in affected individuals. There is a paucity of literature about the pathophysiology of DHS including knowledge about spinal sagittal alignment. We conducted this study to clarify the relationship between cervical sagittal alignment and global sagittal balance in DHS.

Abstract Purpose Patients with low back pain (LBP) rarely have serious underlying pathology but frequently undergo inappropriate imaging. A range of guidelines and red flag features are utilised to characterise appropriate imaging. This scoping review explores how LBP imaging appropriateness is determined and calculated in studies of primary care practice. Methods This scoping review builds upon a previous meta-analysis, incorporating articles identified that were published since 2014, with an updated search to capture articles published since the original search. Electronic databases were searched, and citation lists of included papers were reviewed. Inclusion criteria were studies assessing adult LBP imaging appropriateness in a primary care setting. Twenty-three eligible studies were identified. Results A range of red flag features were utilised to determine imaging appropriateness. Most studies considered appropriateness in a binary manner, by the presence of any red flag feature. Ten guidelines were referenced, with 7/23 (30%) included studies amending or not referencing any guideline. The method for calculating the proportion of inappropriate imaging varied. Ten per cent of the studies used the total number of patients presenting with LBP as the denominator, suggesting most studies overestimated the rate of inappropriate imaging, and did not capture where imaging is not performed for clinically suspicious LBP. Conclusion Greater clarity is needed on how we define and measure imaging appropriateness for LBP, which also accounts for the problem of failing to image when indicated. An internationally agreed methodology for imaging appropriateness studies would ultimately lead to an improvement in the care delivered to patients. Graphic abstract These slides can be retrieved under Electronic Supplementary Material.

To analyze pelvic compensation during walking in patients with severe sagittal plane deformity by using motion analysis.

This is a retrospective, single-institution, cohort study.

The purpose of this study was to evaluate the association between epidemiological, clinical and radiographic factors of patients with tibial shaft fractures and the occurrence of acute compartment syndrome. 270 consecutive adult patients sustaining 273 tibial shaft fractures between January 2005 and December 2009 were included in this retrospective cohort study. The outcome measure was acute compartment syndrome. Patient-related (age, sex), fracture-related (high- vs. low-energy injury, isolated trauma vs. polytrauma, closed vs. open fracture) and radiological parameters (AO/OTA classification, presence or absence of a noncontiguous tibial plateau or pilon fracture, distance from the centre of the tibial fracture to the talar dome, distance between tibial and fibular fracture if associated, and angulation, translation and over-riding of main tibial fragments) were evaluated regarding their potential association with acute compartment syndrome. Univariate analysis was performed and each covariate was adjusted for age and sex. Finally, a multivariable logistic regression model was built, and odds ratios and 95% confidence intervals were obtained. Statistical significance was defined as p < 0.05. Acute compartment syndrome developed in 31 (11.4%) cases. In the multivariable regression model, four covariates remained statistically significantly associated with acute compartment syndrome: polytrauma, closed fracture, associated tibial plateau or pilon fracture and distance from the centre of the tibial fracture to the talar dome ≥15 cm. One radiological parameter related to the occurrence of acute compartment syndrome has been highlighted in this study, namely a longer distance from the centre of the tibial fracture to the talar dome, meaning a more proximal fracture. This observation may be useful when clinical findings are difficult to assess (doubtful clinical signs, obtunded, sedated or intubated patients). However, larger studies are mandatory to confirm and refine the prediction of acute compartment syndrome occurrence. Radiographic signs of significant displacement were not found to be correlated to acute compartment syndrome development. Finally, the higher rate of acute compartment syndrome occurring in tibial shaft fractures associated to other musculoskeletal, thoraco-abdominal or cranio-cerebral injuries must raise the level of suspicion of any surgeon managing multiply injured patients.

It has been reported that miR-93-5p and long non-coding RNA (lncRNA) Cancer Susceptibility 2 (CASC2) play opposite roles in regulating chondrocyte apoptosis, indicating the possible interaction between them. This study aimed to investigate the interaction between miR-93-5p and lncRNA CASC2 in chondrocyte apoptosis, which plays critical roles in osteoarthritis (OA). The interaction between CASC2 and miR-93-5p was analyzed by dual luciferase assay and overexpression experiments. Levels of CASC2 and miR-93-5p in plasma sample from OA patients and healthy controls were measured by RT-qPCR. The roles of CASC2 and miR-93-5p in regulating the apoptosis of chondrocyte induced by LPS were analyzed by cell apoptosis assay. Through bioinformatics analysis we observed the potential interaction between CASC2 and miR-93-5p, which was confirmed by dual luciferase assay. In OA patients, miR-93-5p was downregulated, while CASC2 was upregulated, and they were inversely correlated. LPS treatment led to downregulated miR-93-5p and upregulated CASC2. Overexpression of miR-93-5p led to the downregulated CASC2 in chondrocytes. Under LPS treatment, CASC2 overexpression promoted the apoptosis of chondrocyte. MiR-93-5p overexpression played an opposite role and attenuated the effects of CASC2 overexpression. MiR-93-5p was downregulated in OA may inhibit LPS-induced chondrocyte apoptosis by targeting lncRNA CASC2.

Pseudohypoparathyroidism type 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP) are two rare autosomal dominant disorders caused by loss‐of‐function mutations in the imprinted Guanine Nucleotide Binding Protein, Alpha Stimulating Activity (GNAS) gene, coding Gsα. PHP1A is caused by mutations in the maternal allele and results in Albright's hereditary osteodystrophy (AHO) and hormonal resistance, mainly to the parathormone (PTH), whereas PPHP, with AHO features and no hormonal resistance, is linked to mutations in the paternal allele. This study sought to investigate parental transmission of GNAS mutations. We conducted a retrospective study in a population of 204 families with 361 patients harboring GNAS mutations. To prevent ascertainment bias toward a higher proportion of affected children due to the way in which data were collected, we excluded from transmission analysis all probands in the ascertained sibships. After bias correction, the distribution ratio of the mutated alleles was calculated from the observed genotypes of the offspring of nuclear families and was compared to the expected ratio of 50% according to Mendelian inheritance (one‐sample Z‐test). Sex ratio, phenotype of the transmitting parent, and transmission depending on the severity of the mutation were also analyzed. Transmission analysis was performed in 114 nuclear families and included 250 descendants. The fertility rates were similar between male and female patients. We showed an excess of transmission from mother to offspring of mutated alleles (59%, p = .022), which was greater when the mutations were severe (61.7%, p = .023). Similarly, an excess of transmission was found when the mother had a PHP1A phenotype (64.7%, p = .036). By contrast, a Mendelian distribution was observed when the mutations were paternally inherited. Higher numbers of females within the carriers, but not in noncarriers, were also observed. The mother‐specific transmission ratio distortion (TRD) and the sex‐ratio imbalance associated to PHP1A point to a role of Gsα in oocyte biology or embryogenesis, with implications for genetic counseling. © 2019 American Society for Bone and Mineral Research.

Many individuals with spinal cord injury (SCI) rely on wheelchairs as their primary mode of locomotion leading to reduced weight-bearing on the lower extremities, which contributes to severe bone loss and increased risk of fragility fractures. Engaging in a walking program may reverse this vicious cycle, as this promotes lower extremity weight-bearing and mobility, which may reduce bone loss and fragility fracture risk. However, fragility fracture risk associated with the use of wearable robotic exoskeletons (WREs) in individuals with SCI needs consideration. A 35-year-old man with chronic complete sensorimotor SCI (neurological level = T6) and low initial bone mineral density enrolled in a 6- to 8-week WRE-assisted walking program after successfully completing an initial clinical screening process and two familiarization sessions with the WRE. However, after the first training session with the WRE, he developed bilateral localized ankle edema. Training was suspended, and a CT-scan revealed bilateral calcaneal fractures, which healed with conservative treatment over a 12-week period. Opportunities for improving clinical screening and WRE design are explored. The relevance of developing clinical practice guidelines for safe initiation and progression of intensity during WRE-assisted walking programs is highlighted. This case of bilateral calcaneal fractures illustrates that aiming for “zero risk” during WRE-assisted walking programs may not be realistic. Although WREs are a relatively new technology, current evidence confirms their potential to greatly improve health and quality of life in individuals with chronic SCI. Hence, ensuring their safe use remains a key priority.

Atypical femoral fractures are burdened with a high rate of reoperation. In our nationwide analysis, the increased rate of reoperation was related to patient background characteristics, such as age and health status, rather than fracture type.

Patients with various and indefinite symptoms in the whole body occasionally have coincident with stiffness or tenderness of the cervical muscles. This prospective case series examined the effect of local modulation of the cervical muscles in patients with cervical disorders reporting indefinite whole-body symptoms.

Context Pheochromocytoma (PHEO) and paraganglioma (PGL) (PHEO and PGL: PPGLs) are catecholamine-producing neuroendocrine tumors, which are known to be associated with low bone mineral density (BMD). However, it remains unknown whether PPGLs are associated with high prevalence of osteoporotic fracture and if so, whether their surgical resection improves BMD has been addressed. Objective To evaluate the risk of vertebral fracture (VF) in PPGLs and the improvement of BMD after surgery. Design and settings A retrospective cross-sectional study in a single referral center. Participants This study included the following patients: 1) 49 patients with PPGLs and 61 patients with non-functional AT who were examined radiograph of the spine, 2) 23 patients with PPGLs who were examined BMD at follow-up. Intervention 1) The prevalence of VF was evaluated between PPGLs and non-functional AT. 2) In PPGLs, BMD was evaluated at baseline and after surgery. Results PPGLs had a higher prevalence of VF (43% [21/49]) than non-functional AT (16% [10/61]; p = 0.002). PPGLs were associated with VF after adjusting for age and sex (odds ratio, 4.47; 95% confidence interval, 1.76–11.3; p = 0.001). In PPGLs, BMD at the lumber spine was improved (before: 0.855 ± 0.198 g/cm2, after: 0.888 ± 0.169 g/cm2, mean of the difference: 0.032 g/cm2, p = 0.026), with 3.8% increase. Conclusion This study demonstrates that PPGLs was associated with VF and that their surgical resection contributes to the improvement of BMD in the trabecular bone. These observations support the notion that PPGLs are an emerging cause of secondary osteoporosis.

Objective This multicenter study aimed to evaluate the association between volumetric bone mineral density (vBMD) and abdominal aortic calcification (AAC) in a Chinese population. Methods Quantitative computed tomography (QCT) and Agatston score (AS) were used to measure vBMD and AAC, respectively, in 3457 participants during 2013–2017. The association between vBMD and AAC was assessed using multivariate regression analysis, adjusted for age, residence, education, body mass index, and other cardiovascular risk factors. Results The mean age of women and men was 61.4 and 62.7 years, respectively. In total, 30.4% of women and 37.7% of men were found to have AAC. After full adjustment, higher vBMD was associated with lower AAC score (β, −0.095; 95% confidence interval [CI], −0.167 to −0.024; P = 0.0087) and lower AAC prevalence (odds ratio [OR], 0.873; 95% CI, 0.824 to 0.924; P < 0.0001) in men. Inverse trends were also observed in the association of vBMD quartile with AAC severity (lowest vs highest quartile; β = 0.235; 95% CI, 0.011 to 0.459; Ptrend < 0.0001) and AAC prevalence (lowest vs highest quartile; OR = 1.329; 95% CI, 1.087 to 1.625; Ptrend < 0.0001) in men. However, no significant result was obtained in women, except for the association between quartiles of vBMD and AAC score. Conclusions In our study, vBMD was inversely associated with AAC among men independent of age and shared risk factors. However, the association was not significant among women.

This paper introduces a theoretical framework for the study of the efficacy of romosozumab, a humanized monoclonal antibody targeting sclerostin for the treatment of osteoporosis. We developed a comprehensive mechanistic pharmacokinetic-pharmacodynamic (PK-PD) model of the effect of drug treatment on bone remodeling in postmenopausal osteoporosis (PMO). We utilized a one-compartment PK model to represent subcutaneous injections of romosozumab and subsequent absorption into serum. The PD model is based on a recently-developed bone cell population model describing the bone remodeling process at the tissue scale. The latter accounts for mechanical feedback via incorporating nitric oxide (NO) and sclerostin (Scl) as biochemical feedback molecules. Utilizing a competitive binding model, where Wnt and Scl compete for binding to LRP5/6, allows to regulate anabolic bone remodeling responses. Here, we extended this model with respect to romosozumab binding to sclerostin. For the currently approved monthly injections of 210 mg, the model predicted a 6.59%, 10.38% and 15.25% increase in BMD at the lumbar spine after 6, 12 and 24 months, respectively. These results are in good agreement with the data reported in the literature. Our model is also able to distinguish the bone-site specific drug effects. For instance, at the femoral neck, our model predicts a BMD increase of 3.85% after 12 months of 210 mg injections, which is consistent with literature observations. Finally, our simulations indicate rapid bone loss after treatment discontinuation, indicating that some additional interventions such as use of bisphosphonates are required to maintain bone.

Bone mineral density of the humeral head is an independent determining factor for postoperative rotator cuff tendon healing. Bisphosphonates, which are commonly used to treat osteoporosis, have raised concerns regarding their relationships to osteonecrosis of the jaw and to atypical fracture of the femur. In view of the prevalence of rotator cuff tear in osteoporotic elderly people, it is important to determine whether bisphosphonates affect rotator cuff tendon healing. However, no studies have investigated bisphosphonates’ cytotoxicity to human rotator cuff tendon fibroblasts (HRFs) or bisphosphonates’ effects on rotator cuff tendon healing. The purpose of this study was to evaluate the cytotoxicity of alendronate (Ald), a bisphosphonate, and its effects on HRF wound healing. HRFs were obtained from human supraspinatus tendons, using primary cell cultures. The experimental groups were control, 0.1 μM Ald, 1 μM Ald, 10 μM Ald, and 100 μM Ald. Alendronate exposure was for 48 h, except during a cell viability analysis with durations from 1 day to 6 days. The experimental groups were evaluated for cell viability, cell cycle and cell proliferation, type of cell death, caspase activity, and wound-healing ability. The following findings regarding the 100 μM Ald group contrasted with those for all the other experimental groups: a significantly lower rate of live cells (p < 0.01), a higher rate of subG1 population, a lower rate of Ki-67 positive cells, higher rates of apoptosis and necrosis, a higher number of cells with DNA fragmentation, higher caspase-3/7 activity (p < 0.001), and a higher number of caspase-3 positive staining cells. In scratch-wound healing analyses of all the experimental groups, all the wounds healed within 48 h, except in the 100 μM Ald group (p < 0.001). Low concentrations of alendronate appear to have little effect on HRF viability, proliferation, migration, and wound healing. However, high concentrations are significantly cytotoxic, impairing cellular proliferation, cellular migration, and wound healing in vitro.

Lateral tibial split fractures (LTSF) usually require surgical therapy with screw or plate osteosynthesis. Excellent anatomical reduction of the fracture is thereby essential to avoid post-traumatic osteoarthritis. In clinical practice, a gap and step of 2 mm have been propagated as maximum tolerable limit. To date, biomechanical studies regarding tibial fractures have been limited to pressure measurement, but the relationship between dissipated energy (DE) as a friction parameter and reduction accuracy in LTSF has not been investigated. In past experiments, we developed a new method to measure DE in ovine knee joints. To determine weather non-anatomical fracture reduction with lateral gap or vertical step condition leads to relevant changes in DE in the human knee joint, we tested the applicability of the new method on human LTSFs and investigated whether the current limit of 2 mm gap and step is durable from a biomechanical point of view. Seven right human, native knee joint specimens were cyclically moved under 400 N axial load using a robotic system. During the cyclic motion, the flexion angle and the respective torque were recorded and the DE was calculated. First, DE was measured after an anterolateral approach had been performed (condition “native”). Then a LTSF was set with a chisel, reduced anatomically, fixed with two set screws and DE was measured (“even”). DE of further reductions was then measured with gaps of 1 mm and 2 mm, and a 2 mm step down or a 2 mm step up was measured. We successfully established a measurement protocol for DE in human knee joints with LTSF. While gaps led to small though statistically significant increase (1 mm gap:ΔDE compared with native = 0.030 J/cycle, (+ 21%), p = 0.02; 2 mm gap:ΔDE = 0.032 J/cycle, (+ 22%), p = 0.009), this increase almost doubled when reducing in a step-down condition (ΔDE = 0.058 J/cycle, (+ 56%), p = 0.042) and even tripled in the step-up condition (ΔDE = 0.097 J/cycle, (+ 94%), p = 0.004). Based on our biomechanical findings, we suggest avoiding step conditions in the daily work in the operating theatre. Gap conditions can be handled a bit more generously.

The direct anterior approach for total hip arthroplasty (THA) has specific advantages, but injury to the tensor fasciae lata muscle (TFLM) remains a concern. This injury in part negates some of the advantages of the intermuscular approach, because injury of the muscle fibers of the TFLM can lead to less satisfactory clinical results. Thus, in this study, we propose an intraoperative method to protect the TFLM and demonstrate its feasibility. Fifty-six patients undergoing THA by the direct anterior approach were divided randomly into two groups. In group A, the TFLM was protected by an autogenous tissue “pad” created from the anterior capsule of the joint which protect the TFLM from direct contact with the retractors. In group B, the operation was carried out with no protection of the TFLM except the attempt by the surgeons to consciously avoid injury of the TFLM. We evaluated magnitude of changes in the muscle cross-sectional area (MSCA) and fatty atrophy (FA) by magnetic resonance imaging. The differences in blood hemoglobin and serum levels of myoglobin, lactate dehydrogenase (LDH), and creatine phosphokinase (CPK) were compared at different time, postoperatively. The Harris hip score, postoperative drainage volume and visual analogue scores (VAS) were compared between the two groups. LDH, CPK and myoglobin in group B were significantly higher than group A at 8, 24, and 48 h after the surgery. (p < 0.05) Compared to the group A, the decrease of hemoglobin in group B displayed significantly at 24 and 48 h after surgery. (P < 0.05) The significantly increased MSCA and FA of TFLM were demonstrated in group B. The PDV and VAS in group B were significantly higher than group A. (P < 0.05) The Harris score in group A was significantly higher than group B (P < 0.05) one month after surgery, but there was no significant difference six months later. Using the anterior capsule of the hip joint as an autogenous, protective capsular tissue pad to limit the trauma to the TFLM during a direct anterior approach to THA is an effective method to protect the TFLM and improve the clinical effect. ChiCTR: ChiCTR1900025173. Retrospectively registered August 15, 2019.

The objective of this study is to investigate the prognostic values of median nerve strain and applied pressure measurement for the assessment of clinical recovery after carpal tunnel release. Forty-five wrists, from 45 idiopathic carpal tunnel syndrome patients who treated with open carpal tunnel release, were evaluated by ultrasound. Median nerve strain, pressure applied to the skin, and ratio of pressure-strain were measured at the proximal part of the carpal tunnel. In addition, distal latencies in the motor and sensory nerve conductions studies and cross-sectional area of median nerve were measured. The parameters were compared before and after the open carpal tunnel release. According to patient recovery, the receiver operating characteristic curves were generated to evaluate the prognostic values of the parameters. The areas under the receiver operating characteristic curves were compared among parameters. There was a significant increase in the median nerve strain, and significant decreases in the pressure applied to the skin and ratio of pressure-strain after carpal tunnel release (P < 0.01). There were significant decreases in the distal latencies and the cross-sectional area after carpal tunnel release (P < 0.01). The areas under the curves were 0.689, 0.773, 0.811, 0.668, 0.637, and 0.562 for the pressure, strain, pressure-strain ratio, motor latency, sensory latency, and area, respectively. The results suggest that elasticity of the median nerve and pressure around the nerve recover quickly after carpal tunnel release. Pressure-strain ratio was the most reliable parameter to reflect clinical recovery. The measurement of strain and applied pressure can be useful indicators to evaluate effectiveness of the carpal tunnel release. Registered as NCT04027998 at ClinicalTrials.gov. Retrospectively registered on July 22, 2019.

With ever-increasing numbers of patients undergoing elective total knee arthroplasty (TKA) and as TKA is performed in increasingly younger patients, patient demands and expectations have also increased. With improved patient outcomes, new PROMs with heightened discriminatory power in well-performing patients are needed. The present study aimed to translate and validate the Italian version of the Forgotten Joint Score (FJS-12) as a tool for evaluating pre-operative through longitudinal post-operative outcomes in an Italian population. In this prospective study, patients with unilateral osteoarthritis, undergoing TKA surgery between May 2015 and December 2017 were recruited to participate in the study. The FJS-12 and WOMAC were collected pre-operatively and at six and 12 months post-operatively. According to the COSMIN checklist, reliability, internal consistency, validity, responsiveness, effect size, and ceiling effects and floor effects were evaluated. One hundred twenty patients completed the study, 66 of which participated in the evaluation of test-retest reliability. Good test-retest reliability was found (ICC = 0.90). The FJS-12 also showed excellent internal consistency (Cronbach α = 0.81). Construct validity with the WOMAC, as a measure of the Pearson correlation coefficient, was moderate (r = 0.45 pre-operatively; r = 0.46 at 6 months and r = 0.42 at 12 months post-operatively). From six to 12 months, the change was slightly greater for the WOMAC than for the FJS-12 patients (effect size d = 0.94; d = 0.75, respectively). At 12-months follow-up, the ceiling effects reflecting the maximum score were 12% for the FJS-12 and 6% for the WOMAC; however, scores within 10% of the maximum score were comprised 30% of the FJS-12 scores and 59% for the WOMAC. The Italian FJS-12 demonstrated strong measurement properties in terms of reliability, internal consistency, and construct validity in TKA patients. Furthermore, a more detailed look at ceiling effects shows a superior discriminatory capacity when compared to the WOMAC at 12-months follow-up, particularly in better-performing patients. clinicaltrials.gov NCT03805490. Registered 18 January 2019 (retrospectively registered).

Subacromial decompression, that consists of the release of the coracoid-acromial ligament, subacromial bursectomy and anterior-inferior acromioplasty, has traditionally been performed in the management of this pathology. However, the purpose of subacromial decompression procedure is not clearly explained. Our reaserch aimed to analyse the differences among the outcomes of arthroscopic rotator cuff repair (RCR) made with suture anchors, with or without the subacromial decompression procedure. 116 shoulders of 107 patients affected by rotator cuff (RC) tear were treated with Arthroscopic RCR. In 54 subjectes, the arthroscopic RCR and the subacromial decompression procedure (group A) were executed, whereas 53 took only arthroscopic RCR (group B). Clinical outcomes were evaluated through the use of the modified UCLA shoulder rating system, Wolfgang criteria shoulder score and Oxford shoulder score (OSS). Functional outcomes were assessed utilizing active and passive range of motion (ROM) of the shoulder, and muscle strength. The duration of the follow up and the configuration of the acromion were used to realize the comparison between the two groups. In patients with 2 to 5 year follow up, UCLA score resulted greater in group A patients. In subjectes with longer than five years of follow up, group B patients showed considerably greater UCLA score and OSS if related with group A patients. In subjectes that had the type II acromion, group B patients presented a significant greater strength in external rotation. The long term clinical outcomes resulted significantly higher in patients treated only with RCR respect the ones in patients underwent to RCR with subacromial decompression.

The article Impact of whole dairy matrix on musculoskeletal health and aging–current knowledge and research gaps written by N.R.W. Geiker, C. Mølgaard, S. Iuliano, R. Rizzoli,Y. Manios, L.J.C. van Loon, J.-M. Lecerf, G. Moschonis, J.-Y. Reginster, I. Givens, A. Astrup.

Abstract Summary In this population-based study, we compared the incidence of distal radius fracture in 2016 with that in the same region’s adult general population in 2001 using radiographs to identify fracture cases. We showed that the incidence decreased by 24% in 2016 compared with 2001 indicating an important development. Introduction We conducted an epidemiological study on residents of northeastern Skåne in southern Sweden (population 182,000) to determine the overall incidence of distal radius fracture and the incidence according to age, sex, and fracture characteristics in the region’s adult population during 2016, and to study the change in incidence in the same general population between 2001 and 2016 using wrist radiographs to identify fracture cases. Methods Two orthopedic surgeons examined all wrist radiographs performed at the only two emergency hospitals in the study region to identify individuals, above 18 years of age, who sustained fracture of the distal radius during 2016. We used Poisson regression analysis adjusting for age, sex, and at-risk population to compare the incidence in 2016 with the incidence in 2001, previously estimated using similar methodology. Results The overall incidence in 2016 was 22 (95% CI 20–25) per 10,000; the incidence in women was 34 (95% CI 30–39) and in men was 10 (95% CI 8–12) per 10,000. The overall incidence in 2016 was 0.76 (95% CI 0.70–0.82) of the incidence in 2001 (p < 0.0001). The incidence in the 3 age groups 19–49, 50–79, and ≥ 80 years was 0.91 (95% CI, 0.69–1.20), 0.67 (95% CI, 0.55–0.82), and 0.49 (95% CI, 0.25–0.97) of the incidence in 2001, respectively. Conclusion In a general population in Sweden, a statistically significant and clinically important decrease in the incidence of distal radius fracture occurred between 2001 and 2016, driven by lower incidence in individuals 50 years or older.

Abstract Summary Significant dropout rates have been observed throughout Fracture Liaison Service (FLS) programs, especially for elderly patients. In an FLS program set up specifically for patients over 70, the non-initiation of osteoporosis treatment was the only factor associated with poor adherence to the program. Neither age nor frailty factors affected adherence. Introduction FLS programs are considered the most effective interventions for secondary prevention of osteoporotic fractures. Our objective was to identify risk factors for non-adherence to an FLS program set up specifically for patients over 70. Methods Our multifaceted, intensive program included five appointments over a 2-year period. One hundred sixty-seven patients (mean age 83.5 years) who presented with a recent fragility fracture were enrolled. Multivariable analysis was conducted to determine whether the demographic, clinical, frailty, and osteoporotic risk factors of the patients influenced their adherence to the program. Results About half of the patients did not attend the follow-up visits. According to the regression analysis, non-initiation of osteoporosis treatment was associated with poor adherence to the program (aHR 3.66). Demographic, clinical, dwelling, frailty factors, osteoporotic risk factors, fracture type, or densitometric scores were not associated with adherence. The first self-reported reason for withdrawal was the difficulty of attending several follow-up visits, and the second was the feeling of not being concerned. Conclusion We observed that non-initiation of osteoporosis treatment was the only factor correlated with non-adherence to an FLS program. Thus, neither age nor frailty factors should result in patients not being included in FLS. Beyond the necessity of the osteoporosis treatment, good patient understanding of the relevance of all the interventions included in the program is the key.

The dynamic hip screw (DHS) is widely used for fixing intertrochanteric femur fractures. A porous bionic DHS was developed recently to avoid the stress concentration and risk of post-operative complications associated with titanium alloy DHSs. The purpose of this study was to compare the effects of traditional titanium alloy, bionic titanium alloy, and bionic magnesium alloy DHS fixation for treatment of intertrochanteric fractures using finite element analysis.

The aim of this study is to analyse the results of revision surgery for failed adult spinal deformity patients and to describe the surgical strategy selection process, based on the identification of the main clinical diagnosis responsible for failure.

Selective serotonin reuptake inhibitors (SSRIs) are one of the most commonly prescribed antidepressants worldwide and recent data show significant impairment of fracture healing after treatment with the SSRI fluoxetine in mice. Here, we provide evidence that the negative effects of SSRIs can be overcome by administration of the beta‐blocker propranolol at the time of fracture. First, in vitro experiments established that propranolol does not affect osteogenic differentiation. We then used a murine model of intramembranous ossification to study the potential rescue effect of propranolol on SSRI‐induced impaired fracture healing. Micro‐CT analysis revealed that fluoxetine treatment resulted in a smaller bony regenerate and that this decrease in bone formation can be overcome by co‐treatment with propranolol. We then tested this in a clinically relevant model of endochondral ossification. Fluoxetine‐treated mice with a femur fracture were treated with propranolol initiated at the time of fracture, and a battery of analyses demonstrated a reversal of the detrimental effect of fluoxetine on fracture healing in response to propranolol treatment. These experiments show for the first time to our knowledge that the negative effects of SSRIs on fracture healing can be overcome by co‐treatment with a beta‐blocker. © 2019 American Society for Bone and Mineral Research.