Explore the vast range of titles available.

Summary Once-weekly administration of 56.5 μg teriparatide improved cortical bone parameters and biomechanical parameters at the proximal femur by CT geometry analysis. Introduction The aim of this study was to evaluate the effects of weekly administration of teriparatide [human PTH (1–34)] on bone geometry, volumetric bone mineral density (vBMD), and parameters of bone strength at the proximal femur which were longitudinally investigated using computed tomography (CT). Methods The subjects were a subgroup of a recent, randomly assigned, double-blind study (578 subjects) comparing the anti-fracture efficacy of a once-weekly subcutaneous injection of 56.5 μg teriparatide with placebo (TOWER trial). Results Sixty-six ambulatory postmenopausal women with osteoporosis were enrolled at 15 study sites having multi-detector row CT, and included women injected with teriparatide ( n  = 29, 74.2 ± 5.1 years) or with placebo ( n  = 37, 74.8 ± 5.3 years). CT data were obtained at baseline and follow-up scans were performed at 48 and 72 weeks. The data were analyzed to obtain cross-sectional densitometric, geometric, and biomechanical parameters including the section modulus (SM) and buckling ratio (BR) of the femoral neck, inter-trochanter, and femoral shaft. We found that once-weekly teriparatide increased cortical thickness/cross-sectional area (CSA) and total area, and improved biomechanical properties (i.e., decreasing BR) at the femoral neck and shaft. Teriparatide did not change the cortical perimeter. Conclusions Our longitudinal analysis of proximal femur geometry by CT revealed that once-weekly administration of 56.5 μg teriparatide improved cortical bone parameters at the femoral neck and shaft and also improved biomechanical parameters.

Background Management of osteonecrosis of the femoral head remains challenging. Core decompression and free vascularized fibular grafting are commonly used surgical procedures for treatment of osteonecrosis of the femoral head. Few studies, however, have compared these two procedures in a randomized controlled study, in terms of improved vascularity of the femoral head, progression of disease, or hip scores. Question/purposes (1) What is the effect of core decompression and fibular grafting on vascularity of the femoral head as measured by single-photon emission CT (SPECT)/CT? (2) Does one of these two methods lead to greater progression of Association Research Circulation Osseous (ARCO) stage as determined by serial MRI? (3) What is the relationship between the change in vascularity of the femoral head and hip function as measured by the Harris hip score (HHS) and progression to THA as an endpoint? Methods A randomized controlled trial was performed between June 2010 and October 2012 at Zhongshan Hospital, Fudan University. During the study period, 51 patients who presented with ARCO Stages I to IIIB bilateral osteonecrosis were potentially eligible for inclusion, and 33 patients were identified as meeting the inclusion criteria and offered enrollment and randomization. Six patients declined to participate at the time of randomization, leaving a final sample of 27 participants (54 hips). Bilateral hips of each patient were randomly assigned to surgical options: one side was treated with core decompression and the contralateral side was concurrently treated with fibular grafting. SPECT/CT examinations were performed to quantify radionuclide uptake to evaluate vascularity of the femoral head before treatment and at 6 and 36 months after surgery. With the numbers available, we found no differences between the groups regarding vascularity at baseline (64% ± 8% core decompression-treated hips versus 64% ± 7% in the fibular-grafted hips; 95% CI, −5% to 5%; p = 0.90). MR images of the hips were obtained before surgery and at 6, 12, 24, and 36 months postoperatively and staged based on the ARCO classification. All patients were assessed clinically before treatment and followed up at 6, 12, 18, 24, 30, and 36 months after treatment using the HHS. We considered a difference in the HHS of 10 as the minimal clinically important difference (MCID). Patient progression to THA was defined as the endpoint for followup. Six patients (22%) were lost to followup. Results By SPECT/CT analysis, decompression-treated hips had lower vascularity than fibular-grafted hips at 6 months (68 % ± 6% versus 95% ± 5%; mean difference, −27%; 95% CI, −32% to −23%; p < 0.001) and 36 months (57% ± 4% versus 91% ± 3%; mean difference, −34%; 95% CI, −37% to −32%; p < 0.001). MRI analysis showed no differences between decompression-treated hips and fibular-grafted hips regarding ARCO stage at 12 months (p = 0.306) and 24 months (p = 0.06). Progression of ARCO staging was more severe in the decompression group than the fibular grafting group at 36 months (p = 0.027). The mean HHS was lower in the decompression group than in the fibular grafting group throughout the followup period, although these differences were at or below the MCID of 10 points early on. However, by 18 months, the scores favored fibular grafting (72 ± 4 versus 84 ± 4; mean difference, −13; 95% CI, −15 to −7; p < 0.001), a finding that was maintained at 24, 30, and 36 months. We found no differences between decompression-treated hips and fibular-grafted hips regarding progression to THA at 36 months (two of 21; p = 0.893). Conclusions Hips that underwent a vascularized fibular grafting procedure fared better than hips receiving core decompression as measured by improved vascularity and less progression of osteonecrosis as measured by ARCO staging. The mean HHS of the fibular-grafted hips was better than that of the decompression-treated hips during the entire postoperative period, but the differences were modest early on, and for the early postoperative period the differences were unlikely to have been clinically important; by 18 months after surgery, the differences probably were clinically important. The mid-term outcomes associated with vascularized fibular grafting seen in our patients are associated with improvements in femoral head vascularity and the potential for bone revitalization. Level of Evidence Level I, therapeutic study.

Background Because the clinical and radiographic performance of an ultrashort anatomic cementless stem has been investigated in only two randomized controlled studies, well-designed trials should aim for a thorough comparison of the outcomes of ultrashort anatomic cementless and conventional anatomic cementless stems. Questions/purposes The purposes of this study were to compare (1) the clinical results, including Harris hip score, thigh pain, and WOMAC index score, (2) radiographic results, (3) bone mineral density; and (4) proportions of patients undergoing revision of a THA using an ultrashort anatomic cementless stem versus a conventional anatomic cementless stem in the same patients who underwent bilateral sequential THAs under the same anesthetic. Methods Two hundred patients (mean age, 53 years; range, 26–54 years) who underwent bilateral sequential THAs received an ultrashort anatomic cementless stem in one hip and a conventional anatomic cementless stem in the contralateral hip. From January 2004 to December 2005, we performed 524 same-day bilateral short and conventional anatomic cementless THAs in 262 patients, of whom 212 (81%) participated in this study. Five patients were lost to followup before 2 years, five were lost between 2 to 10 years, and two were lost between 10 to 13 years, leaving 200 patients. Patients who had end-stage bilateral hip disease and were younger than 55 years were selected for inclusion. The predominant diagnoses were osteonecrosis (118 patients, 59%) and osteoarthritis (44 patients, 22%). One hundred thirty-eight were men and 62 were women. At the time of each followup, the patients were assessed clinically and radiographically. In addition, each patient completed the WOMAC and the University of California Los Angeles (UCLA) activity scores. The minimum followup was 10 years (mean, 11.8 years; range, 10–13 years). Followups were done in person, with all images and followup clinic notes. Based on the power analysis, we estimated a sample size of 178 hips was needed in each group to detect a 3-point difference in the Harris hip score with 80% power. Results At the latest followup, there were no differences between the two groups regarding the mean Harris hip scores (94 versus 94 points; p = 0.189), mean WOMAC scores (17 versus 16 points; p = 0.191), or mean UCLA activity scores (9 versus 9 points; p = 0.381). Two patients in the ultrashort stem group and one patient in the conventional stem group had severe (9 points) thigh pain, and 30 patients (15%) in the conventional stem group had mild thigh pain (2 or 3 points) after vigorous exercise. Bone mineral density in the ultrashort and conventional stem groups, respectively, was greater in the ultrashort stem group than in the conventional stem group. Bone mineral density in Zone 1 at 12 years was 3.29 versus 1.88 g/cm 2 (p = 0.021), and 2.97 versus 0.91 g/m 2 in Zone 7 (p = 0.001). With the numbers available, there were no differences between the stem designs in terms of the proportion undergoing revision (one hip, 0.5%, in the short-stem group versus one hip, 0.5%, in the conventional group; p = 1.881). Conclusions At followup into the second decade, ultrashort stems showed no differences from conventional cementless stems in terms of validated outcomes scores or fixation, although less stress shielding was observed. Reduction of stress shielding may reduce the long-term risk of periprosthetic fracture, but this was not shown in our study. Level of Evidence Level I, therapeutic study.

Background Hip dysplasia represents a spectrum of complex deformities on both sides of the joint. Although many studies have described the acetabular side of the deformity, to our knowledge, little is known about the three-dimensional (3-D) head and neck offset differences of the femora of dysplastic hips. A thorough knowledge of proximal femoral anatomy is important to prevent potential impingement and improve results after acetabular reorientation. Questions/purposes (1) Are there common proximal femoral characteristics in patients with symptomatic hip dysplasia undergoing periacetabular osteotomy (PAO)? (2) Where is the location of maximal femoral head and neck offset deformity in hip dysplasia? (3) Do certain subgroups of dysplastic hips more commonly have cam-type femoral morphology? (4) Is there a relationship between hip ROM as well as impingement testing and 3-D head and neck offset deformity? Methods Using our hip preservation database, 153 hips (148 patients) underwent PAO from October 2013 to July 2015. We identified 103 hips in 100 patients with acetabular dysplasia (lateral center-edge angle [LCEA] < 20°) and who had a Tönnis grade of 0 or 1. Eighty-six patients (86%) underwent preoperative low-dose pelvic CT scans at our institution as part of the preoperative planning for PAO. It is currently our standard to obtain preoperative low-dose pelvic CT scans (0.75–1.25 mSv, equivalent to three to five AP pelvis radiographs) on all patients before they undergo PAO unless a prior CT scan is performed at an outside institution. Hips with a history of a neuromuscular disorder, prior trauma, prior surgery, radiographic evidence of joint degeneration, ischemic necrosis, or Perthes-like deformities were excluded. Fifty hips in 50 patients met inclusion criteria and had CT scans available for review. Hips were analyzed with Dyonics Plan software and characterized with regard to version, neck-shaft angle, femoral head diameter, head and neck offset, femoral neck length, femoral offset, head center height, trochanteric height, and alpha angle. The maximum head and neck offset deformity was assessed using an entire clockface and an alpha angle ≥ 55° defined coexisting cam morphology. Subgroups included severity of lateral dysplasia: mild (LCEA 15°–20°) and moderate/severe (LCEA < 15°). Femoral version subgroups were defined as normal (5°–20°), decreased (≤ 5°), or increased (> 20°). The senior author (JCC) performed all physical examination testing. Results The mean LCEA was 14° (±4°), whereas the mean femoral anteversion was 19° (±12°). Eight hips (16%) demonstrated relative femoral retroversion (≤ 5°), whereas 26 (52%) showed excessive femoral anteversion (> 20°). Four hips (8%) had ≥ 35° of femoral anteversion. The mean neck-shaft angle was 136° (±5°). The mean maximum alpha location was 2:00 o’clock (±45 minutes) and the mean maximum alpha angle was 52° (±6°). Minimum head-neck offset ratio was located at 1:30 with a mean of 0.14 (±0.03). An anterior head-neck offset ratio of ≤ 0.17 or an alpha angle ≥ 55° was found in 43 (86%) of hips. Twenty-one dysplastic hips (42%) had an alpha angle ≥ 55°. Mildly dysplastic hips had decreased femoral head and neck offset (9 ± 1) and head and neck offset ratio (0.20 ± 0.03) at 12 o’clock compared with moderate/severe dysplastic hips (10 ± 1 and 0.22 ± 0.03, respectively; p = 0.04 and p = 0.01). With the numbers available, we found that hips with excessive femoral anteversion (> 20°) had no difference in the alpha angle at 3 o’clock (42 ± 7) compared with hips with relative femoral retroversion (≤ 5°; 48 ± 4; p = 0.06). No other differences in femoral morphology were found between hips with mild or moderate/severe dysplasia or in the femoral version subgroups with the numbers available. Anterior impingement test was positive in 76% of hips with an alpha angle ≥ 55° and 83% of the hips with an alpha angle ≤ 55°. No correlation was found between proximal femoral morphology and preoperative ROM. Conclusions In this subset of dysplastic hips, cam deformity of the femoral head and neck was present in 42% of hips with maximal head-neck deformity at 2 o’clock, and 82% had reduced head-neck offset at the 1:30 point. We conclude that cam-type deformities and decreased head-neck offset in developmental dysplasia of the hip are common. Patients should be closely assessed for need of a head and neck osteochondroplasty, especially after acetabular correction. Future prospective studies should evaluate the influence of proximal femoral anatomy on surgical results of PAO for dysplastic hips. Level of Evidence Level IV, prognostic study.

This is a retrospective analysis of the clinical effects of transplant of mesenchymal stem cells (MSCs) derived from human umbilical cord-derived MSCs (hUC-MSCs) for the treatment of osteonecrosis of the femoral head (ONFH). The biological characteristics of hUC-MSCs were assessed using flow cytometry. Nine eligible patients were enrolled in the study as they adhered to the Association Research Circulation Osseous (ARCO) classification of stage II-IIIa, and hUC-MSCs were grafted by intra-arterial infusion. Organize effective perfusion was assessed using the oxygen delivery index (ODI). The results showed that the ODI was increased at three days post-operation. The MRI results revealed that at 12 and 24 months after treatment, the necrotic volume of the femoral heads was significantly reduced. No obvious abnormalities were observed. Taken together, these data indicate that intra-arterially infused hUC-MSCs migrate into the necrotic field of femoral heads and differentiate into osteoblasts, thus improving the necrosis of femoral heads. This finding suggested that intra-arterial infusion of hUC-MSCs MSCs is a feasible and relatively safe method for the treatment of femoral head necrosis.

Osteonecrosis of the femoral head (ONFH) is a progressive and painful disorder due to impaired blood supply to the femoral head, yet little is known about the effect of ozone therapy in femoral head necrosis. We aimed to evaluate the clinical and radiographic outcomes of ozone therapy in the treatment of ONFH. Nonrandomized clinical trial. The study was conducted in a single-center, academic institution. A total of 71 patients (107 hip joints) with Association Research Circulation Osseous (ARCO) stage-I, II, III, and IV ONFH were included and assigned to undergo either intraarticular O2-O3 mixture hip injections with ozonated autohemotherapy (ozone therapy group, n = 39, 58 hip joints) or protected weight bearing (control group, n = 32, 49 hip joints). The primary outcomes included the Visual Analog Scale (VAS) for pain intensity and Harris Hip Score (HHS) for hip function. The secondary outcomes included bone marrow edema examination, and conversion to total hip arthroplasty (THA). Ozone therapy effectively improves VAS for pain intensity and HHS during the follow-up period compared to the control group. Ozone therapy showed a significant resolution of bone marrow edema of the femoral head compared to the control group (P < 0.001). Thirteen of the 49 hips (26.53%) in the control group underwent THA, whereas only 6 hips (10.34%) in the ozone therapy group required THA during a 30-month follow-up (P = 0.041). The cumulative analysis revealed a low rate of conversion to THA in the ozone therapy group (logrank test; P = 0.022). The study is limited by a single treatment protocol in addition to the lack of a randomized design. Ozone therapy was associated with significant pain relief, improvement in hip function, and bone marrow edema resolution that may delay the need for THA in patients affected by ONFH.Institutional Review Board (IRB) approval number: HK2018-10-28.Clinical trials registration number: ChiCTR1900023449.

Recent studies have suggested that exosomes exert similar therapeutic effects to those of mesenchymal stem cells (MSCs) in regenerative medicine and MSCs-derived exosomes exhibit therapeutic effects on steroid-induced osteonecrosis of the femoral head (ONFH). Furthermore, reparative functions of exosomes from MSCs are enhanced by hypoxia treatment of the cells. However, there are no related reports about whether exosomes derived from hypoxia-preconditioned MSCs could show better therapeutic effects on steroid-induced ONFH. In vitro, we investigated the effects of hypoxia precondition on exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) from rats and the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs. In vivo, we investigated the role of exosomes from hypoxia-preconditioned BMMSCs on angiogenesis and protecting osteonecrosis in a rat ONFH model. We found that the potential of the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs was higher than exosomes derived from BMMSCs cultured under normoxia. Exosomes derived from hypoxia-preconditioned BMMSCs significantly promoted proliferation, migration, vascular endothelial growth factor (VEGF) expression, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with exosomes derived from BMMSCs cultured under normoxia. Administration of exosomes derived from hypoxia-preconditioned BMMSCs significantly prevented bone loss and increased vessel volume in the femoral head compared with exosomes derived from BMMSCs cultured under normoxia. Taken together, our data suggest that exosomes derived from hypoxia-preconditioned BMMSCs exert better therapeutic effects on steroid-induced ONFH by promoting angiogenesis and preventing bone loss.

This study delved into the role of the PI3K/AKT signaling pathway and cuproptosis in steroid-induced osteonecrosis of the femoral head (SIONFH), assessing the therapeutic potential of the PI3K agonist 740Y-P. We analyzed femoral head specimens from SIONFH patients using DIA proteomics, identifying differentially expressed proteins linked to cuproptosis. In vitro, MC3T3-E1 cells treated with dexamethasone (DEX) exhibited hallmarks of cuproptosis, including downregulation of DLAT, PDHB, SLC25A3, and FDX1, increased copper ions, and reduced osteogenic potential, as shown by decreased ALP activity and RUNX2/BMP2 expression. The PI3K/AKT pathway’s modulation of FDX1 was key to cuproptosis regulation; activating it with 740Y-P restored FDX1 levels and partially recovered osteogenic capacity. An in vivo rat model of SIONFH treated with 740Y-P demonstrated improved bone parameters, reversed osteogenic suppression, and upregulated PI3K/AKT/FDX1 expression, validating the pathway’s role in cuproptosis and the agonist’s therapeutic potential for treating SIONFH and glucocorticoid-associated bone disorders.

Background There is a medical need for therapies that improve hip fracture healing. Teriparatide (Forteo ® / Forsteo ® , recombinant human parathyroid hormone) is a bone anabolic drug that is approved for treatment of osteoporosis and glucocorticoid-induced osteoporosis in men and postmenopausal women at high fracture risk. Preclinical and preliminary clinical data also suggest that teriparatide may enhance bone healing. Questions/purposes We wished to test the hypotheses that treatment with teriparatide versus placebo would improve femoral neck fracture healing after internal fixation as measured by (1) frequency of revision surgery, (2) radiographic fracture healing, and (3) other outcomes including pain control, gait speed, and safety. Methods We initiated two separate, but identically designed, clinical trials to meet FDA requirements to provide substantial evidence to support approval of a new indication. The two prospective, randomized double-blind, placebo-controlled Phase III studies were designed to evaluate the effect of subcutaneous teriparatide (20 μg/day) for 6 months versus placebo on fracture healing at 24 months. The trials were conducted concurrently with a planned enrollment of 1220 patients per trial. However, enrollment was stopped owing to very slow patient accrual, and an a priori decision was made to pool the results of those studies for statistical analyses before study completion; pooling was specified in both protocols. Randomization was stratified by fixation (sliding hip screw or multiple cancellous screws) and fracture type (displaced or nondisplaced). An independent Central Adjudication Committee reviewed revision surgical procedures and radiographs. A total of 159 patients were randomized in the two trials (81 placebo, 78 teriparatide). The combined program had very low power to detect the originally expected treatment effect but had approximately 80% power to detect a larger difference of 12% between treatment groups for risk of revision surgery. Results The proportion of patients undergoing revision surgery at 12 months was 14% (11 of 81) in the placebo group versus 17% (13 of 78) in the teriparatide group. Central Adjudication Committee review excluded two of these patients treated with placebo from the primary analysis. After exclusions, the proportion of patients who did not undergo revision surgery at 12 months (primary endpoint) was not different between the study and placebo groups, at 88% in the placebo group (90% CI, 0.79–0.93) versus 84% in the teriparatide group (90% CI, 0.75–0.90; p = 0.743). There also were no differences between groups in the proportion of patients achieving radiographic fracture healing at 12 months (75% [61 of 81] placebo versus 73% [57 of 78] teriparatide; odds ratio, 0.89; 90% CI, 0.46–1.72; p = 0.692) or in measures of pain control (such as pain during ambulation, 92% [55 of 62] placebo versus 91% [52 of 57] teriparatide; odds ratio, 0.91; 90% CI, 0.25–3.37; p = 0.681). The frequency of patients reporting adverse events was 49% [40 of 81] in the placebo group versus 45% [35 of 78] in the teriparatide group (p = 0.634) during the 6-month treatment period. Conclusions The small sample size limited this study’s power to detect potential differences, and the results are exploratory. With the patients available, teriparatide did not decrease the risk of revision surgery, improve radiographic signs of fracture healing, or decrease pain compared with the placebo. The adverse event data observed were consistent with the teriparatide safety profile. Functional and health outcome data from the studies may help improve our understanding of patients recovering from femoral neck fractures. Further large controlled studies are required to determine the effect of teriparatide on fracture healing. Level of Evidence Level II, prospective study.

The onset of osteonecrosis of the femoral head (ONFH) is intimately associated with the extensive administration of glucocorticoids (GCs). Long‐term stimulation of GCs can induce oxidative stress in both osteoclasts (OCs) and osteoblasts (OBs), resulting in the disturbance of bone remodelling. An alkaloid named crebanine (CN) demonstrates pharmacological properties including anti‐inflammation and reactive oxygen species (ROS) modulation. Our objective is to assess the therapeutic potential of CN in treating ONFH and elucidate the associated underlying mechanisms. The network pharmacology analysis uncovered that CN played a role in regulating ROS metabolism. In vitro, CN demonstrated its ability to reduce the dexamethasone (DEX)‐stimulated generation of OCs and suppress their resorptive function by downregulating the level of osteoclast marker genes. Concurrently, CN also mitigated DEX‐induced damage to OBs, facilitating the restoration of osteoblast marker gene expression, cellular differentiation and function. These effects were achieved by CN augmenting the antioxidant system to reduce intracellular ROS levels. Furthermore, in vitro results were corroborated by micro‐CT and histological data, which also showed that CN attenuated MPS‐induced ONFH in mice. This study highlights the therapeutic potential of CN in counteracting GCs‐induced ONFH.