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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.

Abstract Context The ACTIVE study demonstrated the antifracture efficacy of abaloparatide in postmenopausal women with osteoporosis. ACTIVExtend demonstrated sustained fracture risk reduction with alendronate in abaloparatide-treated participants from ACTIVE. A direct comparison of the efficacy of abaloparatide and antiresorptive therapies has not been performed. Objective The objective of this analysis is to compare the antifracture efficacy of abaloparatide in ACTIVE with that of alendronate in ACTIVExtend. Design In this post hoc analysis, the rate of new vertebral fractures for women in ACTIVExtend (N = 1139) was calculated based on baseline and endpoint radiographs for placebo or abaloparatide in ACTIVE and alendronate in ACTIVExtend. Vertebral fracture rates between abaloparatide and alendronate were compared in a Poisson regression model. Fracture rates for nonvertebral and clinical fractures were compared based on a Poisson model during 18 months of abaloparatide or placebo treatment in ACTIVE and 18 months of alendronate treatment in ACTIVExtend. Results The vertebral fracture rate was lower during abaloparatide treatment in ACTIVE (0.47 fractures/100 patient-years) than alendronate treatment in ACTIVExtend (1.66 fractures/100 patient-years) (relative risk reduction 71%; P = .027). Although the comparisons did not meet statistical significance, after switching from placebo (ACTIVE) to alendronate (ACTIVExtend), the rate of new vertebral fractures decreased from 2.49 to 1.66 fractures per 100 patient-years, and after switching from abaloparatide to alendronate from 0.47 to 0.19 fractures per 100 patient-years. The rates of nonvertebral fractures and clinical fractures were not significantly different. Conclusion Initial treatment with abaloparatide may result in greater vertebral fracture reduction compared with alendronate in postmenopausal women with osteoporosis.

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 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.

Zoledronate administered every 12 to 18 months prevents fractures in older women. Ten years after initiation of this trial, zoledronate administered at baseline and 5 years prevented vertebral fracture.

Abstract Context In the Denosumab and High-Dose Teriparatide Administration (DATA-HD) study, we reported that 15 months of combined high-dose (HD) teriparatide and denosumab increased mean areal bone mineral density (aBMD) at the hip and spine more than combined denosumab and standard-dose (SD) teriparatide. Objective In the current analysis, we compare the individual rates of aBMD response between the treatment groups. Design Single-site, open-label, randomized controlled trial in which postmenopausal women received either teriparatide 20-μg daily (SD) or 40-μg daily (HD) given months 0 through 9, overlapped with denosumab 60 mg, given months 3 through 15 (15 months’ total duration). The proportion of participants in the SD and HD groups experiencing total hip, femoral neck, and lumbar spine aBMD gains of >3%, >6%, and >9% were compared. Participants Postmenopausal women with osteoporosis completing all study visits (n = 60). Main outcome measure(s) aBMD (dual x-ray absorptiometry). Results At the end of the 15-month treatment period, a higher proportion of women in the HD group had aBMD increases >3% (83% vs. 58%, P = .037) and >6% (45% vs. 19%, P = .034) at the total hip, and >3% at the femoral neck (86% vs. 63%, P = .044). At the lumbar spine, >3% response rates were similar, whereas the >6% and >9% response rates were greater in the HD group (100% vs. 79%, P = .012 and 93% vs. 59%, P = .003, respectively). Conclusion Compared with the SD regimen, more women treated with the HD regimen achieved clinically meaningful and rapid gains in hip and spine aBMD. These results suggest that this approach may provide unique benefits in the treatment of postmenopausal osteoporosis.

SummaryPioglitazone use is associated with an increased risk of fractures. In this randomized, placebo-controlled study, pioglitazone use for 12 months was associated with a significant increase in bone marrow fat content at the femoral neck, accompanied by a significant decrease in total hip bone mineral density. The change in bone marrow fat with pioglitazone use was predominantly observed in female vs. male participants.IntroductionUse of the insulin sensitizer pioglitazone is associated with greater fracture incidence, although the underlying mechanisms are incompletely understood. This study aimed to assess the effect of pioglitazone treatment on femoral neck bone marrow (BM) fat content and on bone mineral density (BMD), and to establish if any correlation exists between the changes in these parameters.MethodsIn this double-blind placebo-controlled clinical trial, 42 obese volunteers with metabolic syndrome were randomized to pioglitazone (45 mg/day) or matching placebo for 1 year. The following measurements were conducted at baseline and during the treatment: liver, pancreas, and femoral neck BM fat content (by magnetic resonance spectroscopy), BMD by DXA, abdominal subcutaneous and visceral fat, and beta-cell function and insulin sensitivity.ResultsResults were available for 37 subjects who completed the baseline and 1-year evaluations. At 12 months, BM fat increased with pioglitazone (absolute change, +4.1%, p = 0.03), whereas BM fat content in the placebo group decreased non-significantly (−3.1%, p = 0.08) (p = 0.007 for the pioglitazone–placebo response difference). Total hip BMD declined in the pioglitazone group (−1.4%) and increased by 0.8% in the placebo group (p = 0.03 between groups). The change in total hip BMD was inversely and significantly correlated with the change in BM fat content (Spearman rho = −0.56, p = 0.01) in the pioglitazone group, but not within the placebo group (rho = −0.29, p = 0.24). Changes in BM fat with pioglitazone were predominantly observed in female vs. male subjects.ConclusionsPioglitazone use for 12 months compared with placebo is associated with significant increase in BM fat content at the femoral neck, accompanied by a small but significant decrease in total hip BMD.

Globally, one in five men aged >50 years is predicted to experience an osteoporotic fracture. Because of the treatment gap in osteoporosis and the paucity of bone-forming agents for men, new osteoporosis treatments are needed. To evaluate the safety and efficacy of romosozumab in men with osteoporosis. Phase III randomized BRIDGE study (placebo-controlled double-blind study evaluating the efficacy and safety of romosozumab in treating men with osteoporosis; ClinicalTrials.gov identifier, NCT02186171) for 12 months. Thirty-one centers in Europe, Latin America, Japan, and North America. Men aged 55 to 90 years with a baseline bone mineral density (BMD) T-score at the lumbar spine (LS), total hip (TH), or femoral neck of ≤-2.5 or ≤-1.5 with a history of a fragility nonvertebral or vertebral fracture. The subjects were randomized 2:1 to receive romosozumab 210 mg subcutaneously monthly or placebo for 12 months. The primary efficacy endpoint was percentage change from baseline in LS BMD at month 12. In 245 subjects (163 romosozumab, 82 placebo), at month 12, the mean percentage change from baseline in the LS and TH BMD was significantly greater for the romosozumab group than for the placebo group (LS, 12.1% vs 1.2%; TH, 2.5% vs -0.5%; P < 0.001). Adverse events and serious adverse events were balanced between the two groups, with a numerical imbalance in the positively adjudicated cardiovascular serious adverse events [romosozumab, 8 (4.9%) vs placebo, 2 (2.5%)]. Treatment with romosozumab for 12 months increased the spine and hip BMD compared with placebo and was well tolerated in men with osteoporosis.

Background Femoral neck fractures are one of the problems in clinical treatment. The prognosis is uncertain. Currently, No internal fixation method is superior to other internal fixation methods in the treatment of femoral neck fractures. Therefore, the internal fixation system needs to be further explored. The aim of this study was to compare clinical outcomes of femoral neck dynamic compression locking system (DCLS) and multiple cannulated compression screws(MCCS) in the treatment of femoral neck fractures. Methods A prospective analysis of 54 cases of femoral neck fractures treated with either a DCLS ( n  = 28) or MCCS ( n  = 26) was conducted between December 2015 and November 2017 in authors’ hospitals. The perioperative and postoperative parameters of the two groups were recorded and evaluated. Results Fifty-four patients were followed up for 24–47 months. The etiology was caused by a fall. There was no significant difference in follow-up time, operation time, incision length, surgical blood loss, the incidence of perioperative and postoperative healing complications, and mobility in the two groups (all P  > 0.05). The Harris score, fracture healing time, femoral neck shortening, partial weight-bearing time and complete weight-bearing time were significantly better in the DCLS group than in the MCCS group (all P  < 0.05). The fracture healing rate in the DCLS group was higher than that in the MCCS group. Conclusions The DCLS and MCCS might be equally effective in terms of operation time, incision length, surgical blood loss, the incidence of perioperative and postoperative healing complications, and mobility in the treatment of femoral neck fractures. However, the DCLS is superior to the MCCS in Harris score, fracture healing time, femoral neck shortening, weight-bearing time and fracture healing rate. So, DCLS deserves further study.

Purpose. To verify the biomechanical importance with respect to the integrity of posteromedial cortex of femoral neck fracture (FNF) and demonstrate whether the modified fixation of cannulated screws (CSs) could increase the biomechanical strength. Methods. A total of 24 left artificial femurs were randomly divided into three groups. The osteotomy was made in the center of the femoral neck at a 20° angle to the shaft axial. The posteromedial cortices of femoral neck were removed in groups B and C. In group A, 8 femurs with intact posteromedial cortex were fixed with three parallel partial thread screws (PTSs), forming a standard triangle. In group B, the femurs were stabilized with the same fixation of CSs like group A. In group C, two inferior PTSs were replaced by two fully thread screws (FTSs). Results. The lower A-P and axial stiffness and load to failure along with higher axial displacement were found in group B compared with group A (p≤0.001 for all). Between groups B and C, the modified fixation of CSs increased A-P and axial stiffness and load to failure and reduced the axial displacement (p≤0.001 for all). Conclusions. We verified that the comminuted posteromedial cortex affected the biomechanical strength adversely and resulted in higher displacement. The modified fixation of CSs characterized by two inferior FTSs could improve the biomechanical performance and buttress the femoral head fragment better.