Baseline serum PINP level is associated with the increase in hip bone mineral density seen with Romosozumab treatment in previously untreated women with osteoporosis.

Baseline serum PINP value was significantly and independently associated with the increased bone mineral density (≥ 3%) in both total hip and femoral necks by 12 months of romosozumab treatment in patients with treatment-naive postmenopausal osteoporosis. PURPOSE: Some patients fail to obtain a sufficiently increased hip bone mineral density (BMD) by romosozumab (ROMO) treatment. This study aimed to investigate the prognostic factor for increased hip BMD with ROMO in patients with treatment-naive postmenopausal osteoporosis. METHODS: This prospective, observational, and multicenter study included patients (n = 63: mean age, 72.6 years; T-scores of the lumbar spine [LS], - 3.3; total hip [TH], - 2.6; femoral neck [FN], - 3.3; serum type I procollagen N-terminal propeptide [PINP], 68.5 µg/L) treated by ROMO for 12 months. BMD and serum bone turnover markers were evaluated at each time point. A responder analysis was performed to assess the patient percentage, and both univariate and multivariate analyses were performed to investigate the factors associated with clinically significant increased BMD (≥ 3%) in both TH and FN. RESULTS: Percentage changes of BMD from baseline in the LS, TH, and FN areas were 17.5%, 4.9%, and 4.3%, respectively. In LS, 96.8% of patients achieved ≥ 6% increased LS-BMD, although 57.1% could not achieve ≥ 3% increased BMD in either TH or FN. Multiple regression analysis revealed that only the baseline PINP value was significantly and independently associated with ≥ 3% increased BMD in both TH and FN (p = 0.019, 95% confidence interval = 1.006-1.054). The optimal cut-off PINP value was 53.7 µg/L with 54.3% sensitivity and 92.3% specificity (area under the curve = 0.752). CONCLUSIONS: In a real-world setting, baseline PINP value was associated with the increased BMD of TH and FN by ROMO treatment in treatment-naive patients.

Percutaneous iliosacral screw and trans-iliac trans-sacral screw with single C-arm fluoroscope intensifier is a safe treatment for pelvic ring injuries.

To elucidate the accuracy, efficacy, and safety of percutaneous iliosacral screw (ISS) and trans-iliac trans-sacral screw (TITS) insertion using a single C-arm fluoroscopy intensifier. Additionally, the potential risk factors that might cause mal-positioned screws were identified. Patients with pelvic ring injuries who underwent percutaneous screw fixation in a single medical institute were divided into an ISS group (n = 59) and a TITS group (n = 62) and assessed. The angles deviated from ideal orientation (ADIO) of the implanted screw were measured, and potential risk factors for mal-positioned screws were analyzed. Overall, the reduction quality of the pelvic ring was good or excellent in 70 patients (82.4%) by Matta's criteria and in 48 patients (56.5%) by Lefaivre's criteria. ADIO measurements of the ISS and TITS groups via multi-planar computed tomography were 9.16° ± 6.97° and 3.09° ± 2.8° in the axial view, respectively, and 5.92° ± 3.65° and 2.10° ± 2.01° in the coronal view, respectively. Univariate statistical analysis revealed body mass index as the single potential risk factor of mal-positioned screws. With careful preoperative planning and intraoperative preparations, placing ISS and TITS under the guidance of single C-arm fluoroscopy intensifier is a reliable and safe technique. Caution should be exercised when performing this procedure in patients with a high body mass index.

Management of ongoing direct anticoagulant treatment in patients with hip fracture.

Aim of the present study was to investigate the effects of ongoing treatment with DOACs on time from trauma to surgery and on in-hospital clinical outcomes (blood losses, need for transfusion, mortality) in patients with hip fracture. Moreover we evaluated the adherence to current guidelines regarding the time from last drug intake and surgery. In this observational retrospective study clinical records of patients admitted for hip fracture from January 2016 to January 2019 were reviewed. 74 patients were in treatment with DOACs at hospital admission. Demographic data, comorbidities and functional status before trauma were retrieved. As control group we evaluated 206 patients not on anticoagulants matched for age, gender, type of fracture and ASA score. Time to surgery was significantly longer in patients treated with DOACs (3.6 + 2.7 vs. 2.15 ± 1.07 days, p < 0.0001) and treatment within 48 h was 47% vs. 80% in control group (p < 0.0001). The adherence to guidelines' suggested time from last drug intake to surgery was 46%. Neither anticipation nor delay in surgery did result in increased mortality, length of stay or complication rates with the exception of larger perioperative blood loss (Hb levels < 8 g/dl) in DOACs patients (34% vs 9% p < 0.0001). Present results suggest that time to surgery is significantly longer in DOAC patients in comparison to controls and adherence to guidelines still limited.

Consequences of Hyperthyroidism and Its Treatment for Bone Microarchitecture Assessed by High-Resolution Peripheral Quantitative Computed Tomography.

Background: Hyperthyroidism is associated with bone mass reduction and increased fracture risk, but the effects on other important bone parameters have been sparsely examined. Therefore, we investigated bone microarchitecture and estimated bone strength by high-resolution peripheral quantitative computed tomography (HR-pQCT) in hyperthyroid patients at diagnosis and after being euthyroid for at least one year. Methods: Two approaches were used: (A) a case-control study comparing 61 hyperthyroid women with 61 euthyroid women matched for age and menopause status; (B) a follow-up study, in which 46 of the 61 women were re-examined after having been euthyroid for one year. HR-pQCT of the distal radius and tibia, and dual-energy X-ray absorptiometry (DXA) of the lumbar spine and the hip were performed. Results: In analysis A: In the radius, compared with the healthy controls, hyperthyroid patients had higher total area (16.9% ± 29.5%; p < 0.001), trabecular area (28.6% ± 45.7%; p < 0.001), and lower cortical area (-11.7% ± 23.2%; p < 0.001). Total volumetric bone mineral density (vBMD) (-13.9% ± 26.5%; p < 0.001), cortical vBMD (-5.8% ± 7.9%; p < 0.001), cortical thickness (-16.7% ± 26.0%; p < 0.001), and estimated bone strength (-6.6% ± 19.5%; p < 0.01) were lower. No significant differences were found in the tibia or in the DXA parameters. In analysis B: In the radius, significant improvements were observed in the cortical area (2.1% ± 4.6%; p < 0.01), cortical thickness (2.5% ± 5.1%; p < 0.001), and total vBMD (0.8% ± 3.0%; p < 0.05). Trabecular area decreased (-0.5% ± 1.0%; p < 0.01) and trabecular separation increased (2.0% ± 8.3%; p < 0.05). In the tibia, cortical area (3.6% ± 7.3%; p < 0.01) and cortical thickness (3.8% ± 7.6%; p < 0.01) increased, and trabecular area decreased (-0.5% ± 1.1%; p < 0.01). Areal BMD, measured by DXA, increased in the spine (1.1% ± 3.4%; p < 0.05) and in the hip (2.0% ± 3.8%; p < 0.01). Conclusions: Compared with the healthy control group, hyperthyroid women had lower vBMD, lower estimated bone strength, and compromised cortical microarchitecture in the radius. After restoration of euthyroidism, significant improvements in vBMD and cortical microarchitecture were observed, highlighting the importance of achieving and maintaining euthyroidism.

Regional improvements in lumbosacropelvic Hounsfield units following teriparatide treatment.

OBJECTIVE: Opportunistic Hounsfield unit (HU) determination from CT imaging has been increasingly used to estimate bone mineral density (BMD) in conjunction with assessments from dual energy x-ray absorptiometry (DXA). The authors sought to compare the effect of teriparatide on HUs across different regions in the pelvis, sacrum, and lumbar spine, as a surrogate measure for the effects of teriparatide on lumbosacropelvic instrumentation. METHODS: A single-institution retrospective review of patients who had been treated with at least 6 months of teriparatide was performed. All patients had at least baseline DXA as well as pre- and post-teriparatide CT imaging. HUs were measured in the pedicle, lamina, and vertebral body of the lumbar spine, in the sciatic notch, and at the S1 and S2 levels at three different points (ilium, sacral body, and sacral ala). RESULTS: Forty patients with an average age of 67 years underwent a mean of 20 months of teriparatide therapy. Mean HUs of the lumbar lamina, pedicles, and vertebral body were significantly different from each other before teriparatide treatment: 343 ± 114, 219 ± 89.2, and 111 ± 48.1, respectively (p < 0.001). Mean HUs at the S1 level for the ilium, sacral ala, and sacral body were also significantly different from each other: 124 ± 90.1, -10.7 ± 61.9, and 99.1 ± 72.1, respectively (p < 0.001). The mean HUs at the S2 level for the ilium and sacral body were not significantly different from each other, although the mean HU at the sacral ala (-11.9 ± 52.6) was significantly lower than those at the ilium and sacral body (p = 0.003 and 0.006, respectively). HU improvement occurred in most regions following teriparatide treatment. In the lumbar spine, the mean lamina HU increased from 343 to 400 (p < 0.001), the mean pedicle HU increased from 219 to 242 (p = 0.04), and the mean vertebral body HU increased from 111 to 134 (p < 0.001). There were also significant increases in the S1 sacral body (99.1 to 130, p < 0.05), S1 ilium (124 vs 165, p = 0.01), S1 sacral ala (-10.7 vs 3.68, p = 0.04), and S2 sacral body (168 vs 189, p < 0.05). CONCLUSIONS: There was significant regional variation in lumbar and sacropelvic HUs, with most regions significantly increasing following teriparatide treatment. The sacropelvic area had lower HU values than the lumbar spine, more regional variation, and a higher degree of correlation with BMD as measured on DXA. While teriparatide treatment resulted in HUs > 110 in the majority of the lumbosacral spine, the HUs in the sacral ala remained suggestive of severe osteoporosis, which may limit the effectiveness of fixation in this region.

The effect of zoledronic acid on attenuation of bone loss at the hip and knee following acute traumatic spinal cord injury: a randomized-controlled study.

STUDY DESIGN: Randomized double blind, placebo-controlled trial. OBJECTIVES: To examine the effect of early intravenous zoledronic acid (ZA) on bone markers and areal bone mineral density (aBMD) in persons with acute ASIA Impairment Scale (AIS) A traumatic spinal cord injury (SCI). SETTING: Two inpatient rehabilitation units. METHODS: Thirteen men, 2 women, aged 19-65, C4-T10 AIS A SCI, received 5 mg intravenous ZA vs. placebo 12-21 days post injury. Markers of bone formation (procollagen N-1 terminal propeptide [P1NP]), bone resorption (serum C-telopeptide [CTX]), and aBMD by dual-energy X-ray absorptiometry (DXA) for hip (femur-proximal, intertrochanteric, neck), and knee (distal femur, proximal tibia) were obtained at baseline, 2 weeks post infusion (P1NP, CTX only), 4 and 12 months post injury. RESULTS: P1NP remained unchanged, while CTX decreased in ZA but increased in controls at 2 weeks (mean difference = -97%, p < 0.01), 4 months (mean difference = -54%, p < 0.05), but not 12 months (mean difference = 3%, p = 0.23). Changes in aBMD at the hip favored ZA at 4 months (mean difference 10.3-14.1%, p < 0.01) and 12 months (mean difference 10.8-13.1%, p < 0.02). At 4 months, changes in aBMD favored ZA at the distal femur (mean difference 6.0%, 95% CI: 0.7-11.2, p < 0.03) but not proximal tibia (mean difference 8.3%, 95% CI: -6.9 to 23.6, p < 0.23). Both groups declined in aBMD at 12 months, with no between group differences. CONCLUSION: ZA administered ≤21 days of complete traumatic SCI maintains aBMD at the hip and distal femur at 4 months post injury. This effect is partially maintained at 12 months.

Sex-specific effects of dehydroepiandrosterone (DHEA) on bone mineral density and body composition: A pooled analysis of four clinical trials.

OBJECTIVE: Studies of dehydroepiandrosterone (DHEA) therapy in older adults suggest sex-specific effects on bone mineral density (BMD) and body composition, but the ability of a single study to reach this conclusion was limited. We evaluated the effects of DHEA on sex hormones, BMD, fat mass and fat-free mass in older women and men enrolled in four similar clinical trials. DESIGN: Pooled analyses of data from four double-blinded, randomized controlled trials. PARTICIPANTS: Women (n = 295) and men (n = 290) aged 55 years or older who took DHEA or placebo tablet daily for 12 months. MEASUREMENTS: Twelve-month changes in BMD, fat mass, fat-free mass and serum DHEA sulphate (DHEAS), (17)estradiol, testosterone and insulin-like growth factor-1 (IGF-1). RESULTS: Women on DHEA had increases (mean ± SD; all P < 0.001 vs placebo) in DHEAS (231 ± 164 µg/dL), testosterone (18.6 ± 20.9 µg/dL), (17)estradiol (8.7 ± 11.0 pg/mL) and IGF-1 (25.1 ± 52.3 ng/mL), and men had increases in DHEAS (269.0 ± 177 µg/dL; P < 0.01), (17)estradiol (4.8 ± 12.2 pg/m; P < 0.01) and IGF-1 (6.3 ± 41.4 ng/mL; P < 0.05). Women on DHEA had increases in lumbar spine (1.0% ± 3.4%) and trochanter (0.5% ± 3.8%) BMD and maintained total hip BMD (0.0% ± 2.8%); men had no BMD benefit and a decrease in fat mass (-0.4 ± 2.6 kg; all P < 0.01 vs placebo). CONCLUSIONS: Dehydroepiandrosterone therapy may be an effective approach for preserving bone and muscle mass in women. Key questions are (a) the extent to which longer duration DHEA can attenuate the loss of bone and muscle in women, and (b) whether DHEA has a more favourable benefit-to-risk profile for women than oestrogen therapy.

Effect of Diphosphonates on Bone Mineral Density in Men Receiving Androgen Deprivation Therapy for Prostate Cancer.

Patients receiving androgen deprivation therapy are associated with increasing loss of bone mineral density (BMD) and higher risk of skeletal-related events. We reviewed and analyzed the influence of diphosphonates on BMD change. A systemic literature research was conducted in PubMed and related bibliographies. The focus of data extraction was BMD percentage change of lumbar spine, total hip, and femoral neck after 12 months. Standardized mean difference (SMD) was pooled with the random-effects model, and metaregression and subgroup analysis were performed to explore heterogeneity. Nine articles (n = 920) were included and finally analyzed after screening 118 articles. We found significant improvement in BMD percentage changes of the lumbar spine, total hip, and femoral neck at 1 year (respectively, SMD = 6.379, 95% confidence interval [CI] = 3.740-9.018, P < .001, I2 = 98.8%, P < .001; SMD = 4.870, 95% CI, 2.256-7.485, P < .001, I2 = 98.9%, P < .001; SMD = 3.634, 95% CI, 1.989-5.279, P < .001, I2 = 97.3%, P < .001). In individual variable metaregression analysis, application zoledronic acid or not showed a statistically significant influence on BMD percentage change of total hip (P = .018). In subgroup analyses, both zoledronic acid and alendronate showed a significant improvement in BMD percentage changes. Diphosphonates significantly increased BMD percentage changes of the lumbar spine, total hip, and femoral neck in men receiving androgen deprivation therapy for prostate cancer. Patients with androgen deprivation therapy should be evaluated BMD loss, and timely therapy with diphosphonates may be an appropriate strategy to prevent osteoporosis.

Efficacy of discontinuing risedronate for patients with systemic lupus erythematosus: a prospective study.

Objective The objective of this study is to investigate the effectiveness of discontinuation of risedronate for patients with systemic lupus erythematosus (SLE) treated with glucocorticoid (GC). Methods The participants were patients with SLE treated with prednisolone (PSL) ≥ 2 mg/day and risedronate for at least three years. Lumbar spine and total hip bone mineral density (BMD) measurements were taken at baseline and 24 and 48 weeks after discontinuation of risedronate, and bone turnover markers were evaluated at baseline, 12, 24, 36, and 48 weeks. Results A total of 36 patients were enrolled, 25 of whom discontinued risedronate. The mean age was 46.8 ± 11.2 years, and 23 were female. The mean duration of GC treatment was 14.8 ± 11.4 years, the mean dose of PSL was 7.8 ± 3.9 mg/day, and the mean duration of risedronate was 5.8 ± 2.4 years. Seventeen patients showed decreased lumbar spine BMD at 48 weeks after discontinuation of risedronate, with a mean lumbar spine lumbar decrease of 1.42% ± 3.20% ( p = 0.034); 17 patients (71%) showed a decreased total hip BMD at 48 weeks after discontinuation of risedronate, with a mean total hip BMD decrease of 0.99% ± 2.10% ( p = 0.021). Serum tartrate-resistant acid phosphatase 5b (TRACP-5b) ≥ 309 mU/dl at baseline was a risk factor for decreased total hip BMD at 48 weeks compared with serum TRACP-5b < 309 mU/dl (56% vs 0%, p = 0.0098). One patient developed a clinical fracture of the lumbar spine at 20 weeks. Conclusions Discontinuation of risedronate treatment in patients with SLE who had received GC therapy led to decreases in lumbar spine and total hip BMD, particularly in patients with high baseline serum TRACP-5b levels.

Teriparatide treatment exerts differential effects on the central and peripheral skeleton: results from the MOAT study.

The central and peripheral skeleton was characterised using imaging techniques during 104 weeks of teriparatide treatment. Teriparatide exerts differential effects on the central and the peripheral skeleton. Overall, we did not observe a change in total body bone mineral. Our conclusions are constrained by the study limitations. INTRODUCTION: Teriparatide stimulates bone formation and resorption and therefore can cause bone gain and loss. We simultaneously characterised the central and peripheral skeleton using imaging techniques to better understand the mechanism of action of teriparatide. METHODS: Postmenopausal, osteoporotic women (n = 20, 65.4 ± 5.5 years) were recruited into a 104-week study of teriparatide. Imaging techniques included DXA, quantitative computed tomography (QCT), and high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: Total lumbar spine areal bone mineral content (aBMC) (+ 11.2%), total lumbar spine areal bone mineral density (aBMD) (+ 8.1%), subregional thoracic spine aBMD (+ 7.5%), lumbar spine aBMC (+ 23.5%), lumbar spine aBMD (+ 11.9%), pelvis aBMC (+ 9.3%), and pelvis aBMD (+ 4.3%) increased. However, skull aBMC (- 5.0%), arms aBMC (- 5.1%), legs aBMC (- 2.9%), and legs aBMD (- 2.5%) decreased. Overall, we did not observe a change in total body bone mineral. Increases in L1-L3 volumetric BMD (vBMD) (+ 28.5%) occurred but there was no change in total proximal femur vBMD. Radius and tibia cortical vBMD (- 3.3 and - 3.4%) and tissue mineral density (- 3.2 and - 3.8%) decreased and there was an increase in porosity (+ 21.2 and + 10.3%). Tibia, but not radius, trabecular inhomogeneity (+ 3.2%), and failure load (+ 0.2%) increased, but cortical thickness (- 3.1%), area (- 2.9%), and pore volume (- 1.6%) decreased. CONCLUSIONS: Teriparatide exerts differential effects on the central and the peripheral skeleton. Central trabecular vBMD (L1-L3) is improved, but there is a concomitant decrease in peripheral cortical vBMD and an increase in porosity. Overall, we did not observe a change in total body bone mineral. We acknowledge that our conclusions may be speculative and are constrained by the technical limitations of the imaging techniques used, the lack of a control group, and the small sample size studied.

Variability of Denosumab densitometric response in postmenopausal osteoporosis.

The objective of our prospective study is to specify the variability of densitometric response to Denosumab, given in the second line, and to try to understand the reasons. All menopausal patients with primary osteoporosis, treated by Denosumab in our centre from 2014 to 2015, were included in this open prospective work. At T0, the patient's age, type of fracture, and previous treatments were collated. At T0 and T1, after 1 year of treatment by Dmab, a DXA of the spine and the hip and a determination of CTX were performed. Sixty-three patients aged 68.8 ± 8.3 years were included. The median number of treatments prescribed for osteoporosis before switch to Denosumab was 2.4. The median duration of these treatments was 7.2 years. At T1, CTX was less than 33 pg/ml (minimum threshold for our assay kit) in all patients. The median BMD in the spine increased by + 5.44% compared to T0. 14 patients in the upper quartile had a median BMD gain in the spine of + 11.07%. Fourteen patients in the lower quartile had a median BMD gain in the spine of + 0.6%. Only the duration of previous treatments, which was greater in the non-responder group, differed between these two groups. In the total cohort, the spinal densitometric gain was negatively correlated with the age of the patient at baseline (p = 0.04), the duration of previous treatment (p = 0.02), and positively with the CTX level (p = 0.05). The Dmab densitometric response is highly variable, partly explained by the duration of previous treatments and the level of bone resorption at initiation of treatment.

High incidence of aseptic hip necrosis in Hodgkin lymphoma patients treated with escalated BEACOPP receiving methylprednisolone.

BACKGROUND: Escalated BEACOPP (eBEACOPP) is an effective but fairly toxic regimen for the treatment of Hodgkin lymphoma (HL). Avascular necrosis (AVN) of femoral head was previously reported to increase in patients treated with eBEACOPP, but so far, no systematic analysis of its frequency has been published. AIMS: To analyse the frequency and identify possible risk factors for AVN development in patients treated with eBEACOPP. METHODS: We identified 26 patients treated with eBEACOPP for newly diagnosed high-risk advanced-stage HL, 25 of whom were alive at the time of study. All patients were invited to participate in a cross-sectional study; 17 patients responded and were evaluated by magnetic resonance imaging and orthopaedic examination. RESULTS: Six patients (35.3%) were diagnosed with AVN after receiving eBEACOPP treatment. AVN was not correlated with age, gender, number of received eBEACOPP cycles, irradiation therapy or cumulative dose of steroids administered. There were significantly more cases of AVN in patients receiving methylprednisolone than prednisone (P = 0.01). CONCLUSION: The use of methylprednisolone was shown to be a risk factor for the development of AVN in patients treated with eBEACOPP and should not be the corticosteroid of choice in the treatment of patients with HL.

Incorporating 18FDG-PET-defined pelvic active bone marrow in the automatic treatment planning process of anal cancer patients undergoing chemo-radiation.

BACKGROUND: To investigate whether the incorporation of 18FDG-PET into the automatic treatment planning process may be able to decrease the dose to active bone marrow (BM) for locally advanced anal cancer patients undergoing concurrent chemo-radiation (CHT-RT). METHODS: Ten patients with locally advanced anal cancer were selected. Bone marrow within the pelvis was outlined as the whole outer contour of pelvic bones or employing 18FDG-PET to identify active BM within osseous structures. Four treatment planning solutions were employed with different automatic optimization approaches toward bone marrow. Plan A used iliac crests for optimization as per RTOG 05-29 trial; plan B accounted for all pelvic BM as outlined by the outer surface of external osseous structures; plan C took into account both active and inactive BM as defined using 18FDG-PET; plan D accounted only for the active BM subregions outlined with 18FDG-PET. Dose received by active bone marrow within the pelvic (ACTPBM) and in different subregions such as lumbar-sacral (ACTLSBM), iliac (ACTIBM) and lower pelvis (ACTLPBM) bone marrow was analyzed. RESULTS: A significant difference was found for ACTPBM in terms of Dmean (p = 0.014) V20 (p = 0.015), V25 (p = 0.030), V30 (p = 0.020), V35 (p = 0.010) between Plan A and other plans. With respect to specific subsites, a significant difference was found for ACTLSBM in terms of V30 (p = 0.020)), V35 (p = 0.010), V40 (p = 0.050) between Plan A and other solutions. No significant difference was found with respect to the investigated parameters between Plan B,C and D. No significant dosimetric differences were found for ACTLSPBM and ACTIBM and inactive BM subregions within the pelvis between any plan solution. CONCLUSIONS: Accounting for pelvic BM as a whole compared to iliac crests is able to decrease the dose to active bone marrow during the planning process of anal cancer patients treated with intensity-modulated radiotherapy. The same degree of reduction may be achieved optimizing on bone marrow either defined using the outer bone contour or through 18FDG-PET imaging. The subset of patients with a benefit in terms of dose reduction to active BM through the inclusion of 18FDG-PET in the planning process needs further investigation.

The Impact of Antihypertensive Medications on Bone Mineral Density and Fracture Risk.

PURPOSE OF REVIEW: This review summarizes the impact of thiazide diuretics on fracture risk in older hypertensive individuals. RECENT FINDINGS: We performed a post hoc evaluation of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a randomized, prospective, double blind hypertension study comparing a thiazide-like diuretic, a calcium channel blocker (CCB), and an angiotensin converting enzyme inhibitor (ACEi). We examined the risk of hip and pelvic fractures during the in-trial period (n = 22,180 participants; mean 4.9-year follow-up) and during the post-trial period using national data bases (n = 16,622 participants) (mean total follow-up 7.8 years). During the trial, participants randomized to the thiazide diuretic versus the CCB or the ACEi had a lower risk of fracture on adjusted analyses (HR 0.79 [95% CI, 0.63, 0.98], p = 0.04). Risk of fracture was significantly lower in participants randomized to the diuretic as compared to those randomized to the ACEi (HR 0.75 [95% CI, 0.58, 0.98]; p = 0.04), but not significantly different compared to the CCB (HR 0.87 [95% CI, 0.71, 1.09]; p = 0.17). Over the entire trial and post-trial period of follow-up, the cumulative incidence of fractures was non-significantly lower in participants assigned to the diuretic vs assignment to the ACEi or the CCB (HR 0.87 [0.74-1.03], p = 0.10) and versus each medication separately. These findings establish a benefit for thiazide diuretic treatment for the prevention of fractures versus other commonly used antihypertensive medications using prospective, randomized data. The effects of the thiazide diuretic on bone appear to be long lasting.

Updated association of tea consumption and bone mineral density: A meta-analysis.

BACKGROUND: Current studies evaluating the association of tea consumption and bone mineral density (BMD) have yielded inconsistent findings. Therefore, we conducted a meta-analysis to assess the relationship between tea consumption and BMD. METHODS: The PubMed, Embase, and Cochrane Library databases were comprehensively searched, and a meta-analysis performed of all observational studies assessing the association of tea consumption and BMD. Forest plots were used to illustrate the results graphically. The Q-test and I statistic were employed to evaluate between-study heterogeneity. Potential publication bias was assessed by the funnel plot. RESULTS: Four cohort, 1 case-control, and 8 cross-sectional studies including a total of 12,635 cases were included. Tea consumption was shown to prevent bone loss [odds ratio (OR): 0.66; 95% confidence interval (CI), 0.47-0.94; P = 0.02], yielding higher mineral densities in several bones, including the lumbar spine [standardized mean difference (SMD): 0.19; 95% CI, 0.08-0.31; P = 0.001], hip (SMD: 0.19; 95% CI, 0.05-0.34; P = 0.01), femoral neck [mean difference (MD): 0.01; 95% CI, 0.00-0.02; P = 0.04], Ward triangle (MD: 0.02; 95% CI, 0.01-0.04; P = 0.001), and greater trochanter (MD: 0.03; 95% CI, 0.02-0.04; P < 0.00001), than the non-tea consumption group. CONCLUSION: This meta-analysis provided a potential trend that tea consumption might be beneficial for BMD, especially in the lumbar spine, hip, femoral neck, Ward triangle, and greater trochanter, which might help prevent bone loss.

Assessment of semaphorin 3A and its role in bone remodelling in a group of ankylosing spondylitis patients.

OBJECTIVES: Several molecules are involved in the pathogenesis of new bone formation in ankylosing spondylitis (AS). The aim of the present study was to evaluate serum levels of semaphoring 3A in AS and to investigate any correlations with radiographic damage, disease activity, function and treatment. METHODS: AS patients who fulfilled the modified New York criteria were enrolled for this study. Healthy subjects were also enrolled as control group. BASDAI, ASDAS-CRP, BASMI, BASFI, patients and physician VAS, C-reactive protein and erythrocyte sedimentation rate were evaluated at baseline visit. Radiographs of the spine and pelvis performed within six months from the enrolment in the study were collected in all patients. Spinal damage was assessed using the mSASSS. Serum concentrations of semaphorin3A were assessed at baseline and after four months of therapy in patients who started an anti-TNF. RESULTS: Twenty healthy subjects and forty AS patients were enrolled in the study. Of these patients, 15 started anti-TNF therapy the day of baseline visit. Semaphorin3A serum concentrations [median (25th-75th)] were similar in AS patients [0.26 (0.20-0.31) ng/ml] and controls [0.28 (0.26-0.3) ng/ml; p=ns). No significant correlation was found between semaphorin 3A serum levels and radiographic damage index. Semaphorin 3A serum levels positively correlated with ESR values (rho=0.37, p=0.049) and with disease activity assessed by the physician VAS (rho=0.47, p<0.01). No differences were found in the semaphorin3A serum levels after 4 months, compared to baseline values. CONCLUSIONS: The results of the present study could contribute to the intriguing topic of bone remodelling in AS.

The Benefit of Menopausal Hormone Therapy on Bone Density and Microarchitecture Persists After its Withdrawal.

CONTEXT: Menopausal hormone therapy (MHT) favorably affects bone mineral density (BMD). Whether MHT also affects bone microarchitecture, as assessed by trabecular bone score (TBS), has never been evaluated. OBJECTIVE: Our objective was to assess the effect of MHT on TBS and BMD before and after its withdrawal. DESIGN: This was a cross-sectional study. SETTING: This study included the general community. PATIENTS OR OTHER PARTICIPANTS: Data were collected from the OsteoLaus cohort (1500 women aged 50-80 years). After exclusion of women with bone-modulating treatments, 1279 women were categorized according to MHT status into current (CU), past (PU), and never (NU) users. MAIN OUTCOME MEASURE(S): Spine TBS and BMD at lumbar spine, femoral neck, and total hip were assessed by dual X-ray absorptiometry. RESULTS: Age- and body mass index-adjusted analysis showed higher TBS values in CU vs PU or NU (1.31 ± 0.01, 1.29 ± 0.01, and 1.27 ± 0.01, respectively; P < .001). All BMD values were significantly higher in CU vs PU or NU. Compared to NU, PU exhibited higher lumbar spine (0.94 ± 0.01 vs 0.91 ± 0.01 g/cm2; P = .017) and total hip (0.86 ± 0.01 vs 0.84 ± 0.01 g/cm2; P = .026) BMD and a trend for higher TBS (P = .066). The 10-year loss of TBS and BMD at lumbar spine and total hip was significantly lower for both CU and PU vs NU. MHT duration had no effect on bone parameters. In PU, the residual effect on TBS and BMD was significantly more prominent in early discontinuers (<2 years). CONCLUSION: MHT is associated with bone microarchitecture preservation, as assessed by TBS. The effect of MHT on TBS and BMD persists at least 2 years after withdrawal.

Assessing the Efficacy of Prothrombin Complex Concentrate in Multiply Injured Patients With High-Energy Pelvic and Extremity Fractures.

OBJECTIVES: Prothrombin complex concentrate (PCC) is being increasingly used for reversing induced coagulopathy of trauma. However, the use of PCC for reversing coagulopathy in multiply injured patients with pelvic and/or lower extremity fractures remains unclear. The aim of our study was to assess the efficacy of PCC for reversing coagulopathy in this group of patients. DESIGN: Two-year retrospective analysis. SETTING: Our level I trauma center. PATIENTS/PARTICIPANTS: All coagulopathic [International normalized ratio (INR) ≥1.5] trauma patients. Patients with femur, tibia, or pelvic fracture were included. Patients were divided into 2 groups: PCC (single dose) and fresh frozen plasma (FFP). Patients in the 2 groups were matched using propensity score matching. MAIN OUTCOME MEASUREMENTS: Time to correction of INR, time to intervention, development of thromboembolic complications, mortality, and cost of therapy. RESULTS: A total of 81 patients (PCC: 27, FFP: 54) were included. Patients who received PCC had faster correction of INR and shorter time to surgical intervention in comparison to patients who received FFP. PCC therapy was also associated with lower overall blood product requirement (P = 0.02) and lower transfusion costs (P = 0.0001). CONCLUSIONS: In a matched cohort of multiply injured patients with pelvic and/or lower extremity fractures, administration of a single dose of PCC significantly reduced the time to correction of INR and time to intervention compared with patients who received FFP therapy. This may allow orthopaedic surgeons to more safely proceed with early, definitive fixation strategies. LEVEL OF EVIDENCE: Therapeutic level III. See Instructions for Authors for a complete description of levels of evidence.

Detection of a primary tumor in the area of the renal artery with 18F-FDG PET/CT in a patient with metastatic undifferentiated sarcoma and a history of mid-aortic syndrome: A case report.

BACKGROUND: We present a case of a 57-year-old woman patient with a history of mid-aortic syndrome, treated with several vascular procedures, who was referred for investigation of metastatic disease of an undifferentiated sarcoma of unknown origin. METHODS: Positron emission tomography/computed tomography (PET/CT) demonstrated multiple fluorodeoxyglucose (F-FDG) avid lung, liver, and osseous metastases as well as a focus of increased F-FDG uptake in the area of the stented left renal artery. RESULT: Histologic evaluation of soft tissue from the region of the left renal artery revealed atypical spindle cells, consistent with an intimal sarcoma, and with histopathological characteristics identical to those of lung metastases, indicating the F-FDG avid lesion in the area of the renal artery as the origin of the metastatic disease. CONCLUSION: This case highlights the capacity of F-FDG PET/CT to detect primary tumors even of small size and in unusual localisations. Moreover, it provides further indications regarding the potential association between foreign body reaction on the basis of chronic inflammation and sarcoma development.

Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial.

IMPORTANCE: Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor. OBJECTIVE: To determine the efficacy and safety of abaloparatide, 80 µg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture. DESIGN, SETTING, AND PARTICIPANTS: The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll. INTERVENTIONS: Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 µg (n = 824); or open-label teriparatide, 20 µg (n = 818) for 18 months. MAIN OUTCOMES AND MEASURES: Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants. RESULTS: Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text]. CONCLUSIONS AND RELEVANCE: Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01343004.