Improving Bone Mineral Density Screening by Using Digital X-Radiogrammetry Combined With Mammography.

Fracture risk evaluation of postmenopausal women is suboptimal, but most women undergo screening mammography. Digital X-radiogrammetry (DXR) determines bone mineral density (BMD) at the metacarpal shaft and can be performed on mammography equipment. This study examined correlations between DXR and dual-energy X-ray absorptiometry (DXA) in women undergoing mammography, to identify optimal DXR thresholds for triage to osteoporosis screening by central DXA. Postmenopausal women over age 50 years, recruited from Westmead Hospital's Breast Cancer Institute, underwent mammography, DXR and DXA. Agreements were determined using the area under the receiver operator characteristic (AUC ROC) curve and Lin's concordance correlation coefficient. Optimal DXR T-scores to exclude osteoporosis by DXA were determined using the Youden's method. Of 200 women aged 64 ± 7 years (mean ± standard deviation [SD]), 82% had been diagnosed with breast cancer and 37% reported prior fracture. DXA T-scores were ≤ -1 at the spine, hip or forearm in 77.5% and accorded with DXR T-scores in 77%. For DXR and DXA T-scores ≤ -2.5, the AUC ROC was 0.87 (95% confidence interval [CI], 0.81-0.94) at the 1/3 radius, and 0.74 (95% CI, 0.64-0.84) for hip or spine. DXR T-scores > -1.98 provided a negative predictive value of 94% (range, 88%, 98%) for osteoporosis by central DXA. In response to a questionnaire, radiography staff responded that DXR added 5 minutes to patient throughput with minimal workflow impact. In the mammography setting, triaging women with a screening DXR T-score < -1.98 for DXA evaluation would capture a significant proportion of at-risk women who may not otherwise be identified and improve current low rates of osteoporosis screening. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Dual Hip DXA. Is it Time to Change Standard Protocol?

Previous studies have examined the utility of bilateral DXA hip bone mineral density (BMD) scans. While most studies demonstrate an advantage of bilateral hip scanning, the studies have been limited by size, or have not included simultaneous lumbar spine scans. To analyse the utility of dual hip scans in a clinical environment, a large retrospective study was performed of DXA BMD of both hips, and lumbar spine, in 17,169 individuals assessed at one centre over 10 years. There was no clinically significant difference in the population mean femoral neck BMD of the left vs the right leg (0.878 vs 0.881g/cm2) or total proximal femoral BMD of the left vs the right leg (0.920 vs 0.919g/cm2). There were however discrepancies in individuals between hip t-scores. For the total hip 1,977 (11.5 %) and 147 (0.9 %) of subjects had absolute t score differences ≥ 0.50 or ≥ 1.00. respectively. For the femoral neck 3,320 (19.3%) and 337 (2.0%) of subjects had absolute t score differences ≥ 0.50 or ≥ 1.00. respectively. Of the total 17,169 individuals there were 2,776 subjects with osteoporosis (T≤ -2.5) using the lumbar spine and right hip, compared to 2,834 subjects using the lumbar spine and left hip. Using the lumbar spine and both hips identified 3,214 individuals with osteoporosis. Diagnosis based on use of the lumbar spine and right hip BMD, or lumbar spine and left hip BMD, therefore failed to identify 15.8%, or 13.4%, of osteoporotic subjects respectively. Additional scanning time required was assessed in 40 subjects prospectively. Performing lumbar spine and both hips, compared to lumbar spine and one hip, required an average additional scan time of 55 seconds. The recommendation of best practise for DXA BMD measurements should be reviewed to consider lumbar spine and dual hip DXA as standard of care.

Roux-en-Y gastric bypass and gastric sleeve surgery result in long term bone loss.

OBJECTIVES: Little is known about the long-term skeletal impact of bariatric procedures, particularly the increasingly commonly performed gastric sleeve surgery (GS). We examined bone density (BMD) change following three types of bariatric surgery Roux-en-Y gastric bypass (RYGB), GS and laparoscopic adjustable gastric banding (LAGB), compared with diet, over 36 months. METHODS: Non-randomized, prospective study of participants with severe obesity (n = 52), undergoing weight-loss interventions: RYGB (n = 7), GS (n = 21), LAGB (n = 11) and diet (n = 13). Measurements of calciotropic indices, gut hormones (fasting and post prandial) peptide YY (PYY), glucagon-like peptide 1 (GLP1) and adiponectin together with dual-X-ray absorptiometry and quantitative computed tomography scans were performed thorough the study. RESULTS: All groups lost weight during the first 12 months. Despite weight stability from 12 to 36 months and supplementation of calcium and vitamin D, there was progressive bone loss at the total hip (TH) over 36 months in RYGB -14% (95% CI: -12, -17) and GS -9% (95% CI: -7, -10). In RYGB forearm BMD also declined over 36 months -9% (95% CI: -6, -12) and LS BMD declined over the first 12 months -7% (95% CI: -3, -12). RYGB and GS groups experienced significantly greater bone loss until 36 months than LAGB and diet groups, which experienced no significant BMD loss. These bone losses remained significant after adjustment for weight loss and age. RYGB and GS procedures resulted in elevated postprandial PYY, adiponectin and bone turnover markers up to 36 months without such changes among LAGB and diet participants. CONCLUSIONS: RYGB and GS but not LAGB resulted in ongoing TH bone loss for three postoperative years. For RYGB, bone loss was also observed at LS and non-weight-bearing forearms. These BMD changes were independent of weight and age differences. We, therefore, recommend close monitoring of bone health following RYGB and GS surgeries.

Clinical Utility of Computer-Aided Diagnosis of Vertebral Fractures From Computed Tomography Images.

Osteoporotic vertebral compression fractures (VCFs) are a risk factor for morbidity and mortality, frequently asymptomatic and often present in computed tomography (CT) scans performed for unrelated conditions. Computer-aided diagnosis (CAD) of VCF from such images can potentially improve identification and treatment of osteoporosis. This single-blinded, single tertiary center study compared a CAD (Zebra Medical Vision®) to an adjudicated imaging specialist reevaluation using a retrospective consecutive sample of abdominal and thoracic CT scans (n = 2357) performed as part of routine care. Subjects over 50 years between January 1, 2019 and May 12, 2019 were included. Duplicates and unanalyzable scans were excluded resulting in a total of 1696 CT scans. The sensitivity, specificity, and accuracy were calculated for all VCF and for Genant grades 2 or 3 (ie, height loss of >25%) using imaging specialist as the gold standard. Prestudy VCF reporting by hospital-rostered radiologist was used to calculate the number of scans needed to screen (NNS) to detect one additional VCF using CAD. Prevalence of any VCF was 24% (406/1696) and of Genant 2/3 VCF was 18% (280/1570). The sensitivity and specificity were 54% and 92%, for all fractures, respectively, and 65% and 92% for Genant 2/3 fractures, respectively. Accuracy for any VCF, and for detection of Genant 2/3 VCF, was 83% and 88%, respectively. Of 221 CAD-detected VCFs, 133 (60.2%) were reported prestudy resulting in 88 additional fractures (72 Genant 2/3) being identified by CAD. NNS to detect one additional VCF was 19 scans for all fractures and 23 for Genant 2/3 fractures. Thus, the CAD tested in this study had a high specificity with moderate sensitivity to detect incidental vertebral fractures in CT scans performed for routine care. A low NNS suggests it is an efficient tool to assist radiologists and clinicians to improve detection and reporting of vertebral fractures. © 2020 American Society for Bone and Mineral Research (ASBMR).

Prolonged Effect of Zoledronic Acid on Bone Mineral Density and Turnover in HIV-Infected Adults on Tenofovir: A Randomized, Open-Label Study.

Zoledronic acid (ZOL) 5 mg annually was more effective than tenofovir disoproxil fumarate (TDF) switching at increasing bone mineral density (BMD) over 24 months in HIV-infected, osteopenic adults. To determine whether the effects of ZOL would persist without further infusions, we compared changes in left hip and spine BMD over 36 months in participants randomized to ZOL 5 mg at baseline and month 12 (and to continue TDF) or to switch TDF (without receiving ZOL). We also compared changes in the plasma bone turnover markers (BTMs) C-terminal telopeptide of type 1 collagen (CTX; bone resorption), and procollagen type 1 N propeptide (P1NP; bone formation) and determined whether CTX and P1NP changes at month 3 predicted BMD changes at month 36. Changes were compared in the per-protocol populations, which included 32 (74%) of 43 participants randomized to ZOL and 37 (88%) of 42 participants who switched TDF. Despite not receiving ZOL after month 12, mean hip and spine BMD change from baseline were stable and remained greater with ZOL at month 36 than with TDF switching (spine: 7.5% versus 2.7%, mean difference 4.7%, p < 0.001; hip: 5.5% versus 1.5%, mean difference 4.0%, p < 0.001). CTX and P1NP levels declined in both groups but significantly more with ZOL. Only percent changes in P1NP at month 3 correlated inversely with BMD changes at month 36 (spine: rho = -0.442, p < 0.001; hip: rho = -0.373, p = 0.002). Two infusions of ZOL (in the presence of ongoing TDF) yielded sustained BMD increases through month 36 that remained greater than with TDF switching. © 2019 American Society for Bone and Mineral Research.

Longitudinal Changes in Insulin Resistance in Normal Weight, Overweight and Obese Individuals.

BACKGROUND: Large cohort longitudinal studies have almost unanimously concluded that metabolic health in obesity is a transient phenomenon, diminishing in older age. We aimed to assess the fate of insulin sensitivity per se over time in overweight and obese individuals. METHODS: Individuals studied using the hyperinsulinaemic-euglycaemic clamp at the Garvan Institute of Medical Research from 2008 to 2010 (n = 99) were retrospectively grouped into Lean (body mass index (BMI) < 25 kg/m2) or overweight/obese (BMI ≥ 25 kg/m2), with the latter further divided into insulin-sensitive (ObSen) or insulin-resistant (ObRes), based on median clamp M-value (M/I, separate cut-offs for men and women). Fifty-seven individuals participated in a follow-up study after 5.4 ± 0.1 years. Hyperinsulinaemic-euglycaemic clamp, dual-energy X-ray absorptiometry and circulating cardiovascular markers were measured again at follow-up, using the same protocols used at baseline. Liver fat was measured using computed tomography at baseline and proton magnetic resonance spectroscopy at follow-up with established cut-offs applied for defining fatty liver. RESULTS: In the whole cohort, M/I did not change over time (p = 0.40); it remained significantly higher at follow-up in ObSen compared with ObRes (p = 0.02), and was not different between ObSen and Lean (p = 0.41). While BMI did not change over time (p = 0.24), android and visceral fat increased significantly in this cohort (ptime ≤ 0.0013), driven by ObRes (p = 0.0087 and p = 0.0001, respectively). Similarly, systolic blood pressure increased significantly over time (ptime = 0.0003) driven by ObRes (p = 0.0039). The best correlate of follow-up M/I was baseline M/I (Spearman's r = 0.76, p = 1.1 × 10-7). CONCLUSIONS: The similarity in insulin sensitivity between the ObSen and the Lean groups at baseline persisted over time. Insulin resistance in overweight and obese individuals predisposed to further metabolic deterioration over time.

Zoledronic acid is superior to tenofovir disoproxil fumarate-switching for low bone mineral density in adults with HIV.

OBJECTIVE: To compare the effects of switching tenofovir disoproxil fumarate (TDF) or treatment with an intravenous bisphosphonate on bone mineral density (BMD) in HIV-positive adults with low bone mass. DESIGN: Two-year, randomized, open-label study at 10 sites in Australia and Spain. PARTICIPANTS: Of 112 adults on TDF-based antiretroviral therapy (ART) screened, 87 with low BMD (T-score < -1.0 at hip or spine by dual-energy X-ray absorptiometry) and undetectable plasma HIV viral load were randomized to either switch TDF to another active antiretroviral drug or to continue TDF-based ART and receive intravenous zoledronic acid (ZOL) 5 mg annually for 2 years. PRIMARY OUTCOME MEASURE: Change in lumbar spine BMD at 24 months by intention-to-treat analysis. Secondary outcomes included changes in femoral neck and total hip BMD, fractures, safety, and virological failure. RESULTS: Forty-four participants were randomized to TDF switch and 43 to ZOL, mean age 50 years (SD 11), 96% men, mean TDF duration 5.9 years (SD 3.1), and mean spine and hip T-scores -1.6 and -1.3, respectively. At 24 months, mean spine BMD increased by 7.4% (SD 4.3%) with ZOL vs. 2.9% (SD 4.5%) with TDF-switch (mean difference 4.4%, 95% CI 2.6-6.3; P < 0.001). Mean total hip BMD increased by 4.6 (SD 2.6%) and 2.6% (SD 4%), respectively (mean difference 1.9%, 95% CI 0.5-3.4; P = 0.009). There was one fracture in the ZOL group vs. seven fractures in four TDF-switch participants. Virological failure occurred in one TDF-switch participant. Other safety endpoints were similar. CONCLUSION: ZOL is more effective than switching TDF at increasing BMD in HIV-positive adults with low bone mass.

Nonstandard Lumbar Region in Predicting Fracture Risk.

Femoral neck (FN) bone mineral density (BMD) is the most commonly used skeletal site to estimate fracture risk. The role of lumbar spine (LS) BMD in fracture risk prediction is less clear due to osteophytes that spuriously increase LS BMD, particularly at lower levels. The aim of this study was to compare fracture predictive ability of upper L1-L2 BMD with standard L2-L4 BMD and assess whether the addition of either LS site could improve fracture prediction over FN BMD. This study comprised a prospective cohort of 3016 women and men over 60 yr from the Dubbo Osteoporosis Epidemiology Study followed up for occurrence of minimal trauma fractures from 1989 to 2014. Dual-energy X-ray absorptiometry was used to measure BMD at L1-L2, L2-L4, and FN at baseline. Fracture risks were estimated using Cox proportional hazards models separately for each site. Predictive performances were compared using receiver operating characteristic curve analyses. There were 565 women and 179 men with a minimal trauma fracture during a mean of 11 ± 7 yr. L1-L2 BMD T-score was significantly lower than L2-L4 T-score in both genders (p < 0.0001). L1-L2 and L2-L4 BMD models had a similar fracture predictive ability. LS BMD was better than FN BMD in predicting vertebral fracture risk in women [area under the curve 0.73 (95% confidence interval, 0.68-0.79) vs 0.68 (95% confidence interval, 0.62-0.74), but FN was superior for hip fractures prediction in both women and men. The addition of L1-L2 or L2-L4 to FN BMD in women increased overall and vertebral predictive power compared with FN BMD alone by 1% and 4%, respectively (p < 0.05). In an elderly population, L1-L2 is as good as but not better than L2-L4 site in predicting fracture risk. The addition of LS BMD to FN BMD provided a modest additional benefit in overall fracture risk. Further studies in individuals with spinal degenerative disease are needed.

Male Osteoporosis Awareness in the Elderly: an Analysis of Dual-Energy X-Ray Absorptiometry Use in Australia Between 1995 and 2015.

Osteoporosis is commonly perceived to be a disease confined to aging females, despite ongoing educational interventions. There are few data on the temporal change of dual-energy X-ray absorptiometry (DXA) use in aging males compared to females. Australian Medicare DXA claims between 1995 and 2015 were analyzed to investigate gender differences and temporal change of DXA use in males and females aged 45-85 yr. In females aged 45-54 and 55-64 yr, there was a progressive increase in DXA claims per capita between 1995 until 2002, with little subsequent change from 2002 to 2015 in the younger group, but a slow subsequent increase in females aged 55-64 yr. In males aged 45-54 and 55-64 yr, there was a progressive increase in DXA claims per capita between 1995 and 2002 with an ongoing slow increase from 2002 to 2015. In older females and males aged 65-74, 75-84, or ≥85 yr, there was a progressive increase in DXA claims per capita between 1995 and 2002, with a slow increase thereafter until 2007. After 2007, following the introduction of Medicare eligibility for age over 70, claims per capita increased sharply in all 3 age groups, with a subsequent ongoing increase. The male : female claim ratio in all groups demonstrates low relative male DXA use, with the ratio consistently below 1.0. Following the 2007 Medicare change, the male : female ratio improved in the 65-74, 75-84, and ≥85 age groups. The rate of increase in the male : female ratio in subjects ≥85 yr was significantly greater than that in the 65-74 (p < 0.001) and 75-84 (p < 0.001) age groups. DXA use in males is consistently lower than that in females. Government funding intervention appears to have been most effective in relation to very elderly males over 85 yr but less so in relation to the age group 65-84. There is a need for improved education of health professionals about the risk of osteoporosis in males aged 65-84 yr.

Use of dual energy X-ray absorptiometry, the trabecular bone score and quantitative computed tomography in the evaluation of chronic kidney disease-mineral and bone disorders.

In subjects with chronic kidney disease (CKD) who suffer a minimal trauma fracture, the problem is to differentiate between osteoporosis and the various forms of renal bone disease associated with CKD-mineral and bone disorder. This problem is exacerbated by the fact that renal osteodystrophy may coexist with osteoporosis. The World Health Organization's bone mineral density (BMD) criteria for osteopenia ( -2.5 < T-score < -1.0) and osteoporosis (a T-score ≤ -2.5) may be used in patients with CKD stages 1-3. In CKD stages 4-5, BMD by dual-energy X-ray absorptiometry (DXA) is less predictive and may underestimate fracture risk. The development of absolute fracture risk (AFR) algorithms, such as FRAX® and the Garvan absolute fracture risk calculator, to predict risk of fracture over a given time (usually 10 years) aims to incorporate non-BMD risk factors into the clinical assessment. FRAX® has been shown to be useful to assess fracture risk in CKD but may underestimate fracture risk in advanced CKD. The trabecular bone score is a measure of grey scale homogeneity obtained from spine DXA, which correlates to trabecular microarchitecture and is an independent risk factor for fracture. Recent data demonstrate the potential utility of the trabecular bone score adjustment of AFR through the FRAX® algorithm in subjects with CKD. Parameters of bone microarchitecture using peripheral quantitative computed tomography (pQCT) or high-resolution pQCT are also able to discriminate fracture status in subjects with CKD. However, there are at present no convincing data that the addition of pQCT or high-resolution pQCT parameters to DXA BMD improves fracture discrimination. More advanced estimates of bone strength derived from measurements of micro-architecture, by QCT-derived finite element analysis may be incorporated into AFR algorithms in the future.

The Effect of Changing Scan Mode on Trabecular Bone Score Using Lunar Prodigy.

Trabecular bone score (TBS) is a measure of gray scale homogeneity that correlates with trabecular microarchitecture and is an independent predictor of fracture risk. TBS is being increasingly used in the assessment of patients at risk of osteoporosis and has recently been incorporated into FRAX®. GE Lunar machines acquire spine scans using 1 of 3 acquisition modes depending on abdominal tissue thickness (thin, standard, and thick). From a database review, 30 patients (mean body mass index: 30.8, range 26.2-34.1) were identified who had undergone lumbar spine DXA scans (GE Lunar Prodigy, software 14.10; Lunar Radiation Corporation, Madison, WI) in both standard mode and thick mode, on the same day with no repositioning. Lumbar spine bone mineral density (L1-L4) and TBS were derived from the 30 paired spine scans. There was no significant difference in lumbar spine bone mineral density between the 2 scanning modes. There were, however, significant higher TBS values from the spine scans acquired in thick mode compared to the TBS values derived from spine acquisitions in standard mode (mean TBS difference: 0.24 [20%], standard deviation ±0.10). In conclusion, these preliminary data suggest that TBS values acquired in the GE Lunar Prodigy are dependent on the scanning mode used. Further evaluation is required to confirm the cause and develop appropriate protocols.

Real-time intravital imaging establishes tumor-associated macrophages as the extraskeletal target of bisphosphonate action in cancer.

UNLABELLED: Recent clinical trials have shown that bisphosphonate drugs improve breast cancer patient survival independent of their antiresorptive effects on the skeleton. However, because bisphosphonates bind rapidly to bone mineral, the exact mechanisms of their antitumor action, particularly on cells outside of bone, remain unknown. Here, we used real-time intravital two-photon microscopy to show extensive leakage of fluorescent bisphosphonate from the vasculature in 4T1 mouse mammary tumors, where it initially binds to areas of small, granular microcalcifications that are engulfed by tumor-associated macrophages (TAM), but not tumor cells. Importantly, we also observed uptake of radiolabeled bisphosphonate in the primary breast tumor of a patient and showed the resected tumor to be infiltrated with TAMs and to contain similar granular microcalcifications. These data represent the first compelling in vivo evidence that bisphosphonates can target cells in tumors outside the skeleton and that their antitumor activity is likely to be mediated via TAMs. SIGNIFICANCE: Bisphosphonates are assumed to act solely in bone. However, mouse models and clinical trials show that they have surprising antitumor effects outside bone. We provide unequivocal evidence that bisphosphonates target TAMs, but not tumor cells, to exert their extraskeletal effects, offering a rationale for use in patients with early disease.

Gender disparity in BMD conversion: a comparison between Lunar and Hologic densitometers.

UNLABELLED: Female-derived inter-conversion and standardised BMD equations at the lumbar spine and hip have not been validated in men. This study of 110 male subjects scanned on Hologic and Lunar densitometers demonstrates that published equations may not applicable to men at the lumbar spine. Male inter-conversion equations have also been derived. PURPOSE: Currently, available equations for inter-manufacturer conversion of bone mineral density (BMD) and calculation of standardised BMD (sBMD) are used in both males and females, despite being derived and validated only in women. Our aim was to test the validity of the published equations in men. METHODS: One hundred ten men underwent lumbar spine (L2-4), femoral neck (FN) and total hip (TH) dual X-ray absorptiometry (DXA) using Hologic and Lunar scanners. Hologic BMD was converted to Lunar using published equations derived from women for L2-4 and FN. Actual Lunar BMD (A-Lunar) was compared to converted (Lunar equivalent) Hologic BMD values (H-Lunar). sBMD was calculated separately using Hologic (sBMD-H) and Lunar BMD (sBMD-L) at L2-4, FN and TH. Conversion equations in men for Hologic to Lunar BMD were derived using Deming regression analysis. RESULTS: There was a strong linear correlation between Lunar and Hologic BMD at all skeletal sites. A-Lunar BMD was however significantly higher than derived H-Lunar BMD (p < 0.001) at L2-L4 (mean difference, 0.07 g/cm(2)). There was no significant difference at the FN (mean difference, 0.01 g/cm(2)). sBMD-L at the spine was significantly higher than sBMD-H (mean difference, 0.06 g/cm(2), p < 0.001), whilst there was little difference at the FN and TH (mean difference, 0.01 g/cm(2)). CONCLUSION: Published conversion equations for Lunar BMD to Hologic BMD, and formulae for lumbar spine sBMD, derived in women may not be applicable to men.

Lesson of the month 2: toxic shock syndrome.

Toxic shock syndrome (TSS) represents a fascinating example of immune activation caused by infection resulting in a dramatic and challenging clinical syndrome. TSS is commonly associated with tampon use and still causes significant morbidity and mortality in young healthy women. A misconception is that TSS presents with a skin rash and only occurs in women and children; however, it can occur in males and can present without skin changes. TSS presents initially as a febrile illness and within a few hours can progress to severe hypotension and multiple organ failure (MOF). Staphylococcus aureus and group A beta haemolytic streptococcus (GABHS) can secrete toxins from a small or hidden focus of infection and hence blood culture and sensitivity (C+S) tests can be negative, thereby making diagnosing this condition challenging. Clindamycin is superior to penicillin in the treatment of this condition and significantly decreases the mortality rate in TSS. However, there is also an important role for intravenous immunoglobulins (IVIG). Early intensive care unit (ICU) as well as surgical team involvement (in selected cases) is required to avoid mortality which may approach 70%.

Hip structural parameters over 96 weeks in HIV-infected adults switching treatment to tenofovir-emtricitabine or abacavir-lamivudine.

BACKGROUND: Therapy with tenofovir is associated with lower bone mineral density (BMD), higher markers of bone turnover and increased fracture risk in HIV-infected adults. Bone structural parameters generated by hip structural analysis may represent a separate measure of bone strength, but have not been assessed in HIV. METHODS: Dual-energy X-ray absorptiometry (DXA) scans from 254 HIV-infected adults randomised to simplify their existing dual nucleoside analogue reverse transcriptase inhibitor therapy to coformulated tenofovir-emtricitabine or abacavir-lamivudine were analysed using DXA-derived hip structural analysis software. Hip structural parameters included femoral strength index, section modulus, cross-sectional area, and cross-sectional moment of inertia. We used one-way ANOVA to test the relationship between nucleoside analogue type at baseline and structural parameters, multivariable analysis to assess baseline covariates associated with femoral strength index, and t-tests to compare mean change in structural parameters over 96 weeks between randomised groups. RESULTS: Participants taking tenofovir at baseline had lower section modulus (-107.3 mm2, p = 0.001), lower cross-sectional area (-15.01 mm3, p = 0.001), and lower cross-sectional moment of inertia (-2,036.8 mm4, p = 0.007) than those receiving other nucleoside analogues. After adjustment for baseline risk factors, the association remained significant for section modulus (p = 0.008) and cross-sectional area (p = 0.002). Baseline covariates significantly associated with higher femoral strength index were higher spine T-score (p = 0.001), lower body fat mass (p<0.001), lower bone alkaline phosphatase (p = 0.025), and higher osteoprotegerin (p = 0.024). Hip structural parameters did not change significantly over 96 weeks and none was significantly affected by treatment simplification to tenofovir-emtricitabine or abacavir-lamivudine. CONCLUSION: In this population, tenofovir use was associated with reduced composite indices of bone strength as measured by hip structural analysis, but none of the structural parameters improved significantly over 96 weeks with tenofovir cessation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00192634.

Radioembolisation with Yttrium-90 microspheres: an effective treatment modality for unresectable liver metastases.

PURPOSE: To compare the outcomes (survival and adverse events) of the authors' use of (90) Y microsphere radioembolisation in patients with chemotherapy-refractory liver metastases with published data from other groups using radioembolisation. To retrospectively evaluate the efficiency, in particular survival benefits, of radioembolisation in the treatment of liver metastases. METHODS AND MATERIALS: Over 5 years, 339 patients underwent (90) Y microsphere radioembolisation for unresectable liver metastases and were evaluated for adverse events at the time of treatment and 1 and 3 months after treatment. Overall survival (OS) was calculated by the Kaplan-Meier method. The results from the present retrospective study were compared with a number of prospective and retrospective clinical trials which have addressed the use of (90) Y microspheres as a salvage treatment for liver metastases. RESULTS: The OS time of the present study (12.0 months) compares favourably with survival times reported by other groups. The incidence of late grade 2 adverse events (e.g. duodenal or gastric ulceration, radiation-induced liver disease, gall bladder complications) is comparable to previous studies, with a lower prevalence of grade 2/3 ulcerations (3.7%) at our centre. CONCLUSIONS: The survival results, together with the low acute and late toxicity observed in our data and previous studies, support the use of radioembolisation to aid in the local control of unresectable liver metastases in the salvage setting. The present study contributes to the growing evidence for efficiency, in particular survival gains, of radioembolisation in the treatment of liver metastases.

Prevention of aromatase inhibitor-induced bone loss with alendronate in postmenopausal women: The BATMAN Trial.

UNLABELLED: Postmenopausal women on aromatase inhibitors (AI) are at risk of aromatase inhibitor-associated bone loss (AIBL) and fractures. In 2005 Osteoporosis Australia proposed an algorithm for bisphosphonate intervention. Three hundred and three postmenopausal women with early breast cancer (EBC) were enrolled (osteoporotic, n=25; osteopaenic, n=146; normal bone mineral density (BMD), n=126). Weekly alendronate (70 mg) treatment efficacy as triggered by the algorithm in preventing bone loss was evaluated. All patients received anastrozole (1 mg daily), calcium and vitamin D. RESULTS: All osteoporotic patients received alendronate at baseline. Eleven out of the 146 (7.5%) osteopaenic patients commenced alendronate within 18 months of participation and eleven commenced after. One hundred and twenty four out of the 146 (84.9%) osteopaenic patients and all 126 with normal baseline BMD did not trigger the algorithm. At three years, lumbar spine mean BMD increased (15.6%, p<0.01) in the osteoporotic group. BMD in the osteopaenic group with early intervention significantly increased at three years (6.3%, p=0.02). No significant change was seen in the late intervention group. No change was observed in those with osteopaenia without alendronate. There was a significant drop in lumbar spine (-5.4%) and hip (-4.5%) mean BMD, in the normal BMD group, none of whom received alendronate. Fracture data will be presented. CONCLUSION: In postmenopausal women with endocrine-responsive EBC, BMD improved over time when a bisphosphonate is administered with anastrozole in osteoporotic patients using an osteoporosis schedule. Subjects with normal baseline BMD experienced the greatest BMD loss, although none became osteoporotic.

Radioembolization versus standard care of hepatic metastases: comparative retrospective cohort study of survival outcomes and adverse events in salvage patients.

PURPOSE: To retrospectively evaluate the safety and survival of patients with chemotherapy-refractory liver metastases treated with yttrium-90 ((90)Y) resin microspheres, and to compare survival in this patient group versus survival after standard/supportive care to assess whether radioembolization contributes to survival gains in the salvage setting. MATERIALS AND METHODS: While 339 patients with chemotherapy-refractory liver metastases underwent (90)Y microspheres radioembolization at a single institution between 2006 and 2011, 51 patients were referred back to their treating physician for conservative treatment or best supportive care. Adverse events were assessed at the time of treatment and at 1 and 3 months after treatment. Overall survival (OS) was calculated by the Kaplan-Meier method for the radioembolization cohort (as a whole and according to two subcohorts: patients with colorectal primary cancer and patients with all other primary cancers, eg, breast or neuroendocrine) and the standard-care cohort. RESULTS: The median OS after (90)Y radioembolization (339 patients) was 12.0 months, versus 6.3 months for the standard-care cohort (51 patients; P < .001). The median OS times for the two subcohorts were 11.9 months and 12.7 months, respectively. At the 3-month follow-up, the incidence of more serious adverse events was low, with 11 cases (3%) of ulceration, 10 cases (2.9%) of radiation-induced liver disease, and six complications (1.8%) involving the gallbladder (eg, cholecystitis). CONCLUSIONS: The present study suggests that radioembolization shows promise as an effective and safe treatment for patients with chemotherapy-refractory hepatic metastases and improves overall survival in a select population of patients in a salvage setting compared with best supportive care alone.

Wound infection after reconstructive arterial surgery of the lower limbs: risk factors and consequences.

OBJECTIVE: To identify predictors, and clinical consequences, of postoperative wound infection after peripheral vascular surgery. MATERIALS AND METHODS: Retrospective cohort study. Potential predictors of wound infection were sought among patient related factors and procedure related factors. Patient outcome was then analysed according to the incidence of wound infection. RESULTS: Following 209 procedures, 20 (9.6%) patients suffered a wound infection. On univariate analysis, infrainguinal surgery, use of vein graft, and tissue loss were associated with wound infection. On multivariate regression, however, only the association with use of a vein graft remained (OR = 4.2; 95%CI = 1.2-14.1; P = .022): the incidence of wound infection was 16/96 (17%; 95%CI = 9.2-24.1) when a vein graft was used and 4/113 (3.5%; 95%CI = .1-7%) when a prosthetic or no graft was used. Wound infection was associated with increased mortality (4/20 versus 9/189; P = .025) but not limb loss (2/20 versus 7/189; P = .208). Median (IQR) postoperative hospital stay in patients with wound infection was 22 (15-45) days and 8 (5-15) days in those without wound infection (P = .001). CONCLUSIONS: In lower limb arterial surgery, wound infection is associated with the use of vein grafts, and results in delayed recovery and increased mortality. Measures to reduce wound infection should be focussed on such patients.