A critical assessment of the potential of pharmacological modulation of aldehyde dehydrogenases to treat the diseases of bone loss.

Chronic alcoholism (CA) decreases bone mass and increases the risk of hip fracture. Alcohol and its main metabolite, acetaldehyde impairs osteoblastogenesis by increasing oxidative stress. Aldehyde dehydrogenase (ALDH) is the rate-limiting enzyme in clearing acetaldehyde from the body. The clinical relevance of ALDH in skeletal function has been established by the discovery of single nucleotide polymorphism, SNP (rs671) in the ALDH2 gene giving rise to an inactive form of the enzyme (ALDH2*2) that causes increased serum acetaldehyde and osteoporosis in the affected individuals. Subsequent mouse genetics studies have replicated human phenotype in mice and confirmed the non-redundant role of ALDH2 in bone homeostasis. The activity of ALDH2 is amenable to pharmacological modulation. ALDH2 inhibition by disulfiram (DSF) and activation by alda-1 cause reduction and induction of bone formation, respectively. DSF also inhibits peak bone mass accrual in growing rats. On the other hand, DSF showed an anti-osteoclastogenic effect and protected mice from alcohol-induced osteopenia by inhibiting ALDH1a1 in bone marrow monocytes. Besides DSF, there are several classes of ALDH inhibitors with disparate skeletal effects. Alda-1, the ALDH2 activator induced osteoblast differentiation by increasing bone morphogenic protein 2 (BMP2) expression via ALDH2 activation. Alda-1 also restored ovariectomy-induced bone loss. The scope of structure-activity based studies with ALDH2 and the alda-1-like molecule could lead to the discovery of novel osteoanabolic molecules. This review will critically discuss the molecular mechanism of the ethanol and its principal metabolite, acetaldehyde in the context of ALDH2 in bone cells, and skeletal homeostasis.

Cystic fibrosis bone disease: Pathophysiology, assessment and prognostic implications.

Cystic fibrosis bone disease (CFBD) is a common long-term complication of cystic fibrosis (CF) that can lead to increased fractures and significant morbidity and mortality in this patient population. CFBD pathophysiology remains poorly understood and is likely to be multifactorial. There are limited studies evaluating diagnostic tools and tests to guide therapeutic decisions and monitoring of CFBD. This review will present and discuss the current evidence.

Evidence of Skeletal Fluorosis at the Ray Site, Illinois, USA: a pathological assessment and discussion of environmental factors.

OBJECTIVE: To carefully assess skeletal lesions in close environment context in order to evaluate whether skeletal fluorosis was present in individuals living in the prehistoric Midwest, USA. MATERIALS: Skeletal remains from minimally 117 individuals recovered from the Ray Site, located in western Illinois (USA) and dated to the Middle/early Late Woodland periods (50 BC-AD 400). METHODS: Macroscopic evaluation of all recovered skeletal elements. RESULTS: Eight individuals display a constellation of abnormal bony changes, including osteosclerosis, a high frequency of fractures, and dental abnormalities. CONCLUSIONS: The osteosclerotic changes along with the naturally high fluoride content of west central Illinois soil and water suggests the presence of skeletal fluorosis. SIGNIFICANCE: This is the first report of skeletal fluorosis from archaeologically recovered human remains from North America. LIMITATIONS: The ambiguous nature of the skeletal changes associated with fluorosis, especially in the less severe stages of the disease, renders determination of the etiology difficult. SUGGESTIONS FOR FURTHER RESEARCH: The continuation of paleopathological investigations of fluoride toxicity within archaeological communities recovered from this region with emphasis on the incorporation of biomedical and environmental data. Furthermore, complementary analyses of the chemical composition and the histological presentation of the skeletons could provide support for this diagnosis.

Neuro-musculoskeletal flexible multibody simulation yields a framework for efficient bone failure risk assessment.

Fragility fractures are a major socioeconomic problem. A non-invasive, computationally-efficient method for the identification of fracture risk scenarios under the representation of neuro-musculoskeletal dynamics does not exist. We introduce a computational workflow that integrates modally-reduced, quantitative CT-based finite-element models into neuro-musculoskeletal flexible multibody simulation (NfMBS) for early bone fracture risk assessment. Our workflow quantifies the bone strength via the osteogenic stresses and strains that arise due to the physiological-like loading of the bone under the representation of patient-specific neuro-musculoskeletal dynamics. This allows for non-invasive, computationally-efficient dynamic analysis over the enormous parameter space of fracture risk scenarios, while requiring only sparse clinical data. Experimental validation on a fresh human femur specimen together with femur strength computations that were consistent with literature findings provide confidence in the workflow: The simulation of an entire squat took only 38 s CPU-time. Owing to the loss (16% cortical, 33% trabecular) of bone mineral density (BMD), the strain measure that is associated with bone fracture increased by 31.4%; and yielded an elevated risk of a femoral hip fracture. Our novel workflow could offer clinicians with decision-making guidance by enabling the first combined in-silico analysis tool using NfMBS and BMD measurements for optimized bone fracture risk assessment.

A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in four European countries: Austria, Belgium, Greece, and Italy.

Aim: The approved indication for denosumab (120 mg) was expanded in 2018 to include skeletal-related event (SRE) prevention in patients with multiple myeloma (MM). Therefore, a cost-effectiveness analysis was conducted comparing denosumab with zoledronic acid (ZA) for SRE prevention in patients with MM from the national healthcare system perspective in a representative sample of European countries: Austria, Belgium, Greece, and Italy. Methods: The XGEVA global economic model for patients with MM was used to calculate incremental cost-effectiveness ratios (ICERs) for denosumab vs ZA over a lifetime horizon. Clinical inputs were derived from the denosumab vs ZA randomized, phase 3 study ("20090482") in patients newly-diagnosed with MM, and comprised real-world adjusted SRE rates, serious adverse event (SAE) rates, treatment duration, dose intensity, progression-free survival (PFS), and overall survival (OS). Economic inputs comprised country-specific denosumab and ZA acquisition and administration costs, SRE and SAE management costs, and discount rates. Health utility decrements associated with MM disease progression, SRE and SAE occurrence, and route of administration were included. Results: Estimated ICERs (cost per quality-adjusted life-year [QALY] gained) for denosumab vs ZA in Austria, Belgium, Greece, and Italy were €26,294, €17,737, €6,982, and €27,228, respectively. Using 1-3 times gross domestic product (GDP) per capita per QALY as willingness to pay thresholds, denosumab was 69-94%, 84-96%, 79-96%, and 50-92% likely to be cost-effective vs ZA, respectively. Limitations: Economic inputs were derived from various sources, and time to event inputs were extrapolated from 20090482 study data. Conclusions: Denosumab is cost-effective vs ZA for SRE prevention in patients with MM in Austria, Belgium, Greece, and Italy, based on often-adopted World Health Organization thresholds. This conclusion is robust to changes in model parameters and assumptions. Cost-effectiveness estimates varied across the four countries, reflecting differences in healthcare costs and national economic evaluation guidelines.

Use of Bisphosphonates in Elderly Patients With Newly Diagnosed Multiple Myeloma.

Background: Bisphosphonates reduce skeletal-related events (SREs) in patients with multiple myeloma (MM) and, in some studies, improved survival. Since 2011, bisphosphonate use has been recommended by NCCN for all patients with newly diagnosed MM receiving antineoplastic therapy independent of the presence of bone disease. This study investigated their use after these guidelines were established. Methods: We identified patients aged ≥65 years in the SEER-Medicare database with newly diagnosed MM between January 1, 2012, and December 31, 2013, who received antineoplastic therapy, had ≥6 months of follow-up, and did not receive prior bisphosphonates. Presence of SREs at diagnosis was identified, including pathologic fracture, spinal cord compression, radiation to bone, or surgery to bone. Use of bisphosphonates was defined as having ≥1 claim for an intravenous or oral bisphosphonate within 6 months after the start of antineoplastic therapy. We used multivariable modeling to compare users with nonusers, controlling for demographic and clinical covariates. We compared overall survival between users and nonusers using proportional hazards analysis. Results: Of 1,309 patients identified, 720 (55%) used a bisphosphonate. Factors associated with use included SRE at diagnosis (adjusted odds ratio [AOR], 2.60; 95% CI, 1.98-3.40), hypercalcemia (AOR, 1.74; 95% CI, 1.26-2.41), and use of proteasome inhibitor + immunomodulatory imide therapy (AOR, 1.70; 95% CI, 1.21-2.39). Chronic kidney disease (AOR, 0.48; 95% CI, 0.35-0.66) was associated with decreased use. Bisphosphonate use was associated with reduced mortality (hazard ratio, 0.70; 95% CI, 0.56-0.88). Conclusions: Although bisphosphonate use is recommended for all patients with newly diagnosed MM receiving antineoplastic therapy, 45% of patients in the United States did not receive this guideline-recommended care.

Economic burden of skeletal-related events in patients with multiple myeloma: analysis of US commercial claims database.

AIMS: To estimate incremental healthcare resource utilization (HRU) and costs associated with skeletal-related events (SREs) secondary to multiple myeloma (MM), and HRU and cost differences in patients with one vs multiple SREs. METHODS: Adults with MM diagnosis between January 1, 2010-December 31, 2014, with benefits coverage ≥12 months pre- and ≥6 months post-diagnosis were followed to last coverage date or December 31, 2015, excluding patients with prior anti-myeloma treatment or cancers. SREs were identified by diagnosis or procedure codes (pathological fracture, spinal cord compression, radiation, or surgery to the bone). SRE patients (index = first post-diagnosis SRE) were propensity score matched 1:1 to patients without SRE (assigned pseudo-index) using baseline characteristics, and ≥1 month of continuous enrollment after index/pseudo-index date was required. Per-patient-per year (PPPY) HRU and costs (2016 US$) were determined for inpatient, outpatient, emergency department (ED), and outpatient pharmacy services during follow-up. Wilcoxon signed rank for means and McNemar's tests for proportions were used to assess differences. Negative binomial regression and generalized linear regression analyses estimated differences in HRU and costs, respectively, for the comparison of single vs multiple SREs. RESULTS: Each cohort included 848 patients (mean age = 61 - 62 years, 57% male) with no significant differences in pre-index demographic or clinical characteristics between matched cohorts. Versus non-SRE patients, SRE patients had significantly higher PPPY use (p < .0001) of inpatient hospitalizations, ED visits, outpatient pharmacy, and higher direct medical costs ($188,723 vs $108,160, p < .0001). Adjusted PPPY total costs were $209,820 in patients with multiple SREs; $159,797 in patients with one SRE. LIMITATIONS: SRE misclassification and residual confounding are possible. CONCLUSIONS: Among patients with MM, average annual costs were substantially higher in patients with SRE compared with matched non-SRE patients. The economic burden of SRE increased further with multiple events.

A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in the United States of America.

OBJECTIVE: A large, pivotal, phase 3 trial in patients with newly diagnosed multiple myeloma (MM) demonstrated that denosumab, compared with zoledronic acid, was non-inferior for the prevention of skeletal-related events (SREs), extended the observed median progression-free survival (PFS) by 10.7 months, and showed significantly less renal toxicity. The cost-effectiveness of denosumab vs zoledronic acid in MM in the US was assessed from societal and payer perspectives. METHODS: The XGEVA Global Economic Model was developed by integrating data from the phase 3 trial comparing the efficacy of denosumab with zoledronic acid for the prevention of SREs in MM. SRE rates were adjusted to reflect the real-world incidence. The model included utility decrements for SREs, administration, serious adverse events (SAEs), and disease progression. Drug, administration, SRE management, SAEs, and anti-MM treatment costs were based on data from published studies. For the societal perspective, the model additionally included SRE-related direct non-medical costs and indirect costs. The net monetary benefit (NMB) was calculated using a willingness-to-pay threshold of US$150,000. One-way deterministic and probabilistic sensitivity analyses were conducted. RESULTS: From a societal perspective, compared with zoledronic acid, the use of denosumab resulted in an incremental cost of US$26,329 and an incremental quality-adjusted life-year (QALY) of 0.2439, translating into a cost per QALY gained of US$107,939 and a NMB of US$10,259 in favor of denosumab. Results were sensitive to SRE rates and PFS parameters. LIMITATIONS: Costs were estimated from multiple sources, which varied by tumor type, patient population, country, and other parameters. PFS and overall survival were extrapolated beyond the follow-up of the primary analysis using fitted parametric curves. CONCLUSION: Denosumab's efficacy in delaying or preventing SREs, potential to improve PFS, and lack of renal toxicity make it a cost-effective option for the prevention of SREs in MM compared with zoledronic acid.

Cost-effectiveness of denosumab versus zoledronic acid for preventing skeletal-related events in the Czech Republic.

AIMS: This study assessed the cost-effectiveness of the subcutaneous RANKL inhibitor, denosumab, vs the intravenous bisphosphonate, zoledronic acid, for the prevention of skeletal-related events (SREs) in patients with prostate cancer, breast cancer, and other solid tumors (OST) in the Czech Republic. MATERIALS AND METHODS: A lifetime Markov model was developed to compare the effects of denosumab and zoledronic acid on costs (including drug costs and administration, patient management, SREs, and adverse events), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios from a national payer perspective. Different discount rates, time horizons, SRE rates, distributions, and nature (asymptomatic vs all SREs), and the inclusion of treatment discontinuation were considered in scenario analyses. The robustness of the model was tested using deterministic and probabilistic sensitivity analyses. RESULTS: Across tumor types, denosumab was associated with fewer SREs, improved QALYs, and higher total costs over a lifetime. The incremental cost per QALY gained for denosumab vs zoledronic acid was 382,673 CZK for prostate cancer, 408,450 CZK for breast cancer, and 608,133 CZK for OST. Incremental costs per SRE avoided for the same tumor type were 54,007 CZK, 51,765 CZK, and 94,426 CZK, respectively. In scenario analyses, the results remained similar to baseline, when different discount rates and time horizons were considered. At a non-official willingness-to-pay threshold of 1.2 million CZK, the probabilities of denosumab being cost-effective vs zoledronic acid were 0.64, 0.67, and 0.49 for prostate cancer, breast cancer, and OST, respectively. LIMITATIONS: The SRE rates used were obtained from clinical trials; studies suggest rates may be higher in clinical practice. Additional evidence on real-world SRE rates could further improve the accuracy of the modeling. CONCLUSIONS: Compared with zoledronic acid, denosumab provides a cost-effective treatment option for the prevention of SREs in patients with prostate cancer, breast cancer, and OST in the Czech Republic.

PET Imaging for Initial Staging and Therapy Assessment in Multiple Myeloma Patients.

Multiple myeloma (MM) is a hematological neoplasm characterized by the clonal proliferation of malignant plasma cells in the bone marrow. MM results in diffuse or focal bone infiltration and extramedullary lesions. Over the past two decades, advances have been made with regard to the diagnosis, staging, treatment, and imaging of MM. Computed tomography (CT) and magnetic resonance imaging (MRI) are currently recommended as the most effective imaging modalities at diagnostic. Yet, recent data from the literature suggest that positron emission tomography combined with computed tomography (PET/CT) using 18F-deoxyglucose (FDG) is a promising technique for initial staging and therapeutic monitoring in this pathology. This paper reviews the recent advances as well as the potential place of a more specific radiopharmaceutical in MM.

Real-World Assessment of Renal and Bone Safety among Patients with HIV Infection Exposed to Tenofovir Disoproxil Fumarate-Containing Single-Tablet Regimens.

OBJECTIVES: Tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens have been associated with an increased incidence of renal and bone adverse outcomes. Here, we estimated the real-world incidence of renal and bone adverse outcomes among patients with HIV infection receiving different TDF-containing single-tablet regimens (STRs). METHODS: This cohort study used US health insurance data spanning the years 2008-2014. We identified HIV-infected patients aged ≥18 years (all HIV patients) and those with ≥6 months of continuous enrollment prior to initiating efavirenz/emtricitabine/TDF (EFV/FTC/TDF), rilpivirine/FTC/TDF (RPV/FTC/TDF) or elvitegravir/cobicistat/FTC/TDF (EVG/COBI/FTC/TDF). Renal adverse outcomes were identified using renal International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Bone adverse outcomes were identified using ICD-9-CM diagnosis codes for fracture. Incidence rates (IRs) and associated 95% confidence intervals (CIs) were estimated assuming a Poisson distribution, and outcomes between STRs were compared using IR ratios (IRRs) and IR differences (IRDs). RESULTS: We identified 9876 and 10,383 eligible patients for the renal and fracture analyses, respectively. Observed IRs for renal adverse outcomes were 9.7, 10.5, 13.6, and 18.0 per 1000 person-years among those receiving EFV/FTC/TDF, RPV/FTC/TDF, or EVG/COBI/FTC/TDF, or all HIV patients, respectively. Corresponding values for IRs of fracture were 3.4, 3.6, 7.2, and 4.4 per 1000 person-years, respectively. Renal adverse outcomes with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRD -3.96; 95% CI: -7.31, -1.06). No IRR differences were identified for the renal analysis. Fractures with EFV/FTC/TDF were significantly less frequent than with EVG/COBI/FTC/TDF (IRR 0.47; 95% CI: 0.27, 0.81 and IRD -3.85; 95% CI: -5.02, -2.78). CONCLUSIONS: In this large real-world database, observed IRs for renal adverse outcomes with TDF-containing STRs were lower or similar to those for all HIV patients, with the lowest IRs observed among patients receiving EFV/FTC/TDF. Compared with all HIV patients, the observed IR for fracture was higher with EVG/COBI/FTC/TDF, comparable with RPV/FTC/TDF, and lower with EFV/FTC/TDF.

Ultrasonographic assessment of bone erosions in the different subtypes of systemic lupus erythematosus arthritis: comparison with computed tomography.

BACKGROUND: The aim was to determine the accuracy of high-resolution ultrasonography (US) for detecting erosion in the metacarpophalangeal (MCP) and wrist joints of patients with different subtypes of systemic lupus erythematosus (SLE) arthritis, using computed tomography (CT) as the gold-standard reference method. METHOD: The ulnar head, radiocarpal and second to fifth MCP joints in 26 patients with SLE - 9 classified as having rhupus syndrome, 10 as having Jaccoud's arthropathy (JA) and 7 as having non-deforming non-erosive (NDNE) arthritis - were subdivided into areas and bilaterally evaluated for the presence of bone erosion by CT and US. On CT, erosion volume was scored according to the outcome measures in rheumatology-rheumatoid arthritis magnetic resonance imaging (OMERACT-RAMRIS) score. On US, erosions were semi-quantitatively scored 0-3 according to scoring by ultrasound structural erosion (ScUSSe) systems. RESULTS: Erosions were detected by CT in 92/728 areas (12.6 %) and by US in 43/728 areas (5.9 %). Sensitivity, specificity and accuracy of US overall was 36 %, 98 % and 90 % compared with 57 %, 98 % and 93 % in the dorsal and lateral aspects of the second and fifth MCP, which were identified as areas with the best US reliability. Adding wrist joints would capture a larger number of erosions without affecting the accuracy. US detected 90.0 % of CT erosions with bone volume loss >20 % and 51.2 % of erosions with bone volume loss >10 %. Patients with rhupus had a greater number of larger erosions than those with JA or NDNE arthritis, with prevalent involvement of the MCP joints. Overall reliability of US in detecting bone erosions was moderate for rhupus syndrome (0.55) and JA (0.58), but poor for NDNE arthritis (0.10). CONCLUSION: US had moderate sensitivity and excellent specificity for detection and semi-quantitative assessment of bone erosions in SLE.

The Biomechanical Testing for the Assessment of Bone Quality in an Experimental Model of Chronic Kidney Disease.

Mineral metabolism disturbances are common in chronic kidney disease (CKD) and have been classified as a new clinical entity, also known as CKD-mineral and bone disorders (CKD-MBD). A decrease in the bone strength, whose clinical manifestation is a tendency for fracture, has been recognized as an important component of CKD-MBD. Because of ethical issues, measurements of the bone strength in the human body are usually limited to noninvasive techniques, such as radiography, dual-energy X-ray absorptiometry and the assays of bone turnover biomarkers. However, it has been postulated recently that the evidence concerning bone strength based solely on the determination of the bone quantity may be insufficient and that bone quality should also be examined. In this regard, an animal model of CKD can represent an experimental tool to test the effectiveness of new therapeutic strategies. Despite the many available methods that are used to diagnose metabolic bone disorders and predict fracture risk especially in small rodents with CKD, it turns out that the most appropriate are biomechanical tests, which can provide information about the structural and material properties of bone. The present review summarizes and discusses the principles for carrying out selected biomechanical tests (3-point bending test and compression test) and their application in clinical practice.

Assessment of scapular morphology and surgical technique as predictors of notching in reverse shoulder arthroplasty.

There has been increased focus on understanding risk factors for scapular notching in reverse shoulder arthroplasty (RSA). We conducted a study to evaluate the scapular notching index and other factors associated with the occurrence of scapular notching. Ninety-one patients treated with primary RSA were followed for a minimum of 24 months. Patients' radiographic assessments were grouped by Nerot grade of scapular notching (group 1, grades 0 and 1; group 2, grades 2, 3, 4). Group mean differences were compared for preoperative scapular neck angle (SNA), prosthesis-scapular neck angle (PSNA), peg glenoid rim distance (PGRD), notching index, and clinical outcomes. There was no significant difference in mean (SD) notching index between group 1, 31.8 (4.4), and group 2, 33.1 (7.3), and there were no significant differences in SNA (102.8° vs 105.4°; P=.3), PSNA (125.8° vs 125.4°; P=.82), PGRD (15.4 vs 16.8 mm; P=.47), or clinical outcomes between the groups. Our results suggest that Grammont-style prostheses have a higher rate of notching regardless of optimal PGRD and variations in PSNA. Perhaps with certain scapular morphology, prosthetic design may be a more significant contributor to notching.

Short-term disability in solid tumor patients with bone metastases and skeletal-related events.

OBJECTIVE: The skeleton is a common site of metastasis in patients with solid tumors. These patients often experience pain and reduced quality-of-life. This analysis evaluated the time and costs associated with short-term disability use among solid tumor patients with bone metastases (BM) and skeletal-related events (SREs). METHODS: Data from patients 18-64 years old with solid tumors and BM, eligible for short-term disability benefits between January 1, 2002 and December 31, 2010, were extracted from MarketScan Research Databases. Short-term disability hours and costs associated with BM and SREs were evaluated. RESULTS: Overall, 1098 patients met the criteria. For all patients with BM, the monthly mean short-term disability hours were 17.7 h pre-BM diagnosis and increased to 60.2 h post-BM diagnosis (p < 0.001). The corresponding mean monthly short-term disability costs were $277 and $963 in the pre- and post-BM diagnosis periods, respectively (p < 0.001). Monthly mean short-term disability hours were higher for the cohort of patients with SREs (21.2 h pre-SRE diagnosis and 67.4 h post-SRE diagnosis) than for those without an SRE (8.6 h pre-SRE diagnosis and 14.4 h post-SRE diagnosis) (p < 0.001). Similarly, the corresponding monthly mean short-term disability costs were higher for patients with SREs ($625 and $1259 pre- and post-SRE diagnosis, respectively) than for patients without an SRE ($452 and $612 pre- and post-SRE diagnosis, respectively) (p < 0.001). RESULTS of a multivariate analysis indicated that SREs were associated with an additional 39.4 short-term disability hours and $613 in short-term disability costs per month (p < 0.001). CONCLUSION: Short-term disability hours and costs increased significantly when patients with solid tumors developed BM and SRE.

Computed tomography assessment of bone lesions in patients with POEMS syndrome.

OBJECTIVES: To describe the imaging findings on computed tomography (CT) and skeletal survey (SS) in patients with POEMS syndrome. METHODS: We retrospectively reviewed, with institutional review board approval, the dysproteinemia database at our institution for patients with new diagnosis of POEMS syndrome between January 1998 and December 2008. Twenty-four patients were identified with PET/CT or CT and had skeletal survey (SS) available for review. RESULTS: Twenty-four patients were included in the study group with median age of 47 years. All CTs demonstrated at least one sclerotic lesion. The most common pattern was multiple small lesions, with 18 patients (75%) having at least 5 lesions less than 1 cm. The larger lesions had a central lytic component and were FDG avid. SS had a false negative rate of 36% (8 patients). Serial CT after treatment showed a decrease in size and number of sclerotic lesions in 53% of cases (13 patients), the majority showing increased sclerosis. Two patients had complete resolution of sclerotic lesions. CONCLUSIONS: CT identified sclerotic lesions in all study patients with POEMS syndrome, the majority being less than 1 cm in size, which were not identified radiographically. CT may demonstrate increased sclerosis or even resolution of sclerotic lesions corresponding to treatment response. KEY POINTS: • CT has high sensitivity in identifying sclerotic lesions in POEMS syndrome • Most common CT patterns are multiple, less than 1 cm, sclerotic lesions • Larger lesions have lytic centres and sclerotic margins • Skeletal surveys may have a false negative rate of 36% • Treatment response includes increased sclerosis, decrease in size or resolution of lesions.

Tarsal navicular bone size in diabetics: radiographic assessment.

OBJECTIVE: To test the anecdotal observation that isolated navicular collapse is associated with diabetes mellitus, we quantified the size of the tarsal navicular bone in subjects with and without diabetes and tested for association of size with age, height, weight, body mass index (BMI), gender, smoking, bone mineral density (BMD), duration, and level of control of diabetes. MATERIALS AND METHODS: Ankle radiographs of 200 patients (122 female; 78 male; mean age 58 years [27-89]), 100 with type II diabetes and 100 age- and gender-matched controls were selected and reviewed. The anteroposterior (AP) dimension of the mid-navicular bone was measured from lateral radiographs. For standardization, the supero-inferior (SI) dimension of the calcaneal was measured and the navicular-calcaneus ratio calculated. Statistical evaluation included independent sample t tests and linear regression analyses. RESULTS: Diabetic subjects had a significantly smaller navicular AP dimension and navicular-calcaneus ratio compared with controls (p = 0.02 and p = 0.0001 respectively). Age, gender, height and duration of diabetes had no association with the navicular-calcaneus ratio. The navicular-calcaneus ratio was inversely correlated with weight (p = 0.01) and BMI (p < 0.001) and directly correlated with smoking (p = 0.04). Reliability of the radiographic measurements was excellent (ICC 0.80-0.97; SEM 0.3-1.7 mm). CONCLUSION: The anteroposterior dimension of the navicular is smaller in type II diabetic subjects than in age- and gender-matched controls. We hypothesize that this might be due to navicular collapse of multifactorial causes.

Healthcare costs associated with skeletal-related events in breast cancer patients with bone metastases.

BACKGROUND: Patients with bone metastases secondary to breast cancer are pre-disposed to skeletal-related events (SREs), including spinal cord compression (SCC), pathologic fracture (PF), surgery to bone (SB), and radiotherapy to bone (RT). OBJECTIVE: To document current patterns of healthcare utilization and costs of SREs in patients with breast cancer and bone metastases. METHODS: This was a retrospective, observational study using the Thomson MedStat MarketScan Commercial Claims and Encounters database from 9/2002 to 6/2011. Study subjects included all persons with claims for breast cancer and for bone metastases, and ≥1 claims for an SRE. Unique SRE episodes were identified based on a gap of at least 90 days without an SRE claim, and classified by treatment setting (inpatient or outpatient) and SRE type (SCC, PF, SB, or RT). RESULTS: Of 17,266 patients with breast cancer and bone metastases, 9142 (53%) had one or more SRE episodes. Among 5809 patients who met all other criteria, there were 7617 SRE episodes over mean (SD) follow-up of 17.2 (15.2) months. The percentage of episodes that required inpatient treatment ranged from 11% (RT) to 76% (SB). On average, inpatient SCC episodes (n=83 episodes) were most costly; while outpatient PF episodes (n=552 episodes) were least costly. Of the total SRE costs (mean [SE] $21,072 [$36,462]/episode), 36% were attributable to outpatient RT (n=5265 episodes) and 31% to inpatient PF (n=838 episodes). LIMITATIONS: The administrative claims data used in this study may lack sensitivity and specificity for identification of clinical events and may not be generalizable to other populations. Also, for some SRE episode categories, the number of events was small and cost estimates may lack precision. CONCLUSION: In patients with breast cancer and bone metastases, SREs are associated with high costs and hospitalizations.

Clinical, social, and economic impacts of home parenteral nutrition dependence in short bowel syndrome.

Home parenteral nutrition (HPN) provides nourishment and hydration to patients with short bowel syndrome and intestinal failure and is thus a life-sustaining therapy for these patients. However, measures of quality of life (QOL) are lower among the HPN-dependent population than among patients with other intestinal diseases who do not require HPN. Multiple factors contribute to lower QOL in HPN-dependent patients, including fears surrounding the increased risk of HPN-associated adverse events, such as catheter-related complications, parenteral nutrition-associated liver disease, and metabolic bone disease. In addition, HPN-dependent patients report impaired sleep and daytime fatigue because of pump noises, equipment alarms, and nocturia. Psychosocial burdens on families of HPN-dependent patients include decreased social activities, disrupted family relationships and friendships, and depression. These families also face imposing financial constraints, including decreased employment and large out-of-pocket expenses for insurance premiums and nonreimbursed copayments, medications, and supplies. Furthermore, HPN technology and HPN-related complications and sequelae contribute to the rapid overall increase in the costs of healthcare systems. Additionally, family caregivers provide unpaid healthcare services for patients who require HPN, often to the detriment of their own physical and mental well-being. Nonetheless, patients dependent on HPN and their caregivers often demonstrate considerable resilience and are frequently able to normalize their response to illness and disability. Interventions that may improve QOL among HPN-dependent patients and caregivers include patient education, affiliation with support groups, treatment of concomitant symptoms, and pharmacotherapies that decrease HPN requirements.