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Although neuraxial anesthesia may promote improved outcomes for patients undergoing lower limb revascularization surgery, its use is decreasing over time. Our objective was to estimate variation in neuraxial (versus general) anesthesia use for lower limb revascularization at the hospital, anesthesiologist, surgeon, and patient levels, which could inform strategies to increase uptake.Following protocol registration, we conducted a historical cross-sectional analysis of population-based linked health administrative data in Ontario, Canada. All adults undergoing lower limb revascularization surgery between 2009 and 2018 were identified. Generalized linear models with binomial response distributions, logit links and random intercepts for hospitals, anesthesiologists, and surgeons were used to estimate the variation in neuraxial anesthesia use at the hospital, anesthesiologist, surgeon, and patient levels using variance partition coefficients and median odds ratios. Patient- and hospital-level predictors of neuraxial anesthesia use were identified.We identified 11,849 patients; 3489 (29.4%) received neuraxial anesthesia. The largest proportion of variation was attributable to the hospital level (50.3%), followed by the patient level (35.7%); anesthesiologists and surgeons had small attributable variation (11.3% and 2.8%, respectively). Mean odds ratio estimates suggested that 2 similar patients would experience a 5.7-fold difference in their odds of receiving a neuraxial anesthetic were they randomly sent to 2 different hospitals. Results were consistent in sensitivity analyses, including limiting analysis to patients with diagnosed peripheral artery disease and separately to those aged66 years with complete prescription anticoagulant and antiplatelet usage data.Neuraxial anesthesia use primarily varies at the hospital level. Efforts to promote use of neuraxial anesthesia for lower limb revascularization should likely focus on the hospital context.

Introduction and Objective: Coronavirus disease 2019 (COVID-19) is associated with respiratory failure and a hypercoagulable state. Studies have shown the use of oral anticoagulants, specifically dabigatran, can significantly decrease mortality from COVID-19. Dabigatran is an oral direct thrombin inhibitor commonly used for nonvalvular atrial fibrillation and for the treatment or prevention of venous thromboembolism. The association of COVID-19-related extensive thrombosis while receiving full therapeutic anticoagulation with dabigatran has not been well-established in current literature. Case Report: We present a 73-year-old male patient with a history of persistent atrial fibrillation anticoagulated with dabigatran presenting with an active COVID-19 infection admitted to the intensive care unit. On hospital day 7, he developed extensive arterial and venous thromboembolisms. To our knowledge, this is the first published case of COVID-19-related extensive thrombosis while receiving full therapeutic anticoagulation with dabigatran. Discussion: Guidelines recommend prophylactic or therapeutic-dose anticoagulation with unfractionated heparin or low-molecular weight heparin for all patients if no contraindications exist; however, recommendations for the use of therapeutic oral anticoagulants have not been well established. Further studies are warranted to establish appropriate use of oral anticoagulants in the setting of COVID-19. Conclusion: Evidence from this report suggests clinicians should closely monitor patients at risk for hypercoagulability regardless of the anticoagulation therapy the patient may be receiving. Additionally, evidence from this case suggests a possible inferiority in the anticoagulation ability of dabigatran in patients with active COVID-19.

Somatostatin analogues, suchas octreotide and lanreotide, are commonly used in the management of enterocutaneous fistula. We report a case of severe and prolonged hyperglycemia that occurred in a patient after receiving a one-time dose of lanreotide, who had previously been stable on octreotide and did not have a history of diabetes mellitus. Management of the patient's hyperglycemia while receiving parenteral nutrition is described.

Pancreatic cancer remains a leading cause of cancer-related death with few available therapies for advanced disease. Recently, patients with germline BRCA mutations have received increased attention due to advances in the management of BRCA mutated ovarian and breast tumors. Germline BRCA mutations significantly increase risk of developing pancreatic cancer and can be found in up to 8% of patients with sporadic pancreatic cancer. In patients with germline BRCA mutations, platinum-based chemotherapies and poly (ADP-ribose) polymerase inhibitors are effective treatment options which may offer survival benefits. This review will focus on the molecular biology, epidemiology, and management of BRCA-mutated pancreatic cancer. Furthermore, we will discuss future directions for this area of research and promising active areas of research.

Large changes in positioning of the global region of interest (ROI) influence the measurement of bone mineral density (BMD) in the hip and forearm regions. However, it is unknown whether minor shifts in the positioning of the bottom of the global hip ROI affect the measurement of total hip BMD.The hip BMDs of 40 clinical densitometry patients were analyzed at baseline with the bottom of the global hip ROI positioned as usual, 10 mm distal to the base of the lesser trochanter (position 0). Then the hip was reanalyzed by shifting the bottom of the global hip ROI 1 mm proximally 10 times (positions +1 through +10) and then by shifting the bottom of the global hip ROI 1 mm distally 10 times (positions -1 through -10). The significance of the differences between mean values at the various distances from baseline was assessed using a Wilcoxon signed-rank test.The mean total hip area, bone mineral content and BMD decreased as the bottom of the global hip ROI was shifted proximally; the decrease was significant when shifted by even 1 mm (p0.001). The mean total hip area, bone mineral content and BMD increased as the bottom of the global hip ROI was shifted distally; the increase was significant when shifted by even 1 mm (p0.001). The change in BMD with each 1 mm shift was uniform across the range studied from positions +10 through -10, and was approx 0.54%/mm. When the least significant change was based on 40 pairs of measurements, where each pair was comprised of the baseline scan and the same scan at -1 position, the least significant change was 0.01 g/cmThe BMD of the total hip is sensitive to even minor changes in the positioning of the bottom of the global hip ROI. Although a 1 mm change in the bottom of the global hip ROI positioning would make little difference in the reported T-score, it could easily affect the determination of significance in changes in BMD over time.

Background Central line–associated bloodstream infection (CLABSI) is a complication of central venous access devices used for parenteral nutrition (PN). PN overfeeding is associated with increased adverse effects; however, whether risk for CLABSI is influenced by PN dosing is uncertain. Objective The purpose of the study was to assess differences in CLABSI risk associated with recommended total energy dosing in hospitalized adult patients receiving PN. Methods A case-control study was conducted in a single United States Veterans Health Administration health system to assess the potential CLABSI risk factor of weight-based PN kilocalorie dosing. Hospitalized adult patients who developed CLABSI while receiving PN were identified and compared to a control group of patients who did not develop CLABSI. The exposures evaluated were overfeeding, defined as greater than 30 kcal/kg/day, and underfeeding, defined as less than 20 kcal/kg/day. Results Twenty-nine cases of CLABSI were identified and compared with 274 controls. Odds of CLABSI were significantly higher in patients receiving greater than 30 kcal/kg/day (OR, 3.63; 95% CI, 1.55-8.48; P < .01). No significant difference in odds was found for patients receiving less than 20 kcal/kg/day (OR, .74; 95% CI, 0.21-2.57; P = .63). Conclusion Increased risk for CLABSI in hospitalized adult patients receiving PN was found to be associated with overfeeding, but not underfeeding. These results may aid clinicians in the management of patients requiring PN and in the generation of hypothesis for future investigations.

Introduction Septic shock is defined as a dysregulated host response to infection characterized by hemodynamic instability. Concern for the increased risk of acute kidney injury (AKI) with piperacillin-tazobactam in combination with vancomycin may prompt more use of alternative broad-spectrum antipseudomonal beta-lactam antibiotics, such as cefepime. This study assessed whether cefepime was associated with improved outcomes compared to piperacillin-tazobactam in patients with septic shock. Methods This retrospective cohort study included veterans treated for septic shock between September 1, 2008, and August 31, 2018. This study compared cefepime and piperacillin-tazobactam as initial antibiotic management for septic shock. Outcomes included AKI, Clostridioides difficile infection (CDI), hospital length of stay, intensive care unit mortality, and mortality within 30 days of hospitalization. Results In total, 240 patients were included in this study (120 in each cohort). The proportion of AKI was 60.0% in the piperacillin-tazobactam cohort compared to 58.3% in the cefepime cohort (p = 0.90). Mortality was significantly higher in the cefepime cohort. There were no significant differences in CDI or hospital length of stay. Conclusion The results of this study do not suggest that the use of the antipseudomonal beta-lactam antibiotic used in the initial management of septic shock is associated with differences in the AKI or CDI. The higher mortality observed with cefepime may warrant further investigation.

Rosen et al. identify a role for the centrosomal protein Bsg25D/Ninein in nuclear positioning and microtubule organization in Drosophila muscle fibers. Genetic, cell biological, and atomic force microscopy analyses demonstrate that complex interactions between Bsg25D and the microtubule-associated protein Ensconsin govern myonuclear positioning in Drosophila., Skeletal muscle consists of multinucleated cells in which the myonuclei are evenly spaced throughout the cell. In Drosophila, this pattern is established in embryonic myotubes, where myonuclei move via microtubules (MTs) and the MT-associated protein Ensconsin (Ens)/MAP7, to achieve their distribution. Ens regulates multiple aspects of MT biology, but little is known about how Ens itself is regulated. We find that Ens physically interacts and colocalizes with Bsg25D, the Drosophila homologue of the centrosomal protein Ninein. Bsg25D loss enhances myonuclear positioning defects in embryos sensitized by partial Ens loss. Bsg25D overexpression causes severe positioning defects in immature myotubes and fully differentiated myofibers, where it forms ectopic MT organizing centers, disrupts perinuclear MT arrays, reduces muscle stiffness, and decreases larval crawling velocity. These studies define a novel relationship between Ens and Bsg25D. At endogenous levels, Bsg25D positively regulates Ens activity during myonuclear positioning, but excess Bsg25D disrupts Ens localization and MT organization, with disastrous consequences for myonuclear positioning and muscle function.

Approximately 1 in 7 patients with metastatic breast cancer (MBC) will receive radiotherapy for brain metastases (BRM). Significant differences in cumulative incidence of BRM by breast cancer subtype may inform future BRM screening protocols.To describe cumulative incidence of BRM among patients with de novo MBC.In this population-based cohort study, population health administrative databases in Ontario, Canada, held at the ICES were used to identify patients diagnosed with de novo MBC between 2009 and 2018. Given that a code for BRM does not exist within ICES, we analyzed the incidence of radiotherapy for BRM. The median (IQR) follow-up was 19.3 (6.2-39.5) months. A total of 100 747 patients with a new diagnosis of breast cancer between January 2009 and December 2018 were identified. Of these patients, 17 955 were excluded because they had previous or subsequent malignant neoplasms, 583 were excluded because they were younger than 18 years, 974 were excluded because there was an invalid Ontario Health Insurance Plan number or a date of death on or before the index date. Among 81 235 remaining patients, 3916 were identified as having de novo MBC.Treatment with radiotherapy for breast cancer BRM.Cumulative incidence of radiotherapy for BRM accounting for the competing risk of death, and time from MBC diagnosis to brain radiotherapy. Kaplan-Meier analyses were performed for time-to-event end points. Logistic regression was used to account for confounding variables.Among 3916 patients with MBC, 1215 (31.0%) had HR-positive/ERBB2 (formerly HER2)-negative cancer, 310 (7.9%) had ERBB2-positive/HR-positive cancer, 200 (5.1%) had ERBB2-positive/HR-negative cancer, 258 (6.6%) had TNBC, and the remaining 1933 patients (49.4%) had an unknown breast cancer subtype. The median (IQR) age at diagnosis was 63 (52-75). A total of 549 (14.0%) underwent stereotactic radiosurgery or whole brain radiotherapy for breast cancer BRM. Cumulative incidence of BRM was higher among patients with ERBB2-positive/HR-negative breast cancer (34.7%), ERBB2-positive/HR-positive breast cancer (28.1%), and triple-negative breast cancer (21.9%) compared to those with HR-positive/ERBB2-negative breast cancer (12.1%). The median (IQR) time from MBC diagnosis to brain radiotherapy ranged from 7.5 (2.3-17.4) months for patients with TNBC to 19.8 (12.2-35.1) months for those with ERBB2-positive/HR-positive breast cancer.Incidence and time to development of BRM vary significantly by breast cancer subtype. A better understanding of the biology of intracranial metastatic disease may help inform potential screening programs or preventative interventions.

Background: Brown tumors are a part of the complex “osteitis fibrosa cystica” which is a diffuse resorptive process of the bone resulting from uncontrolled hyperparathyroidism. Although these brown tumors were fairly common in the past1, the incidence of brown tumors is now extremely rare in the United States due to early diagnosis and treatment of hyperparathyroidism. Here we describe an unusual presentation for osteitis fibrosa cystica. Clinical Case: A 38 year old woman was admitted to the hospital with rapidly growing facial swelling in June 2019. The swelling initially appeared in January 2019 and had rapidly increased in size since April 2019. The mass was malodorous, painful and interfered with oral intake. The patient smoked 1 pack per day for 13 years. A CT scan of the head and neck with contrast showed a 3.6 x 4.5 x 3.3 cm mass destroying the right mandibular body, involving the right platysma muscle and displacing the central and lateral incisor teeth and was concerning for malignancy. The initial impression was that this was likely a squamous cell carcinoma with local and perhaps distant metastases, complicated by humoral hypercalcemia of malignancy and she was admitted for management. Upon admission, her calcium level was 14 mg/dL, albumin 4.1 g/dL, phosphorus 1.4 mg/dL PTH level was 890 pg/mL and vitamin D level was 22 ng/mL. Since the high PTH did not fit with hypercalcemia of malignancy, further evaluation was undertaken. A thyroid ultrasound showed a 4.6 x 1.8 x 1.5 cm isoechoic, heterogeneous lesion in the left lower pole, and Tc-99 sestamibi scan suggested parathyroid origin. The biopsy of the mouth lesion showed fibro histiocytic proliferation with multiple giant cells, negative for malignancy and consistent with a brown tumor. CT scan of the chest, abdomen and pelvis did not reveal any other masses or lytic lesions. . A skeletal survey showed another 2 cm lytic lesion in the proximal left humeral metaphysis which was not biopsied. On parathyroidectomy, the patient was found to have an enlarged left inferior parathyroid gland measuring 3.3 x 3.0 x 0.8 cm weighing 7.093 grams. Intraoperatively PTH level decreased from 890 pg/mL to 69 pg/mL. Her calcium levels returned to normal post-operatively and she was discharged home. Pathologic examination report revealed the mass to be a parathyroid adenoma. The patient reports a reduction in the size of her mandible mass since the surgery. Conclusion: Although uncommon, brown tumors can be seen in uncontrolled primary hyperparathyroidism. The mandible is a common site, though, as in this case, it is less common for it to be the only site affected Reference: 1. Rosenberg, E. H. (1962). Hyperparathyroidism. A review of 220 proved cases with special emphasis on findings in the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 15(2), 84–94.

The decapod crustacean exoskeleton is a multi-layered structure composed of chitin-protein fibers embedded with calcium salts. Decapod claws display tooth-like denticles, which come into direct contact with predators and prey. They are subjected to more regular and intense mechanical stress than other parts of the exoskeleton and therefore must be especially resistant to wear and abrasion. Here, we characterized denticle properties in five decapod species. Dactyls from three brachyuran crabs (Cancer borealis, Callinectes sapidus, and Chionoecetes opilio) and two anomuran crabs (Paralomis birsteini and Paralithodes camtschaticus) were sectioned normal to the contact surface of the denticle, revealing the interior of the denticle and the bulk endocuticle in which it is embedded. Microhardness, micro- and ultrastructure, and elemental composition were assessed along a transect running the width of the cuticle using microindentation hardness testing, optical and scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS), respectively. In all species tested, hardness was dramatically higher-up to ten times-in the denticle than in the bulk endocuticle. Likewise, in all species there was an increase in packing density of mineralized chitin-protein fibers, a decrease in width of the pore canals that run through the cuticle, and a decrease in phosphorous content from endocuticle to denticle. The changes in hardness across the cuticle, and the relationship between hardness, calcium, and magnesium content, however, varied among species. Although mechanical resistance of the denticles was exceptionally high in all species, the basis for resistance appears to differ among species. STATEMENT OF SIGNIFICANCE: Understanding the diverse mechanisms by which animals attain exceptionally high mechanical resistance may enable development of novel, biologically inspired materials. Decapod crustacean claws, and particularly the tooth-like denticles that these claws display, are of interest in this regard, as they must be especially resistant to wear. We assessed mechanical, elemental, and structural properties of the claw cuticle in five decapod species. Without exception, microhardness was dramatically higher in the denticle than in the bulk endocuticle. Multivariant statistical analyses, however, showed that the relationships among microhardness, elemental content, and structural variables differed among species. Such patterns likely result from strong evolutionary pressure on feeding and defensive structures and a trade-off between mechanical properties and energetic cost of exoskeleton formation.

Bisphosphonates constitute a class of drugs that act primarily act by inhibition of bone resorption. These agents are widely used in the treatment calcium and bone metabolic disorders including osteoporosis, Paget's disease, hypercalcemia, and metastatic bone disease. This article will provide an overview of the pharmacology of these compounds.

Inconsistent positioning of patients and region of interest (ROI) is known to influence the precision of bone mineral density (BMD) measurements in the spine and hip. However, it is unknown whether minor shifts in the positioning of the ROI along the shaft of the radius affect the measurement of forearm BMD and its subregions. The ultradistal (UD-), mid-, one-third, and total radius BMDs of 50 consecutive clinical densitometry patients were acquired. At baseline the distal end of the ROI was placed at the tip of the ulnar styloid as usual, and then the forearm was reanalyzed 10 more times, each time shifting the ROI 1 mm proximally. No corrections for multiple comparisons were necessary since the differences that were significant were significant at p 0.001. The UD-radius BMD increased as the ROI was shifted proximally; the increase was significant when shifted even 1 mm proximally (p 0.001). These same findings held true for the mid- and total radius bone density, though the percent increase with moving proximally was significantly greater for the UD radius than for the other subregions. However, there was no significant change in the one-third radius BMD when shifted proximally 1-10 mm. Minor proximal shifts of the forearm ROI substantially affect the BMD of the UD-, mid- and total radius, while having no effect on the one-third radius BMD. Since the one-third radius is the only forearm region usually reported, minor proximal shifts of the ROI should not influence forearm BMD results significantly.

The indications for initial and follow-up bone mineral density (BMD) in transgender and gender nonconforming (TGNC) individuals are poorly defined, and the choice of which gender database to use to calculate Z-scores is unclear. Herein, the findings of the Task Force are presented after a detailed review of the literature. As long as a TGNC individual is on standard gender-affirming hormone treatment, BMD should remain stable to increasing, so there is no indication to monitor for bone loss or osteoporosis strictly on the basis of TGNC status. TGNC individuals who experience substantial periods of hypogonadism (>1 yr) might experience bone loss or failure of bone accrual during that time, and should be considered for baseline measurement of BMD. To the extent that this hypogonadism continues over time, follow-up measurements can be appropriate. TGNC individuals who have adequate levels of endogenous or exogenous sex steroids can, of course, suffer from other illnesses that can cause osteoporosis and bone loss, such as hyperparathyroidism and steroid use; they should have measurement of BMD as would be done in the cisgender population. There are no data that TGNC individuals have a fracture risk different from that of cisgender individuals, nor any data to suggest that BMD predicts their fracture risk less well than in the cisgender population. The Z-score in transgender individuals should be calculated using the reference data (mean and standard deviation) of the gender conforming with the individual's gender identity. In gender nonconforming individuals, the reference data for the sex recorded at birth should be used. If the referring provider or the individual requests, a set of "male" and "female" Z-scores can be provided, calculating the Z-score against male and female reference data, respectively.

To answer important questions in the fields of monitoring with densitometry, dual-energy X-ray absorptiometry machine cross-calibration, monitoring, spinal cord injury, periprosthetic and orthopedic bone health, transgender medicine, and pediatric bone health, the International Society for Clinical Densitometry (ISCD) held a Position Development Conference from March 20 to 23, 2019. Potential topics requiring guidance were solicited from ISCD members in 2017. Following that, a steering committee selected, prioritized, and grouped topics into Task Forces. Chairs for each Task Force were appointed and the members were co-opted from suggestions by the Steering Committee and Task Force Chairs. The Task Forces developed key questions, performed literature searches, and came up with proposed initial positions with substantiating draft publications, with support from the Steering Committee. An invited Panel of Experts first performed a review of draft positions using a modified RAND Appropriateness Method with voting for appropriateness. Draft positions deemed appropriate were further edited and presented at the Position Development Conference meeting in an open forum. A second round of voting occurred after discussions to approve or reject the positions. Finally, a face-to-face closed session with experts and Task Force Chairs, and subsequent electronic follow-up resulted in 34 Official Positions of the ISCD approved by the ISCD Board on May 28, 2019. The Official Positions and the supporting evidence were submitted for publication on July 1, 2019. This paper provides a summary of the all the ISCD Adult and Pediatric Official Positions, with the new 2019 positions highlighted in bold.

Objective: Calcitriol excess is a less common cause of hypercalcemia than hyperparathyroidism. Hypercalcemia due to calcitriol excess is usually managed acutely with intravenous (IV) fluid administration and dietary calcium restriction. Steroids and ketoconazole are second-line agents. There is evidence supporting the role of bone resorption in the genesis of hypercalcemia in vitamin D intoxication and for a rapid response of hypercalcemia to treatment with bisphosphonates. We seek to demonstrate the utility of bisphosphonates in calcitriol-induced hypercalcemia (CIH). Methods: We present the case of a patient with recurrent CIH from a follicular lymphoma who achieved normalization and subsequent stabilization of serum calcium levels following bisphosphonate administration Results: A 77-year-old woman with a history of non-small cell lung cancer was admitted with dry mouth, polyuria, weight loss, and fatigue. She was found to have a calcium level of 14.7 mg/dL (normal range is 8.5 to 10.2 mg/dL), 25-hydroxyvitamin D of 47 ng/mL (normal range is 30 to 60 ng/mL), 1,25-dihydroxyvitamin D of 89 pg/mL (normal range is 18 to 72 pg/mL), and parathyroid hormone of 19 pg/mL (normal range is 15 to 65 pg/mL), which recurred despite treatment with IV fluids and strict low-calcium diet. She received 5 mg of IV zoledronic acid and normocalcemia was maintained thereafter, without any diagnosis-specific treatment for >3 months. Positron emission tomography with computed tomography eventually showed new innumerable foci of increased uptake in the skeleton and lymph node biopsy revealed grade 3A follicular lymphoma. Conclusion: The first choice for CIH is treating the underlying cause. Bisphosphonates are, however, useful until a diagnosis is made, as they may be safer than steroids and can provide rapid relief even with a single treatment with minimal side effects.

Calcitriol excess is a less common cause of hypercalcemia than hyperparathyroidism. While its primary mechanism is thought to be increased intestinal calcium absorption, accelerated bone resorption contributes as well. The mechanism is presumably through a molecular interaction between the receptor activator of NF-κB ligand/osteoprotegerin ligand on marrow stromal cells and receptor activator of NF-κB on osteoclast precursors. It is this component of increased bone resorprtion that is addressed by bisphosphonates. A 77 year old woman with remote history of non-small cell lung cancer status post left lower lobe lobectomy presented with dry mouth, polyuria, 11 pound weight loss in 6 months, fatigue and calcium of 14.7. Examination was unremarkable. Laboratory evaluation included creatinine of 1.4 mg/dl, parathyroid hormone low at 19 pg/ml, 25 hydroxyvitamin D normal at 47 ng/ml, normal kappa/lambda and serum and urine protein electrophoresis, parathyroid hormone-related protein normal at 15 pg/ml, and 1,25 dihydroxyvitamin D was high at 89 pg/ml. A search commenced for the source, during which time hypercalcemia recurred despite strict low-calcium diet and IVF. PET-CT showed innumerable foci of increased uptake in the skeleton and lymph node biopsy revealed grade 3A follicular lymphoma. She received Zoledronic acid 5 mg IV and normocalcemia was maintained thereafter, without any diagnosis-specific treatment for >3 months. She was subsequently started on Rituxan and Bendamustine.This case demonstrates a patient with calcitriol-induced recurrent hypercalcemia from a follicular lymphoma who achieved normalization and subsequent stabilization of serum calcium levels following administration of bisphosphonate. Hypercalcemia due to calcitriol excess is usually managed acutely with intravenous fluid administration and dietary calcium restriction. Second-line agents such as steroids and ketoconazole can also be used, but these interventions alone have side effects and were contraindicated in our case, while the patient was being evaluated for causes of calcitriol excess which would have been masked by the steroids. There is evidence supporting the role of bone resorption in the genesis of hypercalcaemia in vitamin D intoxication and the rapid response of hypercalcaemia to treatment with bisphosphonates. The first choice for calcitriol-induced hypercalcemia is treating the underlying cause. Bisphosphonates are, however, useful until a diagnosis is made, as they may be safer than steroids and can provide rapid relief even with a single treatment, with minimal side effects.

OBJECTIVE The study aimed to investigate the association between BMI, waist circumference, and vertebral fracture (VF) risk in women. METHODS This prospective study was conducted in 54,934 Nurses' Health Study participants. BMI was assessed biennially, and waist circumference was assessed in the year 2000. Self-reports of VF were confirmed by record review. BMI reflects lean body mass, and waist circumference reflects abdominal adiposity when included in the same regression model. RESULTS This study included 536 VF cases (2002 to 2014). Compared with women with BMI of 21.0 to 24.9 kg/m2 , the multivariable-adjusted relative risk (RR) of VF for women with BMI ≥ 32.0 was 0.84 (95% CI: 0.61-1.14; Ptrend = 0.08). After further adjustment for waist circumference, the multivariable-adjusted RR of VF for women with BMI ≥ 32.0 was 0.70 (95% CI: 0.49-0.98; Ptrend = 0.003). Compared with women with waist circumference