Alvin Ng

Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Report of a Task Force of the American Society for Bone and Mineral Research

Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exposure to these drugs. In this report, we review studies on the epidemiology, pathogenesis, and medical management of AFFs, published since 2010. This newer evidence suggests that AFFs are stress or insufficiency fractures. The original case definition was revised to highlight radiographic features that distinguish AFFs from ordinary osteoporotic femoral diaphyseal fractures and to provide guidance on the importance of their transverse orientation. The requirement that fractures be noncomminuted was relaxed to include minimal comminution. The periosteal stress reaction at the fracture site was changed from a minor to a major feature. The association with specific diseases and drug exposures was removed from the minor features, because it was considered that these associations should be sought rather than be included in the case definition. Studies with radiographic review consistently report significant associations between AFFs and BP use, although the strength of associations and magnitude of effect vary. Although the relative risk of patients with AFFs taking BPs is high, the absolute risk of AFFs in patients on BPs is low, ranging from 3.2 to 50 cases per 100,000 person‐years. However, long‐term use may be associated with higher risk (∼100 per 100,000 person‐years). BPs localize in areas that are developing stress fractures; suppression of targeted intracortical remodeling at the site of an AFF could impair the processes by which stress fractures normally heal. When BPs are stopped, risk of an AFF may decline. Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs.

The pathophysiology of the aging skeleton.

In recent decades the population of both elderly men and women has grown substantially worldwide. Aging is associated with a number of pathologies involving various organs including the skeleton. Age-related bone loss and resultant osteoporosis put the elderly population at an increased risk for fractures and morbidity. Fortunately, in parallel our understanding of this malady has also grown substantially in recent years. A number of clinical as well as translational studies have been pivotal in providing us with an understanding of the pathophysiology of this condition. This article discusses the current concepts of age-related modulation of the skeleton involving intrinsic factors such as genetics, hormonal changes, levels of oxidative stress, and changes in telomere length, as well as extrinsic factors such as nutritional and lifestyle choices. It also briefly outlines recent studies on the relationship between bone and fat in the marrow as well as the periphery.

Osteoporosis Screening Using Areal Bone Mineral Density Estimation from Diagnostic CT Images

RATIONALE AND OBJECTIVES A reliable and cost-effective method for osteoporosis screening is important in addressing the increase in osteoporotic fractures due to aging populations. Diagnostic computed tomographic (dCT) images may contain densitometric information useful for osteoporosis screening. The aim of this study was to investigate the relationship between areal bone mineral density (aBMD) and volumetric information on dCT imaging and its suitability for building an osteopenia screening system. The goal of this system is to estimate aBMD and predict bone disease condition on the basis of dCT images of the lumbar spine. MATERIALS AND METHODS Dual-energy x-ray absorptiometry (DXA) aBMD and computed tomographic (CT) images were obtained from 44 male patients (mean age, 60 years). An aBMD from CT images (aBMD(CT)) was computed from the CT volume using established relationships of Hounsfield units to bone density and used to estimate DXA-derived aBMD (aBMD(DxA)). Estimated aBMD(CT) was then applied to diagnose osteopenia of the lumbar spine using statistical methods. RESULTS For the estimation of aBMD(DxA) from aBMD(CT), the proposed approach yielded a high correlation factor of r = 0.852, with a root mean square error of 0.0884 g/cm(2). The correlation was strongest when every slice in the dCT volume and both trabecular and cortical bone components were used. The classifier achieved an overall classification accuracy of 80.1% and an area under the receiver-operating characteristic curve of 0.894. CONCLUSIONS This clinical study demonstrates that aBMD(DxA) can be determined from routine CT data. Estimated aBMD(DxA) can be extended to form a dCT imaging-based opportunistic screening system for the detection and management of osteopenia.

A CAsE OF ADRENAl CAVERNOus HEmANgIOmA PREsENTINg WITH PROgREssIVE ENlARgEmENT AND APPARENT HORmONAl HyPERsECRETION

OBJECTIVE To report the case of a man with an adrenal cavernous hemangioma presenting as a progressively enlarging adrenal mass with apparent hormonal hypersecretion. METHODS We report the clinical, laboratory, imaging findings, and clinical course of this patient, and we highlight the important atypical features of this case. The literature is reviewed for the typical presentations of adrenal cavernous hemangiomas. RESULTS A 59-year-old man presented with an adrenal incidentaloma that had an imaging phenotype suggestive of a pheochromocytoma or an adrenal carcinoma. The hormonal profile also suggested a state of aldosterone and catecholamine hypersecretion. Surgery, however, proved the diagnosis to be an adrenal cavernous hemangioma. CONCLUSION Although adrenal cavernous hemangioma is a rare entity, it should be considered in the differential diagnosis of an adrenal incidentaloma. Its radiologic features are not specific, and the presence of hormonal hypersecretion does not exclude the diagnosis.

Bilateral ulna fractures associated with bisphosphonate therapy

We report a case of bilateral ulna stress fractures following bilateral femoral fractures associated with long-term bisphosphonate use. The patient is an 84-year-old woman receiving 15 years of bisphosphonate therapy. She did not have any preexisting medical conditions which are known secondary causes of bone loss. She was mostly housebound and used a walking frame for ambulation. She presented with atraumatic right ulna pain and subsequent atraumatic left ulna pain a month later. She was treated conservatively in backslabs and her bisphosphonate was stopped. Investigations did not reveal any secondary causes of osteoporosis or metabolic bone disorders.

Ensemble-based regression analysis of multimodal medical data for osteopenia diagnosis

Areal bone mineral density (aBMD) is used in clinical practice to diagnose osteoporosis. In previous studies, aBMD was estimated from diagnostic computed tomography (dCT) images, but a battery of medical tests was also taken that can be used to improve the regression performance. However, it is difficult to exploit the multimodal data as the additional features have poor informativeness and may lead to overfitting. An ensemble-based framework is proposed to improve the regression accuracy and robustness on multimodal medical data with a high relative dimensionality. Instead of case-wise bootstrap aggregating, a filtering-based metalearner scheme was employed to build feature-wise ensembles. The proposed approach was evaluated on clinical data and was found to be superior to bagging and other ensemble methods. The feature-wise ensembling approach can also be used to automatically determine if any multimodal features are related to bone mineral density. Several blood measurements were identified to be linked with bone mineral density, and a literature search supported the automatic identification results.

A case of an atypical femoral fracture associated with bacterial biofilm—pathogen or bystander?

We report a case of an 86-year-old woman with an atypical femoral fracture (AFF) who was treated with intramedullary nailing followed by lateral femoral plating. She developed a second femoral shaft fracture distal to the intramedullary nail which required a second operation. Biopsy of the periosteum overlying the site of the initial proximal AFF was sent for pathogen analysis. Using the Ibis T5000 platform and the BAC plate assay, a polymicrobial infection was diagnosed consisting of Bifidobacterium subtile and Pseudomonas mendocina. This raises the possibility that bacterial infections may play some role in atypical fractures of the femur.

Bone cross-sectional geometry is not associated with atypical femoral fractures in Asian female chronic bisphosphonate users

INTRODUCTION Atypical femoral fractures (AFF) tend to occur in Asian women with prolonged bisphosphonate exposure. Hip geometry is thought to contribute to the risk of AFF formation. We examined the hip structural geometry parameters in Asian female chronic bisphosphonate users who sustained an AFF and compared them to chronic bisphosphonate users who did not sustain any femoral fracture (NFF) and bisphosphonate-naïve patients who sustained an osteoporotic femoral fracture (OFF). MATERIALS & METHODS Thirty-one patients with AFFs were gender and age-matched to 31 patients with NFFs and 49 patients with OFFs. The Hip Structural Analysis parameters analyzed were bone mineral density (BMD), cross-sectional area (CSA; a metric of resistance to axial compression), section modulus (SM; a metric of resistance to tensile loads), average cortical thickness (ACT; mean thickness of the femoral cortices), buckling ratio (BR; an index of likelihood of local buckling), and neck shaft angle (NSA; the angle between the neck and shaft axes). The regions analyzed were three cross-sections measured at the narrowest femoral neck diameter, the intertrochanteric area, and the proximal femoral shaft. One-way ANOVA with Bonferroni adjustment for multiple comparisons was used to compare parameters between the three patient groups, with statistical significance defined as p<0.05. RESULTS There were no statistical differences in parameters between patients with AFFs and patients with NFFs at all measured regions. Patients with AFFs and NFFs had statistically higher BMD, CSA, ACT, SM values and lower BR values at the NN and IT regions than patients with OFFs. Additionally, patients with NFFs had statistically higher SM values at the IT region than patients with OFFs, while patients with AFFs had statistically higher BMD, CSA, and ACT values at the FS region. All other measured parameters were not statistically different between the groups. CONCLUSIONS Chronic bisphosphonate users with and without AFFs had similar femoral structural geometries. Unlike in other populations, varus neck shaft angles were not found to be associated with AFFs in Asian female chronic bisphosphonate users. Thus, bone cross-sectional geometry is not likely to be associated with AFFs in Asian female chronic bisphosphonate users. Hip Structural Analysis does not show an increased predilection for tensile failure in AFFs.

Atypical femoral fractures: transverse morphology at lateral cortex is a critical feature.

In 2010, the American Society for Bone and Mineral Research (ASBMR) task force defined major and minor features to assist in the case finding and reporting of atypical femoral fractures (AFFs). One major feature that was proposed was a “transverse or short oblique configuration.” Our primary aim was to compare the conventional overall fracture morphology (OFM) with its associated angle (OFMA) and our proposed lateral cortical fracture angle (LCFA) in the assessment of fracture configuration in suspected AFFs and non‐AFFs. The radiographs of 79 patients with AFFs and 39 patients with non‐AFFs were each analyzed by two blinded reviewers to obtain the OFM, OFMA, and LCFA. Using the overall fracture morphology to assess the suspected AFFs resulted in discordance between reviewers in 18 cases (22.8%), of which 5 (6.3%) were discordant between short oblique (>30° to 60°) and long oblique (>60° to 90°) configurations, therefore affecting their classifications as AFFs. By assessing only the critical component within the lateral cortex, all the suspected AFFs fell well within the classification as transverse fractures with a mean LCFA of 4.8° (range 0.3 to 18.0, SD = 4.23). The inter‐reader variability was also lower for LCFA versus OFMA (4.1° versus 6.9°, p = 0.001) when used to assess AFFs. Fracture angles were significantly different in AFFs versus non‐AFFs regardless of whether the OFMA or LCFA methodology was employed, but the greater difference associated with LCFA suggests its greater discriminating power. When LCFA was used in conjunction with 0° to 30° as the criteria for transverse morphology, all the AFFs and non‐AFFs were correctly classified. By using a standardized and precise method in measuring the fracture angle, specifically using only the component of the lateral cortex and limiting to truly transverse fractures, ie, between 0° and 30°, the LCFA is a robust and accurate method to assess the fracture morphology in suspected AFFs.

Preoperative thyroid dysfunction predicts 30-day postoperative complications in elderly patients with hip fracture.

Objectives: To investigate the relationship between thyroid function and short-term outcomes in elderly patients undergoing surgery for hip fracture. Methods: Patients aged >60 years admitted from July 2009 to June 2010 who underwent surgical fixation of low-energy hip fracture, excluding those with pathological or periprosthetic fracture, were enrolled in a retrospective observational cohort study. Patients were classified as having biochemically overt or subclinical hyperthyroidism or hypothyroidism, normal thyroid function, or nonclassifiable state based on preoperative thyroid-stimulating hormone and free thyroxine values. Outcome data were collected from hospital records. Biochemical thyroid dysfunction was not systematically treated. Outcomes measured were length of stay (LOS), 30-day postoperative complications, readmissions, and mortality. Results: A total of 254 patients were analyzed; 64 (25.2%) were male and mean age was 77.8 years. There were 128 (50.4%) patients with euthyroid, 68 (26.8%) nonclassifiable, 13 (5.1%) overtly hyperthyroid, 20 (7.9%) subclinically hyperthyroid, 4 (1.6%) overtly hypothyroid, and 21 (8.3%) subclinically hypothyroid. The 30-day postoperative complication rate was 38% (96 patients). The most common complication was urinary tract infection (12.6%), followed by cardiac events (8.3%) and delirium (5.5%). Patients with overt hyperthyroidism had an increased risk of complications in multivariate analysis (odds ratio 3.75, 95% confidence interval 1.10-12.84). Complications in this group were similar to those in the overall cohort. Thyroid function did not predict LOS, readmissions, or mortality. Conclusion: Older patients frequently develop complications following surgery for hip fractures. This risk appears to be increased by preoperative biochemically overt hyperthyroidism. Further study is warranted to confirm this finding and to determine whether preoperative treatment improves outcomes.