Physician-Reported Barriers to Osteoporosis Screening: A Nationwide Survey.

OBJECTIVE: Despite increased awareness, osteoporosis screening rates remain low. The objective of this survey study was to identify physician-reported barriers to osteoporosis screening. METHODS: We conducted a survey of 600 physician members of the Endocrine Society, American Academy of Family Practice, and American Geriatrics Society. The respondents were asked to rate barriers to osteoporosis screening in their patients. We performed multivariable logistic regression analyses to determine correlates with the most commonly reported barriers. RESULTS: Of 566 response-eligible physicians, 359 completed the survey (response rate, 63%). The most commonly reported barriers to osteoporosis screening included patient nonadherence (63%), physician concern about cost (56%), clinic visit time constraints (51%), low on the priority list (45%), and patient concern about cost (43%). Patient nonadherence as a barrier was correlated with physicians in academic tertiary centers (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.06-5.13), whereas clinic visit time constraints were correlated with physicians in both community-based academic affiliates and academic tertiary care ([OR, 1.96; 95% CI, 1.10-3.50] and [OR, 2.48; 95% CI, 1.22-5.07], respectively). Geriatricians (OR, 0.40; 95% CI, 0.21-0.76) and physicians with >10 years in practice were less likely to report clinic visit time constraints as a barrier (11-20 years: OR, 0.41; 95% CI, 0.20-0.85; >20 years: OR, 0.32; 95% CI, 0.16-0.65). Physicians with more patient-facing time (3-5 compared with 0.5-2 d/wk) were more likely to place screening low on the priority list (OR, 2.66; 95% CI, 1.34-5.29). CONCLUSION: Understanding barriers to osteoporosis screening is vital in developing strategies to improve osteoporosis care.

Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post-transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation.

Uncontrolled type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) increase morbidity and mortality after kidney transplantation. Conventional strategies for diabetes management in this population include metformin, sulfonylureas, meglitinides and insulin. Limitations with these agents, as well as promising new antihyperglycemic agents, create a need and opportunity to explore additional options for transplant diabetes pharmacotherapy. Novel agents including sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1RA), and dipeptidyl peptidase IV inhibitors (DPP4i) demonstrate great promise for T2DM management in the non-transplant population. Moreover, many of these agents possess renoprotective, cardiovascular, and/or weight loss benefits in addition to improved glucose control while having reduced risk of hypoglycemia compared with certain other conventional agents. This comprehensive review examines available literature evaluating the use of novel antihyperglycemic agents in kidney transplant recipients (KTR) with T2DM or PTDM. Formal grading of recommendations assessment, development, and evaluation (GRADE) system recommendations are provided to guide incorporation of these agents into post-transplant care. Available literature was evaluated to address the clinical questions of which agents provide greatest short- and long-term benefits, timing of novel antihyperglycemic therapy initiation after transplant, monitoring parameters for these antihyperglycemic agents, and concomitant antihyperglycemic agent and immunosuppression regimen management. Current experience with novel antihyperglycemic agents is primarily limited to single-center retrospective studies and case series. With ongoing use and increasing comfort, further and more robust research promises greater understanding of the role of these agents and place in therapy for kidney transplant recipients.

Managing Hyperglycemia in the COVID-19 Inflammatory Storm.

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) is now at global pandemic levels causing significant morbidity and mortality. Patients with diabetes are particularly vulnerable and more likely to get severe complications when infected with this virus. Although the information continues to emerge, here we provide our perspective on initial outcomes observed in hospitalized patients with diabetes and the potential role played by the proinflammatory metabolic state in these patients that promotes fertile ground for the virus' inflammatory surge, resulting in severe insulin resistance and severe hyperglycemia. The rapidly evolving renal failure, hypotension, pressor and steroid use, and variable nutritional support further complicates their management. Thus, timely implementation of glucose management protocols addressing these complex scenarios while also following COVID-19-related trajectories in inflammatory biomarkers and being cognizant of the health care provider exposure may substantially affect morbidity and mortality.

A rare cause of atraumatic fractures: case series of four patients with tumor-induced osteomalacia.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome that presents with hypophosphatemia, bone pain, muscle weakness and fractures. We report a case series of four patients with TIO that resulted in significant muscle weakness and multiple atraumatic fractures. CASE PRESENTATION: Four patients were referred to an endocrinology clinic for the evaluation of multiple atraumatic fractures, muscle weakness, generalized muscle and joint pain. Laboratory evaluation was notable for persistent hypophosphatemia due to urinary phosphate wasting, low to low-normal 1,25-dihydroxyvitamin D, elevated alkaline phosphatase and elevated fibroblast growth factor 23 (FGF23). Tumor localization was successful, and all four patients underwent resection of phosphaturic mesenchymal tumors. Post-operatively, patients exhibited normalization of serum phosphorus, in addition to significant improvement in their ambulatory function. CONCLUSION: Hypophosphatemia with elevated FGF23 and low 1,25-dihydroxyvitamin D level in the setting of multiple atraumatic fractures necessitates careful evaluation for biochemical evidence of tumor-induced osteomalacia.

Understanding Osteoporosis Screening Practices in Men: A Nationwide Physician Survey.

OBJECTIVE: To understand osteoporosis screening practices, particularly in men, by a diverse cohort of physicians, including primary care physicians, endocrinologists, and geriatricians. METHODS: We surveyed randomly selected members of the American Academy of Family Practice, Endocrine Society, and American Geriatrics Society. Respondents were asked to rate how often they would screen for osteoporosis in four different clinical scenarios by ordering a bone density scan. Multivariable logistic regression analyses were conducted to determine factors associated with offering osteoporosis screening in men in each clinical scenario. Physicians were also asked to note factors that would lead to osteoporosis screening in men. RESULTS: Response rate was 63% (359/566). While 90% respondents reported that they would always or frequently screen for osteoporosis in a 65-year-old post-menopausal woman, only 22% reported they would screen a 74-year-old man with no significant past medical history. Endocrinologists were more likely to screen a 74-year-old man compared to primary care physicians (odds ratio, 2.32; 95% confidence interval, 1.10 to 4.88). In addition to chronic steroid use (94%), history of nontraumatic fractures (88%), and androgen-deprivation therapy for prostate cancer (82%), more than half the physicians reported suppressive doses of thyroid hormone (64%) and history of falls (52%) as factors leading to screening for osteoporosis in men. CONCLUSIONS: Our survey results highlight heterogeneity in osteoporosis screening in men, with underscreening in some scenarios compared to women, and identify factors that lead to screening in men. These findings can help design interventions to improve osteoporosis screening in men.

Weight loss and bone mineral density in obese adults: a longitudinal analysis of the influence of very low energy diets.

BACKGROUND: The long-term effect of weight reduction on skeletal health is not well understood. The purpose of this study was to examine the impact of an intensive medical weight loss intervention using very low energy diet (VLED) (~ 800 cal/day) that result in significant changes in body weight, on total body bone mineral density (BMD) over 2 years. METHODS: We examined the impact of VLED-induced weight loss on BMD and FFM (Fat-free Mass) after 3-6 months and again while in weight maintenance at 2 years in 49 subjects. The effects of absolute and relative rate of weight reduction assessed by change in weight in kilograms were assessed using general linear modeling, with baseline BMD (or FFM) as a covariate, and age, sex and changes in body weight as primary model predictors. RESULTS: At the end of 2 years, the average weight loss was greater for men (weight: 23.51 ± 12.5 kg) than women (weight: 16.8 ± 19.2 kg) and BMD loss was greater among women (0.03 ± 0.04 g/cm2 vs 0.01 ± 0.04 g/cm2) (all p < 0.05). After adjusting for baseline BMD, age, and sex, there was a small but significant association between total weight loss and 2-year BMD (ß = - 0.001 g/cm2; p = 0.01). Similarly, there was a significant independent association between total weight loss and 2-year FFM (ß = - 116.5 g; p < 0.01). CONCLUSIONS: Despite significant weight loss with VLED, there was only a small loss is BMD.

The challenges of diagnosing osteoporosis and the limitations of currently available tools.

Dual-energy X-ray absorptiometry (DXA) was the first imaging tool widely utilized by clinicians to assess fracture risk, especially in postmenopausal women. The development of DXA nearly coincided with the availability of effective osteoporosis medications. Although osteoporosis in adults is diagnosed based on a T-score equal to or below - 2.5 SD, most individuals who sustain fragility fractures are above this arbitrary cutoff. This incongruity poses a challenge to clinicians to identify patients who may benefit from osteoporosis treatments. DXA scanners generate 2 dimensional images of complex 3 dimensional structures, and report bone density as the quotient of the bone mineral content divided by the bone area. An obvious pitfall of this method is that a larger bone will convey superior strength, but may in fact have the same bone density as a smaller bone. Other imaging modalities are available such as peripheral quantitative CT, but are largely research tools. Current osteoporosis medications increase bone density and reduce fracture risk but the mechanisms of these actions vary. Anti-resorptive medications (bisphosphonates and denosumab) primarily increase endocortical bone by bolstering mineralization of endosteal resorption pits and thereby increase cortical thickness and reduce cortical porosity. Anabolic medications (teriparatide and abaloparatide) increase the periosteal and endosteal perimeters without large changes in cortical thickness resulting in a larger more structurally sound bone. Because of the differences in the mechanisms of the various drugs, there are likely benefits of selecting a treatment based on a patient's unique bone structure and pattern of bone loss. This review retreats to basic principles in order to advance clinical management of fragility fractures by examining how skeletal biomechanics, size, shape, and ultra-structural properties are the ultimate predictors of bone strength. Accurate measurement of these skeletal parameters through the development of better imaging scanners is critical to advancing fracture risk assessment and informing clinicians on the best treatment strategy. With this information, a "treat to target" approach could be employed to tailor current and future therapies to each patient's unique skeletal characteristics.

Recurrent Hyperparathyroidism Due to a Novel CDC73 Splice Mutation.

The recognition of hereditary causes of primary hyperparathyroidism (pHPT) is important because clinical care and surveillance differ significantly between sporadic and hereditary pHPT. In addition, the increasing number of genetic tests poses a challenge to classify mutations as benign or pathogenic. Functional work-up of variants remains a mainstay to provide evidence for pathogenicity. We describe a 52-year-old male patient with recurrent pHPT since age 35 years. Despite several neck surgeries with complete parathyroidectomy, he experienced persistent pHPT, necessitating repeated surgery for a forearm autotransplant, which finally resulted in unmeasurable parathyroid hormone (PTH) levels. Genetic testing revealed a new CDC73 variant (c.238-8G>A [IVS2-8G>A]), initially classified as a variant of uncertain significance. Parathyroid tissue from the initial surgeries showed loss of heterozygosity. Using an RT-PCR approach, we show that the mutation leads to the use of a cryptic splice site in peripheral mononuclear cells. In addition, a minigene approach confirms the use of the cryptic splice site in a heterologous cell system. The novel c.238-8G>A CDC73 variant activates a cryptic splice site, and the functional data provided justify the classification as a likely pathogenic variant. Our results underscore the importance of functional work-up for variant classification in the absence of other available data, such as presence in disease-specific databases, other syndromic clinical findings, or family history. In addition, the presented case exemplifies the importance to consider a hereditary condition in young patients with pHPT, particularly those with multi-gland involvement. © 2017 American Society for Bone and Mineral Research.

Abdominal adiposity and low physical activity are independently and inversely associated with bone mineral density.

BACKGROUND AND METHODS: Obesity is a highly heterogeneous condition, and the link between adiposity distribution profiles and skeletal health is not well understood. This study examined the association between adiposity and bone mineral density (BMD) in a large cohort (5268 individuals) of US adults aged 20-85 years. RESULTS: Body mass index (BMI) and moderate-to-vigorous physical activity were positively associated with BMD. Conversely, abdominal adiposity was negatively associated with BMD, even after adjusting for age, race, BMI, and objectively-measured physical activity. CONCLUSIONS: These findings highlight the negative influence of abdominal adiposity on BMD and contradict the notion that excess fat mass is protective for bone health.

Skeletal Complications and Mortality in Thyroid Cancer: A Population-Based Study.

Context: Although bone is a common site for tumor metastases, the burden of bone events [bone metastases and skeletal-related events (SREs)] in patients with thyroid cancer is not well known. Objective: To measure the prevalence of bone events and their impact on mortality in patients with thyroid cancer. Patients, Design, and Setting: We identified patients diagnosed with thyroid cancer between 1991 and 2011 from the linked Surveillance Epidemiology and End Results-Medicare dataset. Multivariable logistic regression was used to identify the risk factors for bone metastases and SREs. We used Cox proportional hazards regressions to assess the impact of these events on mortality, after adjusting for patient and tumor characteristics. Results: Of the 30,063 patients with thyroid cancer, 1173 (3.9%) developed bone metastases and 1661 patients (5.5%) developed an SRE. Compared with papillary thyroid cancer, the likelihood of developing bone metastases or an SRE was higher in follicular thyroid cancer [odds ratio (OR), 2.25; 95% confidence interval (CI), 1.85 to 2.74 and OR, 1.40; 95% CI, 1.15 to 1.68, respectively] and medullary thyroid cancer (OR, 2.16; 95% CI, 1.60 to 2.86 and OR, 1.62; 95% CI, 1.23 to 2.11, respectively). The occurrence of a bone event was associated with greater risk of overall and disease-specific mortality [hazard ratio (HR), 2.14; 95% CI, 1.94 to 2.36 and HR, 1.59; 95% CI, 1.48 to 1.71, respectively]. Bone events were a poor prognostic indicator even when compared with patients with other distant metastases (P < 0.001 and P < 0.001 for overall and disease-specific mortality, respectively). Conclusions: Bone events in patients with thyroid cancer are a poor prognostic indicator. Patients with follicular and medullary thyroid cancers are at especially high risk for skeletal complications.

Adjuvant Aromatase Inhibitors in Early Breast Cancer May Not Increase the Risk of Falls.

BACKGROUND: Falling increases the risk for fracture. The impact of adjuvant aromatase inhibitors (AI) on the risk of falls is undefined. METHODS: A retrospective case control study was performed examining women with early stage breast cancer on adjuvant AI and matched controls without cancer. Fall and fracture data were abstracted from the medical record. RESULTS: Matched pairs of 332 women were identified (total N = 664). There was no statistically significant difference in the odds of a fall between cases and controls, p = 0.86. Similarly, the odds of a fracture between cases and controls was not significantly different, p = 1.0. There were 35 pairs in which the case fractured but the control did not and equal number of pairs where the control fractured but the case did not. For pairs in which control fractured but case did not, the median age at fracture was significant higher than that for pairs in which case fractured but the control did not (71 vs. 63 years p = 0.0003). CONCLUSION: This study did not identify a difference in the incidence of falls or fractures in women on adjuvant AI compared to their age matched controls without breast cancer. Prospective studies of falls and fracture in women on adjuvant AI therapy compared to age match controls would aid in the identification of fracture risk.

Muscle Weakness Thresholds for Prediction of Diabetes in Adults.

BACKGROUND: Despite the known links between weakness and early mortality, what remains to be fully understood is the extent to which strength preservation is associated with protection from cardiometabolic diseases, such as diabetes. PURPOSE: The purposes of this study were to determine the association between muscle strength and diabetes among adults, and to identify age- and sex-specific thresholds of low strength for detection of risk. METHODS: A population-representative sample of 4066 individuals, aged 20-85 years, was included from the combined 2011-2012 National Health and Nutrition Examination Survey (NHANES) data sets. Strength was assessed using a handheld dynamometer, and the single highest reading from either hand was normalized to body mass. A logistic regression model was used to assess the association between normalized grip strength and risk of diabetes, as determined by haemoglobin A1c levels ≥6.5 % (≥48 mmol/mol), while controlling for sociodemographic characteristics, anthropometric measures and television viewing time. RESULTS: For every 0.05 decrement in normalized strength, there were 1.26 times increased adjusted odds for diabetes in men and women. Women were at lower odds of having diabetes (odds ratio 0.49; 95 % confidence interval 0.29-0.82). Age, waist circumference and lower income were also associated with diabetes. The optimal sex- and age-specific weakness thresholds to detect diabetes were 0.56, 0.50 and 0.45 for men at ages of 20-39, 40-59 and 60-80 years, respectively, and 0.42, 0.38 and 0.33 for women at ages of 20-39, 40-59 and 60-80 years, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: We present thresholds of strength that can be incorporated into a clinical setting for identifying adults who are at risk of developing diabetes and might benefit from lifestyle interventions to reduce risk.

Adjuvant Endocrine Therapy and Bone Health in Breast Cancer.

Breast cancer is one of the most common malignancies of women. The majority of breast cancers express estrogen and/or progesterone receptors, permitting anticancer targeting strategies to reduce estrogen signaling in the cancer cells and thereby lowering the risk of breast cancer recurrence. The development of the selective estrogen receptor modulator (SERM) tamoxifen marked a significant milestone in breast cancer care that transcended older estrogen ablative strategies such as oophorectomy and ovarian irradiation. An unintended benefit of tamoxifen in postmenopausal women was bone density preservation. The third generation of aromatase inhibitors (AIs) have demonstrated superior efficacy to tamoxifen in improving disease-free survival in postmenopausal women. However, the AIs significantly increase bone resorption, reduce bone mineral density, and increase the risk of fracture above that of tamoxifen. As a consequence of this, clinical oncologists have assumed a larger role in the screening and treatment of the skeletal complications of breast cancer therapies. The key features of managing bone health in women with early stage breast cancer receiving adjuvant endocrine therapy are reviewed here.

Bizarre parosteal osteochondromatous proliferation: a novel case report of recurrence in the toe.

Bizarre parosteal osteochondromatous proliferation (BPOP) is an uncommon reactive mesenchymal lesion mainly affecting the small bones of the hands and feet. They frequently occur in young adults. It is important to understand and differentiate BPOP from other lesions, especially because of its atypical microscopic features and tendency to recur. We present a case of a recurrent lesion involving the toe and discuss management options. To our knowledge, our current case report is the first in the literature to report a recurring BPOP lesion of the toe.

Skeletal manifestations of treatment of breast cancer.

Breast cancer and osteoporosis are common diagnoses in women. Breast cancer survival has improved due to earlier detection and improved treatments. As most breast cancers are estrogen receptor positive, treatment is often aimed at altering the hormonal environment. Both pre and postmenopausal women undergoing these therapies are at risk for bone loss. The patient's health care team ought to have an awareness of the potential for breast cancer treatments to accelerate bone loss. Women with early stage breast cancer are treated with curative intent and, therefore, maintaining bone health is important and is part of the survivorship care to ensure an optimal quality of life.

The management of osteoporosis in breast cancer survivors.

Breast cancer is a common diagnosis and the majority of women treated will be cured. Women with early stage breast cancer may be at increased risk for osteoporosis due to anticancer therapies. Chemotherapy induced amenorrhea and the use of anti-estrogens can promote bone loss; thus, the management of bone health in women with breast cancer is an important component of survivorship care. Osteoporosis is considered a "silent" disease as there are often no discrete warning signs, until a fracture occurs; therefore, clinicians must be cognizant of the underlying risk for osteoporosis and co-morbid conditions and/or medications that accelerate risk of fracture. Breast cancer therapies that effect bone, screening for bone loss and interventions to mitigate the treatment toxicities are reviewed.

Relation of baseline serum potassium levels to angiographic findings in patients with known or suspected coronary artery disease.

BACKGROUND: In experimental animal studies, potassium has been demonstrated to protect against the development of atherosclerosis through a variety of mechanisms. Data regarding the role of potassium in the development of human atherosclerosis are sparse. The objective of this study was to determine the association between plasma potassium levels and angiographically defined coronary artery disease (CAD). METHODS: In a cohort of 389 male patients undergoing coronary angiography for a variety of clinical indications, the association between baseline serum potassium levels and the extent of angiographically defined atherosclerosis was analyzed. Adjustments were made for clinical and laboratory variables (including inflammatory markers) known to be associated with atherosclerosis. RESULTS: By multivariate logistic regression analysis, baseline serum potassium levels were an independent predictor of the presence of multivessel disease (odds ratio (OR) 1.31, 95% confidence interval (CI) 1.01-1.69; P < 0.05). In addition, in the non-myocardial infarction subpopulation of patients, serum potassium was also an independent predictor of the presence of multivessel disease by multivariate logistic regression analysis (OR 1.34, 95% CI, 1.02-1.76; P < 0.05). In the myocardial infarction (MI) subpopulation, serum potassium was not a predictor of multivessel disease, possibly due to the confounding effect of hypokalemia known to be present during MI. CONCLUSIONS: These data demonstrate that a simple baseline serum potassium level is independently associated with the presence of multivessel disease, even in the context of clinical CAD risk factors and other established inflammatory markers.

Beyond lipid lowering: the anti-hypertensive role of statins.

INTRODUCTION: The management of the hypercholesterolemic patient has evolved tremendously with the introduction of the HMG-CoA Reductase inhibitors, a class of drugs better known as the statins. Statins modify cholesterol metabolism by inhibiting the rate-limiting enzyme of cholesterol biosynthesis, producing greater decreases in plasma cholesterol levels than previously realized with hypolipidemic therapy. With the advent of the classic statin-megatrials such as the Scandinavian Simvastatin Survival Study (4S), WOSCOPS, CARE, and the more recent Heart Protection Study (HPS), the role of statins in both the primary and secondary prevention and ultimate risk reduction of patients with coronary disease has been firmly established. DISCUSSION: With an increase in use and popularity, a number of beneficial actions of the statins unrelated to their cholesterol-lowering ability have been reported. These effects have generated greater interest in the possible additional roles and indications for the use of these drugs. Of central focus in this paper is the cholesterol-independent benefit of this group of agents on the cardiovascular system, particularly on the lowering of systemic blood pressure. A number of hypotheses have been proposed for this action and these shall be reviewed within this paper. CONCLUSION: We explore recent data that suggests that statins may provide substantial reduction of blood pressure in the hypertensive, hypercholesterolemic patient independent of their lipid-lowering effect. In addition, we review several notable publications that postulate unique mechanisms for this action and benefit. We also present plausible explanations as to why some of the larger statin trials did not report similar such findings.

Charcot arthropathy. An often overlooked complication of diabetes mellitus.

Charcot's arthropathy is a rare complication of diabetes that can result in significant morbidity. It may have a similar presentation to cellulitis, which often delays its recognition. While the pathogenesis remains unclear, timely diagnosis and treatment can help prevent the deformities associated with the late stages. It is important for physicians to recognize this complication early and use a team approach that includes an experienced orthopedic surgeon and/or podiatrist. We present a case and review the presentation, diagnosis and treatment of Charcot's arthropathy.