Evaluation of Secondary Causes of Bone Loss in a Primary Care Setting

ObjectiveTo evaluate the clinical and laboratory work-up for secondary causes of bone loss in a primary care setting.MethodsWe conducted a retrospective review of medical records of 100 patients with either osteoporosis or osteopenia, who presented to a university-based primary care clinic. Patients with chronic kidney disease or a history of organ transplantation were excluded, as were premenopausal women.ResultsAge at menopause was ascertained in 43% of female patients. Only 2% of patients were asked specifically about symptoms of malabsorption, whereas a history of malignant disease or its treatment was elicited from 24%. Of the overall study group, 50% were asked about a history of thyroid disease and 18% about a history of liver disease. Testicular examination was documented in 40% of male patients. Serum calcium and creatinine, complete blood cell count, and thyroid function tests were evaluated in 100% of patients. Vitamin D status was assessed in only 1 patient; no study patient had a 24-hour urine collection for determination of calcium excretion. Serum parathyroid hormone was measured in 7% and serum phosphorus in 10% of patients. Sixty percent of male patients had their testosterone levels assessed. Although the serum creatinine level was determined in all patients, only 1% had a formal estimation of the creatinine clearance or glomerular filtration rate.ConclusionThe evaluation of secondary causes of bone loss was notably inadequate in our study population. Because most patients with osteoporosis or osteopenia are managed in the primary care setting, a distinct need exists for consensus guidelines and recommendations from professional endocrine organizations to advise primary care physicians in the appropriate diagnostic evaluation for secondary causes of bone loss in such patients. (Endocr Pract. 2009;15:410-414)     

Iatrogenic Osteoporosis,Bilateral Hip Osteonecrosis,and Secondary Adrenal Suppression in an Hiv-Infected Man Receiving Inhaled Corticosteroids and Ritonavir-Boosted Highly Active Antiretroviral Therapy

ObjectiveTo report the first case of severe osteoporosis associated with a vertebral pathologic fracture and osteonecrosis of femoral heads in an HIV-infected man receiving inhaled corticosteroids and ritonavir-boosted antiretroviral therapy.MethodsWe describe an HIV-infected man with severe osteoporosis, bilateral hip osteonecrosis, and secondary adrenal suppression, including detailed clinical, laboratory, and radiographic data, and review the related literature.ResultsA 60-year-old man with a 15-year history of HIV infection and a medical history of long-standing bronchiectasis treated with inhaled corticosteroids and hypogonadism treated with testosterone was referred to the endocrinology clinic after experiencing an osteoporotic vertebral fracture. He was taking ritonavir-boosted antiretroviral therapy. Osteonecrosis of both hips was also diagnosed, which required total hip replacement therapy.Laboratory evaluation revealed adrenal insufficiency due to increased effect of exogenous inhaled steroids and no other secondary causes of osteoporosis. A bone densitometry study showed osteoporosis of both hips and the lumbar spine. He was treated with intravenous pamidronate. During treatment, he developed bilateral femoral fractures after minor trauma.ConclusionsGiven the potential for increased serum levels of inhaled corticosteroids in patients taking ritonavirboosted highly active antiretroviral therapy, attention must be paid to the risk of bone loss in HIV-infected patients taking inhaled corticosteroids. Prescribing calcium and vitamin D supplementation and considering early osteoporosis screening are reasonable measures for this patient population. Interaction between inhaled corticosteroids and ritonavir may increase risk of hypothalamus-pituitary-adrenal axis suppression. (Endocr Pract. 2011;17:74-78)     

American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis— 2020 Update Executive Summary

Objective: The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs).Methods: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols.Results: The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 368 citations: 123 (33.5%) evidence level (EL) 1 (highest), 132 (36%) EL 2 (intermediate), 20 (5.5%) EL 3 (weak), and 93 (25%) EL 4 (lowest). New or updated topics in this CPG include: clarification of the diagnosis of osteoporosis, stratification of the patient according to high-risk and very-high-risk features, a new dual-action therapy option, and transitions from therapeutic options.Conclusion: This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of post-menopausal osteoporosis.     

Guías de práctica clínica para la evaluación y tratamiento de la osteoporosis asociada a enfermedades endocrinas y nutricionales

ObjectiveTo provide practical recommendations for evaluation and treatment of osteoporosis associated to endocrine diseases and nutritional conditions.ParticipantsMembers of the Bone Metabolism Working Group of the Spanish Society of Endocrinology, a methodologist, and a documentalist.MethodsRecommendations were formulated according to the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed), using the following terms associated to the name of each condition: AND “osteoporosis”, “fractures”, “bone mineral density”, and “treatment”. Papers in English with publication date before 18 October 2011 were included. Current evidence for each disease was reviewed by two group members, and doubts related to the review process or development of recommendations were resolved by the methodologist. Finally, recommendations were discussed in a meeting of the Working Group.ConclusionsThe document provides evidence-based practical recommendations for evaluation and management of endocrine and nutritional diseases associated to low bone mass or an increased risk of fracture. For each disease, the associated risk of low bone mass and fragility fractures is given, recommendations for bone mass assessment are provided, and treatment options that have shown to be effective for increasing bone mass and/or to decreasing fragility fractures are listed.     

Hirsutism: Diagnosis and management

Background:Hirsutism is defined as excess hair growth in androgen-dependent areas of the body in women.Objective: This article provides an updated review of hirsutism, focusing on the etiologies, clinical features, approach to diagnostic evaluation, and treatment options.Methods: The PubMed database was searched for English-language articles published from 1981 to the present, using the terms hirsutism, polycystic ovarian syndrome, congenital adrenal hyperplasia, hirsutism diagnosis, and hirsutism treatment. Reference lists from review articles on hirsutism during this time period were also examined.Results: While there are many causes of hirsutism, the majority of patients have a benign process that may be idiopathic. In some circumstances, hirsutism is a sign of functional ovarian hyperandrogenism or congenital adrenal hyperplasia. Even more rarely, it is the presenting sign of an internal malignancy.Conclusions: Hirsutism clinically presents in women as excessive hair growth in androgen-dependent areas. It is a particularly important diagnosis to make, because it often significantly affects a woman's perception of her femininity and less commonly can be a sign of an underlying malignancy or a cutaneous manifestation of a condition with significant cardiovascular or other morbidity. A variety of treatments exist to help minimize the appearance of unwanted hair.     

A Simple Intervention for Improving the Implementation Rate of a Recommended Osteoporosis Treatment After Hip Fracture

ObjectiveOsteoporosis is often under-treated, and hip fracture is frequently its first manifestation. Hospitalization for a hip fracture is an opportunity to initiate osteoporosis treatment. The aim of this study was to investigate whether a simple intervention improves the implementation rate of a recommended osteoporosis treatment.MethodsOne hundred elderly patients admitted with low-impact hip fracture were given a 10 minute explanation about osteoporosis and its treatment during their postoperative hospital stay. In addition, the patients received an explanatory brochure and a letter to their primary care physician that included an article on fracture rate reduction with osteoporosis treatment. Implementation of therapy was assessed by a telephone survey 3 and 6 months postoperatively. The patients who had not received treatment at 3 months were given a repeated explanation. The historical control group was comprised of 100 hip fracture patients with similar demographic characteristics, who were operated on and discharged with the standard care recommendations for osteoporosis prevention.ResultsAt the 3 month follow-up, the therapy rate in both groups was similar (19%). Fifty-eight percent of the patients in the study group had no recollection of the intervention. However, after a repeated explanation, at the 6 month follow-up, 39% of the intervention group had received drug therapy for fracture prevention (P<.001).ConclusionA simple intervention enlisting the patients' help to involve their primary care physician can increase treatment rates for osteoporosis following a hip fracture. During the immediate postoperative period, the patients and their families have difficulty implementing the recommendations. Therefore, repeated communications are recommended. (Endocr Pract. 2013;19:46-50)     

Frax Prediction without BMD for Assessment of Osteoporotic Fracture Risk

ObjectiveTo compare Fracture Risk Assessment Tool (FRAX) calculations with and without bone mineral density (BMD) in predicting the 10-year probability of hip and major osteoporotic fractures (MOF).MethodsA cross-sectional review of patients requiring screening for osteoporosis as part of their routine medical care was conducted. Postmenopausal women and men over 50 years of age who were never diagnosed with osteoporosis or treated with U.S. Food and Drug Administration-approved agents for osteoporosis were included. Height, weight, FRAX questionnaire, femoral neck BMD, and T-score data were obtained. FRAX scores with BMD (FRAX/BMD) and without BMD (FRAX) were calculated. Subjects were separated on the basis of identical and different treatment recommendations. Fracture risk factors were compared between groups using simple Student’s t test analysis of numerical variables and Fisher’s exact test analysis of binary variables.ResultsOf 151 total subjects, 127 (84%) had identical fracture risk predictions with or without BMD included in the FRAX calculation. Thirty subjects met treatment criteria and 97 did not, but the FRAX prediction was the same with risk factors alone or with risk factors plus BMD. Age was the only risk factor that was significantly different between those with identical and different predictions (median age, 64.42 and 76.25 years, respectively; P&#x003C;.001).ConclusionIn most cases, FRAX alone provides the same prediction as FRAX with BMD. Younger age is more indicative of an identical prediction. (Endocr Pract. 2013;19:780-784)     

The Risk of Bone Fractures in Post-Poliomyelitis Patients Transitioning to Middle Adulthood

ObjectiveWhile osteoporotic fractures are reported in up to 40% of adults with post-poliomyelitis syndrome (PPS), clinical guidelines regarding bone mineral density (BMD) and indications for treatment are scarce. We investigated the characteristics of PPS patients, focusing on fractures and osteoporosis as the primary outcomes.MethodsA cross-sectional retrospective data analysis from medical records of 204 PPS patients regarding their clinical characteristics and long-term outcome, with emphasis on bone metabolism status.ResultsOur cohort included 53% women; mean age was 65 years at study entry and 1.7 years at the diagnosis of acute poliomyelitis. The lower limb was involved in 97.5% of patients, and the BMD in the affected limb tended to be lower than the unaffected, with a mean T-score of -1.64 vs. -1.19, respectively (P = .06). Recurrent falls were documented in 39.2% of patients, and osteoporosis in 20.6%, being more frequent in women (P = .003) and patients with fractures (P = .002). At least one fracture occurred in 52.2% of patients, and more than one in 40.3%. The median age for the first fracture was 57.5 years (range, 30 to 83 years), and most fractures occurred in the affected limb (73.2%).ConclusionsUnderdiagnosis and delayed treatment of osteoporosis in late-adulthood post-poliomyelitis patients underlie the need for comprehensive clinical guidelines to manage these patients, including recommendations on bone health assessment, medical treatment, and their inclusion as a high-risk group for bone fractures.     

High-dose Insulin Therapy: is it Time for U-500 Insulin?

ObjectiveTo provide an overview of U-500 regular insulin action, review published clinical studies with U- 500 regular insulin, and offer guidance to practicing endocrinologists for identifying patients for whom U-500 regular insulin may be appropriate.MethodsThis review has been produced through a synthesis of relevant published literature compiled via a literature search (MEDLINE search of the English-language literature published between January 1969, and July 2008, related to U-500, insulin resistance, concentrated insulin, high-dose insulin, insulin pharmacokinetics, and diabetes management) and the authors’ collective clinical experience.ResultsThe obesity epidemic is contributing to an increase in the prevalence of type 2 diabetes, as well as to increasing insulin requirements in insulin-treated patients. Many of these patients exhibit severe insulin resistance, manifested by daily insulin requirements of 200 units or greater or more than 2 units/kg. Delivering an appropriate insulin volume to these patients can be difficult and inconvenient and may be best accomplished with U-500 regular insulin by multiple daily injections or with continuous subcutaneous insulin infusion, rather than with standard U-100 insulin. Implementation of U-500 regular insulin in patients previously on other insulin formulations is described with a treatment algorithm covering dosage requirements ranging from 150 to more than 600 units per day on the basis of the authors’ experience.ConclusionRegimen conversion of appropriately selected patients from high-dose, U-100 insulin to U-500 regular insulin therapy on the basis of the recommendations presented in this article may potentially result in improved glycemic control and lower cost. (Endocr Pract. 2009;15:71-79)     

Correlation Between Bone Markers and Bone Mineral Density in Postmenopausal Women with Osteoporosis

ObjectiveTo study the relationship between bone markers and bone mineral density (BMD) in an effort to identify their utility in postmenopausal women with osteoporosis.MethodsEighty-two consecutive postmenopausal women with untreated osteoporosis were included in the study. Forearm, spinal, and femoral BMD by dual-energy x-ray absorptiometry and markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) and bone resorption (urinary free deoxypyridinoline) were measured in all patients. Patients with low serum vitamin D levels, secondary osteoporosis, or clinically significant systemic disease were excluded from the study. The patients were classified on the basis of BMD of the lumbar spine into the following 3 groups: mild (n = 23) (T score -2.5 through -3), moderate (n = 42) (T score -3.1 through -4), or severe (n = 17) (T score ≤-4.1) osteoporosis. One-way analysis of variance and Pearson correlation were used for statistical analysis, with a P value < .05 being considered significant.ResultsSerum osteocalcin was significantly different among the 3 study groups (4.1 ± 2.7, 4.5 ± 3.1, and 6.7 ± 5.6 ng/mL, respectively; P = .0349) and had a significant negative correlation with BMD (r² = -0.0779; P = .0168). Other bone markers such as bone-specific alkaline phosphatase and urinary free deoxypyridinoline did not correlate with the underlying BMD.ConclusionIn our study, osteocalcin was significantly correlated with BMD in postmenopausal women with osteoporosis. Other bone markers did not correlate with BMD. Further large-scale population data and analyses are needed to confirm these findings. (Endocr Pract. 2008;14:1102-1107)     

New Treatment Modalities in Osteoporosis

ObjectiveTo describe recently discovered agents for the management of osteoporosis.MethodsA literature review (PubMed search) was conducted to identify agents at various stages of development for osteoporosis treatment. Agents under study or review for approval were included.ResultsIn menopause, bone remodeling is increased, and agents that suppress bone resorption can stabilize bone mass. In contrast, agents that target the osteoblast can increase bone formation and bone mass. Novel antiresorptive agents can target the formation or the activity of osteoclasts. They include denosumab, an antibody to receptor activated nuclear factor kB; new selective estrogen receptor modulators, such as bazedoxifene; and cathepsin K inhibitors, such as odanacatib. Src kinase inhibitors are in the early phases of development. Parathyroid hormone is the only approved anabolic agent for the treatment of osteoporosis. Novel anabolic therapies for osteoporosis may include the use of factors with anabolic properties for bone or the neutralization of growth factor antagonists. Recent discoveries have demonstrated that the Wnt/β-catenin signaling pathway has a central role in osteoblastic cell differentiation. Antibodies to Wnt antagonists, such as sclerostin, are under development as new therapeutic approaches for osteoporosis. Anabolic therapies have the potential to enhance bone mass, but their long-term safety must be proven.ConclusionsNew developments in the treatment of osteoporosis include novel antiresorptive and anabolic agents. Their success will depend on their long-term effectiveness and safety profile. (Endocr Pract. 2010;16:855-863)     

Evaluation and Treatment of Osteoporosis in Patients with a Fragility Hip Fracture

ObjectiveTo determine whether patients with fragility hip fractures underwent assessment and treatment of osteoporosis during initial hospitalization or recommendations for such intervention were made to the primary care provider (PCP) at the time of hospital dismissal.MethodsA review of medical records of patients admitted with a low-impact hip fracture to the Royal University Hospital in Saskatoon, Saskatchewan, Canada, was performed to determine whether recommendations were made to evaluate for or treat osteoporosis. In addition, a questionnaire was sent to the orthopedic surgeons practicing at the hospital to help identify barriers to widespread diagnosis and treatment of osteoporosis in such patients.ResultsBetween January and December 2004, 174 patients with fragility hip fractures were admitted to the Royal University Hospital. The mean age of these patients was 82.5 ± 9.8 years. Evaluation for treatment of osteoporosis was recommended in only 9 patients (5%). We found no significant differences in the intervention rates between male and female patients, between patients with and those without a prior history of osteoporosis or fracture, between patients who were previously taking osteoporosis medications and those who were not, and between patients who were seen by a medical consultant and those who were not. Most orthopedic surgeons believed that they were primarily responsible for the surgical care of these patients, and because they did not see these patients in regular follow-up, the management of osteoporosis was considered the responsibility of the PCP.Conclusion: The results of this study indicate that only a small number of patients with fragility hip fractures receive appropriate evaluation or treatment for underlying osteoporosis either during initial hospitalization or at the time of dismissal from the hospital. In this study, most orthopedic surgeons believed that evaluation and treatment of osteoporosis were the responsibility of the PCP. Because these patients have an increased risk for future fractures, barriers to the diagnosis and treatment of osteoporosis need to be removed, and health-care professionals need to be educated about appropriate risk factor modification in these patients. (Endocr Pract. 2005;11:370-375)     

Prevalence of Osteoporosis in Ambulatory Postmenopausal Women from A Semiurban Region in Southern India: Relationship to Calcium Nutrition and Vitamin D Status

ObjectiveTo assess the prevalence of osteoporosis in healthy ambulatory postmenopausal Indian women as measured by dual-energy x-ray absorptiometry and to study the dietary calcium intake and vitamin D status and their influence on bone mineral density (BMD).MethodsWe conducted a community-based crosssectional study in a semiurban region. A randomized cluster sampling technique was used. The study cohort consisted of 150 ambulatory postmenopausal women (≥ 50 years old). Dual-energy x-ray absorptiometry for BMD was performed at the lumbar spine and femoral neck. Dietary calcium intake and biochemical variables were assessed.ResultsThe prevalence of osteoporosis was 48% at the lumbar spine, 16.7% at the femoral neck, and 50% at any site. The mean dietary calcium intake was much lower than the recommended intake for this age-group. There was a significant positive correlation between body mass index and BMD at the lumbar spine and the femoral neck (r = 0.4; P = .0001). BMD at the femoral neck was significantly less (mean, 0.657 versus 0.694 g/cm²) in the vitamin D-insufficient study subjects in comparison with the vitamin D-sufficient women (P = .03).ConclusionThe high prevalence of osteoporosis and vitamin D insufficiency in this semiurban group of postmenopausal women in India is a major health concern. Measures such as adequate calcium intake and vitamin D supplementation in women of this age-group may be beneficial. (Endocr Pract. 2008;14:665-671)     

Vitamin D for Treatment and Prevention of Infectious Diseases; A Systematic Review of Randomized Controlled Trials

ObjectiveTo review the existing human controlled intervention studies of vitamin D as adjunctive therapy in settings of infection and provide recommendations for design and implementation of future studies in this field on the basis of the evidence reviewed.MethodsWe conducted a systematic review of randomized controlled clinical trials that studied vitamin D for treatment or prevention of infectious diseases in humans. Studies from 1948 through 2009 were identified through search terms in PubMed and Ovid MEDLINE.ResultsThirteen published controlled trials were identified by our search criteria. Ten trials were placebo controlled, and 9 of the 10 were conducted in a rigorous double-blind design. The selected clinical trials demonstrated substantial heterogeneity in baseline patient demographics, sample size, and vitamin D intervention strategies. Serious adverse events attributable to vitamin D supplementation were rare across all studies. On the basis of studies reviewed to date, the strongest evidence supports further research into adjunctive vitamin D therapy for tuberculosis, influenza, and viral upper respiratory tract illnesses. In the selected studies, certain aspects of study design are highlighted to help guide future clinical research in the field.ConclusionMore rigorously designed clinical trials are needed for further evaluation of the relationship between vitamin D status and the immune response to infection as well as for delineation of necessary changes in clinical practice and medical care of patients with vitamin D deficiency in infectious disease settings. (Endocr Pract. 2009;15:438-449)     

Bone Mineral Density in Patients with Nonalcoholic Steatohepatitis among End-Stage Liver Disease Patients Awaiting Liver Transplantation

ObjectiveSeveral studies have shown that patients with end-stage liver disease (ESLD) have lower bone mineral density (BMD) and a higher prevalence of osteoporosis compared to an age-matched population. Hyperinsulinemia and insulin resistance are typically associated with increased BMD. We hypothesized that patients with nonalcoholic steatohepatitis (NASH) and underlying insulin resistance may have higher BMD than patients with cirrhosis from other causes.MethodsWe performed a retrospective chart review of patients with ESLD who underwent liver transplant evaluation at Ochsner Clinic Foundation and had a BMD study as part of initial work up and compared BMD values of patients diagnosed with NASH to patients with cirrhosis due to other causes. Patients were categorized into 3 groups based on the etiology of their liver disease as NASH, alcoholic cirrhosis, or viral hepatitis C or B (HCV/ HBV).ResultsA total of 63 patients met the study inclusion criteria, including 15 with NASH, 17 with alcoholic cirrhosis, and 31 with HCV/HBV. The overall prevalence rates of osteopenia and osteoporosis were 44% and 12%, respectively. BMD values were higher in the NASH group than the HCV/HBV group at lumbar spine, total hip, and femoral neck (P = .01, .03, and .02, respectively). There were no statistical differences in BMD values between NASH and alcoholic cirrhosis groups at any site.ConclusionsWe found a high prevalence of low BMD among patients with ESLD awaiting liver transplantation. NASH patients had higher BMDs than HCV/ HBV patients. The effects of NASH and insulin resistance on bone are complex and should be examined further. (Endocr Pract. 2013;19:414-419)     

Osteoporosis in Men

ObjectiveTo review information pertinent to bone health and osteoporosis in men.MethodsA review of pertinent literature was conducted.ResultsOsteoporosis affects approximately 2 million men in the US and accounts for an estimated 600,000 fractures each year. There are significant differences in skeletal size and structure between men and women that account for differences in fracture incidence, location, and outcomes. Bone density testing is appropriate for men age 70 and older and younger men (50-69) who have risk factors for osteoporosis. Lifestyle management, including adequate calcium and vitamin D intake, appropriate physical activity, and avoidance of tobacco and heavy alcohol use, is appropriate for all men. Pharmacologic therapy to reduce fracture risk is advisable for men with a clinical diagnosis of osteoporosis (a spine or hip fracture) or a T-score of −2.5 or below in the spine, femoral neck, total hip or 1/3 radius; however, the majority of men at high risk will only be identified using a fracture risk assessment tool, such as FRAX. Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide are Food and Drug Administration (FDA)-approved therapeutic options.ConclusionOsteoporosis in men presents an important public health problem with significant morbidity and mortality. There are recommended strategies for identifying men at high risk of fracture, and effective agents are available for treatment. (Endocr Pract. 2013;19:834-838)     

Management of Diabetes During Air Travel: A Systematic Literature Review of Current Recommendations and their Supporting Evidence

Objective: Individuals with diabetes are increasingly seeking pretravel advice, but updated professional recommendations remain scant. We performed a systematic review on diabetes management during air travel to summarize current recommendations, assess supporting evidence, and identify areas of future research.Methods: A systematic review of the English literature on diabetes management during air travel was undertaken utilizing PubMed and MEDLINE. Publications regarding general travel advice; adjustment of insulin and noninsulin therapies; and the use of insulin pumps, glucometers and subcutaneous glucose sensors at altitude were included. Gathered information was used to create an updated summary of glucose-lowering medication adjustment during air travel.Results: Sixty-one publications were identified, most providing expert opinion and few offering primary data (47 expert opinion, 2 observational studies, 2 case reports, 10 device studies). General travel advice was uniform, with increasing attention to preflight security. Indications for oral antihyperglycemic therapy adjustments varied. There were few recommendations on contemporary agents and on nonhypoglycemic adverse events. There was little consensus on insulin adjustment protocols, many antedating current insulin formulations. Most publications advocated adjusting insulin pump time settings after arrival; however, there was disagreement on timing and rate adjustments. Glucometers and subcutaneous glucose sensors were reported to be less accurate at altitude, but not to an extent that would preclude their clinical use.Conclusion: Recommendations for diabetes management during air travel vary significantly and are mostly based on expert opinion. Data from systematic investigation on glucose-lowering medication adjustment protocols may support the development of a future consensus statement.Abbreviations:CSII = continuous subcutaneous insulin infusion (device)DPP-4 = dipeptidyl peptidase 4EGA = error grid analysisGDH = glucose dehydrogenaseGOX = glucose oxidaseGLP1 = glucagon-like peptide-1NPH = neutral protamine HagedornSGLT2 = sodium-glucose cotransporter-2     

AACE/ACE Disease State Clinical Review: Dopamine Agonists for Hyperprolactinemia and the Risk of Cardiac Valve Disease

ObjectiveTo review the current literature regarding dopamine agonists (DAs) and the risk of the development of cardiac valve disease.MethodsPubMed searches were performed to identify all of the available published data on DAs and valve disease in patients with hyperprolactinemia.ResultsMost of the available echocardiographic data from patients treated for hyperprolactinemia are from case-control studies, and prospective data are limited. The majority of the studies do not support an increased risk of clinically significant valve disease in hyperprolactinemic patients treated with cabergoline. Evidence for the use of echocardiography is needed to limit unnecessary procedures and healthcare costs. Based on the published literature describing Parkinson’s disease (PD) patients, the daily and cumulative doses of cabergoline are important factors. Considerations to minimize exposure to cabergoline, such as surgical resection of adenomas or medication withdrawal in responders, may be appropriate depending on the clinical setting.ConclusionThere is no conclusive evidence that cabergoline causes clinically significant cardiac valve disease at the usual doses for the treatment of hyperprolactinemia. Although current recommendations from regulatory agencies advise routine echocardiography for patients receiving cabergoline, evidence-based criteria would be useful both to identify patients at risk and generate appropriate screening protocols. (Endocr Pract. 2014;20:608-616)     

Phytochemicals from fern species: potential for medicine applications

Ferns are an important phytogenetic bridge between lower and higher plants. Historically they have been used in many ways by humans, including as ornamental plants, domestic utensils, foods, and in handicrafts. In addition, they have found uses as medicinal herbs. Ferns produce a wide array of secondary metabolites endowed with different bioactivities that could potentially be useful in the treatment of many diseases. However, there is currently relatively little information in the literature on the phytochemicals present in ferns and their pharmacological applications, and the most recent review of the literature on the occurrence, chemotaxonomy and physiological activity of fern secondary metabolites was published over 20 years ago, by Soeder (Bot Rev 51:442–536, 1985). Here, we provide an updated review of this field, covering recent findings concerning the bioactive phytochemicals and pharmacology of fern species.     

Anabolic Therapy and Optimal Treatment Sequences for Patients With Osteoporosis at High Risk for Fracture

Objective: Provide an update regarding anabolic medications for osteoporosis, which are often considered to be the last resort for patients with osteoporosis, after multiple fractures have already occurred and other medications have already been administered.Methods: Literature review and discussion.Results: Recent pivotal trial data for anabolic agents and randomized trials comparing anabolic and antiresorptive medications suggest that three anabolic agents (teriparatide, abaloparatide, and romosozumab) reduce nonvertebral and vertebral fractures faster and to a greater extent than potent antiresorptive treatments. Furthermore, bone density accrual is maximized when patients are given anabolic agents first, followed by potent antiresorptive therapy. Since total hip bone density during or after osteoporosis treatment has emerged as an excellent surrogate for future fracture risk, attaining a greater hip bone mineral density is a treatment goal for high-risk osteoporosis patients.Conclusion: This review defines the highest-risk patients and summarizes the rationale for the evolving role of anabolic therapy in the management of postmenopausal women at high risk for fracture.Abbreviations: ACTIVE = Abaloparatide Comparator Trial in Vertebral Endpoints; ARCH = Active Controlled Fracture Study in Postmenopausal Women with Osteoporosis at High Risk; BMD = bone mineral density; FRAME = Fracture Study in Postmenopausal Women with Osteoporosis; FRAX = Fracture Risk Assessment Tool; PTH = parathyroid hormone; TBS = trabecular bone score