Allison J. Hahr

Bisphosphonates and nonhealing femoral fractures: analysis of the FDA Adverse Event Reporting System (FAERS) and international safety efforts: a systematic review from the Research on Adverse Drug Events And Reports (RADAR) project.

BACKGROUND In the United States, hip fracture rates have declined by 30% coincident with bisphosphonate use. However, bisphosphonates are associated with sporadic cases of atypical femoral fracture. Atypical femoral fractures are usually atraumatic, may be bilateral, are occasionally preceded by prodromal thigh pain, and may have delayed fracture-healing. This study assessed the occurrence of bisphosphonate-associated nonhealing femoral fractures through a review of data from the U.S. FDA (Food and Drug Administration) Adverse Event Reporting System (FAERS) (1996 to 2011), published case reports, and international safety efforts. METHODS We analyzed the FAERS database with use of the proportional reporting ratio (PRR) and empiric Bayesian geometric mean (EBGM) techniques to assess whether a safety signal existed. Additionally, we conducted a systematic literature review (1990 to February 2012). RESULTS The analysis of the FAERS database indicated a PRR of 4.51 (95% confidence interval [CI], 3.44 to 5.92) for bisphosphonate use and nonhealing femoral fractures. Most cases (n = 317) were attributed to use of alendronate (PRR = 3.32; 95% CI, 2.71 to 4.17). In 2008, international safety agencies issued warnings and required label changes. In 2010, the FDA issued a safety notification, and the American Society for Bone and Mineral Research (ASBMR) issued recommendations about bisphosphonate-associated atypical femoral fractures. CONCLUSIONS Nonhealing femoral fractures are unusual adverse drug reactions associated with bisphosphonate use, as up to 26% of published cases of atypical femoral fractures exhibited delayed healing or nonhealing.

Addressing secondary prevention of osteoporosis in fracture care: follow-up to "own the bone".

The majority of the 1.8 million individuals who sustain a fracture annually in the United States have osteopenia or osteoporosis, yet <15% of these patients subsequently receive treatment for osteoporosis. A prospective cohort study was conducted to assess the effect of two different interventions on the rate of osteoporosis treatment in patients with a fragility fracture. Patients who were fifty years of age or older and were hospitalized for the treatment of a fragility fracture at either of two academic institutions were eligible for inclusion in the study. The intervention at one hospital involved immediate care for osteoporosis, including initiation of pharmacologic therapy during hospitalization. The intervention at the other hospital involved delayed care, including recommendations for osteoporosis counseling, bone-mineral density testing, and potential treatment for osteoporosis that were communicated to the primary care physician after the patient was discharged from the hospital. Patients were surveyed by telephone six months after the fracture, and their medical and pharmacy records were reviewed to verify the osteoporosis treatment that they had received. The mean age was 73 ± 10 years in the immediate-care group and 74 ± 12 years in the delayed-care group. Eighty percent of the patients were women. Sixty-five percent of the patients in each group completed the telephone interview six months after the fracture, and most had seen their primary care physician and undergone bone-mineral density testing. The rate of bone-mineral density testing was 92% in the immediate-care group compared with 76% in the delayed-care group. Both immediate and delayed care for osteoporosis resulted in a significant increase in the treatment rate compared with the baseline rate of 0% (p < 0.001). However, the primary care physician had initiated osteoporosis therapy by six months after the fracture in only 30% of the patients in the delayed-care group compared with a treatment rate of 67% in the immediate-care group (p < 0.001). Limitations of the study include the possibility that the findings resulted from a difference between the two study centers rather than between the two strategies. In addition, because of the academic and integrated nature of the medical systems at which the study was conducted, the findings cannot necessarily be extrapolated to other types of institutions. In summary, a recommendation for osteoporosis treatment made by an orthopaedic surgeon to the patients primary care physician resulted in an increase in the rate of bone-mineral density testing and in the rate of therapy compared with baseline. However, immediate initiation of osteoporosis care during hospitalization for the fragility fracture resulted in a higher rate of treatment--with two-thirds of the patients receiving therapy six months after the fracture--compared with delayed initiation.

Diabetes, Cardiovascular Risk and Nephropathy

Diabetic patients with chronic kidney disease are at high risk for cardiovascular disease (CVD). All aspects of risk reduction should be rigorously applied to such patients. Statins should be used with reduction of low-density lipoprotein cholesterol levels, and blood pressure management is important. Glycemic control remains important for reduction in the development and progression of retinopathy, neuropathy, and even nephropathy itself. Reduction of other risk factors, such as smoking cessation and weight reduction, should also be implemented. Multiple risk factor reduction can have a large effect on reduction of CVD outcomes.

Optimizing insulin therapy in patients with type 1 and type 2 diabetes mellitus: Optimal dosing and timing in the outpatient setting

Management of type 1 and type 2 diabetes is continually evolving, and among these evolving therapies is administration of insulin in its various forms. The insulin regimen needs to be tailored to each individual, not only to maximize compliance and glycemic control but also to minimize hypoglycemia and weight gain.

Optimizing Insulin Therapy in Patients With Type 1 and Type 2 Diabetes Mellitus: Optimal Dosing and Timing in the Outpatient Setting

Management of type 1 and type 2 diabetes is continually evolving, and among these evolving therapies is administration of insulin in its various forms. The insulin regimen needs to be tailored to each individual, not only to maximize compliance and glycemic control but also to minimize hypoglycemia and weight gain.

Primary hyperaldosteronism: challenges in subtype classification

BackgroundPrimary hyperaldosteronism (PA) is a serious and potentially debilitating disease. Detailed guidelines have been written to guide endocrinologists in establishing the diagnosis of PA as well as in subtype classification of PA. The objective of this case report is to present a case where subtype classification of PA was challenging and repeated imaging of the adrenal glands helped establish the diagnosis in a patient with initial normal adrenal glands on CT and MRI images.Case presentationWe report a case of a 29-year-old woman with an established diagnosis of PA, but unclear subtype, who presented to us for further management. She initially presented for medical evaluation of uncontrolled hypertension and spontaneous hypokalemia 4 years prior. In the investigation of secondary causes of hypertension, plasma aldosterone-to-plasma renin activity ratio was elevated on two separate occasions, and primary hyperaldosteronism was confirmed by saline infusion test. Also during this time, she had adrenal venous sampling done 3 times at multiple institutions yielding confusing results. Initially, imaging by CT and MRI showed normal adrenal glands. To help establish the subtype of PA, we reimaged this patient’s adrenal glands one year later revealing a 2 cm left adrenal adenoma. Laparoscopic left adrenalectomy improved her hypertension and was curative of her hypokalemia.ConclusionThis case presents an unusual case where reimaging of the adrenal glands led to the discovery of a single adenoma, initially not observed on imaging studies.

Management of Diabetes in the Pre-End-Stage Renal Disease and Chronic Kidney Disease

Diabetic kidney disease (DKD) affects approximately 20–40 % of individuals who have diabetes [1]. Given the frequency of nephropathy, it is important to understand the safe use of diabetes medications in this population. Glycemic control in chronic kidney disease (CKD) adds a level of complexity that requires detailed knowledge of which medications can be safely used and how kidney disease affects their metabolism. Additionally, glycemic targets should be individualized for each patient.