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.

Glycemic control is essential to delay or prevent the onset of diabetic kidney disease. There are a number of glucose-lowering medications available but only a fraction of them can be used safely in chronic kidney disease and many of them need an adjustment in dosing. The ideal target hemoglobin A1c is approximately 7 % but this target is adjusted based on the needs of the patient. Diabetes control should be optimized for each individual patient, with measures to reduce diabetes-related complications and minimize adverse events. Overall care of diabetes necessitates attention to multiple aspects, including reducing the risk of cardiovascular disease, and often, multidisciplinary care is needed.

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 patient's 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.

Purpose: To determine whether acute kidney injury (AKI) is identified within the US Food and Drug Administration's Adverse Events and Reporting System (FDA AERS) as an adverse event resulting from bisphosphonate (BP) use in cancer therapy. Methods:A search of the FDA AERS records from January 1998 through June 2009 was performed; search terms were "renal problems" and all drug names for BPs. The search resulted in 2,091 reports. We analyzed for signals of disproportional association by calculating the proportional reporting ratio for zoledronic acid (ZOL) and pamidronate. Literature review of BP-associated renal injury within the cancer setting was conducted.Results: Four hundred eighty cases of BP-associated acute kidney injury (AKI) were identified in patients with cancer. Two hundred ninety-eight patients (56%) were female; mean age was 66 Ϯ 10 years. Multiple myeloma (n ϭ 220, 46%), breast cancer (n ϭ 98, 20%), and prostate cancer (n ϭ 24, 5%) were identified. Agents included ZOL (n ϭ 411, 87.5%), pamidronate (n ϭ 8, 17%), and alendronate (n ϭ 36, 2%). Outcomes included hospitalization (n ϭ 304, 63.3%) and death (n ϭ 68, 14%). The proportional reporting ratio for ZOL was 1.22 (95% CI, 1.13 to 1.32) and for pamidronate was 1.55 (95% CI, 1.25 to 1.65), reflecting a nonsignificant safety signal for both drugs.

The thrombospondin (TSP) family of extracellular glycoproteins consists of five members in vertebrates, TSP1 to -4 and TSP5/cartilage oligomeric matrix protein, and a single member in Drosophila. TSPs are modular multimeric proteins. The C-terminal end of a monomer consists of 3-6 EGF-like modules; seven tandem 23-, 36-, or 38-residue aspartate-rich, Ca 2؉ -binding repeats; and an ϳ230-residue C-terminal sequence. The Ca 2؉ -binding repeats and C-terminal sequence are spaced almost exactly the same in different TSPs and share many blocks of identical residues. We studied the C-terminal portion of human TSP2 from the third EGF-like module through the end of the protein (E3CaG2). E3CaG2, CaG2 lacking the EGF module, and Ca2 composed of only the Ca 2؉ -binding repeats were expressed using recombinant baculoviruses and purified from conditioned media of insect cells. As previously described for intact TSP1, E3CaG2 bound Ca 2؉ in a cooperative manner as assessed by equilibrium dialysis, and its circular dichroism spectrum was sensitive to the presence of Ca 2؉ . Mass spectrometry of the recombinant proteins digested with endoproteinase Asp-N revealed that disulfide pairing of the 18 cysteines in the Ca 2؉ -binding repeats and C-terminal sequence is sequential, i.e. a 1-2, 3-4, 5-6, etc., pattern.