Suzanne M. Cadarette

A Cohort Study of Thiazolidinediones and Fractures in Older Adults with Diabetes

CONTEXT Thiazolidenediones (TZDs) are selective ligands of peroxisome-proliferator-activated receptor-gamma and have been shown to reduce bone mineral density. Recent results from several randomized controlled trials find an increased risk of fracture with TZDs compared with other oral antidiabetic agents. OBJECTIVE The aim of the study was to determine the association between TZD use and fracture risk among older adults with diabetes. DESIGN We conducted a cohort study. PARTICIPANTS Medicare beneficiaries with at least one diagnosis of diabetes initiating monotherapy for an oral hypoglycemic agent participated in the study. MAIN OUTCOME We measured the incidence of fracture within the cohort. RESULTS Among the 20,964 patients with diabetes eligible for this study, 686 (3.3%) experienced a fracture during the median follow-up of approximately 10 months. Although not statistically significant, patients using only a TZD were more likely to experience a fracture than those using metformin (adjusted relative risk, 1.31; 95% confidence interval, 0.98-1.77; P = 0.071) or a sulfonylurea (adjusted relative risk, 1.21; 95% confidence interval, 0.94-1.55; P = 0.12). Each individual TZD was associated with an increased risk, with confidence intervals overlapping unity, compared with both metformin and sulfonylureas. The adjusted risk of any fracture associated with TZD use compared with metformin was elevated for non-insulin-using patients, women and men. If TZD use is associated with fractures, the number needed for one excess fracture when comparing TZD users to sulfonylurea users was 200, and the number was 111 when comparing TZDs with metformin. CONCLUSIONS As has been found with other analyses, our data suggest that TZDs may be associated with an increased risk of fractures compared with oral sulfonylureas and metformin.

Is There a Relationship Between Patient Beliefs or Communication About Generic Drugs and Medication Utilization

Background:Insurers and policymakers strive to stimulate more cost-effective prescribing and, increasingly, are educating beneficiaries about generics. Objectives:To evaluate the relationship between patient beliefs and communication about generic drugs and actual drug use. Research Design and Subjects:We performed a national mailed survey of a random sample of 2500 commercially-insured adults. Patient responses were linked to pharmacy claims data to assess actual generic medication use. Measures:We used factor analysis to develop 5 multi-item scales from patient survey responses that measured: (1) general preferences for generics, (2) generic safety/effectiveness, (3) generic cost/value, (4) comfort with generic substitution, and (5) communication with providers about generics. The relationship between each scale and the proportion of prescriptions filled for generics was assessed using linear regression, controlling for demographic, health, and insurance characteristics. Separate models were created for each scale and then all 5 scales were included simultaneously in a fully-adjusted model. Results:The usable response rate was 48%. When evaluated independently, a 1 SD increase in each of the 5 scales was associated with a 3.1% to 6.3% increase in generic drug use (P < 0.05 for each). In the fully adjusted model, only 2 scales were significantly associated with generic drug use: comfort with generic substitution (P = 0.021) and communication with providers about generic drugs (P = 0.012). Conclusions:Generic drug use is most closely associated with the 2 actionable items we evaluated: communication with providers about generics and comfort with generic substitution. Educational campaigns that focus on these 2 domains may be most effective at influencing generic drug use.

Osteoporosis treatments and adverse events.

Purpose of reviewOsteoporosis treatments will be used with increasing frequency as the population ages; however, relatively little is known about their long-term safety. Recent case reports cite a range of potential adverse events. We review data regarding atrial fibrillation, bone pain, osteonecrosis of the jaw (ONJ), atypical fractures, and osteosarcoma. Recent findingsIncidence of bisphosphonate-related ONJ in osteoporosis patients is unclear, but several studies suggest rates may be higher than one in 100 000. Severe bone pain and esophageal cancer have been described among bisphosphonate users, but their relationship has not been carefully studied. The relationship between atrial fibrillation and bisphosphonates is unclear based on existing data, but the Food and Drug Administrations (FDA) analyses suggest no clear association. Although several case series discuss atypical fractures associated with bisphosphonate use, one epidemiologic study found no association. Finally, one case of osteosarcoma has been reported in a woman using teriparatide. One case in over 200 000 users suggests no increase in risk beyond background risk, but further evaluation is necessary. SummaryAlthough case reports of adverse events with osteoporosis medications suggest potential links, epidemiological analyses have largely failed to illuminate a strong, clear link between osteoporosis therapies and many adverse events, with ONJ an exception. Until further data are available, providers should be aware of these potential side effects, and inform their patients accordingly.