Bisphosphonates in the treatment of osteoporosis: a review of skeletal safety concerns.

INTRODUCTION: The use of bisphosphonates in treatment of osteoporosis declined significantly over the past decade. There is currently great concern, among patients and physicians, about two potential skeletal adverse effects associated with bisphosphonates- jaw osteonecrosis and atypical femur fractures. This has become a major public health issue since untreated osteoporosis carries a significant burden in terms of fracture-related morbidity and mortality, and bisphosphonates, considered first-line therapy for osteoporosis, have established efficacy in fracture and mortality reduction. Areas covered: In this review we discuss current literature on osteonecrosis of the jaw and atypical femur fractures in patients with osteoporosis treated with bisphosphonates, including case definition, pathogenesis, epidemiology, risk factors, clinical presentation, management and prevention. We conducted a literature search using PubMed and PubMed Central, using the search terms 'bisphosphonates', 'osteonecrosis of the jaw', and 'atypical fractures'. We selected relevant articles including meta-analyses, clinical trials, observational studies, and major society guidelines published between 2010 and 2016, to be included in this review. A few articles published prior to 2010 were also included as references. Expert commentary: The rare skeletal side effects of bisphosphonates should not preclude their use in patients with osteoporosis and high fracture risk, as benefits significantly outweigh the risks.

Thiazolidinedione use and the longitudinal risk of fractures in patients with type 2 diabetes mellitus.

CONTEXT: Thiazolidinedione (TZD) use has recently been associated with an increased risk of fractures. OBJECTIVE: The aim of this study was to determine the time-dependent relationship between TZD use and fracture risk. DESIGN: We conducted a retrospective cohort study in a large health system in southeast Michigan. PATIENTS: PATIENTS who received care from the health system were included if they were at least 18 yr of age, had a diagnosis of diabetes, and had at least one prescription for an oral diabetes medication. These criteria identified 19,070 individuals (9,620 women and 9,450 men). INTERVENTION: This study compared patients treated with TZDs to patients without TZD treatment. Cox proportional hazard models were used to assess the relationship between exposure and outcomes. MAIN OUTCOME MEASURES: The primary outcome was the time to fracture. Secondary analyses examined the risk of fractures in subgroups defined by sex and age. RESULTS: TZD use was associated with an increased risk of fracture in the cohort overall [adjusted hazard ratio (aHR), 1.35; 95% confidence interval (CI), 1.05-1.71] and in women (aHR, 1.57; 95% CI, 1.16-2.14), but not in men (aHR, 1.05; 95% CI, 0.70-1.58). Women more than 65 yr of age appeared to be at greatest risk for fracture (aHR, 1.72; 95% CI, 1.17-2.52). Among women, the increased fracture risk was not apparent until after 1 yr of TZD treatment. CONCLUSIONS: TZD use was associated with an increased risk for fractures in women, particularly at ages above 65 yr. Clinicians should be aware of this association when considering TZD therapy so as to appropriately manage and counsel their patients.

Relationship between thiazolidinedione use and cardiovascular outcomes and all-cause mortality among patients with diabetes: a time-updated propensity analysis.

PURPOSE: To investigate the association of the thiazolidinediones (TZDs), rosiglitazone, and pioglitazone, together and individually on the risk of cardiovascular outcomes and all-cause mortality, using time-updated propensity score adjusted analysis. METHODS: We conducted a retrospective cohort study in a large vertically integrated health system in southeast Michigan. Cohort inclusion criteria included adult patients with diabetes treated with oral medications and followed longitudinally within the health system between 1 January 2000 and 1 December 2006. The primary outcome was fatal and non-fatal acute myocardial infarction (AMI). Secondary outcomes included hospitalizations for congestive heart failure (CHF), fatal, and non-fatal cerebrovascular accidents (CVA) and transient ischemic attacks (TIA), combined coronary heart disease (CHD) events, and all-cause mortality. RESULTS: 19,171 patients were included in this study. Use of TZDs (adjusted hazard ratio (aHR) with propensity adjustment (PA), 0.92; 95% confidence interval (CI) 0.73-1.17), rosiglitazone (aHR with PA, 1.06; 95%CI 0.66-1.70), and pioglitazone (aHR with PA, 0.91; 95%CI 0.69-1.21) was not associated with a higher risk of AMI. However, pioglitazone use was associated with a reduction in all-cause mortality (aHR with PA, 0.60; 95%CI 0.42-0.96). Compared with rosiglitazone, pioglitazone use was associated with a lower risk of all outcomes assessed, particularly CHF (p = 0.013) and combined CHD events (p = 0.048). CONCLUSIONS: Our findings suggest that pioglitazone may have a more favorable risk profile when compared to rosiglitazone, arguing against a singular effect for TZDs on cardiovascular outcomes.

Long-term projections for diabetes-related work loss and limitations among U.S. adults.

We used data from the U.S. National Health Interview Survey to estimate the effect of diabetes on labor market outcomes. In the year 2050 an estimated 1.46 million U.S. adults will not be working; 597,000 will be work disabled; and 780,000 will have work limitations as a result of diabetes.