Risk of hip, subtrochanteric, and femoral shaft fractures among mid and long term users of alendronate: nationwide cohort and nested case-control study

Objectives To determine the skeletal safety and efficacy of long term (≥10 years) alendronate use in patients with osteoporosis. Design Open register based cohort study containing two nested case control studies. Setting Nationwide study of population of Denmark. Participants 61 990 men and women aged 50-94 at the start of treatment, who had not previously taken alendronate, 1996-2007. Interventions Treatment with alendronate. Main outcome measures Incident fracture of the subtrochanteric femur or femoral shaft (ST/FS) or the hip. Non-fracture controls from the cohort were matched to fracture cases by sex, year of birth, and year of initiation of alendronate treatment. Conditional logistic regression models were fitted to calculate odds ratios with and without adjustment for comorbidity and comedications. Sensitivity analyses investigated subsequent treatment with other drugs for osteoporosis. Results 1428 participants sustained a ST/FS (incidence rate 3.4/1000 person years, 95% confidence interval 3.2 to 3.6), and 6784 sustained a hip fracture (16.2/1000 person years, 15.8 to 16.6). The risk of ST/FS was lower with high adherence to treatment with alendronate (medication possession ratio (MPR, a proxy for compliance) >80%) compared with poor adherence (MPR 80% was associated with a decreased risk of hip fracture (0.73, 0.68 to 0.78; P<0.001) as was longer term cumulative use for 5-10 dose years (0.74, 0.67 to 0.83; P<0.001) or ≥10 dose years (0.74, 0.56 to 0.97; P=0.03). Conclusions These findings support an acceptable balance between benefit and risk with treatment with alendronate in terms of fracture outcomes, even for over 10 years of continuous use

Oral bisphosphonates and colon cancer:an update

Bisphosphonates (BPs) are widely used as the main treatment for osteoporosis. In vitro and animal studies suggest that use of BPs may have a potential for colorectal cancer (CRC) prevention. Safety and efficacy in terms of osteoporosis prevention have only been evaluated in randomized controlled trials (RCTs) of relatively short duration (3–5 years), with smaller extension studies. The evidence for a benefit beyond 5 years is limited and intake of BPs has not shown any relationship with CRC in intervention studies. Observational studies and meta-analysis have shown unchanged or decreased risk of CRC. BPs used for treatment and prevention of osteoporosis should not be applied for prevention of CRC in clinical practice