Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years

Limited data exist on the efficacy of long-term therapies for osteoporosis. In osteoporotic postmenopausal women receiving denosumab for 7 years, nonvertebral fracture rates significantly decreased in years 4-7 versus years 1-3. This is the first demonstration of a further benefit on fracture outcomes with long-term therapy for osteoporosis. INTRODUCTION This study aimed to evaluate whether denosumab treatment continued beyond 3 years is associated with a further reduction in nonvertebral fracture rates. METHODS Participants who completed the 3-year placebo-controlled Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were invited to participate in an open-label extension. The present analysis includes 4,074 postmenopausal women with osteoporosis (n = 2,343 long-term; n = 1,731 cross-over) who enrolled in the extension, missed ≤1 dose during their first 3 years of denosumab treatment, and continued into the fourth year of treatment. Comparison of nonvertebral fracture rates during years 1-3 of denosumab with that of the fourth year and with the rate during years 4-7 was evaluated. RESULTS For the combined group, the nonvertebral fracture rate per 100 participant-years was 2.15 for the first 3 years of denosumab treatment (referent) and 1.36 in the fourth year (rate ratio [RR] = 0.64; 95 % confidence interval (CI) = 0.48 to 0.85, p = 0.003). Comparable findings were observed in the groups separately and when nonvertebral fracture rates during years 1-3 were compared to years 4-7 in the long-term group (RR = 0.79; 95 % CI = 0.62 to 1.00, p = 0.046). Fracture rate reductions in year 4 were most prominent in subjects with persisting low hip bone mineral density (BMD). CONCLUSIONS Denosumab treatment beyond 3 years was associated with a further reduction in nonvertebral fracture rate that persisted through 7 years of continuous denosumab administration. The degree to which denosumab further reduces nonvertebral fracture risk appears influenced by the hip bone density achieved with initial therapy.

A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX

Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. This article is protected by copyright. All rights reserved.

Surgical exposures and options for instrumentation in acetabular fracture fixation: Pararectus approach versus the modified Stoppa.

BACKGROUND As an alternative to the modified Stoppa approach, the Pararectus approach is used clinically for treatment of acetabular fractures involving the anterior column. The current study assessed the surgical exposure and the options for instrumentation using both of these approaches. METHODS Surgical dissections were conducted on five human cadavers (all male, mean age 88 years (82-97)) using the modified Stoppa and the Pararectus approach, with the same skin incision length (10cm). Distal boundaries of the exposed bony surfaces were marked using a chisel. After removal of all soft-tissues, distances from the boundaries in the false and true pelvis were measured with reference to the pelvic brim. The exposed bone was coloured and calibrated digital images of each inner hemipelvis were taken. The amount of exposed surface using both approaches was assessed and represented as a percentage of the total bony surface of each hemipelvis. For instrumentation, a suprapectineal quadrilateral buttress plate was used. Screw lengths were documented, and three-dimensional CT reconstructions were performed to assess screw trajectories qualitatively. Wilcoxon's signed rank test for paired groups was used (level of significance: p<0.05). RESULTS After utilization of the Pararectus approach, the distances from the farthest boundaries of exposed bone towards the pelvic brim were significantly higher in the false but not the true pelvis, compared to the modified Stoppa approach. The percentage (mean±SD) of exposed bone accessible after utilizing the Pararectus approach was 42±8%, compared to 29±6% using the modified Stoppa (p=0.011). In cadavers exposed by the Pararectus approach, screws placed for posterior fixation and as a posterior column screw were longer by factor 1.8 and 2.1, respectively (p<0.05), and screws could be placed more posteromedial towards the posterior inferior iliac spine or in line with the posterior column directed towards the ischial tuberosity. CONCLUSION Compared to the modified Stoppa, the Pararectus approach facilitates a greater surgical access in the false pelvis, provides versatility for fracture fixation in the posterior pelvic ring and allows for the option to extend the approach without a new incision.