Denosumab is an effective antiresorptive medication that is typically administered by injection every 6 months. Delayed dosing of denosumab is common in clinical practice. This analysis examined th... Visual Delayed Denosumab and Fracture Risk Denosumab is an effective antiresorptive medication that is typically administered by injection every 6 months. Delayed dosing of denosumab is co... Background: Denosumab is effective for osteoporosis, but discontinuation leads to rapid reversal of its therapeutic effect. Objective: To estimate the risk for fracture among users of denosumab who...

Background Among the currently available osteoporosis therapeutics, bisphosphonates and denosumab are widely used. However, it remains uncertain which therapy is more effective. Objective To determine whether the use of denosumab increases bone mineral density (BMD) and reduces the risk of fractures more than bisphosphonates in patients with low BMD or osteoporosis. Data Sources We searched PubMed, Embase and the Cochrane Library through Nov 2018. Study Selection Head-to-head randomized controlled trials comparing denosumab versus bisphosphonates among adult patients with low BMD or osteoporosis. Data Extraction and Synthesis Random-effects models were used. We identified 10 eligible trials including 5361 participants. Denosumab increased BMD more than bisphosphonate at 12 months, with a mean difference of 1.42% (95% CI 0.95-1.89%, p<0.001) at lumbar spine, 1.11% (95% CI 0.91-1.30%; p<0.001) at total hip, and 1.00% (95% CI 0.78-1.22%, p<0.001) at femoral neck. At 24 months, the increase difference was 1.74% (95% CI 1.05-2.43%, p<0.001) at lumbar spine, 1.22% (95% CI 0.66-1.77%, p<0.001) at total hip, and 1.19% (95% CI 0.65-1.72%, p<0.001) at femoral neck. There was no difference in fracture endpoint at 12 months, but denosumab had a lower osteoporotic fracture incidence than alendronate at 24 months (RR 0.51, 95% CI 0.27-0.97). Conclusions Denosumab improved BMD significantly more than bisphosphonates at the lumbar spine, total hip and femoral neck at 12 and 24 months. There was only one study demonstrating greater osteoporotic fracture reduction using denosumab. Future longitudinal studies with longer follow-up and large sample size are needed to confirm the efficacy difference.

Background: The prognostic nutritional index (PNI) has been proposed as a useful prognostic tool in multiple populations. However, its prognostic value has not been fully evaluated in the hip fracture population. We aimed to assess the relationship between PNI and postoperative complications as well as 2-year all-cause mortality in the hip fracture population. Materials and Methods: We included patients aged 45 or older who underwent surgery for hip fracture between 2000 and 2022. The baseline serum albumin and total lymphocyte count were used to calculate PNI with the following formula: 10×serum albumin level (g/dl)+0.005×total lymphocyte count (per mm³). Patients were classified into low, medium, and high categories based on tertiles of PNI (≤43.23, 43.23–47.35, and >47.35, respectively). Logistic regression and Cox proportional hazards models were used to calculate the odds ratio (OR) for postoperative compilations and the hazard ratio (HR) for mortality, adjusting for potential confounders. Results: Of 3351 hip patients, 236 (7.04%) developed postoperative complications, and 305 (9.10%) died during the 2-year follow-up. Compared to the low-category patients, the medium-category and high-category patients showed lower odds of postoperative complications (ORs 0.69, 95% CI 0.48–0.98; and 0.61, 95% CI 0.40–0.93, respectively), and lower hazards of 2-year mortality (HRs 0.66, 95% CI 0.49–0.88; and 0.61, 95% CI 0.42–0.88, respectively). These associations were robust across a series of analyses, including subgroup analyses and dose–response sensitivity analyses. Conclusion: PNI is an independent predictor of postoperative complications and 2-year all-cause mortality in hip fracture patients. PNI can be used to identify patients who may be at high risk of a poor prognosis.

Objective To estimate the effect of denosumab compared with oral bisphosphonates on reducing the risk of type 2 diabetes in adults with osteoporosis. Design Population based study involving emulation of a randomized target trial using electronic health records. Setting IQVIA Medical Research Data primary care database in the United Kingdom, 1995-2021. Participants Adults aged 45 years or older who used denosumab or an oral bisphosphonate for osteoporosis. Main outcome measures The primary outcome was incident type 2 diabetes, as defined by diagnostic codes. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals, comparing denosumab with oral bisphosphonates using an as treated approach. Results 4301 new users of denosumab were matched on propensity score to 21 038 users of an oral bisphosphonate and followed for a mean of 2.2 years. The incidence rate of type 2 diabetes in denosumab users was 5.7 (95% confidence interval 4.3 to 7.3) per 1000 person years and in oral bisphosphonate users was 8.3 (7.4 to 9.2) per 1000 person years. Initiation of denosumab was associated with a reduced risk of type 2 diabetes (hazard ratio 0.68, 95% confidence interval 0.52 to 0.89). Participants with prediabetes appeared to benefit more from denosumab compared with an oral bisphosphonate (hazard ratio 0.54, 0.35 to 0.82), as did those with a body mass index ≥30 (0.65, 0.40 to 1.06). Conclusions In this population based study, denosumab use was associated with a lower risk of incident type 2 diabetes compared with oral bisphosphonate use in adults with osteoporosis. This study provides evidence at a population level that denosumab may have added benefits for glucose metabolism compared with oral bisphosphonates.

Purpose: To evaluate the impact of preoperative anemia on postoperative complications after hip fracture surgery. Patients and Methods: We conducted a retrospective study including hip fracture patients at a teaching hospital between 2005 and 2022. We defined preoperative anemia as the last hemoglobin measurement level before surgery < 130 g/L for men and < 120 g/L for women. The primary outcome was a composite of in-hospital major complications, including pneumonia, respiratory failure, gastrointestinal bleeding, urinary tract infection, incision infection, deep venous thrombosis, pulmonary embolism, angina pectoris, arrhythmia, myocardial infarction, heart failure, stroke, and death. Secondary outcomes were cardiovascular events, infection, pneumonia, and death. We used multivariate negative binomial or logistic regression to evaluate the impact of anemia and its severity, categorized as mild (90– 130 g/L for men, 90– 120 g/L for women) or moderate-to-severe (< 90 g/L for both) anemia on outcomes. Results: Of the 3540 included patients, 1960 had preoperative anemia. 188 anemic patients experienced 324 major complications, while 63 non-anemic patients had 94 major complications. The risk of major complications was 165.3 (95% CI, 149.5– 182.4) and 59.5 (95% CI, 48.9– 72.3) per 1000 persons in anemic and non-anemic patients, respectively. Anemic patients were more likely to have major complications than non-anemic patients (adjusted incidence rate ratio (aIRR), 1.87; 95% CI, 1.30– 2.72), which was consistent in mild (aIRR, 1.77; 95% CI, 1.22– 2.59) and moderate-to-severe (aIRR, 2.97; 95% CI, 1.65– 5.38) anemia. Preoperative anemia also increased the risk of cardiovascular events (aIRR, 1.96; 95% CI, 1.29– 3.01), infection (aIRR, 1.68; 95% CI, 1.01– 2.86), pneumonia (adjusted odds ratio (aOR), 1.91; 95% CI, 1.06– 3.57), and death (aOR, 3.17; 95% CI, 1.06– 11.89). Conclusion: Our findings suggest that even mild preoperative anemia is associated with major postoperative complications in hip fracture patients. This finding highlights considering preoperative anemia as a risk factor in surgical decision-making for high-risk patients.

Crump et al. (Biometrika. 2009;96(1):187-199), Stürmer et al. (Am J Epidemiol. 2010;172(7):843-854), and Walker et al. (Comp Eff Res. 2013;2013(3):11-20) proposed propensity score (PS) trimming methods as a means to improve efficiency (Crump) or reduce confounding (Stürmer and Walker). We generalized the trimming definitions by considering multinomial PSs, one for each treatment, and proved that these proposed definitions reduce to the original binary definitions when we have only 2 treatment groups. We then examined the performance of the proposed multinomial trimming methods in the setting of 3 treatment groups, in which subjects with extreme PSs more likely had unmeasured confounders. Inverse probability of treatment weights, matching weights, and overlap weights were used to control for measured confounders. All 3 methods reduced bias regardless of the weighting methods in most scenarios. Multinomial Stürmer and Walker trimming were more successful in bias reduction when the 3 treatment groups had very different sizes (10:10:80). Variance reduction, seen in all methods with inverse probability of treatment weights but not with matching weights or overlap weights, was more successful with multinomial Crump and Stürmer trimming. In conclusion, our proposed definitions of multinomial PS trimming methods were beneficial within our simulation settings that focused on the influence of unmeasured confounders.