Predicting Imminent Fractures in Patients With a Recent Fracture or Starting Oral Bisphosphonate Therapy: Development and International Validation of Prognostic Models

Abstract

The availability of anti‐osteoporosis medications with rapid onset and high potency requires tools to identify patients at high imminent fracture risk (IFR). There are few tools that predict a patient's IFR. We aimed to develop and validate tools for patients with a recent fracture and for patients initiating oral bisphosphonate therapy. Models for two separate cohorts, those with incident fragility fracture (IFx) and with incident oral bisphosphonate prescription (OBP), were developed in primary care records from Spain (SIDIAP database), UK (Clinical Practice Research Datalink GOLD), and Denmark (Danish Health Registries). Separate models were developed for hip, major, and any fracture outcomes. Only variables present in all databases were included in Lasso regression models for the development and logistic regression models for external validation. Discrimination was tested using area under curve (AUC) and calibration was assessed using observed versus predicted risk plots stratified by age, sex, and previous fracture history. The development analyses included 35,526 individuals in the IFx and 41,401 in the OBP cohorts, with 671,094 in IFx and 330,256 in OBP for the validation analyses. Both the IFx and OBP models demonstrated similarly good performance for hip fracture at 1 year (with AUCs of 0.79 [95% CI 0.75 to 0.82] and 0.87 [0.83 to 0.91] in Spain, 0.71 [0.71 to 0.72] and 0.73 [0.72 to 0.74] in the UK, and 0.70 [0.70 to 0.70] and 0.69 [0.68 to 0.70] in Denmark), and lower discrimination for major osteoporotic and any fracture sites. Calibration was good across all three countries. Discrimination and calibration for the 2‐year models was similar. The proposed IFR prediction models could be used to identify more precisely patients at high imminent risk of fracture and inform anti‐osteoporosis treatment selection. The freely available model parameters permit local validation and implementation. © 2021 American Society for Bone and Mineral Research (ASBMR).

Impact of Stroke History on the Risk of Recurrent Hip Fracture or Major Osteoporotic Fractures among Patients with Incident Hip Fracture: A Nationwide Cohort Study

“…The 1‐year cumulative incidence of recurrent hip fracture varied from 2% to 9% in previous reports. ( 1 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 33 ) Thus, our results fall in the middle of this spectrum and in line with a recent study also using Danish data. ( 33 ) The variation from previous reports may be due to different statistical approaches, different methods for detecting recurrent fractures in the clinical registries, and because many studies base their results on relatively few outcomes (i.e., 50–100), resulting in considerable uncertainty.…”

“…We followed patients from the date of discharge from admission for first‐time hip fracture and up to 2 years. Recurrent hip fracture was identified in the NPR in accordance with previously published studies on this topic using Danish data: ( 14,33 ) All new hip fracture diagnoses during an emergency admission were regarded as recurrent hip fracture, although the same type of fracture on the same side in the first 6 months of follow‐up was interpreted as a duplicate diagnosis and was therefore removed. The secondary outcome of MOF was a composite outcome including recurrent hip fracture (identified as for the primary outcome), fractures of the proximal humerus, distal forearm fractures, and vertebral fractures (see Table S1 for codes).…”

“…(57) Defining recurrent hip fracture can be challenging in the NPR, because reoperation or recoding of the original hip fracture diagnosis could mistakenly be interpreted as a recurrent fracture. In our opinion, two recent studies using Danish data (14,33) balanced this well, and we therefore chose to use the same procedure. On the other hand, an older study (1) used both diagnosis and procedure code for defining recurrent fracture and found extraordinarily high incidences.…”

“…(6) Several studies have investigated risk factors for recurrent fracture, but the results are inconsistent. (7)(8)(9)(10)(11)(12)(13)(14)(15)(16) A 2016 systematic review failed to establish any definite agreement on risk factors for recurrent hip fracture. (17) In this context, stroke history is no exception.…”

Management of patients at very high risk of osteoporotic fractures through sequential treatments

“…The study also examined major osteoporotic fracture risk after index hip fracture at 1-year follow-up in men and women aged over 50 years; incidence rates were low, however, and provided a 1-year risk of around 2% in CPRD/SIDIAP and 5% in DHR [ 24 ]. The incident fragility fracture prediction model (in which the model parameters are freely available) demonstrated good performance for hip fracture at 1 year in Spain, Denmark and the UK, and calibration was good across all three countries, with the authors concluding that such imminent fracture risk prediction models could be used to precisely identify patients at high imminent risk of fracture, thereby informing antiosteoporosis treatment selection [ 25 ].…”