Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Dietary acid load, trabecular bone integrity, and mineral density in an ageing population: the Rotterdam study.

We studied the relation between a diet that is high in acid-forming nutrients (e.g. proteins) and low in base-forming nutrients (e.g. potassium) and bone structure. We showed a negative relation, which was more prominent if proteins were of animal rather than of vegetable origin and if intake of dietary fibre was high. INTRODUCTION: Studies on dietary acid load (DAL) and fractures have shown inconsistent results. Associations between DAL, bone mineral density (BMD) and trabecular bone integrity might play a role in these inconsistencies and might be influenced by renal function and dietary fibre intake. Therefore, our aim was to study (1) associations of DAL with BMD and with the trabecular bone score (TBS) and (2) the potential influence of renal function and dietary fibre in these associations. METHODS: Dutch individuals aged 45 years and over (n = 4672) participating in the prospective cohort of the Rotterdam study were included. Based on food frequency questionnaires, three indices of DAL were calculated: the net endogenous acid production (NEAP) and the ratios of vegetable or animal protein and potassium (VegPro/K and AnPro/K). Data on lumbar spinal TBS and BMD were derived from dual-energy X-ray absorptiometry measurements. RESULTS: Independent of confounders, NEAP and AnPro/K, but not VegPro/K, were associated with low TBS (standardized ß (95%) = -0.04 (-0.07, -0.01) and -0.08 (-0.11, -0.04)) but not with BMD. Associations of AnPro/K and VegPro/K with TBS were non-linear and differently shaped. Unfavourable associations between NEAP, BMD and TBS were mainly present in subgroups with high fibre intake. CONCLUSIONS: High NEAP was associated with low TBS. Associations of AnPro/K and VegPro/K and TBS were non-linear and differently shaped. No significant associations of DAL with BMD were observed, nor was there any significant interaction between DAL and renal function. Mainly in participants with high intake of dietary fibre, DAL might be detrimental to bone.