The Global Burden Attributable to Low Bone Mineral Density, 1990 to 2020: An Updated and Expanded Analysis of a Modifiable Risk Factor from the Global Burden of Disease Study 2021

Abstract

Background: Fractures lead to significant morbidity, mortality and cost to individuals and health systems. Low bone mineral density (BMD) is a modifiable risk factor for fractures. Building on our previous studies on the global burden from falls attributable to low BMD in the global burden of disease (GBD) 2010 analysis, this expanded GBD 2021 analysis of data from 1990-2020 quantifies the contribution from additional categories of injuries, including road traffic accidents, interpersonal violence, exposure to mechanical forces and animal contact.

Methods: Applying the comparative risk assessment methodology, the burden of low BMD was expressed in terms of years lived with disability (YLDs), disability-adjusted life years (DALYs) and deaths. Global BMD data were obtained from an updated systematic review of population-based studies. In a meta-analysis, we estimated a pooled relative risk of fractures per unit decrease in BMD (g/cm2). Analyses focused on individuals 40 years and above. The population-attributable fraction for low BMD was calculated by comparing the observed distributions to an age- and sex-specific counterfactual distribution defined as the 99th percentile of five rounds of the National Health and Nutrition Examination Survey in the United States by 5-year age group and sex. Hospital and emergency department data were used to derive the incidence of fractures from each type of injury. Because ICD rules assign injury deaths to injury causes (such as falls or road injuries) rather than by nature of injury (such as fractures) deaths due to fractures were estimated as the proportion of in-hospital deaths due to the specified injury causes for which a fracture was the most severe nature-of-injury category. A decomposition analysis was performed to demonstrate the relative contribution of population growth, population ageing, changes in exposure to low BMD, and changes in injury rates of deaths and DALYs between 1990 and 2020.

Findings: In 2020, 8.32 million (UI: 5.58 – 10.84) YLDs, 17.2 million (14.1 – 20.2 million) DALYs, and 477,000 (411,000 – 536,000) deaths were attributable to low BMD. Falls accounted for 65.2% (62.9 – 67.6) of DALYs and 71.0% (67.4 – 72.8) of deaths attributable to low BMD, while road injuries accounted for most of the remainder: 24.6% (22.5 – 27.1) of DALYs and 23.1% (21.6 – 26.2) of deaths. As a proportion of all falls, low BMD accounted for 25.6% (22.1 – 27.4) of DALYs and 40.6% (35.4 – 44.0) of deaths. Of all road injuries, 6.3% (5.35 – 6.94) of DALYs and 8.9% (7.55 – 9.63) of deaths were attributable to low BMD in 2020. Among men, between the ages of 40 and 70, road injuries accounted for the majority of DALYs and deaths attributable to low BMD. Over age 70, falls were the leading cause of low BMD burden. Among women, the proportion of DALYs and deaths due to low BMD were similar for road injuries and falls before age 50, after which falls contributed most to low BMD attributed burden. An approximately two-fold increase in overall DALYs and deaths attributable to low BMD was observed globally in 2020 compared with 1990.

Interpretation: Low BMD is a key modifiable risk factor for fractures, which are an important cause of morbidity and mortality particularly in ageing populations. This analysis calls attention to low BMD as a cause of health loss not just from falls, but also from road injuries.

Funding: This study was supported by the Bill and Melinda Gates Foundation.

Declaration of Interest: All the authors have seen and agree with the contents of this manuscript, and have no competing interests to declare 422 related to the information presented here. DPA’s department has received grant/s from Amgen, Chiesi-Taylor, Lilly, 423 Janssen, Novartis, and UCB Biopharma. His research group has received consultancy fees from Astra Zeneca and 424 UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or 425 supported training programmes organised by DPA's department. LSR is an employee and holds stock at Pfizer.

Keywords: Low Bone Mineral Density, Fractures, Death, DALYs, YLDs