Bone mineral density and osteoporosis in relation to all-cause and cause-specific mortality in NHANES: A population-based cohort study

doi:10.1016/j.bone.2020.115597

Bone

Volume 141, December 2020, 115597

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Highlights

•
Higher risk of all-cause mortality among participants with osteoporosis compared with normal in femur was found.
•
Non-linear dose-response analyses showed a L-shaped association for all-cause mortality with BMD increment in femur.
•
The relation between higher BMD level in femur with decreased mortality of cancer and heart diseases varied by gender.
•
No relation was found between BMD and osteoporosis in lumbar spine with risk of all-cause and cause-specific mortality.

Abstract

Objective

The majority of the published studies ascertaining the relationships between low bone mineral density (BMD) and mortality highlighted the elderly population with limited sample size. Our study aimed to ascertain the relationships in general population.

Methods

This study ascertained the relationships between BMD levels in femur and lumbar spine with all-cause and cause-specific mortality in the National Health and Nutrition Examination Survey (NHANES) (n = 15,076, mean age 48.6 years). Cox proportional hazards models were adopted to calculate the hazard ratios (HR) and the corresponding 95% confidence intervals (CIs) for mortality.

Results

During a 6.8-year median follow-up, 1216 men and women in the cohort died. There was a higher risk of all-cause mortality among participants with osteoporosis compared with normal in the regions of total femur (HR = 1.36, 95% CI = 1.07–1.73), femur neck (HR = 1.41, 95% CI = 1.11–1.78), intertrochanter (HR = 1.34, 95% CI = 1.05–1.72), as well as overall (HR = 1.36, 95% CI = 1.09–1.69). Non-linear dose-response analyses showed a statistically significant L-shaped association for all-cause mortality with BMD increment in the regions of total femur, femur neck, trochanter, and intertrochanter. The protective role of higher BMD level in femur for decreased risk of cancer mortality and heart diseases mortality was more evident in male participants and female participants, respectively.

Conclusions

In summary, our results revealed that maintaining normal BMD is critical to lower the risk of mortality. The association between higher BMD level in femur and decreased risk of cancer as well as heart diseases mortality varies by gender.

Introduction

Osteoporosis refers to a vital public health problem that is considerably and progressively prevalent in developing and developed countries [1]. In 2010, the U.S. was estimated to have 10.2 million cases of osteoporosis among population aged over 50 years; such number was expected to reach 13.5 million in 2030 [2,3]. Osteoporosis refers to a metabolic condition characterized by decreased bone mineral density (BMD) and enhanced risk of fragility fractures, capable of causing increased risk of all-cause, cardiovascular and cancer mortality [[4], [5], [6], [7]]. In fact, only less than one-third of hip and vertebral fractures resulted from low BMD and advancing age [8,9]. Low BMD was reported to be linked to the elevated risk of mortality independent of fragility fracture [[10], [11], [12]].

BMD is a critical component in osteoporosis assessment and diagnosis. Low BMD is related to multiple factors (e.g., nutrition [13], calcium metabolism [14], estrogen metabolism [15], environmental xenoestrogens [16], as well as genetic factors [17]. A systematic review and meta-analysis conducted in 2013 concluded that lower BMD displayed a correlation with the elevated risk of all-cause and cardiovascular mortality [18]. However, the involved studies in the meta-analysis and newly published studies after 2013 were primarily conducted in the elderly with a limited sample size [10,11,[19], [20], [21]]. Thus, whether low BMD can predict the risen risk of mortality in general population (aged 20 years or more) remains unclear. Moreover, the BMD level of different sites was correlated with different mortality risks [20,22]. The exploration and comparison in the relationships between BMD in different sites and mortality are required to delve into the biochemical mechanism of bone metabolism and death.

To this end, this study ascertained the relationships between BMD levels of total femur, femur neck, trochanter and intertrochanter in femur and lumbar spine with all-cause mortality, as well as the underlying causes of death (e.g., cancer and heart diseases) in a cohort representative of the U.S. adult population. Furthermore, the relationships between BMD and risk of mortality in different subgroups were also ascertained.

Section snippets

Study population

The publicly data files from the National Health and Nutrition Examination Survey (NHANES) released by the Centers for Disease Control and Prevention (CDC) were used. In brief, NHANES is an ongoing and continuous program to harvest health-related data representing the U.S. population of all ages by multistage and stratified sampling design since 1999. Recruited participants were asked to sign an informed consent and invited to complete an interviewer-administrated questionnaire; subsequently,

Description of study participants

In the analysis reported here (Fig. 1), 22,901 participants aged ≥20 years were included in continuous NHANE (2005–2010,2013–2014) datasets. Participants with missing information regarding mortality (n = 40) and other covariates (n = 5196) were excluded. Furthermore, participants who had incomplete femur status and invalid data (n = 2589) were excluded from the final model. Lastly, 15,076 aged over 20 years with complete data of interest were analyzed in this study.

During a 6.8-year median

Discussion

In the present cohort study of U.S. adults from NHANES, participants with osteoporosis in femur were identified to be correlated with higher risk of all-cause mortality and mortality of other causes. The similar association was observed in younger adults, older adults, males, and females. The study reported a statistically significantly L-shaped association for all-cause mortality with BMD increment in femur. Statistically significant L-shaped relationships were also identified for heart

Funding

This study was supported by National Natural Science Foundation of China (No. 81703289).

CRediT authorship contribution statement

Shaofang Cai:Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Writing - original draft, Writing - review & editing.Jiayao Fan:Conceptualization, Investigation, Methodology, Project administration, Writing - review & editing.Lina Zhu:Conceptualization, Investigation, Methodology, Project administration, Writing - review & editing.Jianhong Ye:Conceptualization, Project administration, Writing - review & editing.Xianming Rao:Conceptualization,

Declaration of competing interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this study.

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Full Length ArticleBone mineral density and osteoporosis in relation to all-cause and cause-specific mortality in NHANES: A population-based cohort study

Highlights

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Description of study participants

Discussion

Funding

CRediT authorship contribution statement

Declaration of competing interest

Am. J. Clin. Nutr.

Int. J. Cardiol.

Study of Osteoporotic Fractures Research Group, Lancet

J. Clin. Epidemiol.

Ann. Epidemiol.

J. Clin. Densitom.

Lancet

Osteoporosis and osteopenia in the distal forearm predict all-cause mortality independent of grip strength: 22-year follow-up in the population-based Tromso study

Osteoporos. Int.

The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine

J. Bone Miner. Res.

A review and clinical perspective of the impact of osteoporosis on the spine

Geriatr Orthop Surg Rehabil

Extensive undertreatment of osteoporosis in older Swedish women

Osteoporos. Int.

Osteoporosis treatment: raloxifene (Evista) and stroke mortality

CMAJ

Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women

JAMA

Bone mass density and risk of breast cancer and survival in older women

Eur. J. Epidemiol.

Identification and fracture outcomes of undiagnosed low bone mineral density in postmenopausal women: results from the National Osteoporosis Risk Assessment

JAMA

Two-thirds of all fractures are not attributable to osteoporosis and advancing age: implications for fracture prevention

J. Clin. Endocrinol. Metab.

Proximal femur volumetric bone mineral density and mortality: 13 years of follow-up of the AGES-Reykjavik study

J. Bone Miner. Res.

Bone mineral density and parathyroid hormone as independent risk factors for mortality in community-dwelling older adults: a population-based prospective cohort study in Brazil

The Sao Paulo Ageing & Health (SPAH) Study, J Bone Miner Res

Low bone mineral density is an independent risk factor for stroke and death

Cerebrovasc. Dis.

Effects of milk powder intervention on bone mineral density and indicators related to bone metabolism in Chinese adolescents

Osteoporos. Int.

Association of genetic variants related to serum calcium levels with reduced bone mineral density

J. Clin. Endocrinol. Metab.

Association between urinary triclosan with bone mass density and osteoporosis in US adult women, 20052010

J. Clin. Endocrinol. Metab.

ESR1 polymorphism (rs2234693) influences femoral bone mass in patients with Turner syndrome

Endocr Connect

Full Length Article
Bone mineral density and osteoporosis in relation to all-cause and cause-specific mortality in NHANES: A population-based cohort study