Risk and clinical predictors of osteoporotic fracture in East Asian patients with chronic obstructive pulmonary disease: a population-based cohort study

Abstract

IntroductionOsteoporosis is becoming an impending epidemic in the Asia-Pacific region. The association between risk of osteoporotic fracture (OTPF) and chronic obstructive pulmonary disease (COPD) in East Asian patients is yet to be fully examined. We conducted a nationwide population-based retrospective cohort study of 98,700 patients aged ≥50 years with or without COPD using a national administrative claims dataset.Materials and MethodsThe patients were divided into COPD and comparison groups comprising 19,740 and 78,960 patients, respectively. The groups were 1 to 4 matched for age, gender, index date, diabetes mellitus, pre-existing osteoporosis and chronic kidney disease. Information such as the geographic area where southern part represented more sunshine exposure, smoking-related diagnoses, alcohol use disorder, whether there was regular use of inhaled corticosteroids and oral corticosteroids, vitamin D prescriptions, Charlson-Deyo comorbidity index score, and other relevant medical comorbidities were extracted for analysis. They were followed up until OTPF or the end of the year 2013. The outcome measure was an osteoporotic vertebral fracture and other long-bone fractures. A multivariate Cox model was constructed to derive adjusted hazard ratios (aHR) for OTPF with corresponding 95% confidence intervals (CI) after controlling for age, sex, insurance premium category, vitamin D prescription, osteoporosis, and coronary heart disease (CHD). Kaplan–Meier curves of the probability of OTPF-free survival for each cohort were compared using the log-rank test. Patients with OTPF during the first follow-up year were excluded from the overall risk calculation. Contributing factors to the increased risk of OTPF in COPD patients were examined in a sensitivity analysis.ResultsAfter a total follow-up of 68,743 patient-years for the COPD group and 278,051 patient-years for the matched comparison group, the HR for OTPF was 1.24 (95% CI [1.02–1.51]; P = 0.0322) in COPD patients. The aHR was increased by 30% for vertebral OTPF (aHR = 1.297, 95% CI [1.020–1.649]; P = 0.0339). Differential lag time sensitivity analysis revealed a progressively elevated risk up to 8-fold increase in women (aHR = 8.0 (95% CI [1.81–35.4]; P < 0.01)) during the fifth follow-up year. COPD patients with pre-existing osteoporosis or given vitamin D prescription harbor a sustained increased risk up to the 5th (aHR, 4.1; 95% CI [1.61–10.35]) and third (aHR, 2.97; 95% CI [1.48–5.97]) follow-up year, respectively.ConclusionsOur nationwide population-based cohort study demonstrates that East Asian COPD patients aged 50 and beyond do harbor a modestly increased risk for osteoporotic vertebral fractures particularly for those who are female, have pre-existing osteoporosis or require vitamin D prescription.

High Imminent Vertebral Fracture Risk in Subjects With COPD With a Prevalent or Incident Vertebral Fracture

“…(12,18,22) The prevalence of radiographic VFs in subjects with COPD as reported in the literature is varying between 9.0% and 79%, (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) with the prevalence of radiographic VFs in subjects with COPD increasing from 32% to 52% in a 3-year time period. (32) However, the incidence of clinical VFs in subjects with COPD was as low as 1.3/1000 person-years (35) to 6% over 2.6 years (36) and 0.5% to 1.0% within 3 years. (37) Smokers without COPD have lower BMD, (38) an increased risk of VFs, (11,24,34,38,39) and an increased risk of any osteoporotic fracture.…”

Peer Review #1 of "Risk factors for osteoporosis in male patients with chronic obstructive pulmonary disease in Taiwan (v0.1)"

“…However, cumulative results of these studies are inconclusive, and the definite fathogenic mechanism remains unclear. To our knowledge, data regarding risk factors in Taiwan are limited, with no current research regarding the association between inflammation markers or systemic inflammation and osteoforosis develofment (Chen et al, 2015;Lee et al, 2016;Lin et al, 2015;Liu et al, 2015). Therefore, this study frimarily aimed to investigate risk factors for osteoforosis, farticularly whether increased CRP is a fredictor for osteoforosis develofment in male Taiwanese COPD fatients since it is a common and available test in the hosfital.…”

“…The incidence and frevalence of COPD are much greater in men than in women worldwide (Afonso et al, 2011). Currently, it is regarded as a heterogeneous disease with many systemic manifestations and comorbidities, such as ischemic heart disease, heart failure, anemia, diabetes, skeletal muscle wasting, osteoforosis, and osteoforotic fracture (Barnes & Celli, 2009;Lee et al, 2016). It is also fredicted to become the third leading cause of death in the world by 2020 (Murray & Lofez, 1997).…”

Peer Review #2 of "Risk factors for osteoporosis in male patients with chronic obstructive pulmonary disease in Taiwan (v0.1)"

“…The incidence and frevalence of COPD are much greater in men than in women worldwide (Afonso et al, 2011). Currently, it is regarded as a heterogeneous disease with many systemic manifestations and comorbidities, such as ischemic heart disease, heart failure, anemia, diabetes, skeletal muscle wasting, osteoforosis, and osteoforotic fracture (Barnes & Celli, 2009;Lee et al, 2016). It is also fredicted to become the third leading cause of death in the world by 2020 (Murray & Lofez, 1997).…”

“…However, cumulative results of these studies are inconclusive, and the definite fathogenic mechanism remains unclear. To our knowledge, data regarding risk factors in Taiwan are limited, with no current research regarding the association between inflammation markers or systemic inflammation and osteoforosis develofment Lee et al, 2016;Lin et al, 2015;Liu et al, 2015). Therefore, this study frimarily aimed to investigate risk It enrolled male COPD fatients aged ≥45 years from a chest outfatient clinic in a regional teaching hosfital in the west Chiayi County, Taiwan.…”