Comorbidities Only Account for a Small Proportion of Excess Mortality After Fracture: A Record Linkage Study of Individual Fracture Types

Abstract

Nonhip, nonvertebral (NHNV) fractures constitute the majority of osteoporotic fractures, but few studies have examined the association between these fractures, comorbidity, and mortality. Our objective was to examine the relationship between individual nonhip, nonvertebral fractures, comorbidities, and mortality. The prospective population-based cohort of 267,043 subjects (45 and Up Study, Australia) had baseline questionnaires linked to hospital administrative and all-cause mortality data from 2006 to 2013. Associations between fracture and mortality were examined using multivariate, time-dependent Cox models, adjusted for age, prior fracture, body mass index, smoking, and comorbidities (cardiovascular disease, diabetes, stroke, thrombosis, and cancer), and survival function curves. Population attributable fraction was calculated for each level of risk exposure. During 1,490,651 person-years, women and men experienced 7571 and 4571 fractures and 7064 deaths and 11,078 deaths, respectively. In addition to hip and vertebral fractures, pelvis, humerus, clavicle, rib, proximal tibia/fibula, elbow and distal forearm fractures in both sexes, and ankle fractures in men were associated with increased multivariable-adjusted mortality hazard ratios ranging from 1.3 to 3.4. Comorbidity independently added to mortality such that a woman with a humeral fracture and 1 comorbidity had a similarly reduced 5-year survival as that of a woman with a hip fracture and no comorbidities. Population mortality attributable to any fracture without comorbidity was 9.2% in women and 5.3% in men. All proximal nonhip, nonvertebral fractures in women and men were associated with increased mortality risk. Coexistent comorbidities independently further increased mortality. Population attributable risk for mortality for fractures was similar to cardiovascular disease and diabetes, highlighting their importance and potential benefit for early intervention and treatment. © 2018 American Society for Bone and Mineral Research.

Pituitary Adenylate Cyclase Activating Polypeptide Elicits Neuroprotection Against Acute Ischemic Neuronal Cell Death Associated with NMDA Receptors

“…Of note, aging is major co-morbidity factor of stroke [43,44]. An impaired neurovascular unit has been implicated as a key pathology of stroke [45,46], and aging appears to dampen PACAP expression in the vasculature of mice, rendering the blood supply to the brain vulnerable to stroke [47,48].…”

Does the Prediction Accuracy of Osteoporotic Fractures by BMD and Clinical Risk Factors Vary With Fracture Site?

“…Fracture events have a substantial impact in terms of quality of life, particularly after hip and vertebral fracture . Population attributable risk for mortality from fracture is similar to that from cardiovascular disease and diabetes, highlighting their importance and potential benefit for early prevention treatment (population mortality attributable to any fracture without comorbidity is 9.2% in women, which is similar in magnitude to other well‐described causes of mortality, including cardiovascular disease, diabetes, and cancer) …”

“…Hip fractures are the most relevant fractures in terms of mortality, worse quality of life, functional dependence, and social and economic costs, especially among the elderly . Besides hip and vertebral fractures that are associated, respectively, with a threefold and 2.7‐fold increase in mortality, pelvis, humerus, clavicle, proximal tibia/fibula, elbow, distal forearm, and ribs fractures are also associated with mortality HRs ranging from 1.3 to 3.4 …”

“…(3) Population attributable risk for mortality from fracture is similar to that from cardiovascular disease and diabetes, highlighting their importance and potential benefit for early prevention treatment (population mortality attributable to any fracture without comorbidity is 9.2% in women, which is similar in magnitude to other well-described causes of mortality, including cardiovascular disease, diabetes, and cancer). (4) Deaths after a fracture are in part related to comorbidities, but can also result from the fracture event itself, either directly or indirectly. Hip fractures are the most relevant fractures in terms of mortality, worse quality of life, functional dependence, and social and economic costs, especially among the elderly.…”

“…(5) Besides hip and vertebral fractures that are associated, respectively, with a threefold and 2.7-fold increase in mortality, pelvis, humerus, clavicle, proximal tibia/fibula, elbow, distal forearm, and ribs fractures are also associated with mortality HRs ranging from 1.3 to 3.4. (4) Because osteoporotic fractures cause a huge financial burden worldwide, osteoporosis should ideally be prevented, diagnosed, and treated before a fracture occurs. As a low BMD is an important factor predicting increased fracture risk, the diagnosis of osteoporosis relies on the assessment of BMD by DXA.…”