Accepted Manuscript Determinants of short term fracture risk in patients with a recent history of low-trauma non-vertebral fracture
Aude Deloumeau, Anna Moltó, Christian Roux, Karine Briot PII: DOI: Reference:
S8756-3282(17)30314-9 doi: 10.1016/j.bone.2017.08.018 BON 11404
To appear in:
Bone
Received date: Revised date: Accepted date:
5 May 2017 30 July 2017 19 August 2017
Please cite this article as: Aude Deloumeau, Anna Moltó, Christian Roux, Karine Briot , Determinants of short term fracture risk in patients with a recent history of low-trauma non-vertebral fracture, Bone (2017), doi: 10.1016/j.bone.2017.08.018
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Determinants of short term fracture risk in patients with a recent history of low-trauma
PT
non-vertebral fracture
RI
Aude Deloumeau1, Anna Moltó1-2, Christian Roux1-2 Karine Briot1-2
Paris Descartes University, Cochin Hospital, Department of Rheumatology, Paris, France
2
U1153 Institut National de la Santé et de la Recherche Médicale ; PRESS Sorbonne Paris
SC
1
NU
Cité, Paris Descartes University, Cochin Hospital, Department of Rheumatology, Paris, France
MA
Corresponding author: Aude Deloumeau, [email protected], Cochin Hospital,
AC
CE
PT E
D
Department of Rheumatology, 27 rue du Faubourg Saint Jacques, 75014 Paris, France
ACCEPTED MANUSCRIPT 2 Abstract : Low-trauma fractures tend to cluster in time, and subsequent fractures have a role in increased morbidity and mortality in osteoporotic patients. The aim of this study was to identify the risk factors of short-term subsequent non-vertebral fracture (NVF). Patients were included from the Fracture Liaison Service (FLS) which provides assessment
PT
for osteoporosis to all in-hospital patients admitted for a low-trauma NVF in the Orthopaedics
RI
department. Location and date of occurrence of previous fractures, risk factors for
SC
osteoporosis and falls were collected. Bone mineral density was measured at the lumbar spine and total hip; presence of vertebral fractures was evaluated using vertebral fracture
NU
assessment (VFA).
Nine hundred and fifty patients were included (84% women; 75 ± 12 years), with a mean T-
MA
score at the femoral neck of -2.3 ± 1.0. Four hundred and sixty eight (49%) patients were in the FLS because of a hip fracture. Using multivariable analysis, the risk of being in the FLS
D
with a previous fracture less than 3 years before was associated with: history of fall in the year
PT E
before the admission (OR = 2.75, CI 95% 1.55-4.93), history of severe low-trauma NVF (OR = 2.54; CI 95% 1.45-4.52), and BMI lower than 20 kg/m2 (OR = 2.45, CI 95% 1.25-4.87);
CE
age older than 78 years-old was protective to the risk of re-fracture (OR = 0.44, CI 95% 0.240.80).
AC
Some risk factors (age, history of fall and of previous severe non-vertebral fracture) can help in the selection of patients at high risk of refracture, who should receive the highest priority for a treatment.
Key words: fracture risk, hip fracture, fall, fracture, osteoporosis
ACCEPTED MANUSCRIPT 3 Introduction: With the ageing of population, the number of frail elderly people at risk of falls and fractures is increasing. As a consequence, the number of fragility fractures has increased and is expected to keep on increasing: in the past 10 years, the number of hip fractures has increased in France by 5 % in women aged 60-84 years, and by 22% in women over 85 years [1]. In the
PT
United States, the number of hip fractures is projected to rise by 11.9 %-from 258,000 in 2010
RI
to 289,000 in 2030 [2], and similar data are reported worldwide [3,4]. These low trauma
SC
fractures are associated with increased morbidity, excess mortality and impose a large financial burden on healthcare systems. Prospective studies showed that the excess of
NU
mortality is increased for 5 years after a major osteoporotic fracture and is increased up to 10 years after a hip fracture [5].
MA
These low-trauma fractures expose to a higher risk of subsequent fractures. Patients with an osteoporotic fracture have on average a two-fold higher risk of refracture as compared to
D
individuals without a fracture [6]. Almost half of patients with hip fractures had a previous
from 2.3% to 10.6% [8].
PT E
fracture before the hip fracture [7], and the estimated risk of a second hip fractures ranges
CE
These subsequent fractures have a key role in increased morbidity and premature mortality. In the DUBBO study, the mortality rate was 24% after a first fragility fracture, and increased to
AC
50% after a second one [9]. In another study, subsequent fracture was associated with an increased mortality hazard ratio of 1.91 (95% CI, 1.54-2.37) in women and 2.99 (95% CI, 2.11-4.24) in men [5]. Importantly, the risk of refracture is the highest within the first 2 to 3 years after a first fracture: the relative risk of subsequent fracture is 5 at two years after a first osteoporotic fracture [10] and 75% of subsequent fractures occur within the 3 years after the first clinical
ACCEPTED MANUSCRIPT 4 fracture in a study following 60 to 80 years old patients for 5 years after a first osteoporotic clinical fracture [11]. Because of these well-known consequences of osteoporotic fractures and refractures, guidelines are available worldwide for appropriate treatments of patients with a recent fragility fracture. However, several studies show a decline in osteoporosis management after
PT
fragility fractures [12–14], with a rate of osteoporosis medication use after a hip fracture
RI
decreasing from 40 % in 2002 to 20% in 2011 in a U.S retrospective study [13]. This
SC
insufficiency in osteoporosis management is multifactorial as shown by qualitative studies: women consider osteoporosis to be somewhat normal wear-and-tear associated with ageing,
NU
ignoring the devastating consequences of severe osteoporotic fractures [15]. The “increased fracture risk” is perceived as a vague concept and the prospect of starting a treatment
MA
according to a 10 year-fracture risk is not motivating enough [16]. As a consequence, the identification of patients with an imminent risk of fracture of refracture
D
could effectively improve osteoporosis management. The rationale of our study is that, among
PT E
patients with a low trauma fracture, some may have risk factors for imminent refracture. We used a population of patients at the time they were included in a fracture liaison service and
CE
identified those who had a recent fracture before (i.e. in the previous 3 years). The aim of our study was to determine the characteristics of these patients, by identifying the variables
AC
associated with this short term risk of subsequent fracture.
Patients and Methods
Patients Patients were selected from the Fracture Liaison Service (FLS) of Cochin hospital (Paris, France). This FLS was established to provide routine assessment for osteoporosis to all men and women over the age of 50 years who had sustained a low-trauma NVF and are
ACCEPTED MANUSCRIPT 5 hospitalized in the Orthopaedic surgery department. Low-trauma fractures are defined as those sustained in falls from standing height or less. Exclusion criteria are: pathological and traumatic fractures, outpatients, and severe impaired cognitive functions. A senior physician, dedicated to the task of identification of patients with fragility fractures, selects these patients in the Orthopaedic surgery department and prescribes Dual-energy X-
PT
ray absorptiometry (DXA) scanning and Vertebral Fracture Assessment (VFA). For this
RI
study, we used the data of the FLS between February 2009 and September 2016.
SC
Variables
They were collected 4-90 days after the index fracture i.e. the one leading to inclusion in the
NU
FLS. The characteristics of the patients at the time of evaluation were considered to be similar to their characteristics immediately before the fracture.
MA
Clinical assessment includes demographic data: age, height, weight, BMI (Body Mass Index) (kg/m²) and the risk factors included in the FRAX (gender, history of low trauma fracture,
D
parental history of hip fracture, smoking, history of glucocorticorticoids therapy, rheumatoid
PT E
arthritis, three or more alcohol units per day, secondary cause of osteoporosis (early menopause age, malabsorption, osteogenesis imperfectas and untreated hyperthyroidism)).
CE
Among the other secondary osteoporosis categories in FRAX, data on malabsorption and chronic liver disease were not available. Number of falls in the previous year (excluding the
AC
fall leading to the fracture of inclusion), use of a walking aid and visual impairment (excluding glasses wearing only) and intake of anti-osteoporotic treatment in the year before the current fracture (raloxifene, bisphosphonates, strontium ranelate, teriparatide and denosumab) were also collected. Bone mineral density was measured at the lumbar spine and total hip using DXA (Hologic QDR-4500; Hologic, Bedford, MA, USA). Vertebral fractures from T4 to L4 were evaluated using Vertebral Fracture Assessment (VFA) software on the DXA device.
ACCEPTED MANUSCRIPT 6 We collected location and date of all prevalent vertebral and non-vertebral fractures, i.e. all fragility fractures that occurred before the index fracture. We only included patients with a history of VF that were known prior to VFA by the patients. Vertebral fractures diagnosed on VFA at the inclusion in this study were not included in the prevalent fractures because their date of occurrence was unknown. The index fracture was not considered to calculate the
PT
FRAX® score. The presence of vertebral(s) fracture(s) on VFA was taken into account to
SC
population and was not included in the logistic regression.
RI
calculate the FRAX® score. FRAX® was used to describe the characteristics of the
We defined severe NV fractures as those associated with an increased mortality according to
NU
prospective studies [5]: hip, humerus, pelvis, proximal tibia, or distal femur.
MA
Statistical analysis
We conducted this analysis in the group of patients included in the FLS with at least one
D
prevalent low-trauma non-vertebral fracture. Depending on the time between the index
PT E
fracture and the most recent prevalent fracture, we defined 2 groups: patients with prevalent low-trauma non-vertebral fracture that occured less than 3 years before the index fracture vs
CE
others. In order to assess the factors associated with a short-term fracture recurrence, we compared the characteristics of the two groups by Fisher’s and T-tests, accordingly.
AC
Thereafter, we performed a multivariable logistic regression to estimate that risk, only including in the model the variables associated in the univariable analysis (i.e. with a p
Aude Deloumeau, Anna Moltó, Christian Roux, Karine Briot PII: DOI: Reference:
S8756-3282(17)30314-9 doi: 10.1016/j.bone.2017.08.018 BON 11404
To appear in:
Bone
Received date: Revised date: Accepted date:
5 May 2017 30 July 2017 19 August 2017
Please cite this article as: Aude Deloumeau, Anna Moltó, Christian Roux, Karine Briot , Determinants of short term fracture risk in patients with a recent history of low-trauma non-vertebral fracture, Bone (2017), doi: 10.1016/j.bone.2017.08.018
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Determinants of short term fracture risk in patients with a recent history of low-trauma
PT
non-vertebral fracture
RI
Aude Deloumeau1, Anna Moltó1-2, Christian Roux1-2 Karine Briot1-2
Paris Descartes University, Cochin Hospital, Department of Rheumatology, Paris, France
2
U1153 Institut National de la Santé et de la Recherche Médicale ; PRESS Sorbonne Paris
SC
1
NU
Cité, Paris Descartes University, Cochin Hospital, Department of Rheumatology, Paris, France
MA
Corresponding author: Aude Deloumeau, [email protected], Cochin Hospital,
AC
CE
PT E
D
Department of Rheumatology, 27 rue du Faubourg Saint Jacques, 75014 Paris, France
ACCEPTED MANUSCRIPT 2 Abstract : Low-trauma fractures tend to cluster in time, and subsequent fractures have a role in increased morbidity and mortality in osteoporotic patients. The aim of this study was to identify the risk factors of short-term subsequent non-vertebral fracture (NVF). Patients were included from the Fracture Liaison Service (FLS) which provides assessment
PT
for osteoporosis to all in-hospital patients admitted for a low-trauma NVF in the Orthopaedics
RI
department. Location and date of occurrence of previous fractures, risk factors for
SC
osteoporosis and falls were collected. Bone mineral density was measured at the lumbar spine and total hip; presence of vertebral fractures was evaluated using vertebral fracture
NU
assessment (VFA).
Nine hundred and fifty patients were included (84% women; 75 ± 12 years), with a mean T-
MA
score at the femoral neck of -2.3 ± 1.0. Four hundred and sixty eight (49%) patients were in the FLS because of a hip fracture. Using multivariable analysis, the risk of being in the FLS
D
with a previous fracture less than 3 years before was associated with: history of fall in the year
PT E
before the admission (OR = 2.75, CI 95% 1.55-4.93), history of severe low-trauma NVF (OR = 2.54; CI 95% 1.45-4.52), and BMI lower than 20 kg/m2 (OR = 2.45, CI 95% 1.25-4.87);
CE
age older than 78 years-old was protective to the risk of re-fracture (OR = 0.44, CI 95% 0.240.80).
AC
Some risk factors (age, history of fall and of previous severe non-vertebral fracture) can help in the selection of patients at high risk of refracture, who should receive the highest priority for a treatment.
Key words: fracture risk, hip fracture, fall, fracture, osteoporosis
ACCEPTED MANUSCRIPT 3 Introduction: With the ageing of population, the number of frail elderly people at risk of falls and fractures is increasing. As a consequence, the number of fragility fractures has increased and is expected to keep on increasing: in the past 10 years, the number of hip fractures has increased in France by 5 % in women aged 60-84 years, and by 22% in women over 85 years [1]. In the
PT
United States, the number of hip fractures is projected to rise by 11.9 %-from 258,000 in 2010
RI
to 289,000 in 2030 [2], and similar data are reported worldwide [3,4]. These low trauma
SC
fractures are associated with increased morbidity, excess mortality and impose a large financial burden on healthcare systems. Prospective studies showed that the excess of
NU
mortality is increased for 5 years after a major osteoporotic fracture and is increased up to 10 years after a hip fracture [5].
MA
These low-trauma fractures expose to a higher risk of subsequent fractures. Patients with an osteoporotic fracture have on average a two-fold higher risk of refracture as compared to
D
individuals without a fracture [6]. Almost half of patients with hip fractures had a previous
from 2.3% to 10.6% [8].
PT E
fracture before the hip fracture [7], and the estimated risk of a second hip fractures ranges
CE
These subsequent fractures have a key role in increased morbidity and premature mortality. In the DUBBO study, the mortality rate was 24% after a first fragility fracture, and increased to
AC
50% after a second one [9]. In another study, subsequent fracture was associated with an increased mortality hazard ratio of 1.91 (95% CI, 1.54-2.37) in women and 2.99 (95% CI, 2.11-4.24) in men [5]. Importantly, the risk of refracture is the highest within the first 2 to 3 years after a first fracture: the relative risk of subsequent fracture is 5 at two years after a first osteoporotic fracture [10] and 75% of subsequent fractures occur within the 3 years after the first clinical
ACCEPTED MANUSCRIPT 4 fracture in a study following 60 to 80 years old patients for 5 years after a first osteoporotic clinical fracture [11]. Because of these well-known consequences of osteoporotic fractures and refractures, guidelines are available worldwide for appropriate treatments of patients with a recent fragility fracture. However, several studies show a decline in osteoporosis management after
PT
fragility fractures [12–14], with a rate of osteoporosis medication use after a hip fracture
RI
decreasing from 40 % in 2002 to 20% in 2011 in a U.S retrospective study [13]. This
SC
insufficiency in osteoporosis management is multifactorial as shown by qualitative studies: women consider osteoporosis to be somewhat normal wear-and-tear associated with ageing,
NU
ignoring the devastating consequences of severe osteoporotic fractures [15]. The “increased fracture risk” is perceived as a vague concept and the prospect of starting a treatment
MA
according to a 10 year-fracture risk is not motivating enough [16]. As a consequence, the identification of patients with an imminent risk of fracture of refracture
D
could effectively improve osteoporosis management. The rationale of our study is that, among
PT E
patients with a low trauma fracture, some may have risk factors for imminent refracture. We used a population of patients at the time they were included in a fracture liaison service and
CE
identified those who had a recent fracture before (i.e. in the previous 3 years). The aim of our study was to determine the characteristics of these patients, by identifying the variables
AC
associated with this short term risk of subsequent fracture.
Patients and Methods
Patients Patients were selected from the Fracture Liaison Service (FLS) of Cochin hospital (Paris, France). This FLS was established to provide routine assessment for osteoporosis to all men and women over the age of 50 years who had sustained a low-trauma NVF and are
ACCEPTED MANUSCRIPT 5 hospitalized in the Orthopaedic surgery department. Low-trauma fractures are defined as those sustained in falls from standing height or less. Exclusion criteria are: pathological and traumatic fractures, outpatients, and severe impaired cognitive functions. A senior physician, dedicated to the task of identification of patients with fragility fractures, selects these patients in the Orthopaedic surgery department and prescribes Dual-energy X-
PT
ray absorptiometry (DXA) scanning and Vertebral Fracture Assessment (VFA). For this
RI
study, we used the data of the FLS between February 2009 and September 2016.
SC
Variables
They were collected 4-90 days after the index fracture i.e. the one leading to inclusion in the
NU
FLS. The characteristics of the patients at the time of evaluation were considered to be similar to their characteristics immediately before the fracture.
MA
Clinical assessment includes demographic data: age, height, weight, BMI (Body Mass Index) (kg/m²) and the risk factors included in the FRAX (gender, history of low trauma fracture,
D
parental history of hip fracture, smoking, history of glucocorticorticoids therapy, rheumatoid
PT E
arthritis, three or more alcohol units per day, secondary cause of osteoporosis (early menopause age, malabsorption, osteogenesis imperfectas and untreated hyperthyroidism)).
CE
Among the other secondary osteoporosis categories in FRAX, data on malabsorption and chronic liver disease were not available. Number of falls in the previous year (excluding the
AC
fall leading to the fracture of inclusion), use of a walking aid and visual impairment (excluding glasses wearing only) and intake of anti-osteoporotic treatment in the year before the current fracture (raloxifene, bisphosphonates, strontium ranelate, teriparatide and denosumab) were also collected. Bone mineral density was measured at the lumbar spine and total hip using DXA (Hologic QDR-4500; Hologic, Bedford, MA, USA). Vertebral fractures from T4 to L4 were evaluated using Vertebral Fracture Assessment (VFA) software on the DXA device.
ACCEPTED MANUSCRIPT 6 We collected location and date of all prevalent vertebral and non-vertebral fractures, i.e. all fragility fractures that occurred before the index fracture. We only included patients with a history of VF that were known prior to VFA by the patients. Vertebral fractures diagnosed on VFA at the inclusion in this study were not included in the prevalent fractures because their date of occurrence was unknown. The index fracture was not considered to calculate the
PT
FRAX® score. The presence of vertebral(s) fracture(s) on VFA was taken into account to
SC
population and was not included in the logistic regression.
RI
calculate the FRAX® score. FRAX® was used to describe the characteristics of the
We defined severe NV fractures as those associated with an increased mortality according to
NU
prospective studies [5]: hip, humerus, pelvis, proximal tibia, or distal femur.
MA
Statistical analysis
We conducted this analysis in the group of patients included in the FLS with at least one
D
prevalent low-trauma non-vertebral fracture. Depending on the time between the index
PT E
fracture and the most recent prevalent fracture, we defined 2 groups: patients with prevalent low-trauma non-vertebral fracture that occured less than 3 years before the index fracture vs
CE
others. In order to assess the factors associated with a short-term fracture recurrence, we compared the characteristics of the two groups by Fisher’s and T-tests, accordingly.
AC
Thereafter, we performed a multivariable logistic regression to estimate that risk, only including in the model the variables associated in the univariable analysis (i.e. with a p
