Risk Factors for Fall and Fracture - A Cohort Study of Fall-related Factors Obtained in Routine Orthopaedic Fracture Care
Conditions: Fall Injury, Hip Fractures, Risk Reduction, Osteoporosis, Osteopenia, Frailty
Sponsor: Region Skane

 
  
 
Research Protocol & Statistical Analysis Plan 
Project Title:  
“Risk Factors for Fall and Fracture – A Cohort Study of 
Fall-related Factors Obtained in Routine Orthopaedic 
Care” 
Protocol ID:  
2022-01997-01 (The Swedish Ethical Review Board) 
ClinicalTrials Identifier: NCT05712252 
Document Date:  
2023-02-13 
Responsible Party: 
Region Skåne 
Principal Investigator:  Cecilia Rogmark, Department of Orthopaedics, Skane 
University Hospital & Lund University, Malmö, Sweden 
Developed by:  
Helmi-Sisko Pyrhönen, Cecilia Rogmark, Linnea Malmgren 

Statistical Analysis Plan: Risk Factors for Fall and Fracture – A Cohort Study of Fall-Related Factors Obtained in Routine 
Orthopaedic Care 
 
 
 
Table of Contents 
1. 
Introduction .......................................................................................................................................................... 2 
2. 
Project aims ........................................................................................................................................................... 2 
3. 
Planned studies ..................................................................................................................................................... 2 
1. Risk factors associated with falls in an orthopaedic cohort – prevention possible? ............................. 2 
2. Association between factors identified at admission due to fall and 1-year clinical outcome ............. 2 
3. Is calprotectin a more accurate predictor of bacterial infection than conventional testing?  .............. 3 
4. Is harmful alcohol consumption an underrated cause of falls in the older population? ...................... 3 
5. How to best depict the functional capacity of an older individual in need of treatment and 
rehabilitation after a fall? ..................................................................................................................................... 4 
6. What are the differences between those with fall only or fall leading to fracture? ............................... 4 
7. Is shrunken pore syndrome associated with 1-year mortality and frailty in patients after a fall? ........ 4 
8. Is there a correlation between pro-BNP and orthostatic hypotension and 1-year outcome after a 
fall? .......................................................................................................................................................................... 5 
4. 
Study design .......................................................................................................................................................... 5 
Inclusion & Exclusion Criteria ............................................................................................................................... 5 
5. 
Covariates .............................................................................................................................................................. 5 
6. 
Outcome measures............................................................................................................................................... 7 
7. 
Study groups .......................................................................................................................................................... 8 
8. 
Study Assessments (Timing) ............................................................................................................................... 8 
9. 
Time Plan ............................................................................................................................................................... 9 
10. Missing Data ......................................................................................................................................................... 9 
11. Statistical Methods ............................................................................................................................................... 9 
Descriptive Statistics ................................................................................................................................................ 9 
Inferential Statistics .................................................................................................................................................. 9 
Statistical Significance .............................................................................................................................................. 9 
12. Importance and novelty ...................................................................................................................................... 9 
13. Collaborations .....................................................................................................................................................10 
14. References ...........................................................................................................................................................10 
 
 
 
 

Statistical Analysis Plan: Risk Factors for Fall and Fracture – A Cohort Study of Fall-Related Factors Obtained in Routine 
Orthopaedic Care 
 
 
 
RISK FACTORS FOR FALL AND FRACTURE – A COHORT STUDY OF FALL 
RELATED FACTORS OBTAINED IN ROUTINE OTHOPAEDIC CARE 
1. Introduction 
The knowledge of risk factors for falls and fractures amongst older individuals are enormous, still 
identification of fallers and prevention of falls is not part of standard of care. Some risk factors are more or 
less overlooked, such as alcohol consumption, orthostatic reactions, as are increased risks related to 
common medications such as certain antidepressants, opioids and sedatives (1-3) 
Functional activity and frailty scores have been suggested to be potential predictors of adverse events, length 
of hospital stay and mortality (4-6), but has not been implemented in routine care in Sweden. 
Outcomes after fragility fractures are continuously poor, in particular well studied after hip fractures, 
although palpable improvements have been reached regarding surgical treatment. Are there other factors 
that are equally or more decisive for the global outcome from the patient’s point of view? 
2. Project aims  
The overall aim of this project is to improve the global outcome for an ageing individual after a traumatic 
fall through promoting recovery and rehabilitation, and preventing complications, new falls and fractures. 
This will be addressed in the specific studies listed below, all of which will be based on an annual cohort of 
older individuals admitted due to a fall to the Department of Orthopedics, Malmö.  
3. Planned studies 
1. Risk factors associated with falls in an orthopaedic cohort – prevention possible? 
 
Background: Risk factors associated with falls among the elderly have historically been well studied. However, 
the knowledge of risk factors for falls/fractures is mostly outdated, as those entering old age today have 
different health history, medications and lifestyle than the generations before them (7). Also, the routine 
health care is challenged by the growing the proportion of aged individuals in Sweden and the consequent 
increase in fall-related trauma and related conditions. 
Many known risk factors, such as infection or orthostatic hypotension, arise from medically treatable 
conditions. However, mapping of factors contributing to fall is seldom done in routine healthcare, with 
the consequence that subsequent individualized fall prevention is obstructed (2). 
Objective: This study aims to analyze results from a standardized set of blood tests, orthostatic test, hand grip 
test and scores for frailty and activity as explanatory variables for fall. 
Material and Methods: An annual cohort of older individuals admitted due to a fall to the Department of 
Orthopedics, Malmö, will be screened with tests and scores. This data, together with basic demographics 
including +/– fracture, will be gathered in a RedCap-database. 
Importance: Preventative measures can be tailored through early identification of individual risk factors. Also, 
early identification and treatment of simultaneous, feasibly severe, medical conditions might improve the 
morbidity and mortality of the frail elderly patient. 
2. Association between factors identified at admission due to fall and 1-year clinical outcome  
 

Statistical Analysis Plan: Risk Factors for Fall and Fracture – A Cohort Study of Fall-Related Factors Obtained in Routine 
Orthopaedic Care 
 
Background: See study 1. 
Objective: Do risk factors identified at the time of the initial fall/fracture show an association with adverse 
events, re-admission, new fractures, or death? The study aims to analyze a standardized set of blood tests, 
orthostatic test, hand grip test and scores for frailty and activity as risk factors for an unfavorable outcome. 
Material and Methods: Data from a 1-year-follow-up will be analyzed regarding readmission, new fractures 
and death. 
Importance: See study 1. 
3. Is calprotectin a more accurate predictor of bacterial infection than conventional testing? 
 
Background: Bacterial infections (pneumonia, urinary tract infections, sepsis) are diagnostic challenges in the 
care of individuals suffering fall-related trauma. Infection as an underlying cause for falls is routinely 
assessed through clinical assessment and conventional blood work with C-Reactive Protein (CRP), white 
blood cell count (WBC) and body temperature at hospital admission. However, when a patient suffers a 
fracture, and in particular when surgically treated, the bodily response to trauma mimics the response to 
an infection, with elevated CRP and subfebrility (8-11). Meanwhile, geriatric patients frequently present 
with atypical signs of infection, such as confusion or absence of fever (12). As many aged individuals 
either have a concurrent infection as cause for their fall or early develop urinary tract infection or 
pneumonia, diagnostic difficulties occur. 
Several biochemical markers have been suggested to be more sensitive and specific markers of infection. 
Elevated levels of CRP and procalcitonin (PCT), two common markers used in clinical settings, can be 
measures after 4 hours. PCT has been proposed to be a more sensitive marker for bacterial infection vs 
non-viral infection than CRP (13). However, it has been criticized for its non-specificity in differential 
diagnostics (14). Another marker, calprotectin, is released from neutrophiles at the time of activation in 
response to bacterial infection, and elevated levels can be measured within a few hours of activation. It has 
been proposed to be a more sensitive and a better prognostic marker in patients presenting with sepsis 
(11) and more sensitive in distinguishing bacterial respiratory infections (10) compared to PCT. However, 
the diagnostic value of calprotectin as an early infection marker in routine orthopaedic care has not yet 
been assessed. 
Objective: To determine whether serum-calprotectin is a more specific test in the early stage of bacterial 
infection concurrent to a fracture, and if the test can improve the diagnostic accuracy.  
Material & Methods: Individuals with hip fractures will be monitored with calprotectin as part of the 
routine blood test at admission and at 3rd day. Correlation between elevated calprotectin and other 
infection markers and any infection diagnosed by conventional means (culture, radiology etcetera) will be 
studied. Prognostic value of calprotectin, PCT vs CRP will be assessed. 
Importance: Through early and correct diagnosis of infection, early treatment can be initiated and more 
severe conditions associated with high morbidity and mortality, such as sepsis, might be prevented. 
Objective and routine testing is particularly important in patients with cognitive impairment, who cannot 
communicate their symptoms. 
4. Is harmful alcohol consumption an underrated cause of falls in the older population? 
 
Background: Excess alcohol consumption might be an underestimated risk factor for fall among the elderly. 
During 2006–2021 in Sweden, an increase in self-reported hazardous alcohol consumption was found in 
age groups 45–64 and 65–84 years. For women >65 yrs, an increase from 3 to 8% was seen, and for men 9 
to 14% (15). Phosphatidylethanol (PEth) is a measurable marker for alcohol consumption with high 
specificity and sensitivity. Accumulation of these phospholipid groups is seen through repeated alcohol 
intake which makes PEth a marker suitable for screening long-term (a few weeks) consumption. PEth is 
routinely analyzed in Swedish laboratories and is used as a routine blood test in psychiatric and cognitive 

Statistical Analysis Plan: Risk Factors for Fall and Fracture – A Cohort Study of Fall-Related Factors Obtained in Routine 
Orthopaedic Care 
 
assessments. To our knowledge, the use of PEth in routine orthopaedic care to evaluate excess alcohol 
consumption has not been described in previous literature. 
Objective: To describe the rate of harmful alcohol consumption in a cohort of individuals ≥65 years who 
need hospital treatment due to fall with or without fracture. 
Material & Methods: By integrating phosphatidylethanol (PEth) into the routine blood tests taken after 
admittance, individuals with harmful consumption or substance use disorder can be better identified. 
Importance: The readiness to identify and offer treatment for individuals with harmful alcohol consumption 
is low. In the acute trauma setting, untreated withdrawal symptoms can impact both somatic and 
psychological function.  
5. How to best depict the functional capacity of an older individual in need of treatment and 
rehabilitation after a fall? 
 
Background: Both the immediate treatment after a fall and the rehabilitation plan are guided by the functional 
demands and physical capacity of the patient. This is often left to plain “eyeballing” based on clinical 
experience. Such subjective methods can lead to unequal provision of healthcare (16). 
Objective: To compare the concordance between simple methods to evaluate the physical and functional 
capacity of an individual over 60 years of age. 
Material & Methods: By scoring of frailty and activity aided by validated score systems, and by measuring 
hand grip strength, the capacity of the individual will be depicted in different aspects. Both the concordance 
of the measurements, and the association of each with 30-day- and 1-year-mortality will be studied. 
Importance: To our knowledge, the value of using these validated instruments in clinical orthopaedic care has 
not been studied previously. With the help of these instruments, the frailest individuals might be identified 
in-patient and tailored further support may be provided. 
6. What are the differences between those with fall only or fall leading to fracture? 
Background: The prognosis and management after a hip fracture is well described in the literature, but little 
is known about the clinical outcome of individuals who “only” fall without a fracture (17). Furthermore, 
there are no standardized follow-up- or rehabilitation schedules up to date. 
Objective: To compare the baseline characteristics during hospitalization and clinical outcome (adverse events, 
re-admission, new fractures or death) of individuals over 60 years of age who fall without vs with a fracture. 
Material & Methods: By using the standardized blood tests, frailty and activity scores measuring hand grip 
strength after a fall, possible baseline differences between individuals who need hospital care due to a fall 
without versus with a fracture will be detected. Adverse events, re-admission, new fractures or death in the 
two groups will be analyzed during the 1st year after the fall. 
Importance: Through knowledge of the outcome after a “simple” fall without a fracture, further standardized 
care models can be established. 
7. Is shrunken pore syndrome associated with 1-year mortality and frailty in patients after a fall? 
Baackground: SPS is a selective filtration defect of the kidneys, which has previously been associated with 
mortality and cardiovascular diseases in selected cohorts (18, 19). SPS was first described in 2015, hence, 
questions regarding prevalence, stability over time and association with adverse outcomes remains to be 
answered. 
Objective: To determine if shrunken pore syndrome (SPS) is associated with frailty and 1-year mortality in 
older patients admitted to Skåne university hospital after a fall. 

Statistical Analysis Plan: Risk Factors for Fall and Fracture – A Cohort Study of Fall-Related Factors Obtained in Routine 
Orthopaedic Care 
 
Material & Methods: Estimated glomerular filtration rate (eGFR) will be assessed in each individual based on 
creatinine and cystatin C. SPS will be defined as an eGFRcysC/eGFRcrea ratio < 0.6. Association between 
SPS, frailty and 1-year mortality will be assessed in the cohort described above. 
Importance: Given the novelty of SPS, studies investigating this syndrome is frontline research.   
8. Is there a correlation between pro-BNP and orthostatic hypotension and 1-year outcome after a 
fall? 
Background: Orthostatic hypotension is a known risk factor for falls and fractures (20). Pro-BNP is a marker 
for diagnosing and monitoring congestive heart failure. These clinically readily available tests have not been 
routinely used in orthopaedic care in Sweden, although the orthogeriatric cohort represents with multiple 
comorbidities including cardiovascular dysfunction. 
Objective: To study the correlation between pro-BNP and the results from orthostatic tests and to describe 
the prevalence of orthostatic hypotension (symptomatic versus asymptomatic) and to study the association 
between biomarkers, blood pressure and 1-year fracture rate and mortality in patients admitted to Skåne 
university hospital for falls and fractures. 
Material & Methods: Pro-BNP will be assessed in each individual and a modified orthostatic test will be 
performed. Association between biomarkers, blood pressure and 1-year fracture rate and mortality will be 
assessed. 
Importance: Further research is needed to determine the value of cardiovascular markers and orthostatic tests 
in clinical settings. Through identification and treatment of orthostatic hypotension and congestive heart 
disease during hospital stay, improvements in the short- and long-term outcome might be done. 
4. Study design 
This is a longitudinal observational cohort study. Study inclusion period starts in February 1st 2023 and 
ends 365 days after the study started. Each individual is followed up for 1 year, calculated from the date of 
admission to in-patient ward. 
 
Inclusion & Exclusion Criteria 
Individuals aged 65 years or older at the time of admission to Department of Orthopaedics at Skåne 
University Hospital in Malmö, Sweden, due to a fall-related trauma will be available for inclusion. 
Only individuals for whom the standard clinical pathway is followed are included. This means that 
individuals who are treated at any other department (including ICU) prior to their care at the Department 
of Orthopaedics are excluded. Those transferred from other hospitals for further care are also excluded. 
Those who suffer trauma through high-energy injury are included but may be separately analyzed. 
Cognitive impairment or other native tongue language are not reasons for exclusion as no active participant 
contribution is requested. 
 
5. Covariates 
Baseline demographic characteristics and clinical measurements are expected to have an influence on 
primary and secondary outcomes, to different degrees. Depending on the specific objective in each study 
described in the study protocol, these data are to be used 1) as covariates for risk analyses, 2) for 
subgrouping individuals, and 3) to adjust for confounders in survival analyses. 
Type of data collected 

Statistical Analysis Plan: Risk Factors for Fall and Fracture – A Cohort Study of Fall-Related Factors Obtained in Routine 
Orthopaedic Care 
 
1. Demographics 
Age/Date of birth 
Sex 
2. Circumstances 
Date of fall, admission & discharge 
Living alone versus not (including assisted living facilities) 
Alcohol (current/previous/no known or suspected excess use) 
Smoking (yes/previous/no) 
Oral health (good/poor/unknown) 
Immobilization >24 h prior to admission (yes/no) 
Readmission (yes/no) 
3. Injury characteristics 
Type of injury (no fracture/fracture type) 
Treatment (surgical versus non-surgical, primary vs reoperation) 
Date of surgery 
Type of surgery/reoperation (internal fixation/arthroplasty/revision surgery or amputation due to 
infection/other) 
4. Comorbidities  
Chronic illnesses or past conditions with sequele (e.g. stroke) before admission versus acute 
conditions are separately assessed through medical records, including the following diagnoses 
according to ICD-codes: C00-C97, C79.5, D50-64, E00-E07, E10.4, E11.4, E10-E14, E20-E21, 
E86.9, F00-F09, G30-G32, F10-F19, F30-F39, G20-G26, G40-G41, G60-G64, G80-G83, H53-
H54, I20-I25, I48, I50, I60-I64, I95.1, J40-J47, K70-K77, M05-M14, M80-M85, N17-N19, R41, 
R42 
In case of hip fracture, following comorbidities are further specified: B20-B24, C81-C96, D80-
D84, E10.6D+E11.6D, L89, L97, R13, I70-I79, E10.5+E11.5 
In case of hip fracture: ASA grade from the anesthesiologist’s preoperative assessment. 
5. Medication 
Medicines before admission are assessed (“at home” -medication) and are classified according to 
ATC-groups, and including the following: A02BC, A10A, A10B, B01A, C03A-C, C03D-E, C07, 
C08-C09, G03XC, H02AB, H03A, H03B, H05A, L01+L04, L02AE, L02BA, L02BG, M01A, 
M03B, M05B, N02A, N03A, N04B, N05A, N05BA+N05CD, N05CF, N06AA+N06AF-G, 
N06AB, N06AX, R06AD+N05BB+N05CM, N06D 
6. Physical assessments during hospital stay 
Body Mass Index (weight/height2) 
Body temperature (twice daily, tympanic measurement) 
Hand grip strength (dominant or uninjured hand, best out of three measurements) 
Orthostatic test (a drop of ≥ 20 mmHg in the systolic blood pressure or a drop of ≥ 10 mmHg in 
diastolic blood pressure are considered significant results, and orthostatic symptoms within 3 
minutes of standing are noted) 
7. Scoring of frailty/activity 
Clinical Frailty Score (1-9 p, status before fall) 
Frändin-Grimby scale (1-6 p, status before fall) 
Cumulative Ambulation Score (0-6 p, status before fall, daily current status) 
ASA-score (1-5 p, before surgery) 
8. Blood samples 
Taken at the time of admission: Albumin, ESR, CRP, WBC with differential count, Ca-ion, 
vitamin D, ALP, TSH, T4, PTH, PEth (hip fracture patients only), estimated eGFR, cystatin C, 
creatinine, potassium, sodium, B12, folate, glucose, pro-BNP (fracture patients only), calprotectin 
(hip fracture patients only), procalcitonin (hip fracture patients only) 
Taken on the 3rd day of admission/post-surgery: Hb, creatinine, potassium, sodium, CRP, WBC, 
calprotectin (hip fracture patients only), procalcitonin (hip fracture patients only) 

Statistical Analysis Plan: Risk Factors for Fall and Fracture – A Cohort Study of Fall-Related Factors Obtained in Routine 
Orthopaedic Care 
 
9. Surgical factors for hip fractures 
Surgery time (from knife start to end, min) 
Surgical method (internal fixation vs arthroplasty) 
Waiting time (from diagnostic X-ray to knife start, hours). 
10. Local surgical complications (early=0-30 days vs late=30-365 days, from date of admission) 
Surgical site infection  
Other surgical wound complication (bleeding/hematoma/increased discharge) 
Implant failure 
Reoperation (reason, type) 
11. Medical complications (early, 0-30 days vs late, 31-365 days, from date of admission) 
Medical complications are assessed at the time of admission, during in-patient care (pre-/post-
surgery) and after discharge from hospital, and include the following: 
UTI, pneumonia (radiological verification – yes/no), DVT (ultrasound verification – yes/no), LE 
(CT-scan verification – yes/no), confusion/delirium (through medical records), acute coronary 
syndrom (unstable angina, STEMI, NSTEMI), acute kidney failure (laboratory tests), pre- and 
post-surgical anaemia (Hb<100 post-surgery), stroke/intracranial hemorrhage (radiological 
verification), atrial fibrillation (ECG), sepsis (defined by Sepsis3). 
12. Readmission 
Date of readmission 
Reason of readmission 
13. Other complications 
New fall 
New fracture 
Death (date of death) 
 
 
Control groups for baseline data: 
- Blood samples = predefined pathological norm values according to local laboratory 
- Hand grip strength classified as weak / normal / strong according to norm values 
- Alcohol consumption: Data based on reading of medical journals exist from an annual cohort of older 
patients with hip fracture in Malmö 2011. Alcohol use measured by the AUDIT questionnaire was 
obtained from a Malmö cohort of 57 hip fracture patients aged 20 to 60 years. Self-reported alcohol 
consumption is available from a Swedish national sample divided in age groups. 
 
6. Outcome measures 
The outcome measures differ between the substudies. The primary outcomes in each substudy are the 
following 
1. Prevention: Prevalence of risk factors associated with falls in an orthopaedic cohort. 
2. Predictors: Association between risk factors identified at admission due to fall and clinical outcome 
within 1 year (complications, readmission, new falls, death) 
3. Infection: Correlation between elevated calprotectin and any infection diagnosed conventionally 
(culture, radiology, etc.) within 1 month. The performance of calprotectin as markers for bacterial 
infection and 1-month mortality compared to procalcitonin, C-reactive protein, ESR, leukocytes and 
temperature. Clinical course during 1 year post-fracture, regarding death, readmission, new cases/fractures 
and adverse events – group comparisons between those who develop early infection and those who do 
not. 

Statistical Analysis Plan: Risk Factors for Fall and Fracture – A Cohort Study of Fall-Related Factors Obtained in Routine 
Orthopaedic Care 
 
4. Alcohol: Prevalence of harmful alcohol consumption in association with a fall injury. Association 
between such and 1-month (confusion, infection) and 1-year complications. 
5. Renal disease: Prevalence of shrunken pore syndrome in association with a fall injury. Association 
between such and 1-month (acute renal failure) and 1-year complications. 
6. Scores for frailty and activity: Correlation between the different instruments and 1-month and 1-year 
mortality. 
7. Study groups 
The study participants will be grouped depending on the specific objectives of each planned study.  
Planned study groups are the following: 
1) All individuals included regardless of presence or absence of fracture 
a. Study 1, 2 & 5: All individuals, no group comparison. 
b. Study 6: Subanalysis of individuals who fall without vs with a fracture (with subsets 
according to type of fracture) 
c. Study 7: Subanalysis of individuals with shrunken pore syndrome vs no shrunken pore 
syndrome. 
d. Study 8: Subanalysis of individuals with elevated proBNP or orthostatic hypotension vs 
with “normal” parameters. 
2) Individuals who obtained a fracture  
a. Study 4: Comparison with historical records of estimated alcohol consumption. 
Subanalysis of individuals with low alcohol comsumption (pETh <0,05 µ/L), 
intermediate consumption 0,05–0,3 µ/L) and high consumption (>0,3 µ/L). 
3) Individuals who obtained a hip fracture 
a. Study 3. Subanalysis of individuals with with or without elevated calprotectin. 
 
8. Study Assessments (Timing) 
The following measurements will be assessed within a 1-year study period, starting February 1st, 2023:  
Frailty: Classification based on the Clinical Frailty Score (CFS) (21). Activity: Classifications based on Frändin-
Grimby scale (22) and Cumulative Ambulation Score (CAS) (23). Blood samples: Albumin, CRP, WBC with 
differential count, ESR, Ca-ion, vitamine D, ALP, TSH, T4, PTH, PEth, pro-BNP, eGFR, cystatin C, 
creatinine, potassium, sodium, B12, folate, glucose, procalcitonin and calprotectin. Temperature: Taken twice 
daily. Orthostatic test: Up until max 3 minutes only. Hand grip strength: Best hand (dominate or the uninjured 
side, in case of arm injury) (24). BMI: Weight/(height)2. 
 
Table 1: Schedule for routine testing.  
Explanations: X=Recommended timing..  
Scheme  
At Admission to 
Dept of Ort. 
Day 1 as In-patient 
Days 3-4 as In-
patient 
Day 5 as In-patient 
– Discharge from 
Ward 
Blood samples 
X 
 
X2 
 
Temperature  
X 
X 
X 
X 
Grip Strength Test1 
 
 
X 
X 
Orthostatic Test1 
 
 
X 
X 
Questionnaires1 (CFS, 
Activity Score, CAS) 
 
X 
X 
X 
Weight/height 
 
 
X 
 

Statistical Analysis Plan: Risk Factors for Fall and Fracture – A Cohort Study of Fall-Related Factors Obtained in Routine 
Orthopaedic Care 
 
1To be assessed only once at any timing. Orthostatic test is only assessed in individuals with injury in upper extremities only. 
2Calprotectin and procalcitonin are to be taken on 1st and 3rd day of admission/or post-surgery, together with other standardized “3rd day-tests”. 
 
9. Time Plan 
2022 – autumn:  
Practical preparations at the wards 
2023 – entire year:  
Inclusion 
2024 – entire year:  
Follow-up period. Analysis of baseline data. Manuscript writing. 
2025 – spring:   
Analysis of 1-year data. 
2025 – autumn:  
Manuscript writing, 1-year data. 
10. Missing Data 
Due to the nature of acute trauma care, we expect that not all individuals receive all the planned 
assessments described in Section 3.  The extent of missing data will be quantified and presented. Possible 
selection bias due to missing data will be addressed by identification of the cause, when available. The 
results might be biased e.g. due to early discharge or death, missing patient co-operation due to confusion 
or dementia. Therefore, individuals are not excluded from analyses due to missing data as a fundamental 
rule. 
11. Statistical Methods 
Descriptive Statistics 
Descriptive statistics will mainly be presented in table format, in means (± standard deviations), medians 
(range) and in proportions (%) depending on the type of data. 
Inferential Statistics 
Statistical methods will vary between studies, depending on the specific objectives. T-test and ANOVA, 
and their alternative non-parametric methods for continuous parameters and Chi-square or Z test for 
proportions will be used to compare characteristics between two or more groups. Different regression 
models, depending on the specific objective, will be applied to assess predictors of outcome measures. 
Survival analyses might be adjusted for confounders, such as significant differences between studied 
groups in age or gender at the baseline. Competing risk models are to be applied in substudies with 
longitudinal design, where mortality is expected to be a competing risk. 
Statistical Significance 
A p-value <0.05 is considered statistically significant. Decreasing statistical strength through smaller 
sample sizes will be taken into consideration when discussing the results. 
 
12. Importance and novelty 
In general, a new generation is suffering frailty, falls and injuries coupled to ageing. We need to explore if 
people born in the 1940’s enter this phase in life due to the same reasons as previous generations, and if 
they meet the same severe consequences of such injuries. Updated knowledge is needed to tailor further 
treatment and preventive measures, thus meeting the need of health care today and in the future. Also, using 
updated methods and technology will improve care and outcome. Better diagnostic tools for infection, renal 
disease and orthostatism can speed up correct diagnosis and specific treatment.  
The quality of the care, treatment and rehabilitation given depends on a proper understanding of the person 
in front of you. Understanding that the person escaping a fall without a fracture may have the same 
pessimistic outcome as the one who suffer a fracture, or that hazardous alcohol consumption is a reality 

Statistical Analysis Plan: Risk Factors for Fall and Fracture – A Cohort Study of Fall-Related Factors Obtained in Routine 
Orthopaedic Care 
 
also in the oldest, will affect how we provide a better care in the future. Likewise, more objective methods 
of evaluate physical capacity to design a valid rehabilitation plan will have clinical importance.   
13. Collaborations 
Skane University Hospital: 
Cecilia Rogmark – principal investigator. MD, PhD, ass. prof. Orthopaedic surgeon. 
Linnea Malmgren – MD, PhD. Geriatrician. 
Helmi-Sisko Pyrhönen – PhD student, MD. Junior physician. 
Viktor Hamrefors – MD, PhD, ass. prof.  Cardiologist. 
Lund University: 
Eva Ekvall-Hansson – PT, PhD, prof. Physioth. 
Karolinska Institute: 
Åsa Magnusson – MD, PhD, lecturer. Specialist in addictive medicine. 
Additional researchers are to be recruited, including PhD students, and a physiotherapist. 
 
14. References 
1. 
Taylor B, Irving HM, Kanteres F, Room R, Borges G, Cherpitel C, et al. The more you 
drink, the harder you fall: a systematic review and meta-analysis of how acute alcohol consumption and 
injury or collision risk increase together. Drug Alcohol Depend. 2010;110(1-2):108-16. 
2. 
Davenport K, Alazemi M, Sri-On J, Liu S. Missed Opportunities to Diagnose and 
Intervene in Modifiable Risk Factors for Older Emergency Department Patients Presenting After a Fall. 
Ann Emerg Med. 2020;76(6):730-8. 
3. 
The National Board of Health and Wellfare. Drugs that can increase risk for fall or 
gastrointestinal bleeding in older - Focus on antidepressants. In Swedish.  2016 March 3, 2022. Available 
from: https://www.socialstyrelsen.se/globalassets/sharepoint-dokument/artikelkatalog/ovrigt/2016-6-
60.pdf. 
4. 
Bae GC, Moon KH. Effect of Osteosarcopenia on Postoperative Functional Outcomes 
and Subsequent Fracture in Elderly Hip Fracture Patients. Geriatr Orthop Surg Rehabil. 
2020;11:2151459320940568. 
5. 
Hjaltadóttir I, Hallberg IR, Ekwall AK, Nyberg P. Predicting mortality of residents at 
admission to nursing home: a longitudinal cohort study. BMC Health Serv Res. 2011;11:86. 
6. 
Krishnan M, Beck S, Havelock W, Eeles E, Hubbard RE, Johansen A. Predicting outcome 
after hip fracture: using a frailty index to integrate comprehensive geriatric assessment results. Age Ageing. 
2014;43(1):122-6. 
7. 
Court-Brown CM, Clement ND, Duckworth AD, Biant LC, McQueen MM. The changing 
epidemiology of fall-related fractures in adults. Injury. 2017;48(4):819-24. 
8. 
Neumaier M, Braun KF, Sandmann G, Siebenlist S. C-Reactive Protein in Orthopaedic 
Surgery. Acta Chir Orthop Traumatol Cech. 2015;82(5):327-31. 
9. 
Neumaier M, Metak G, Scherer MA. C-reactive protein as a parameter of surgical trauma: 
CRP response after different types of surgery in 349 hip fractures. Acta Orthop. 2006;77(5):788-90. 
10. 
Havelka A, Sejersen K, Venge P, Pauksens K, Larsson A. Calprotectin, a new biomarker 
for diagnosis of acute respiratory infections. Sci Rep. 2020;10(1):4208. 
11. 
Larsson A, Tydén J, Johansson J, Lipcsey M, Bergquist M, Kultima K, et al. Calprotectin is 
superior to procalcitonin as a sepsis marker and predictor of 30-day mortality in intensive care patients. 
Scand J Clin Lab Invest. 2020;80(2):156-61. 
12. 
Norman DC. Fever in the elderly. Clin Infect Dis. 2000;31(1):148-51. 
13. 
Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-
reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect 
Dis. 2004;39(2):206-17. 

Statistical Analysis Plan: Risk Factors for Fall and Fracture – A Cohort Study of Fall-Related Factors Obtained in Routine 
Orthopaedic Care 
 
14. 
Tang BM, Eslick GD, Craig JC, McLean AS. Accuracy of procalcitonin for sepsis diagnosis 
in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis. 2007;7(3):210-7. 
15. 
Folkhälsomyndigheten. Alkohol, riskkonsumtion. 2022. 
16. 
Perry DC, Metcalfe D, Griffin XL, Costa ML. Inequalities in use of total hip arthroplasty 
for hip fracture: population based study. Bmj. 2016;353:i2021. 
17. 
Larsson G, Strömberg U, Rogmark C, Nilsdotter A. It was not a hip fracture - you were 
lucky this time - or perhaps not! A prospective study of clinical outcomes in patients with low-energy 
pelvic fractures and hip contusions. Injury. 2019;50(4):913-8. 
18. 
Åkesson A, Lindström V, Nyman U, Jonsson M, Abrahamson M, Christensson A, et al. 
Shrunken pore syndrome and mortality: a cohort study of patients with measured GFR and known 
comorbidities. Scand J Clin Lab Invest. 2020;80(5):412-22. 
19. 
Malmgren L, McGuigan FE, Christensson A, Akesson KE. Impaired selective renal 
filtration captured by eGFR(cysC)/eGFR(crea) ratio is associated with mortality in a population based 
cohort of older women. Sci Rep. 2022;12(1):1273. 
20. 
Johansson M, Rogmark C, Sutton R, Fedorowski A, Hamrefors V. Risk of incident 
fractures in individuals hospitalised due to unexplained syncope and orthostatic hypotension. BMC Med. 
2021;19(1):188. 
21. 
Dillström I, Ahmadul K, Metzner C, Kivipelto M, Boström A, Religa D, et al. Frailty Scale 
can contribute to the evaluation of length of hospital stay and risk of death. Läkartidningen. 2021;118. 
22. 
Central Unit of Occupational Therapists and Physiotherapists. Frändin Grimby Activity 
Scale. In Swedish. 2022. 
23. 
Kristensen M, Hommel A, Jakobsson K. The Cumulated Ambulation Score - Swedish 
Version. 2013. 
24. 
Rikkonen T, Sirola J, Salovaara K, Tuppurainen M, Jurvelin JS, Honkanen R, et al. Muscle 
strength and body composition are clinical indicators of osteoporosis. Calcif Tissue Int. 2012;91(2):131-8.