Hip Fracture in Individuals Under 60 Years of Age: A Prospective Multi-center Study of the Epidemiology, Treatment, Outcome and Patient Satisfaction Regarding Hip Fractures
Conditions: Hip Fractures
Sponsor: Lund University

HFU-60  
 
 
 
 
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Hip Fracture in Individuals under 60 Years of Age. A Prospective Multi-
Center Study of the Epidemiology, Treatment, Outcome and Patient 
Satisfaction Regarding Hip Fractures. 
Study protocol 
 
10 November 2018 
 
 

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Hip fracture in individuals under 60 years of age. A prospective multi-center 
study of the epidemiology, treatment, outcome and patient satisfaction regarding 
hip fractures. 
 
Background:  
Hip fractures are rare in young and middle aged adults, but an increase in incidence is seen in women 
around 50 years (Borgstrom et al. 2006, Karantana et al. 2011). Elderly hip fracture patients 
constitute a quite homogenic group; frail, biologically aged individuals who sustain the fracture due 
to a low-energy trauma, and have a high risk of mortality. The group under 60 years is more 
heterogenic (Zetterberg et al. 1982). Some may have severe diseases, functional limitations or 
alcohol/drug abuse. Others appear healthy and sustain their fracture in high-energy accidents. Some 
studies identify risk factors for hip fractures in younger age groups; hormonal deficiency, low 
cognitive function, smoking and alcohol abuse (Jackson et al. 1992, Karantana et al. 2011). Still, the 
literature is scarce, probably mainly because of the low incidence and the variations in both patient 
characteristics and injury mechanisms.  
Hip fractures can be divided into intracapsular and extracapsular fractures, the latter are treated 
with internal fixation in all patients. For intracapsular fractures, the patient’s age determines the 
type of surgery. In “elderly”, arthroplasty is the treatment of choice in displaced fractures, this can be 
either a total hip arthroplasty or a hemiarthroplasty. “Younger” patients are treated with internal 
fixation after fracture reduction. There is no consensus regarding which age limit should be used, and 
the assessment is complicated by the fact that “biological age” is more relevant than chronological 
age. In practical use, 60, 65 or 70 years are mostly used as the divide. Arthroplasty leads to fewer 
reoperations, and better pain relief and function (at least during the first years). Due to an assumed 
long life expectancy, internal fixation is used in younger individuals, as arthroplasty might lead to 
complications after 10-20 years. The short term risk of complications after internal fixation – 20-50% 
- is usually accepted, as these patients can tolerate secondary surgery with arthroplasty after failed 
fixation. The exact failure rate in younger patients is not known, and they may have better ability to 
heal their fracture than the geriatric population. Younger patients may have better bone quality, 
better blood supply to the femoral neck and head and better nutritional status, which all promotes 
fracture healing. On the other hand, we suspect hip fracture to be a sign of frailty, regardless of the 
patient’s age. 
 
Overall Aim: 
The overall aim is to investigate the epidemiology of hip fractures in younger patients (regarding 
hormonal status, bone density and health profiles in comparison to a standard population), analyze 
of trauma and fracture type, fracture treatment and outcome as well as patient satisfaction during 
two years. 
 
Material and Method: 
The study is a prospective multi-center cohort study of young and middle-aged adults who have 
incurred a hip fracture; describing epidemiology of hip fracture in this age group, clinical results and 

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patient reported outcome during two years following the hip fracture. Patients aged 18 to 59 years, 
who sustain an acute non-pathological hip fracture (defined by ICD-codes S72.00, S72.10 and S72.20) 
and are treated within four weeks at any of the participating hospitals, are invited to participate in 
the study. All patients are invited, regardless of medical, cognitive and functional pre-fracture status. 
The patients’ informed consent is to be obtained before inclusion in the study. 
 
Participating hospitals and approximate annual number of hip fractures in patients under 60 years:  
- 
Skåne University Hospital (Malmö and Lund, Sweden) - 45 
- 
Hvidovre Hospital (Copenhagen, Denmark) - 50 
- 
Odense University Hospital (Odense and Svendborg, Denmark) - 50 
- 
Kolding Hospital – part of Lillebælt Hospital (Kolding, Denmark) - 50  
 
The projected number of included patients in the study is 200 to 300 individuals, which would 
require inclusion during one and a half to two years at all units, depending on the degree of patients 
accepting inclusion in the study. The study is mainly descriptive, wherefore power calculations are 
not considered feasible.  
 
Patients are treated according to the department’s standard rationale. In addition, the study will 
comprise interview and written enquires, blood tests regarding medical, hormonal and nutritional 
status, bone density measurement (DEXA scans), magnetic resonance imaging (MRI) and follow-up 
visits with x-ray and functional assessment. The x-ray controls are standardized to follow the 
standard guidelines of Hvidovre Hospital and Skåne University Hospital, which at most means three 
more x-rays for some patients (in total approximately 1mSv with minimal life time risk of cancer). In 
patients accepting study participation, the researchers are allowed to read hospital files regarding 
pre- and postoperative health status. Patients will be followed for two years after inclusion. Analysis 
of hormonal status, health profile and bone density are compared to a standard population. Risk 
factor analysis will be performed, regarding the risk of sustaining a hip fracture per se as well as the 
risk of complications and re-operations after hip fracture treatment. 
 
As a collaborating but separate study with a separate study protocol, bone biopsies taken intra-
operatively at participating Danish departments will be analyzed regarding the micro- and ultra 
architecture of trabecular and cortical bone by means of nano-CT and micro-CT imaging techniques. 
 
 
Study inclusion and informed consent 
The patient will, during admission, be invited to participate in the study by a medical doctor, nurse or 
physiotherapist associated to the study who will provide information regarding the study orally and 
in written form. The patients are usually bedridden so the interview is planned at the ward in a 
private room or by closed curtains. The patient can choose to have a relative or other person of 
choice present if so wanted. Informed consent to participate in study 5 shall be obtained prior to 
surgery. For study 1 to 4, informed consent given post-operatively will be accepted for inclusion if 
not already obtained prior to surgery together with consent to participate in study 5. The patient will 
at most have 24 hours to review the information to be included in study 5, but at least one hour of 
reflection will be given for study 1 to 5.  
 

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Follow-up scheme  
  
Pre-
operatively Surgery Day 1-10 
6 weeks 
4 months 1 year 
2 years 
 
 
Hospital 
Letter or phone 
call**** 
Visit 
Visit 
Visit 
Study inclusion 
(X) 
  
X 
  
  
  
  
Blood tests 
X* 
  
X* 
  
  
  
  
Surgery 
  
X 
  
  
  
  
  
Bone biopsy** 
 
X 
 
 
 
 
 
Visit 
  
  
  
  
X 
X 
 X 
PROM 
 
 
X 
(prefracture 
recall) 
X 
X 
X 
X 
Questionnaire/ 
interview 
 
 
X 
 
X 
X 
X 
Functional tests 
  
  
X 
  
X 
X 
  
X-ray 
X 
  
X 
  
X 
X 
X 
MRI (MARS), if 
cervical 
fracture*** 
 
 
X 
 
 
X 
 
X 
 
 
DEXA scan  
  
  
X***** 
  
  
 
X  
* Standard screening blood test shall be taken as early as possible, as they may be disturbed by 
trauma and surgery. 
** Bone biopsy taken at Danish departments. 
*** MRI MARS performed at Skåne University Hospital initially. 
**** Phone call to patients not responding to letter. 
***** DEXA no. 1 should be performed within the first month after trauma 
 
Functional assessment is to be done on the day before discharge from the ward or the 10th day 
postoperatively, which day shall be noted in the protocol. Functional assessment is performed in-
ward, at follow-ups at 4 months and 1 year post-operatively, not at the 2-year follow-up. 
 
MRI with metal artefact reduction technique (MRI MARS) is performed in patients with a femoral 
neck fracture, dislocated and non-dislocated treated with internal fixation, to assess signs of femoral 
head necrosis. MRI MARS is performed early postoperatively and at follow up visits at 4 and 12 
months postoperatively. In Malmö, MRI MARS is performed using Siemens commercially available 
standard sequences (MARS + VAT) for metal reduction imaging together with intravenous gadolinium 
contrast. 
 
Patients not meeting for follow-ups will be called upon three times, thereafter they are contacted by 
phone, to complete the interview normally performed at the visit. 
 
Assessment of radiographs will be performed using standardized definitions, by one of the local 
researchers from each of the departments and SSR will co-assess all radiographs.  
 
Recorded data  
Basic demographic indicators: 

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Gender 
Age 
Type of living (alone, together with someone else, institution, lacks permanent residence) 
Extent of work (full time, part time, sick leave, disability pension, not working for other reason) 
 
Health indicators: 
BMI 
Comorbidity (ASA and Charlson) 
History of previous fractures – patient recall and medical files 
Hospital admission during the year preceding the hip fracture 
Use of particular medication during 5 years leading up to the fracture 
Use of tobacco, alcohol or other recreational drugs – prefracture –AUDIT- and DUDIT-questionnaire. 
Physical activity level 
Bone mass density – DEXA scan 
Regular menstruation 
Laboratory blood tests:  
Test: 
 
 
 
Purpose: 
- hemoglobin, leucocytes w. differential count,  
normal blood samples and pathological 
platelet count, erythrocyte sedimentation rate  
and/or C-reactive protein (a.s.a.p. after trauma) 
- electrolytes (Na+, K+), creatinine  
 
renal function 
- total calcium + albumin,  
 
 
hypo-/hyperparathyroidism 
parathyroid hormone (a.s.a.p. after trauma) 
 
- 25-hydroxyvitamin D  
 
 
vitamin D deficiency 
- alkaline phosphatase, INR 
 
 
bone metabolism, liver disease 
- TSH, T3, T4 
 
 
  
thyroid disease 
- testosterone (men) / estradiol (women) 
 
hypogonadism 
- tissue transglutaminase antibody 
  
coeliac disease 
 
Regarding the injury: 
Information about the accident – mechanism of injury, other injuries apart from hip fracture. 
Fracture type classification according to Garden (displaced vs. undisplaced) and AO – classified by 
local researcher, not surgeon. 
Type of surgery and implant. 
 
Outcome: 
Patient reported outcome measure (PROM): 
- EQ5D (3 level), EQ-VAS, Oxford hip score – prefracture recall, 6 wks, 4, 12 and 24 months. 
- VAS-psr (pain, satisfaction, rehabilitation) – 6 wks, 4, 12 and 24 months. 
- New mobility score (NMS) – prefracture recall, 4, 12 and 24 months.  
Functional outcome – Timed up and go (TUG), 10 meter walking test (10MWT) and hand grip 
strength test (HGS) – in-ward, 4 and 12 months. 
Clinical outcome, complications and reoperations. 
Radiological outcome - definition of radiological outcome and complications in separate appendix. 

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Avascular necrosis is assessed clinically and radiologically by MRI and X-ray and findings are graded 
according to predefined definitions, sorting patients into one of three categories: no AVN, possible 
AVN, manifest AVN.  
 
 
Ethical considerations 
The study has been approved by ethical committees in Sweden (Regionala etikprövningsnämnden 
Lund (Diarienummer: 2015/28)) and Denmark (Videnskabsetisk Komité for Region Syddanmark 
(Projekt ID: s-20150137)), as well as permission granted to create a computer database on the 
subjects in accordance with the Swedish Personal Data Act (Samråd KVB, Region Skåne (Ärendenr 202-
14) and the Danish Data Protection Agency (Datatilsynet for Syddanmark (Journal nr. 15/51398). Study 
subjects will be included in the study only after giving their informed consent to participate in the 
study. The study will be conducted in accordance with the Helsinki Declaration(World Medical 2013). 
  
Data  
The Danish Data Protection Agency (Datatilsynet) has been notified regarding this project and the 
Danish law about personal data will be met, as well as the Swedish Personal Data Act. The following 
data can be acquired from the patients’ medical records:  
• Type of living  
• Work level  
• BMI  
• Co-morbidity – ASA and Charlson 
• History of previous fractures – patient recall and medical files  
• Hospital admission during the year preceding the hip fracture  
• Use of particular medication – prefracture – patient recall and medical files  
• Information about the accident – mechanism of injury, other injuries apart from hip 
fracture.  
• Fracture type classification  
• Type of surgery and implant  
• Radiological outcome  
• Complications  
• All blood test results  
• MR results  
• DEXA results  
 
This information as well as the information from patient interview will give a better understanding of 
the patients’ health status.  
 
Budget, strategy, financial support 
There are no financial supports or donations for this study in Denmark, but a grant of 100.000 SEK 
has been given for the Swedish part by a local fund (Kockska stiftelserna) for secretary salary. Funds 
have been applied for to pay for costs associated to the project (e.g. project nurse, project 
physiotherapist, travel between involved departments, etc). 

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Project co-workers 
Skånes Universitetssjukhus / Lunds universitet 
Cecilia Rogmark – MD, PhD, Senior Consultant – Orthopaedic department – project leader 
Sebastian Strøm Rönnquist – MD, PhD student – Orthopaedic department– project secretary 
Kristina Åkesson – MD, PhD, Professor – Orthopaedic department 
Felix Narin – Physiotherapist – Orthopaedic department 
 
Hvidovre Hospital 
Henrik Palm – MD, PhD, Senior Consultant – Orthopaedic department – local project leader 
Morten Tange Kristensen – Physiotherapist, PhD – Department of Physiotherapy 
Jens-Erik Bech Jensen – MD, PhD, Senior Consultant – Department of Endocrinology 
 
Odense Universitets Hospital 
Carsten Fladmose Madsen – MD, PhD, Consultant – Orthopaedic department – local project leader 
Søren Overgaard – MD, DmSc, Professor, Head of Research – Orthopaedic department 
Trine Torfing – MD, PhD, Senior Consultant – Radiology department 
 
Sygehus Lillebælt Kolding 
Bjarke Viberg – MD, PhD, postdoc – Orthopaedic department– local project leader 
Lis R. Andersen – MD, Senior Consultant – Orthopaedic department 
 
 
 
References:  
Borgstrom F, Johnell O, Kanis J A, Jonsson B, Rehnberg C. At what hip fracture risk is it cost-effective 
to treat? International intervention thresholds for the treatment of osteoporosis. Osteoporosis 
international : a journal established as result of cooperation between the European Foundation for 
Osteoporosis and the National Osteoporosis Foundation of the USA 2006; 17 (10): 1459-71. 
Jackson J A, Riggs M W, Spiekerman A M. Testosterone deficiency as a risk factor for hip fractures in 
men: a case-control study. The American journal of the medical sciences 1992; 304 (1): 4-8. 
Karantana A, Boulton C, Bouliotis G, Shu K S S, Scammell B E, Moran C G. Epidemiology and outcome 
of fracture of the hip in women aged 65 years and under: A COHORT STUDY. Journal of Bone & Joint 
Surgery, British Volume 2011; 93-B (5): 658-64. 
World Medical A. World medical association declaration of helsinki: Ethical principles for medical 
research involving human subjects. JAMA 2013; 310 (20): 2191-4. 
Zetterberg C H, Irstam L, Andersson G B. Femoral neck fractures in young adults. Acta Orthop Scand 
1982; 53 (3): 427-35.