ORIGINAL ARTICLE

Screening for osteoporosis following non-vertebral fracturesin patients aged 50 and older independently of gender or levelof trauma energy—a Swiss trauma center approach

Christoph Hemmeler1 & Sabrina Morell2 & Felix Amsler3 & Thomas Gross2

Received: 27 December 2016 /Accepted: 3 April 2017# International Osteoporosis Foundation and National Osteoporosis Foundation 2017

AbstractSummary Screening in a standardized manner for osteoporo-sis in non-vertebral fracture patients aged 50 and older inde-pendently of both gender and level of trauma energy yieldedthe indication for osteoporotic therapy for every fourth malehigh-energy fracture patient.Purpose This study aimed to identify the rate of osteoporosisin patients of both genders after fracture independently of theunderlying level of trauma energy.Methods A random cohort of patients aged 50 or older withnon-vertebral fractures participated in a standardized diagnos-tic protocol to evaluate the indication for treatment of osteo-porosis (number needed to screen (NNS)). Univariate andmultivariate analysis as well as correlation testing were per-formed to determine statistical relationships. Significance wasset at p < 0.05.Results Of 478 fracture patients with a mean age of69.3 ± 11.8 years, 317 (66.3%) were female and 161(33.7%) male. One hundred nineteen patients (24.9%)sustained high-energy fractures (HEFs) and 359 (75.1%)low-energy fractures (LEFs). Twenty-eight percent of malesand 47% of females qualified as osteoporotic in densitometry

(dual-energy X-ray absorptiometry (DXA)), resulting in aNNS of 2.1 for women and 3.6 for men. The indication fortreatment of osteoporosis increased to an NNS of 1.5 for fe-males and 2.4 for males if the fracture risk assessment tool(FRAX) was included in the diagnostics (DXA and FRAX).With regard to the energy of trauma, the NNS for treatmentfollowing DXA and FRAX was 1.5 for LEF and 2.9 for HEF.Subgroup analysis revealed that HEF males within thedecennia 50+ and 80+ had an NNS of around 3, i.e., compa-rable to females and about twice as high as LEF patients.Conclusions These preliminary findings appear to confirmthe pragmatic approach to screening in a standardized mannerfor osteoporosis in all non-vertebral fracture patients aged 50and older—independently of both gender and level of traumaenergy.

Keywords Osteoporosis . Fracture . Densitometry . Fracturerisk assessment tool . Gender . Trauma energy

Introduction

The importance of adequate diagnostics and osteoporosis ther-apy in the context of fracture treatment is being increasinglyacknowledged not only in the literature but also in daily or-thopedic practice [1, 2]. Osteoporosis results in an increasedrisk of fragility fractures [3]. These fractures are associatedwith substantial pain and suffering and frequently require op-erative stabilization. Despite all efforts, they often result indisability, increased mortality, and substantial costs to society[4]. In 2014, 74,000 cases in Switzerland cost an estimated1558 million Swiss Francs [5]. In the USA, two million fra-gility fractures occurred in 2005 with costs of $17 billion. Thisis expected to rise by 50% by 2025 [6]. Following an osteo-porotic fracture and depending on age, the risk of a subsequent

Electronic supplementary material The online version of this article(doi:10.1007/s11657-017-0334-3) contains supplementary material,which is available to authorized users.

* Thomas Grossthomas.gross@ksa.ch

1 Department of Rheumatology, Cantonal Hospital, Tellstr.1,CH-5001 Aarau, Switzerland

2 Department of Traumatology, Cantonal Hospital, Trauma Unit,Tellstr.1, CH-5001 Aarau, Switzerland

3 Amsler Consulting, Gundeldingerrain 111,CH-4059 Basel, Switzerland

Arch Osteoporos (2017) 12:38 DOI 10.1007/s11657-017-0334-3

fracture varies between 9 and 30% in women and 10 and 26%in men [6, 7].

With regard to osteoporotic fractures, most studies andguidelines focus on reduced bone mineral density in femalesfollowing low-energy trauma (measured by dual-energy X-ray absorptiometry (DXA)) as an indicator of a patient’s sub-sequent risk of further fractures.

The implicit assumption is that fractures in male patients orthose resulting from high-energy trauma (HEF) do not have anelevated fracture risk [8, 9]. Consequently, in clinical practice,male and/or HEF patients rarely undergo osteoporotic diag-nostics with the potential consequence of insufficient second-ary prevention and misinterpretation of the socioeconomicimpact of osteoporotic fractures [4, 5].

On the other hand, recent data indicate reduced bone min-eral density and an increased rate of osteoporosis even in oldermen and following HEF. For example, the GeelongOsteoporosis Study demonstrated that women over 50 yearswho sustained HEF had significantly reduced bone mineraldensity compared to a control cohort of the population [9].Mackey found a positive correlation with subsequent fracturesfor both HEF and LEF in both women and men over 65 [8].As a consequence, even though almost all studies on the topicfocused on elderly women and/or specific fracture regions,there is evidence to suggest that diagnostics for osteoporosismight be very worthwhile after high-energy fractures [8, 9]and for males [10]. To exacerbate the situation, the exact def-initions of HEF and LEF differ between studies, if cited at all[11, 12]. Further, the age threshold for recommendation forosteoporosis diagnostics differs significantly between nationaland specialty guidelines, e.g., followingmenopause or startingat 50 or 65 years of age depending also on gender [13–15].

With this in mind and as a teaching hospital, we decided toscreen all fracture patients aged 50 or older for osteoporosis aspart of daily clinical routine, independently of gender andtrauma energy, and to recommend therapy if indicated. Withthis simple cutoff, we tried to keep the organizational barrierfor diagnostics low. On the other hand, we were interested ininvestigating this apparently aggressive screening for osteo-porosis in detail with the aim of finding out which patients andfracture constellations would profit from a standardizedprocedure.

Therefore, the primary objective of this investigation inpatients 50 years and older who had sustained non-vertebralfractures was to identify the effective rate of cases in ourdepartment in which osteoporotic therapy would be required.The resulting number needed to screen (NNS) was differenti-ated for the specific risk groups: male versus female, HEF vs.LEF, and between stratified age groups (decennia). Given thefinding that many professionals and laymen still only usepathologic osteodensitometry (DXA) values to define osteo-porosis and identify the need to initiate osteoporotic therapy,we additionally aimed to discover how many more cases in

our cohort received therapy if fracture risk assessment tool(FRAX) scoring was performed in addition to DXA.

Methods

Between March 2012 and November 2014, patients of bothgenders aged 50 or older and hospitalized in the trauma unit ofthe hospital for non-vertebral fractures were prospectively in-vestigated for osteoporosis following a standardized protocolapproved by the Cantonal Ethics Board (EK2013/036;NCT02157753). The teaching hospital (1 of 12 Swiss highlyspecialized major trauma centers) treats >800 fracture patientsa year on a non-ambulatory basis at its trauma unit. Of those,about 60% are aged 50 or older, 70% of the latter being oper-ated on, and all of them subject to the described procedure.

Bone mineral density (BMD) was measured using a stan-dardized procedure with DXA for the above patients as part ofthe outpatient procedure (S/N 82833, Hologic Inc., DiscoveryW, Waltham, MA, USA). The measurements were performedby specifically trained and certified operators at the proximalfemur (neck and total), the lumbar spine, and the distal third ofthe radius. Physicians interpreting DXA scans were fully cer-tified and had extensive experience in this area. The lowestvalue obtained was used for the analysis.

Patients were categorized as having osteopenia (a DXA Tscore of −1.1 to −2.4) or osteoporosis (a DXA T score of≤−2.5) [16]. Those with a T score ≤-2.5 and hip or vertebralfracture without adequate trauma were directly considered fortreatment.

For cases of osteopenia, FRAX scoring was additionallyperformed drawing upon the guidelines of the SwissAssociation Against Osteoporosis (SVGO) 2010 and basedon DXA and FRAX; the absolute risk of fracture in each agedecennia was then estimated [16]. As a reference, the latestNational Osteoporosis Foundation (NOF) guidelines 2014give a low bone mass (T score between −1.0 and −2.5 at thefemoral neck or lumbar spine) and a 10-year probability of ahip fracture ≥3% or a 10-year probability of a majorosteoporosis-related fracture ≥20% [15].

In addition to the analysis of basic medical records, a stan-dard questionnaire to record risk factors for osteoporosis wasdistributed to enable further evaluation using theWorld HealthOrganization (WHO) online FRAX. We used the algorithmfor Switzerland to estimate the 10-year fracture risk for indi-vidual patients. Registered risk factors of osteoporosis werepositive family history of femoral neck fracture, smoking,current intake of alcohol, cortisone or aromatase inhibitors,low body mass index (<20 kg/m2), decrease of body height(>3 cm), COPD, IBD, signs of hypogonadism, or rheumatoidarthritis. On the basis of these outcomes for each option, i.e.,DXA only or DXA combined with FRAX, the patients werestratified into those having osteoporosis (yes/no) and those

38 Page 2 of 9 Arch Osteoporos (2017) 12:38

qualifying for treatment (treatment indication yes/no).Furthermore, an extensive laboratory workup was performedincluding values for liver and kidney function, erythrocytesedimentation rate, calcium, 25-hydroxy vitamin D, phos-phate, albumin, thyroid-stimulating hormone (TSH), parathy-roid hormone (PTH), as well as a hemogram. Evaluation ofthese measurements, including FRAX, was conducted in astandardized manner by a specialist from the Department ofRheumatology (C.H.). A subsequent therapy recommendationwas forwarded to the family doctor and the orthopedic sur-geon in charge for each patient.

Data for this investigation were collected by a trained studynurse (S.M.), specifically evaluating parameters such as low-energy vs. high-energy trauma or the age unadjusted and ad-justed Charlson scores [17, 18] to determine patients’ comor-bidities in a standardized manner. Missing data were obtainedby contacting patients and/or primary care physicians. Withregard to the energy of trauma, LEF was defined as falls fromstanding height or less or stairs ≤50 cm high or injuriesresulting from walking velocity or less. In contrast, HEF wasdefined as falls from greater than standing height or stairsmore than 50 cm high or with a velocity >5 km/h (modifiedaccordingly [8, 9]). Standard stratification was undertaken bythe study nurse based on patients’ or independent observers’descriptions of the relevant trauma mechanism as evaluated inthe emergency department at the time of hospital admission.

With regard to age, the decennials 50–59 (50+), 60–69(60+), 70–79 (70+), and 80 years of age and older (80+) wereinvestigated separately. NNS to find a patient with osteoporo-sis confirmed by densitometry (DXA) or with the indicationfor treatment following additional FRAX (DXA and FRAX)was calculated and presented with 95% confidence intervals.

Statistical analysis

Chi-squared tests were used to compare binary variables andanalysis of variance (ANOVA) to compare mean values ofcontinuous variables. Correlations between categorized oste-oporosis diagnosis and laboratory values were calculatedusing non-parametric Spearman correlations. Forward step-wise multivariate logistic regression analysis was performedto identify independent predictors of the indication for treat-ment of osteoporosis. The significance of each variable wasassessed using the likelihood ratio test. Odds ratios (OR) and95% confidence intervals (CI) were calculated. All p valuesare two-tailed.

Results

During the study period, 849 patients qualified for inclusion.Three hundred seventy-one patients (43.7%) did not undergothe standard procedure. The reasons for excluding patients

were not available for every single case, but major reasonswere as follows: The stipulated process was not followedthrough; screening for osteoporosis was performed at a differ-ent institution, mostly with DXA only; participating patients,their next of kin, care, and or nursing homes or doctors did notagree to the procedure. Detailed univariate and multivariatecomparison of the study cohort with the group of excludedpatients is given in supplemental Tables A and B. Overall,excluded patients more often lived in a nursing home (i.e.,not in their own homes) and more often underwent conserva-tive therapy of their fracture. No significant differences werefound between groups with regard to gender, length of hospi-tal stay, or inclusion rate over the study period.

A total of 478 patients aged 50 or older with non-vertebralfractures hospitalized at the trauma unit of the CantonalHospital Aarau were investigated for osteoporosis.

Characteristics of the study cohort are given in Table 1.Two hundred two fractures were localized in the lower ex-tremities, 203 in the upper extremities; all other cases involvedthe torso or multiple fractures.

At the time of injury, 5.2% of cases were known to haveosteoporosis.

The mean interval between the first clinical visit after frac-ture and subsequent DXA performed according to the protocolwas 71 ± 40 days.

Overall, 13.8% of examined patients revealed normal Tscore values (Table 2). In comparison to a DXA osteoporosisrate of 40.6%, the indication for treatment increased to 59.4%if FRAX was included. The resulting NNS to identify indica-tions for osteoporotic treatment was 2.5 for DXA only com-pared to 1.7 for the combined use of DXA and FRAX.

In univariate analysis in relation to gender, both men andwomen presented with normal T values (19.3% [n = 31] and11.0% [n = 35], respectively) in less than one fifth of cases.Given a total rate of 28% of male and 47% of female fracturesqualifying as osteoporotic in DXA, the resulting NNS was 2.1for women and 3.6 for men. The indication for treatment ofosteoporosis rose to 41% in male and 69% in female fracturepatients if FRAX screening was included. The overall NNSfor recommendation of treatment based on combined DXAand FRAX risk assessments was 1.5 for women and 2.4 formen.

With regard to the energy of injury, 24.9% of patients suf-fered high-energy trauma. These HEF patients were more of-ten male, younger, healthier (Charlson), and presented moreoften with multiple fractures and a shorter length of stay thanlow-energy trauma patients (all p < 0.001; Table 1).

Operative fixation rate was comparable between groups.Detailed analysis revealed significantly more multiple frac-tures and, at the same time, less radial and femoral fracturesin high-energy trauma patients (Table 2). In both LEF (10.0%)and HEF (25.2%), only a minority of patients demonstratednormal T score values (Table 2).

Arch Osteoporos (2017) 12:38 Page 3 of 9 38

Given a rate of 46.2% LEF and 23.5% HEF presenting asosteoporotic in DXA, the resulting NNSwas 2.16 for LEF and4.25 for HEF, respectively. The indication for treatment ofosteoporosis rose to 67.6% in LEF and 34.4% in HEF ifFRAX screening was included. The overall NNS for recom-mendation of treatment based on combinedDEXA and FRAXwas 1.5 for LEF and 2.9 for HEF.

Combined analysis, which allowed for the influences ofgender and trauma energy, revealed that male HEF patientswithin the decennia 50+ had an NNS of 3 (13 patients out of39) and those who were 80+ of 2 (3 patients out of 6) for thetreatment of osteoporosis (DXA and FRAX), i.e., similar tofemale patients and about twice as high as LEF patients.Figures 1 and 2 illustrate these findings in comparison toage, gender, and trauma energy specific prevalence data forosteoporosis from Sweden [21].

In contrast, male HEF patients of the decennia 60+ to 70+had a conspicuously much lower risk in terms of treatmentneeds (NNS 15 (1 patient out of 15) and 11 (1 patient out of11), respectively).

Overall, increasing age was associated with a higher rate ofosteoporosis (p = 0.018). High significance (p < 0.001) wasfound for both, for DXA stratification only (mean63.5 ± 9.5 years normal, 66.1 ± 10.2 years osteopenic,74.8 ± 11.8 years osteoporotic) and for the combined assess-ment to indicate treatment using DXA and FRAX (treatmentindicated 70.9 ± 12.2 years/treatment not indicated66.9 ± 10.7 years). Stratified for decennial age groups begin-ning at the age of 50 years (Table 3), it was found that belowthe age of 80, the NNS for the treatment of osteoporosis (DXAand FRAX) in high-energy fracture patients was about twiceas high as for the low-energy group (e.g., for patients 50+years of age 3.1 in HEF vs. 1.4 in LEF).

In patients of 80 years and older, this difference related totrauma energy almost disappeared (Fig. 2). Including gender,the overall NNS of 1.5 for the treatment of osteoporosis (DXAand FRAX) in female patients (Table 3) remained almost un-changed over all decennia in contrast to male patients overallNNS of 2.4 demonstrating a peak of 4.8 at the decennium 70+and arriving at the NNS for women at 80+ (Fig. 2).

Detailed univariate analysis of lab values or specific riskconstellations such as hyperparathyroidism or smoking didnot reveal any indicative correlations with the indication forthe need to treat osteoporosis (all rho < 0.2; data not shown).

In multivariate analysis using a model that included thevariables identified as significant by univariate analysis,namely LEF, female gender, and the fracture regions femur,pelvis, and radius, they were found to account for 23.3% ofvariance for the need of osteoporotic therapy (Table 4). In alogistic regressionmodel including only age, gender, and trau-ma energy, age was not significant and female gender togetherwith low-energy trauma explained 15.9% of the variance forthe need for osteoporotic therapy. In this model, no interactionT

able1

Characteristicsof

thestudycohort(n

=478)

Total

Sex

Traum

a

Male(N

=161)

Female(N

=317)

pLow

energy

(N=359)

Highenergy

(N=119)

p

Genderfemale

317(66.3%

)–

––

269(74.9%

)48

(40.3%

)<0.001

Gendermale

161(33.7%

)–

–90

(25.1%

)71

(59.7%

)

Low

-energytrauma

359(75.1%

)90

(55.9%

)269(84.9%

)<0.001

––

–High-energy

trauma

119(24.9%

)71

(44.1%

)48

(15.1%

)–

–

Age

(attim

eof

DXA)

69.3±11.8

65.7±11.2

71.1±11.6

<0.001

71.2±11.6

63.7±10.3

<0.001

Age

unadjusted

Charlsonscore

0.68

±1.23

0.63

±1.11

0.71

±1.29

0.489

0.8±1.31

0.32

±0.82

<0.001

Age

adjusted

Charlsonscore

3.79

±1.68

3.47

±1.59

3.95

±1.71

0.003

4.03

±1.73

3.04

±1.27

<0.001

Operativ

efracture

fixatio

n423(88.5%

)142(88.2%

)281(88.6%

)0.886

320(89.1%

)103(86.6%

)0.445

Hospitallengthof

stay

9.9±7.8

11.4±8.4

9.2±7.3

0.004

9.1±6.6

12.5±10.2

<0.001

DXAosteoporosis

194(40.6%

)45

(28.0%

)149(47.0%

)<0.001

166(46.2%

)28

(23.5%

)<0.001

Indicatio

nfortherapyDXAandFR

AX

284(59.4%

)66

(41.0%

)218(68.8%

)<0.001

243(67.7%

)41

(34.5%

)<0.001

DXAosteodensitometry,F

RAXfracture

risk

assessmenttool

38 Page 4 of 9 Arch Osteoporos (2017) 12:38

effect could be found between gender and trauma energy(p = 0.545).

Discussion

To our knowledge, this prospective investigation is the firstclinical evaluation with the specific objective of systematical-ly screening fracture patients aged 50 or older in a simplemanner for osteoporosis, independently of gender and the lev-el of trauma energy involved. Subsequently, therapy was rec-ommended to patients if indicated based on a standard proto-col. The primary objective was to identify the actual rate ofcases (NNS) requiring osteoporotic therapy following non-vertebral fractures. The secondary objective was to furtherstratify the resulting NNS for the major risk groups of maleversus female, HEF vs. LEF, and age decennia.

First, the overall results are in line with those published inmore recent literature to show that female gender, low-energyfracture, and specific fracture regions (such as the femur) arethe main indicators of osteoporosis [19].

Second, we found an impressively low overall NNS todetect patients needing osteoporotic therapy, independentlyof gender or trauma energy and in all age groups over 50.Even the subgroup demonstrating the lowest efficacy in theinvestigation, i.e., HEF male patients aged 60–70 yielded anNNS of 15. Of course, one can argue that for 60+ and 70+male, this NNS corresponds to known osteoporosis preva-lence data such as those from Sweden [21]. But for all othergroups under investigation, demonstrated NNS were consid-erably lower than expected from prevalence data. In addition,such numbers have to be viewed in the context of the fact that,for example, for patients taking statins as the most widelyaccepted standard prevention after stroke, there is an NNS>30 [20]. Against this background, it appears worthwhile tosystematically screen fracture patients aged 50 or older forosteoporosis, independently of gender and the level of traumaenergy involved.

Third, this study revealed an indication for osteoporosistreatment in a surprisingly high number of HEF cases: Thecorresponding NNS following HEF was 2.9 vs. 1.5 in LEF.

Fig. 2 Relationship of NNS and age in comparison to level of traumaenergy and population of males and females for osteoporosis fromSweden

Fig. 1 Relationship of NNS and age in comparison to gender, level oftrauma energy, and population for osteoporosis from Sweden

Table 2 DXA and FRAX results according to gender and trauma energy (N = 478)

Trauma energy Gender Normal Tscore ≥−1

Osteopenia T score −1.1 to −2.5 Osteoporosis Tscore <−2.5

Total DXA alone DXA and FRAX

No indication fortreatment (FRAX)

Indication fortreatment (FRAX)

NNS 95% CI NNS 95% CI

Low Male 10 (11.1%) 32 (35.6%) 17 (18.9%) 31 (34.4%) 90 (100%) 2.90 2.26–4.06 1.88 1.57–2.32

Female 26 (9.7%) 48 (17.8%) 60 (22.3%) 135 (50.2%) 269 (100%) 1.99 1.78–2.26 1.38 1.28–1.49

Total 36 (10%) 80 (22.3%) 77 (21.4%) 166 (46.2%) 359 (100%) 2.16 1.95–2.43 1.48 1.38–1.59

High Male 21 (29.6%) 32 (45.1%) 4 (5.6%) 14 (19.7%) 71 (100%) 5.07 3.45–9.56 3.94 2.82–6.56

Female 9 (18.8%) 16 (33.3%) 9 (18.8%) 14 (29.2%) 48 (100%) 3.43 2.38–6.13 2.09 1.61–2.96

Total 30 (25.2%) 48 (40.3%) 13 (10.9%) 28 (23.5%) 119 (100%) 4.25 3.21–6.29 2.90 2.33–3.86

Total Male 31 (19.3%) 64 (39.8%) 21 (13%) 45 (28%) 161 (100%) 3.58 2.87–4.76 2.44 2.06–2.99

Female 35 (11%) 64 (20.2%) 69 (21.8%) 149 (47%) 317 (100%) 2.13 1.90–2.41 1.45 1.35–1.57

Total 66 (13.8%) 128 (26.8%) 90 (18.8%) 194 (40.6%) 478 (100%) 2.46 2.22–2.76 1.68 1.57–1.82

NNS number needed to screen, DXA osteodensitometry, FRAX fracture risk assessment tool

Arch Osteoporos (2017) 12:38 Page 5 of 9 38

With the exception of a few high-risk constellations, manyauthors and guidelines appear to keep the approach to osteo-porotic fractures very limited by making the diagnosis depen-dent on low-energy trauma only [5, 21]. In this way, onlypatients without a so-called adequate trauma [22] are investi-gated for osteoporosis. This practice seems astonishing giventhe lack of evidence as to where the exact line is between low-energy and high-energy trauma [23, 24]. Additionally, studieshave questioned the assumption that a healthy bone will notbreak on low-energy impact [25, 26]. In fact, even a fall fromstanding height may generate enough energy to fracture anormal bone [27]. There is good evidence that both low-trauma and high-trauma fractures are strongly associated withlow BMD and an increased risk for subsequent fractures inolder women and men and should therefore be included inobservational studies [8]. Several authors have suggested thatany prior fracture whether a high-trauma or low-trauma onemay indicate underlying skeletal fragility and an increasedrisk for future fracture [9, 19]. The authors of a meta-analysis including randomized fracture prevention trials

summarized that the potential benefits of treatment for an in-dividual patient would be best described for all non-vertebralfractures, not just a subset such as low-trauma fragility frac-tures [28]. Against this background, it is our opinion that ourprospective cohort data on non-vertebral fracture patients aged50 or older argue for an aggressive screening approach forosteoporosis, independently of the level of trauma energy in-volved. In spite of these strong arguments, the qualifyingstatement must be made that to date, evidence on the effec-tiveness of antiosteoporosis treatment in patients with high-trauma fractures is missing.

Fourth, the observed difference in NNS between men andwomen of the same age or fracture type was less than gener-ally expected; for example, the NNS was about 5 in 70+ year-old male in comparison to a NNS of about 1.5 in 70+ female.

The risk for osteoporosis in males continues to beunderestimated by both the population and bymedical doctorswith the consequence that male fracture patients less common-ly undergo any diagnostic tests for osteoporosis [29, 30]. Mostpublications report prevalence data for women only [31], and

Table 3 Detailed NNS for the indication for osteoporotic treatment with regard to trauma energy or age groups (N = 478)

Agegroup

Gender No indication fortreatment (DXAand FRAX)

Indication for treatment (DXAand FRAX)

NNS 95% CI Trauma energy No indication fortreatment (DXAand FRAX)

Indication fortreatment (DXAand FRAX)

NNS 95% CI

50+ Male 38 (58.5%) 27 (41.5%) 2.41 1.86–3.38 Low 21 (28%) 54 (72%) 1.39 1.22–1.62

Female 20 (30.8%) 45 (69.2%) 1.44 1.24–1.72 High 37 (67.3%) 18 (32.7%) 3.06 2.22–4.92

Total 58 (44.6%) 72 (55.4%) 1.81 1.56–2.13 Total 58 (44.6%) 72 (55.4%) 1.81 1.56–2.13

60+ Male 26 (59.1%) 18 (40.9%) 2.44 1.80–3.79 Low 34 (34.3%) 65 (65.7%) 1.52 1.33–1.78

Female 30 (34.9%) 56 (65.1%) 1.54 1.33–1.82 High 22 (71%) 9 (29%) 3.44 2.22–7.66

Total 56 (43.1%) 74 (56.9%) 1.76 1.53–2.07 Total 56 (43.1%) 74 (56.9%) 1.76 1.53–2.07

70+ Male 23 (79.3%) 6 (20.7%) 4.83 2.82–16.82 Low 36 (39.6%) 55 (60.4%) 1.65 1.42–1.98

Female 28 (33.7%) 55 (66.3%) 1.51 1.31–1.78 High 15 (71.4%) 6 (28.6%) 3.50 2.09–10.81

Total 51 (45.5%) 61 (54.5%) 1.84 1.57–2.21 Total 51 (45.5%) 61 (54.5%) 1.84 1.57–2.21

80+ Male 8 (34.8%) 15 (65.2%) 1.53 1.18–2.19 Low 25 (26.6%) 69 (73.4%) 1.36 1.21–1.55

Female 21 (25.3%) 62 (74.7%) 1.34 1.19–1.53 High 4 (33.3%) 8 (66.7%) 1.50 1.07–2.50

Total 29 (27.4%) 77 (72.6%) 1.38 1.23–1.56 Total 29 (27.4%) 77 (72.6%) 1.38 1.23–1.56

Total 194 (40.6%) 284 (59.4%) 1.68 1.57–1.82 194 (40.6%) 284 (59.4%) 1.68 1.57–1.82

NNS number needed to screen,DXA osteodensitometry, FRAX fracture risk assessment tool,DXA and FRAX combined assessment of both DXA and FRAX

Table 4 Multivariate analysis (stepwise logistic regression) regarding the indication for the treatment of osteoporosis (DXA and FRAX; N = 478)

Variables B Wald p Odds ratioexp (B)

99% CI General Improvement

Lower Upper Chi2 p Nagelkerke R2 Chi2 p Nagelkerke R2

Low energy 1.05 18.2 <0.001 2.84 1.76 4.59 40. 6 <0.001 0.11

Fracture femur 1.53 24.1 <0.001 4.63 2.51 8.53 60.1 <0.001 0.16 19.5 <0.001 0.05

Gender 0.92 16.7 <0.001 2.51 1.61 3.91 79.9 <0.001 0.21 19.8 <0.001 0.05

Fracture pelvis 1.37 6.7 0.010 3.92 1.39 11.04 86.0 <0.001 0.22 6.2 0.013 0.02

Fracture radius 0.56 4.6 0.032 1.75 1.05 2.93 90.7 <0.001 0.23 4.7 0.030 0.01

Constant −2.34 34.7 0.000 0.10

38 Page 6 of 9 Arch Osteoporos (2017) 12:38

the same applies to FRAX threshold values [14, 32]. The riskof fracture in men over 50 years of age has been described torange between 20 and 27%, which is lower than the compa-rable risk in women (50%) [33]. For Danish men >50 years,the prevalence of osteoporosis was estimated to be 17.7%[34], but only 1.3% of men >60 years of age actuallyunderwent the relevant pharmacotherapy. A recent report onover 129,000 US patients with a fragility fracture stated thatonly 10% of men underwent DXA testing and only 9.6%received antiosteoporosis treatment [35]. A retrospectivesingle-center evaluation on patients with distal radius fracturesindicated that a male with a fragility fracture is 9.7 times lesslikely to undergo DXA testing than is a woman with the samefracture [36]. Our prospective findings favor screening forosteoporosis following non-vertebral fractures in both menand women.

Fifth, although we found a significant association in therate of osteoporosis with increasing age in correlation withthe literature, the NNS to detect an osteoporotic patient inthe decennium 50–60 was only marginally worse than inhigher decennia (e.g., 2.4 in men 50+ vs. 1.5 in men 80+).Originally, this decision emanated from the assumption that asimple concept such as including Ball fracture patients aged 50or older,^ independently of trauma and gender, would be morefeasible within the daily clinical routine of a teaching hospital.The literature reports continuation of mostly very low screen-ing rates for osteoporosis in fracture patients [10, 35, 37, 38],partly due to the additional effort and specific knowledge re-quired of the physicians involved [39–41]. No unique andwell-accepted screening approach can be found in the currentliterature. The detailed criteria on when to screen which pa-tients with which kind of examination vary widely, e.g., be-ginning at what age, for females depending on menopause,including what type of trauma or depending on which defini-tion for fragility fracture, using different approaches to mea-sure BMD and additional risk scoring instruments such asFRAX, etc. [34, 42–46]. Due to the limited number of patientsin single decennia groups, especially if additionally stratifiedfor gender or trauma energy, further interpretation is limiteddue to the possibility of random statistical findings. The ex-ample of a lower NNS found in HEF men aged 50+ comparedto those aged 60+ or 70+ that is almost comparable to thoseaged 80+ underlines this statistical limitation. Overall, we areof the opinion that our preliminary data provide strong evi-dence for the simple approach of screening all fracture patientsfor osteoporosis beginning at the age of 50.

Sixth, we were interested in the differences between theNNS obtained for the more restricted assessment based onpathologic DXA measurement only (T score ≤−2.5) to indi-cate treatment compared with the assessment that includedFRAX scoring. With the inclusion of FRAX, the overall treat-ment prescription rate increased by almost 20%, i.e., the re-quired NNS to initiate any treatment for osteoporosis would

decrease from 2.5 for DXA only to 1.7 with the additional useof FRAX. Originally, the definition of osteoporosis relied onthe WHO-based T score of BMD. Following this definition,only subjects with a T score at or below −2.5 were consideredto have osteoporosis [47]. Almost all modern guidelines forosteoporosis [15, 31] include additional risk factors and scoressuch as the FRAX to indicate therapy, but some omit DXAmeasurement of patients [32, 42, 48]. In the Rotterdam epide-miologic study, only 44% of women and 21% of men aged 55and older with a non-vertebral fracture had a T score lowerthan −2.5 [47]. Follow-up studies on the long-term effects ofsuch a more aggressive approach to indication are required toobjectify the approach presented here. Given our NNS dataand reports in recent literature suggesting that treatment ofosteoporosis in patients with fragility fractures can reducethe risk of subsequent fractures by up to 50% and mortalityrates by up to 30% [43, 49, 50], we believe that the affectedfracture patients will profit importantly.

In addition, even though patients underwent detailed labo-ratory examination and a questionnaire for well-known riskfactors of osteoporosis, we could not find any auxiliary rela-tionship to the results of osteodensitometry or subsequent os-teoporotic treatment. For example, neither 25-hydroxy vita-min D, TSH, PTH, nor self-declared alcohol intake showeda significant correlation to the obtained T score values. Acomparison of these findings with the literature is difficult asmost of the studies so far were undertaken in patients withwell-known risk factors for osteoporosis and not in unselectedfracture patients as in our study [51–54]. Kanis et al. addressthe problem of low sensitivity and low positive predictivevalues when screening a population of 50 years of age withouta prevalent fracture [55].

Limitations

Until confirmed in other centers and larger cohorts, the find-ings from this preliminary study are limited to the setting ofthis monocentric evaluation and the patients under investiga-tion. The public hospital is open to all patients, but there are nodata available to confirm that the cohort under investigation isrepresentative of the relevant population. The prospectivestudy was performed with unselected fracture patients hospi-talized at the trauma unit of a Swiss teaching hospital. Eventhough, hardly more than every second consecutive patient(56.3%) could be included. Although excluded patients werefound to be older in univariate analysis, multivariable analysisrevealed that it was mainly the fact that a person lived in anursing home (and not their own home) that was associatedwith non-compliance with our standard procedure.Additionally, conservative treatment of the indicator fracturecorrelated significantly with exclusion from the study. Giventhese comparative data and arguments based on the well-founded assumption that the NNS for the treatment of

Arch Osteoporos (2017) 12:38 Page 7 of 9 38

osteoporosis in the group of more elderly and dependent pa-tients would, in fact, be even higher than in our study cohort,we see no reason why this inclusion limitation should princi-pally detract from our major findings. Indeed, given the NNSfor single risk groups, they should be considered even moreimpressive. Recent reports and population-based evaluationsfrom different countries [35, 56–58] show that only in about10–30% of cases where treatment is indicated are the relevantdiagnostics and/or treatments for osteoporosis actually imple-mented following fragility fractures or the diagnosis of osteo-porosis. A recent review of randomized controlled trials inves-tigating the professional care of patients with a fragility frac-ture and a variety of interventions to improve the implemen-tation of osteoporotic therapy revealed an overall 36% abso-lute increase in scanning rates for osteoporosis following ap-propriate interventions [59]. The diagnostic approach follow-ed Swiss guidelines at the time of the study, which may differin certain details from other countries. However, the majorfindings presented here should be largely independent of finerdetails in the diagnosis of osteoporosis but do need to beverified in larger studies. Especially subgroup findings suchas the unexpectedly low NNS for male HEF patients aged 50and older need to be reappraised because of the resulting smallnumber of patients. Although we worked with a standardizedstratification of trauma energy undertaken by one of the inves-tigators, we had to depend on the assumed best anamnesticinformation given by patients and/or any observers of trauma.

In summary, against the background of the recent literature,our preliminary findings reveal strong arguments in favor ofperforming standard screening for osteoporosis in all fracturepatients aged 50 or older (women and men) independently ofthe trauma energy involved. The approach described here andthe results obtained should be confirmed by larger studies andin other countries.

Acknowledgements The authors would like to thank all hospital col-laborators and Ms. J. Buchanan for editorial assistance.

Compliance with ethical standards The study was approved by theCantonal Ethics Board and supported financially by the Research Fund ofthe Hospital.

Conflicts of interest None.

References

1. Jeray K (2015) Osteoporosis and fragility fractures. What progresshave we made? J Bone Joint Surg Am 97:1553–1554

2. Neuerburg C, Stumpf U, Schmidmaier R, Kammerlander C,Pfeilschifter J, Mutscher W, Böcker W (2015) NewDVO guidelinefor ostoeporosis management 2014 and its importance for traumasurgeons. Unfallchirurg 118:905–912

3. Bouillon R, Burckhardt P, Christiansen C et al (1991) Consensusdevelopment conference: prophylaxis and treatment of osteoporo-sis. Am J Med 90:107–110

4. Lippuner K (2009) Epidemiology of osteoporotic fractures inSwitzerland. Revue Médicale Suisse 5:1304–1308

5. Svedbom A, Ivergard M, Hernlund E, Rizzoli R, Kanis J (2014)Epidemiology and economic burden of osteoporosis inSwitzerland. Arch Osteoporos 9:186–187 (1–8)

6. Burge R, Dawson-Hughes B, Solomon D, Wong J, King A,Tosteson A (2007) Incidence and economic burden ofosteoporosis-related fractures in the United States, 2005-2025. JBone Miner Res 22:465–475

7. Ahmed L, Center J, Bjoernerem A, Bluic D, Joakimsen R,Joergensen L, Meyer H, Nguyen N, Nguyen T, Omsland T,Stoermer J, Tell G, van Geel T, Eisman J, Emaus N (2013)Progressively increasing fracture risk with advancing age after ini-tial incident fragility fracture: the Tromsoe study. J BoneMiner Res28:2214–2221

8. Mackey D, Lui L-Y, Cawthon P, Bauer D, Nevitt M, Cauley JA,Hillier T, Lewis C, Barrett-Connor E, Cummings S (2007) Hightrauma fractures and low bone mineral density in older women andmen. JAMA 298:2381–2388

9. Sanders K, Pasco J, Ugoni A, Nicholson G, Seeman E, Martin T,Skoric B, Panahi S, Kotowicz M (1998) The exclusion of hightrauma fractures may undererstimate the prevalence of bone fragil-ity fractures in the community: the Geelon osteoporosis study. JBone Miner Res 13:1337–1342

10. Dirschl D (2014) Shame on us! Men need osteoporsis care, too! JBone Joint Surg Am 96:e186

11. Nguyen T, Sambrook P, Kelly P, Jones G, Lord S, Freund J, EismanJ (1993) Prediction of osteoporotic fractures by postural instabilityand bone density. BMJ 307:1111–1115

12. Lippuner K, von Overbeck J, Perretta L, Bosshard H, Jaeger P(1997) Incidence and direct medical costs of hospitalizations dueto osteoporotic fractures in Switzerland. Osteoporos Int 7:414–425

13. DVO (2014) [Prophylaxis, diagnostics and therapy of osteoporo-sis]. www.dv-osteologie.org/dvo_leitlinien/osteoporose-leitlinie-2014

14. SVGO (2015) [Osteoporosis recommendations 2015—diagnostics,prevention, therapy]. www.svgo.ch

15. Cosman F, de Beur S, Lewiecki E, Tanner B, Randall S, Lindsay R(2014) Clinician’s guide to prevention and treatment of osteoporo-sis. Osteoporos Int 25:2359–2381

16. Kanis J, the WHO study group (1994) Assessment of fracture riskand its application to screening for postmenopausal osteoporosis:synopsis of a WHO report. Osteoporos Int 4:368–381

17. Charlson M, Charlson R, Peterson J, Marinopoulos S, Briggs W,Hollenberg J (2008) The Charlson comorbidity index is adapted topredict costs of chronic disease in primary care patients. J ClinEpidemiol 61:1234–1240

18. CharlsonM, Szatrowski T, Peterson J, Gold J (1994) Validation of acombined comorbidity index. J Clin Epidemiol 47:1245–1251

19. Warriner A, Patkar N, Yun H, Delzell E (2011) Minor, major, low-trauma, and high-trauma fractures: what are the subsequent fracturerisks and how do they vary? Curr Osteoporos Rep 9:122–128

20. Huisa B, Stemer A, Zivin J (2010) Atorvastatin in stroke: a reviewof SPARCL and subgroup analysis. Vasc Health Risk Manag 6:229–236

21. Hernlund E, Svedbom A, Ivergard M, Compston J, Cooper C,Stenmark J, McCloskey E, Jönsson B, Kanis J (2013)Osteoporosis in the European Union: medical management, epide-miology and economic burden: a report prepared in collaborationwith the International Osteoporosis Foundation (IOF) and theEuropean Federation of Pharmaceutical Industry Associations(EFPIA). Arch Osteoporos 8:136

38 Page 8 of 9 Arch Osteoporos (2017) 12:38

22. National Osteoporosis Foundation (2014) Clinician’s guide to pre-vention and treatment of osteoporosis. National OsteoporosisFoundation 1:1–55

23. Lofthus C, Osnes E, Meyer H, Kristiansen I, Nordsletten L, Falch J(2006) Young patients with hip fracture: a population-based studyof bone mass and risk factors for osteoporosis. Osteoporos Int 17:1666–1672

24. Hedlund R, Lindgren U (1987) Trauma type, age, and gender asdeterminants of hip fracture. J Orthop Res 5:242–246

25. Robinovitch S, HayesW,McMahon T (1991) Prediction of femoralimpact forces in falls on the hip. J Biomech Eng 113:366–374

26. Chiu J, Robinovitch S (1998) Predicition of upper extremitiy im-pact forces during falls on the outstretched hand. J Biomech 31:1169–1176

27. Choi W, Cripton P, Robinovitch S (2015) Effects of hip abductormuscle forces and knee boundary conditions on femoral neckstresses during simulated falls. Osteoporos Int 26:291–301

28. Mackey D, Black D, Bauer D,McCloskey E, Eastell R,MesenbrinkP, Thompson J, Cummings S (2011) Effects of antiresorptive treat-ment on nonvertebral fracture outcomes. J Bone Miner Res 26:2411–2418

29. Szulc P, Munoz F, Duboeuf F, Marchand F, Delmas P (2005) Bonemineral density predicts osteoporotic fractures in elderly men: theMINOS study. Osteoporos Int 16:1184–1192

30. Mussolino M, Looker A, Madans J, Langlois J, Orwoll E (1998)Risk factors for fip fracture in white men: the NHANES I epidemi-ologic follow-up study. J Bone Miner Res 13:918–924

31. Kanis J, McCloskey E, Johansson H, Cooper C, Rizzoli R,Reginster J-Y, ESCEO, IOF (2012) European guidance for diagno-sis and management of osteoporosis in postmenopausal women.Osteoporos Int 24(1):23–57

32. Kanis J, Harvey N, Cooper C, Johansson H, Odén A, McCloskey E(2016) A systematic review of intervention thresholds based onFRAX. Arch Osteoporos 11:25

33. Frost M, Gudex C, Rubin K, Brixen K, Abrahamsen B (2012)Pattern of the use of DXA scans in men: a cross sectionalpopulation-based study. Osteoporos Int 23:183–191

34. Vestergaard P, Rejnmark L, Mosekilde L (2005) Osteoporosis ismarkedly underdiagnosed: a nationwide study from Denmark.Osteoporos Int 16:134–141

35. Balasubramanian A, Tosi L, Lane J, Dirschl D, Ho P, O’Malley C(2014) Declining rates of osteoporosis management following fra-gility fractures in the U.S., 2000 through 2009. J Bone Joint SurgAm 96:e52

36. Harper C, Fitzpatrick S, Zurakowski D, Rozental T (2014) Distalradial fractures in older men. J Bone Joint Surg Am 96:1820–1827

37. Giangregorio L, Papaioannou A, Cranney A, Zytaruk N, Adachi J(2006) Fragility fractures and the osteoporosis care gap: an interna-tional phenomenon. Semin Arthritis Rheum 35:293–305

38. Leslie W, Giangregorio L, Yogendran M, Azimaee M, Morin S,Metge C, Caetano P, Lix L (2012) A population-based analysis ofthe post-fracture care gap 1996-2008: the situation is not improving.Osteoporos Int 23:1623–1629

39. Edwards B, Koval K, Bunta A, Genuario K, Hahr A, Andruszyn L,WilliamsM (2011) Adressing secondary prevention of osteoporosisin fracture care: follow-up to Bown the bone^. J Bone Joint SurgAm 93:e87(1)–e87(7)

40. Chenot R, Scheidt-Nave C, Gabler S, Kochen M, Himmel W(2007) German primary care doctor’s awareness of osteoporosisand knowledge of national guidelines. Exp Clin EndocrinolDiabetes 115:584–589

41. Rosenwasser M, Cuellar D (2016) Medical management of osteo-porosis and the surgeons’ role. Injury 47(Supplement 1):S62–S64

42. Kanis J, Harvey N, Johansson H, Odén A, Leslie W, McCloskey E(2015) FRAX and fracture prediction without bone mineral density.Climacteric 18:2–9

43. Hochberg M (2000) Preventing fractures in postmenopausal wom-en with osteoporosis. Drugs Aging 17:317–330

44. Papaioannou A, Morin S, Cheung A, Aktinson S, Brown J,Feldman S, Hanley D, Hodsman A, Jamal S, Kaiser S, Kvern B,Siminoski K, Leslie W (2010) 2010 clinical practice guidelines forthe diagnosis and management of osteoporosis in Canada: summa-ry. CMAJ 182(17):1864–1873

45. Leslie W, Schousboe J (2011) A review of osteoporosis diagnosisand treatment options in new and recently updated guidelines oncase finding around the world. Curr Osteoporos Rep 9:129–140

46. Kanis J, Compston J, Cooper C, Harvey N, Johansson H, Odén A,McCloskey E (2016) SIGN guidelines for Scotland: BMD versusFRAX versus QFracture. Calcif Tissue Int 98:417–425

47. Schuit S, van der Klift M, Weel A, de Laet C, Burger H, Seeman E,Hofman A, Uitterlinden A, van Leeuwen J, Pols H (2004) Fractureincidence and association with bone mineral density in elderly menand women: the Rotterdam study. Bone 34:195–202

48. Kanis J, McCloskey E, Branco J, Brandi M, Dennison E,Devogelaer J, Ferrari S, Kaufman J, Papapoulos S, Reginster J,Rizzoli R (2014) Goal-directed treatment of osteoporosis inEurope. Osteoporos Int 25:2533–2543

49. Grey A, BollandM (2013) The effect of treatments for osteoporosison mortality. Osteoporos Int 24:1–6

50. BollandM, GreyA,Gamble G, Reid I (2010) Effect of osteoporosistreatment on mortality: a meta-analysis. The Journal of ClinicalEndocrinology & Metabolism 95:1174–1181

51. Hudec S, Camacho P (2012) Secondary causes of osteoporosis.Endocr Pract 19:120–128

52. Waring A, Harrison S, Fink H, Samuels M, Cawthon P, Zmuda J,Orwoll E, Bauer D (2013) A prospective study of thyroid function,bone loss, and fractures in older men: the MrOS study. J BoneMiner Res 28:472–479

53. Kushnir-Sukhov N, Brittain E, Reynolds J, Akin C, Metcalfe D(2006) Elevated tryptase levels are associated with greater bonedensity in a cohort of patients with mastocytosis. Int Arch AllergyImmunol 139:265–270

54. Bours S, van Geel T, Geusens P, Janssen M, Janzing H, HofflandGA, Willems P, van den Bergh J (2011) Contributors to secondaryosteoporosis and metabolic bone disease in patients presenting withclinical fracture. The Journal of Clinical Endocrinology &Metabolism 96:1360–1367

55. Kanis, JA and on behalf of the WHO Scientific Group (2007)Assessment of osteoporosis at the primary health care level.www.shef.ac.uk/FRAX/pdfs/WHO_Technical_Report.pdf

56. Vogel T, Kampmann P, Bürklein D, Böhm H, Ockert B, KirchhoffC, Kanz K, Pfeifer K, Mutschler W (2008) Reality of treatment ofosteoporotic fractures in German trauma department. Unfallchirurg111:869–877

57. Suhm N, Lamy O, Lippuner K (2008) Management of fragilityfractures in Switzerland: results of a nationwide survey. SwissMed Wkly 138:674–683

58. McLellan A, Wolowacz S, Zimovetz E, Beard S, Lock S, McCrinkL, Adekunle F, Roberts D (2011) Fracture liaison services for theevaluation and management of patients with osteoporotic fracture:cost-effectiveness evaluation based on data collected over 8 years ofservice provision. Osteoporos Int 22:2083–2098

59. Little E, EcclesM (2010) A systematic review of the effectivness ofinterventions to improve post-fracture investigation andmanagment of patients at risk of osteoporosis. Implement Sci 5:80–97

Arch Osteoporos (2017) 12:38 Page 9 of 9 38