Advertisement

Osseous microarchitecture in frequent fracture zones of the distal clavicle

Open AccessPublished:October 19, 2022DOI:https://doi.org/10.1016/j.jseint.2022.09.015

      Abstract

      Introduction

      Fracture classifications of the distal clavicle are based on ligamentous integrity. The influence of osseous microarchitecture on fracture occurrence, morphology and the lesion’s stability has not yet been investigated. We aimed to characterize osseous microarchitecture according to common fracture classification systems based on ligamentous integrity and investigated the possible effects of age, gender, and osteoporosis in distal clavicle fractures.

      Methods

      n=20 human cadaveric distal clavicles were scanned using XtremeCT with an isometric voxel size of 82μm. In the sagittal plane, each dataset was evaluated in eleven sections of approx. 7mm thickness. Three topographic regions were defined: The bone lateral to the trapezoid (LTR), intertubercular (ITR) and medial to the conoid (MCR) ligament. Cortical bone mineral density (BMD)[mgHA/cm3], and cortical porosity (1- (BV/TV) [%]) were determined and evaluated relative to age and gender.

      Results

      Along the mediolateral axis, there was an >20fold increase in median cortical porosity (p≤0.001). There were significant differences in cortical porosity between LTR and ITR (p≤0.001) but not between ITR and MCR (p=0.09). In ITR, cortical porosity was significantly greater in >60-year-old compared to younger donors (p=0.01). For BMD, there was an >2fold decrease towards the distal apex (p≤0.001). BMD was significantly greater in ITR compared to LTR (p≤0.001) and in MCR compared to ITR (p=0.02). In ITR and MCR, clavicles of >60-year-old donors had significantly lower BMD values compared to younger donors (p<0.01). Across all three regions, frequency distribution of low bone mass did not significantly differ between <60year-olds and >60year-olds (p>0.6).

      Conclusion

      The distal clavicle features a characteristic bony microarchitecture. The present study revealed a significant difference in bone quality of lateral, intertubercular, and medial zones of the distal clavicle and could specify target areas and strategies for surgical treatment of unstable fractures. Age, gender, and osteoporosis have a limited effect on bone quality and fracture genesis. In contrast, ligamentous quality is supposed to exert a substantial influence on fracture characteristics, especially in ITR. Fracture morphology of the distal clavicle is determined by a bony-ligamentous conjunction, which remains to be characterized.

      Keywords

      Clavicle fractures account for almost half of all fractures in the shoulder girdle [
      • Postacchini F.
      • Gumina S.
      • De Santis P.
      • Albo F.
      Epidemiology of clavicle fractures.
      ]. In 10-30%, the distal third is affected [
      • Ockert B.
      • Wiedemann E.
      • Haasters F.
      [Distal clavicle fractures. Classifications and management].
      ]. Differential therapeutic management is indicated based on fracture stability, age, and functional demands [
      • Banerjee R.
      • Waterman B.
      • Padalecki J.
      • Robertson W.
      Management of distal clavicle fractures.
      ,
      • Rieser G.R.
      • Edwards K.
      • Gould G.C.
      • Markert R.J.
      • Goswami T.
      • Rubino L.J.
      Distal-third clavicle fracture fixation: a biomechanical evaluation of fixation.
      ].
      Conclusions regarding stability of distal clavicle lesions can be drawn from fracture classification systems. Common fracture classification systems of Neer [
      • Neer 2nd, C.S.
      Fractures of the distal third of the clavicle.
      ], Jaeger and Breitner [
      • Jäger M.
      • Breitner S.
      [Therapy related classification of lateral clavicular fracture].
      ], or Robinson [
      • Robinson C.M.
      Fractures of the clavicle in the adult. Epidemiology and classification.
      ] illustrate the role of ligamentous integrity in determining fracture stability, following anatomical considerations of the fracture configuration in relation to the acromio-clavicular (AC) and the coraco-clavicular (CC) ligaments. Given the lesion’s heterogeneity, no single of the existing classification systems has proven to be comprehensive [
      • Kim D.W.
      • Kim D.H.
      • Kim B.S.
      • Cho C.H.
      Current Concepts for Classification and Treatment of Distal Clavicle Fractures.
      ]. This inconsistency might reflect the so far uncharted osseous microstructure and its implications regarding the predetermination of fracture configuration and stability.
      Various bones are subject to age and gender related remodeling processes with an associated risk of fracture. As such, the proximal humeral fracture is considered as an indicator for osteoporosis of the shoulder girdle [
      • Yamada M.
      • Briot J.
      • Pedrono A.
      • Sans N.
      • Mansat P.
      • Mansat M.
      • et al.
      Age- and gender-related distribution of bone tissue of osteoporotic humeral head using computed tomography.
      ]. Similarly, distal clavicle fractures have been shown to affect different age groups with two incidental peaks [
      • Kihlström C.
      • Möller M.
      • Lönn K.
      • Wolf O.
      Clavicle fractures: epidemiology, classification and treatment of 2 422 fractures in the Swedish Fracture Register; an observational study.
      ,
      • Sambandam B.
      • Gupta R.
      • Kumar S.
      • Maini L.
      Fracture of distal end clavicle: A review.
      ]: While young and active male adults usually present with injuries resulting from a direct blow to the shoulder, there is an increasing number of distal clavicle fractures in elderly females with low bone quality. An investigation of the osseous microstructure of the distal clavicle may provide an explanation comparable to those widely accepted for proximal humeral fractures.
      Using XtremeCT scans of human cadavers, this study aimed to characterize the osseous microstructure of the distal clavicle, to correlate these findings to common fracture classification systems, and to investigate the effect of age and gender on bone quality.

      Methods

      Material and Parameters

      N=20 (n=10 male, n=10 female, mean age (SD) = 57 (20.7) years) fresh frozen left human cadaveric clavicles were examined, with the soft tissue removed, leaving only the ligamentous entheses in place (tab. 1). Specimens were recruited from the Forensic Institute of the Ludwig-Maximilians-University (LMU) after approval by the local ethics committee (registration nr.: 499-15). CT scans with an isotropic voxel size of 82 μm were preserved using XtremeCT (XtremeCT, Scanco Medical AG, Brüttisellen, Switzerland). Normalized to each bone’s individual length, the distal thirds of the clavicles were subdivided into 11 sections at approx. 7 mm distances in the sagittal plane (fig. 1). Centers and footprints of the CC- entheses were referenced and normalized according to Rios et al with the center of the trapezoid enthesis being located at a mean distance of 25.9 mm and the center of the conoid enthesis at a mean distance of 35mm from the distal apex. Along the mediolateral axis, different fracture types were localized according to the following regions of interest (ROI, fig. 1): medial to the conoid tubercle (MCR, two ROI), conoid tubercle (one ROI), intertubercular region (ITR; two ROI), trapezoid tubercle (one ROI) and lateral to the trapezoid tubercle (LTR, three ROI). Each ROI consisted of 25 consecutive images (approx. 2 mm). Across each ROI, parameters of bone quality were determined using a standardized and previously described method based on automated image segmentation using adaptive thresholding [
      • Mys K.
      • Stockmans F.
      • Vereecke E.
      • van Lenthe G.H.
      Quantification of bone microstructure in the wrist using cone-beam computed tomography.
      ]. Bone mineral density (BMD)[mgHA/cm3], cortical bone volume (BV)[mm³], and cortical porosity, described as 1- bone volume/total volume (1-(BV/ (TV))[%]) were evaluated [
      • Berli M.
      • Borau C.
      • Decco O.
      • Adams G.
      • Cook R.B.
      • García Aznar J.M.
      • et al.
      Localized tissue mineralization regulated by bone remodelling: A computational approach.
      ]. All parameters of cortical bone quality were compared between male and female, and between <60-year-old (25-59y) and >60-year-old (60-87y) donors (fig. 2).
      Table 1Overview of clavicle donors.
      IDage [y]sexclavicle length [mm]mean BMD [mgHA/cm3]median cortical porosity [%]
      25-59y144m180909.21.5
      226m100882.61.5
      345m120804.53.6
      425f80856.60.7
      529f85941.50.8
      637f80709.34.5
      736f145761.24.1
      840f1451008.30.9
      central tendency35 (7.8)
      mean (standard deviation)
      117 (37)
      mean (standard deviation)
      859.2 (97.9)
      mean (standard deviation)
      1.5 (2.2)
      median (interquartile range); BMD = bone mineral density
      60-87y972f165761.02.2
      1078m170800.43.2
      1162m180833.03.0
      1282m170797.12.4
      1386m190704.15.2
      1467m185796.12.0
      1587f90722.54.7
      1664m90733.910.0
      1781f90555.97.7
      1866f100921.41.7
      1964m110800.12.4
      2064f120762.22.2
      central tendency73 (9.5)
      mean (standard deviation)
      138 (42)
      mean (standard deviation)
      765.6 (87.3)
      mean (standard deviation)
      2.7 (2.6)
      median (interquartile range); BMD = bone mineral density
      1 mean (standard deviation)
      2 median (interquartile range); BMD = bone mineral density
      Figure thumbnail gr1
      Figure 1According to fracture classification systems, the distal clavicle was sectioned in regions located medial to the conoid tubercle (blue), intertubercular (green) and lateral to the trapezoid tubercle (yellow). A: Fracture regions of the distal clavicle according to common classification systems of Neer, Jäger/ Breitner, Craig and Edinburgh. Fracture stability depends on concomitant ligamentous injury. Instability is assumed in Neer IIA, Jäger/ Breitner III, Neer IIB, Jäger/ Breitner IIA, Neer V, Edinburgh 3B and Craig IIC [
      • Sheehan S.E.
      • Gaviola G.
      • Sacks A.
      • Gordon R.
      • Shi L.L.
      • Smith S.E.
      Traumatic Shoulder Injuries: A Force Mechanism Analysis of Complex Injuries to the Shoulder Girdle and Proximal Humerus.
      ]. B: Scheme of ROI distribution along the mediolateral axis in relation to anatomic landmarks. We designed 4 regions of interest (ROI) medial to the conoid tubercle center (MCR), one ROI at the conoid tubercle center, two ROI within the intertubercular region (ITR), one ROI at the trapezoid tubercle center and three ROI lateral to the trapezoid tubercle (LTR).
      Figure thumbnail gr2
      Figure 2XtremeCT scans of clavicle fracture sections in representative 72-year-old female (upper row) and 26-year-old male (lower row) specimen. The clavicular cross sectional bone morphology features high inter-individual variance with a remarkable flattening and cortical thinning towards the lateral apex existent consistently regarding age and gender. Bar = 5mm.
      According to the WHO, osteoporosis is defined by a BMD of 2.5 SD or more below the young adult mean of 30-year-old, healthy individuals. In this cohort, the age group of <60-year-olds had a mean age of 35.3 ± 7.5 years and the age group of >60-year-olds had a mean age of 72.8 ± 9.2 years. Following the WHO definition, BMD values of <60-years-olds were used to define ‘osteoporosis’ and ‘low bone mass’ to demonstrate the occurrence of these in the distal clavicle.

      Statistical Analysis

      Statistical evaluation was performed using ‘R’ (R Core Team, Version 4.1.0; R Foundation for Statistical Computing, Vienna, Austria) and GraphPad Prism (Version 9.3.1 (2022); GraphPad Software, La Jolla, CA, USA). For determination of the minimal sample size required, an a priori power analysis was conducted using previously published BMD values of the distal clavicle [
      • Chen R.E.
      • Soin S.P.
      • El-Shaar R.
      • Nicandri G.T.
      • Awad H.A.
      • Maloney M.D.
      • et al.
      What Regions of the Distal Clavicle Have the Greatest Bone Mineral Density and Cortical Thickness? A Cadaveric Study.
      ], which lie within the range of 800 ± 38 mgHA/cm3. Considering the WHO definition with osteoporosis being present at -2.5 standard deviations, the required sample size to achieve 80% power for detecting this effect, at a significance criterion of α = .05, was n = 3 per group for an independent samples t-test.
      Normal distribution was tested using the Shapiro-Wilk test. Data description was performed using mean and standard deviation (SD) for parametric and median and interquartile range (IQR; Q3-Q1) for non-parametric data. Correlation analyses were performed using two-sided Pearson’s and Spearman’s methods, respectively. Frequency comparisons were performed using Chi-squared and Fisher’s exact test for expected frequencies <5. Unpaired group comparisons were performed using t-test for parametric and Mann-Whitney U-test for non-parametric data. Pairwise comparisons were performed using paired t-tests for parametric and Wilcoxon matched-pairs signed rank test for non-parametric data. Unpaired multiple comparisons were performed using one-way ANOVA with Tukey’s correction for parametric data and Kruskal-Wallis test with Dunn’s correction for non-parametric data. Paired multiple comparison tests were performed using mixed-effects analysis with Tukey’s correction for parametric and Friedman test with Dunn’s correction for non-parametric data. The level of significance was set at p = 0.05.

      Results

      Demographic and specimen characterization

      Mean age of donors was 57.8 (25-87) in female and 61.8 (26-86) in male (table 1; p=0.4). Median overall clavicle length was 120mm (min=90mm; max=190 mm) and median length of the distal third was 56mm (min = 5.3mm; max = 6.7mm). Male specimens were longer compared to female specimens (p = 0.01). Lengths of the distal thirds were comparable between gender groups (p = 0.68).

      Cortical Porosity

      There were significant differences between LTR and ITR (median 9.7%, IQR = 7.7 and 2.9%, IQR = 2.2; p < 0.001) but not between ITR and MCR (2.9%, IQR = 2.2 and 1.9%, IQR = 1.6; p > 0.9; table 2, fig. 4). In MCR, there was a trend towards greater cortical porosity in male specimen (p=0.068) and >60-year-old donors (p=0.0548). There was no significant gender-related difference in ITR (p=0.753). In ITR, cortical porosity was significantly greater in >60-year-old compared to younger donors (2.8%, IQR = 2 and 1.3%, IQR = 2.3; p = 0.01).
      Table 2Medians of cortical porosity (1-(BV/TV) [%]) values across investigated anatomical regions and ROI.
      RegionLTRTTITRCTMCR
      ROI A12345678910
      27.4%12.9%4.4%3.6%3.3%3.5%4.20%3%3.6%1.5%
      ROI B234567891011
      12.9%4.4%3.6%3.3%3.5%4.2%3%3.6%1.5%1.3%
      CT = conoid tubercle, ITR = intertubercular region, LTR = lateral to trapezoid, MTR = medial to conoid, ROI = region of interest, TT = trapezoid tubercle.
      Figure thumbnail gr3
      Figure 3Cortical porosity [%]) and cortical BMD [mgHA/cm3] along the mediolateral axis of the clavicle. Fracture regions are displayed according to common fracture classification systems. There was a significant, >20fold increase in cortical porosity towards the lateral apex. There was a significant, >2fold decrease in BMD towards the lateral apex. Cortical porosity: bar = median; whiskers = IQR; BMD: bar = mean; whiskers = SD.
      Figure thumbnail gr4
      Figure 4BMD and age in fracture zones of the distal clavicle. According to the WHO, osteoporosis is defined by a BMD of 2.5 SD or more below the young adult mean of 30-year-old, healthy individuals. In this cohort, the age group of <60-year-olds had a mean age of 35.3 ± 7.5 years and the age group of >60-year-olds had a mean age of 72.8 ± 9.2 years. Mean BMD (SD) for <60-years-olds were 959.2 (99.9) mgHA/cm3 medial to the conoid, 914.8 (133.9) mgHA/cm3 in the intertubercular region, and 652.5 (207.2) mgHA/cm3 lateral to the trapezoid. BMD values of both, female and male specimen were altered with age in a similar fashion. Frequencies of low bone mass (MCR: 12.5% and 33.3%; ITR and LTR: 12.5% and 16.7%) and osteoporosis (MCR: 0% and 8.3%; ITR and LTR: 0% in both groups) did not differ between both age groups in the respective fracture region (p>0.6). Dotted line = -1 SD of 25-59y (threshold of low bone mass). Dashed line = -2.5 SD of 25-59y (threshold of osteoporosis).
      There were no significant age-related or gender-related differences in LTR (p=0.2026 and p=0.997). However, across all three regions, there were no significant differences between young female, young male, old female, and old male donors regarding cortical porosity (p>0.0761).

      Bone Mineral Density (BMD)

      Mean cortical BMD in the distal third of all clavicles was 806.8 mgHA/cm3. There was an >2fold decrease towards the distal apex (mean BMD ROI 1 = 427.6 ± 120.5 mgHA/cm3 and ROI 11 = 974.7 ± 58.8 mgHA/cm3; p < 0.001) (table 3, fig. 3). BMD was significantly greater in ITR compared to LTR (858.5 ± 118.9 mgHA/cm3 vs. 603.9 ± 188.9 mgHA/cm3; p < 0.001) and in MCR compared to ITR (905.7 ± 100.8 mgHA/cm3 vs. 858.5 ± 118.9 mgHA/cm3; p = 0.042) (fig. 3).
      Table 3Means of BMD [mgHA/cm3] values across investigated anatomical regions and ROI.
      RegionLTRTTITRCTMCR
      ROI A12345678910
      427.6 ± 120.5606.7 ± 134.1777.3 ± 118.0824.8 ± 117.9853.6 ± 122.1863.5 ± 118.6863.4 ± 120.8889.8 ± 105.2894.0 ± 107.5955.0 ± 76.9
      ROI B234567891011
      606.7 ± 134.1777.3 ± 118.0824.8 ± 117.9853.6 ± 122.1863.5 ± 118.6863.4 ± 120.8889.8 ± 105.2894.0 ± 107.5955.0 ± 76.9974.7 ± 58.8
      CT = conoid tubercle, ITR = intertubercular region, LTR = lateral to trapezoid, MTR = medial to conoid, ROI = region of interest, TT = trapezoid tubercle.
      In LTR, there was no significant difference in BMD of <60-year-old and >60-year-old donors (652.5 ± 207.2 mgHA/cm3 and 571.5 ± 171 mgHA/cm3; p = 0.1). In ITR and MCR, clavicles of <60-year-old donors had significantly greater BMD values compared >60-year-old donors (ITR: 914.8 ± 133.9 mgHA/cm3 and 821 ± 92.8 mgHA/cm3; MCR: 959 ± 99.9 mgHA/cm3 and 877 ± 87.8 mgHA/cm3; p < 0.01).
      Mean BMD was lower in clavicles of female donors across the distal third, but significant gender-related differences could not be established (LTR, male: 616. 2 ± 154.8 mgHA/cm3; female: 591.5 ± 219.8 mgHA/cm3; ITR, male: 866 ± 77.5 mgHA/cm3; female: 851 ± 151.3 mgHA/cm3; MCR, male: 912 ± 49.8 mgHA/cm3; female: 910.7 ± 134 mgHA/cm3; p > 0.6; fig. 4).
      BMD was greater across all three regions in <60-year-old compared to >60-year-old female donors, but significance was present in MCR only (LTR: 464.8 ± 147.5 mgHA/cm3 and 314.8 ± 79.1 mgHA/cm3; p=0.343; ITR: 890.5 ± 191.7 mgHA/cm3 and 804 ± 124.6 mgHA/cm3; p=0.1871; MCR: 67 ± 124.5 mgHA/cm3 and 854.4 ± 122.2 mgHA/cm3; p=0.012). Clavicles of the old female group consistently had the lowest BMD values regarding fracture zone, however in ITR and LTR, there were no significant differences any of the groups (young female, young male, old female, and old male; p>0.187).
      Correlation analysis showed a trend towards consistently reduced BMD with increasing age across all three regions but did not reach statistical significance. Across the distal third, frequency distribution of osteoporosis (0% in both groups) and low bone mass (0% 25-59y and 8.3% in 60-87y) did not significantly differ between age groups (p > 0.99). When adjusting for the respective fracture region, no further significant difference was established (Fig. 4).

      Discussion

      Common systems for distal clavicle fracture classification according to Neer [
      • Neer 2nd, C.S.
      Fractures of the distal third of the clavicle.
      ], Jaeger and Breitner [
      • Jäger M.
      • Breitner S.
      [Therapy related classification of lateral clavicular fracture].
      ], Robinson or Craig [
      • Robinson C.M.
      Fractures of the clavicle in the adult. Epidemiology and classification.
      ] are geared to the fracture’s localization in relation to the concomitant integrity of the coracoclavicular ligaments. To evaluate the influence of bony microstructure on distal clavicle fracture occurrence in its ligamentous context, the present study evaluated XtremeCT scans of human cadaveric distal clavicles.
      Specimen were representatively selected regarding age and gender distribution. Demographic data did not significantly differ between investigated groups. Methodological considerations such as age group definitions [
      • Kamer L.
      • Noser H.
      • Popp A.W.
      • Lenz M.
      • Blauth M.
      Computational anatomy of the proximal humerus: An ex vivo high-resolution peripheral quantitative computed tomography study.
      ,
      • Yamada M.
      • Briot J.
      • Pedrono A.
      • Sans N.
      • Mansat P.
      • Mansat M.
      • et al.
      Age- and gender-related distribution of bone tissue of osteoporotic humeral head using computed tomography.
      ], parameters regarding length and localization of ligamentous enthesis areas [
      • Fontana A.D.
      • Hoyen H.A.
      • Blauth M.
      • Galm A.
      • Schweizer M.
      • Raas C.
      • et al.
      The variance of clavicular surface morphology is predictable: an analysis of dependent and independent metadata variables.
      ,
      • Huang J.I.
      • Toogood P.
      • Chen M.R.
      • Wilber J.H.
      • Cooperman D.R.
      Clavicular anatomy and the applicability of precontoured plates.
      ] as well as the use of XtremeCT and the modality of fractionation [
      • Chen R.E.
      • Soin S.P.
      • El-Shaar R.
      • Nicandri G.T.
      • Awad H.A.
      • Maloney M.D.
      • et al.
      What Regions of the Distal Clavicle Have the Greatest Bone Mineral Density and Cortical Thickness? A Cadaveric Study.
      ,
      • Helfen T.
      • Sprecher C.M.
      • Eberli U.
      • Gueorguiev B.
      • Müller P.E.
      • Richards R.G.
      • et al.
      High-Resolution Tomography-Based Quantification of Cortical Porosity and Cortical Thickness at the Surgical Neck of the Humerus During Aging.
      ] for the evaluation of our hypothesis have been approved regarding eligibility in previous studies.
      According to ligamentous and bony topography, we defined three different sections within the distal clavicle. Cortical porosity continuously increased from the medial to the lateral section.
      A highly significant increase in cortical porosity could be shown especially for the most lateral section. Here, fracture types Neer I (Jaeger/ Breitner I), Neer III and Craig IIc are located. While Neer I (Jaeger/ Breitner I) and Neer III fractures represent stable fractures, Craig IIc fractures are considered unstable [
      • Ockert B.
      • Wiedemann E.
      • Haasters F.
      [Distal clavicle fractures. Classifications and management].
      ]. Assumptions on stability are derived from ligamentous integrity. Despite the nonexistence of comparative epidemiological data, our results suggest an ancillary influence of bony microstructural processes on injury pattern within the lateral distal clavicle section. Consequently, the Craig IIc injury pattern might be related to compromised quality or aberrant course of stabilizing ligaments [
      • Chahla J.
      • Marchetti D.C.
      • Moatshe G.
      • Ferrari M.B.
      • Sanchez G.
      • Brady A.W.
      • et al.
      Quantitative Assessment of the Coracoacromial and the Coracoclavicular Ligaments With 3-Dimensional Mapping of the Coracoid Process Anatomy: A Cadaveric Study of Surgically Relevant Structures.
      ,
      • Moya D.
      • Poitevin L.A.
      • Postan D.
      • Azulay G.A.
      • Valente S.
      • Giacomelli F.
      • et al.
      The medial coracoclavicular ligament: anatomy, biomechanics,and clinical relevance-a research study.
      ], marked changes to their entheses [
      • Ockert B.
      • Braunstein V.
      • Sprecher C.
      • Shinohara Y.
      • Kirchhoff C.
      • Milz S.
      Attachment sites of the coracoclavicular ligaments are characterized by fibrocartilage differentiation: a study on human cadaveric tissue.
      ] or the mechanistic scenario and acting force vectors [
      • Sheehan S.E.
      • Gaviola G.
      • Sacks A.
      • Gordon R.
      • Shi L.L.
      • Smith S.E.
      Traumatic Shoulder Injuries: A Force Mechanism Analysis of Complex Injuries to the Shoulder Girdle and Proximal Humerus.
      ].
      Distinct age and gender related differences in cortical porosity were particularly observed in the transitional zone towards the diaphysis. The authors attributed these changes to common bony remodeling aspects rather than osteoporotic transformation. The observed significant age-related increase in cortical porosity in the intertubercular region is liable to a similar interpretation.
      Corresponding to cortical porosity, BMD was found to decrease from the medial towards the lateral section of the distal clavicle. Differences were significant regarding all three defined sections of the distal clavicle. Based on this observation, most fracture types would be expected within the section borders, if bony influence was clearly relevant. However, regarding the above-mentioned classification systems, only half of all fractures feature a respective localization (Neer I, Neer III, Neer IIa, Craig IIc). The remainder is localized within the intertubercular region (Jaeger/ Breitner IIb, Edinburgh 3A1 & 3A2, Neer IIb, Neer V). Again, fracture genesis cannot be sufficiently explained by bone quality in general, and BMD in particular, and rather has to be interpreted considering an interplay of course and quality of surrounding ligaments, entheses and acting force vectors.
      Concordantly to the observed conditions regarding cortical porosity of the most lateral section, there was a comparably lower BMD of younger male specimens. Besides an argumentation regarding skeletal maturation, higher prevalence of arthritis of the acromioclavicular joint in the elderly may provide further explanation. A clinically relevant contribution of osteoporosis as deducted in the present study in distal clavicle fracture genesis can be considered virtually nonexistent: An analysis using cohort specific results of the present study yields an estimated power value of 1.
      Regarding both parameters, cortical porosity and BMD, bone morphology is characteristic but can only partially be considered to exert an influential effect on the occurrence and stability of distal clavicle fractures. Thus, an in-depth imaging, histological, and biomechanical analysis of the coracoclavicular ligaments, their entheses, and the acromioclavicular joint including the surrounding capsule during the fracture process may provide further clarification.
      Within the intertubercular region, some uncertainty remains regarding the bony-ligamentous ratio and its influence on fracture occurrence. However, compared to the lateral section, a significantly better bone quality with respect to osteosynthesis was shown in the present study. The area of central insertion of the coracoclavicular ligaments at the clavicle includes approximately 20.1 mm in females and 22.3 mm in males [
      • Rios C.G.
      • Arciero R.A.
      • Mazzocca A.D.
      Anatomy of the clavicle and coracoid process for reconstruction of the coracoclavicular ligaments.
      ]. Thus, this section is relatively broad and bone stock for osteosynthesis varies depending on fracture localization. Importantly, age and gender turned out not to be reliable predictors of bone quality. For unstable fractures of this region (Neer IIb, Jaeger/ Breitner IIa, Neer V, unstable Edinburgh 3B1), the authors recommend techniques, which allow sufficient neutralization of cranialization forces exerted by dynamic stabilizers, e.g., plate osteosynthesis, which may be augmented by coracoclavicular stabilization. In this situation, any attempt of neutralization by the use of isolated coracoclavicular stabilization techniques seems to be associated undertreatment [
      • Dey Hazra R.-O.
      • Blach R.
      • Ellwein A.
      • Lill H.
      • Jensen G.
      3-Year results of arthroscopic management of lateral clavicle fractures.
      ].
      This study has several limitations including the absence of health records of respective donors. Unequal gender distributions complicated conclusions regarding age-related alternations of BMD. However, this effect was equally present in female and male specimen. Thus, the presented approach to identify low bone stock or osteoporosis can only be approximative. Image analysis with automated and autonomic segmentation using adaptive thresholding, though eliminating the subjective impact of interpretation, theoretically risks preclusion of user-controlled visualized correction. The suggested approach of defining cortical porosity based on cortical bone volume fraction cannot meet histological precision as the partial volume effect must be considered to preclude identification of even the smallest vascular and resorption cavities. Otherwise, this shortcoming might be limited at least partially by its consistency across all measurements. Importantly, and given the heterogenous morphology of the clavicle, an exact definition of the location of ligamentous entheses and the intertubercular region from XtremeCT-scans is not possible. Besides epidemiologic fracture characterization, future research might engage imaging, histological and biomechanical methods in order to mimic and understand fracture genesis in light of exact anatomic relations.

      Conclusion

      The distal clavicle features a characteristic bony microarchitecture. The present study revealed a significant difference in bone quality of lateral, intertubercular, and medial regions of the distal clavicle and could specify target areas and strategies for surgical treatment of unstable fractures. Age, gender, and osteoporosis have a limited effect on bone quality and fracture genesis. In contrast, ligamentous quality is supposed to exert a substantial influence on fracture characteristics, especially in ITR. Fracture morphology of the distal clavicle is determined by a bony-ligamentous conjunction, which remains to be characterized. Further studies on ligaments are necessary.

      References

        • Banerjee R.
        • Waterman B.
        • Padalecki J.
        • Robertson W.
        Management of distal clavicle fractures.
        J Am Acad Orthop Surg. 2011; 19: 392-401https://doi.org/10.5435/00124635-201107000-00002
        • Berli M.
        • Borau C.
        • Decco O.
        • Adams G.
        • Cook R.B.
        • García Aznar J.M.
        • et al.
        Localized tissue mineralization regulated by bone remodelling: A computational approach.
        PLoS One. 2017; 12e0173228https://doi.org/10.1371/journal.pone.0173228
        • Chahla J.
        • Marchetti D.C.
        • Moatshe G.
        • Ferrari M.B.
        • Sanchez G.
        • Brady A.W.
        • et al.
        Quantitative Assessment of the Coracoacromial and the Coracoclavicular Ligaments With 3-Dimensional Mapping of the Coracoid Process Anatomy: A Cadaveric Study of Surgically Relevant Structures.
        Arthroscopy. 2018; 34: 1403-1411https://doi.org/10.1016/j.arthro.2017.11.033
        • Chen R.E.
        • Soin S.P.
        • El-Shaar R.
        • Nicandri G.T.
        • Awad H.A.
        • Maloney M.D.
        • et al.
        What Regions of the Distal Clavicle Have the Greatest Bone Mineral Density and Cortical Thickness? A Cadaveric Study.
        Clin Orthop Relat Res. 2019; 477: 2726-2732https://doi.org/10.1097/corr.0000000000000951
        • Dey Hazra R.-O.
        • Blach R.
        • Ellwein A.
        • Lill H.
        • Jensen G.
        3-Year results of arthroscopic management of lateral clavicle fractures.
        Obere Extremität. 2020; 15: 111-117https://doi.org/10.1007/s11678-020-00565-1
        • Fontana A.D.
        • Hoyen H.A.
        • Blauth M.
        • Galm A.
        • Schweizer M.
        • Raas C.
        • et al.
        The variance of clavicular surface morphology is predictable: an analysis of dependent and independent metadata variables.
        JSES Int. 2020; 4: 413-421https://doi.org/10.1016/j.jseint.2020.05.004
        • Helfen T.
        • Sprecher C.M.
        • Eberli U.
        • Gueorguiev B.
        • Müller P.E.
        • Richards R.G.
        • et al.
        High-Resolution Tomography-Based Quantification of Cortical Porosity and Cortical Thickness at the Surgical Neck of the Humerus During Aging.
        Calcif Tissue Int. 2017; 101: 271-279https://doi.org/10.1007/s00223-017-0279-y
        • Huang J.I.
        • Toogood P.
        • Chen M.R.
        • Wilber J.H.
        • Cooperman D.R.
        Clavicular anatomy and the applicability of precontoured plates.
        J Bone Joint Surg Am. 2007; 89: 2260-2265https://doi.org/10.2106/jbjs.G.00111
        • Jäger M.
        • Breitner S.
        [Therapy related classification of lateral clavicular fracture].
        Unfallheilkunde. 1984; 87: 467-473
        • Kamer L.
        • Noser H.
        • Popp A.W.
        • Lenz M.
        • Blauth M.
        Computational anatomy of the proximal humerus: An ex vivo high-resolution peripheral quantitative computed tomography study.
        J Orthop Translat. 2016; 4: 46-56https://doi.org/10.1016/j.jot.2015.09.006
        • Kihlström C.
        • Möller M.
        • Lönn K.
        • Wolf O.
        Clavicle fractures: epidemiology, classification and treatment of 2 422 fractures in the Swedish Fracture Register; an observational study.
        BMC Musculoskelet Disord. 2017; 18: 82https://doi.org/10.1186/s12891-017-1444-1
        • Kim D.W.
        • Kim D.H.
        • Kim B.S.
        • Cho C.H.
        Current Concepts for Classification and Treatment of Distal Clavicle Fractures.
        Clin Orthop Surg. 2020; 12: 135-144https://doi.org/10.4055/cios20010
        • Moya D.
        • Poitevin L.A.
        • Postan D.
        • Azulay G.A.
        • Valente S.
        • Giacomelli F.
        • et al.
        The medial coracoclavicular ligament: anatomy, biomechanics,and clinical relevance-a research study.
        JSES Open Access. 2018; 2: 183-189https://doi.org/10.1016/j.jses.2018.07.001
        • Mys K.
        • Stockmans F.
        • Vereecke E.
        • van Lenthe G.H.
        Quantification of bone microstructure in the wrist using cone-beam computed tomography.
        Bone. 2018; 114: 206-214https://doi.org/10.1016/j.bone.2018.06.006
        • Neer 2nd, C.S.
        Fractures of the distal third of the clavicle.
        Clin Orthop Relat Res. 1968; 58: 43-50
        • Ockert B.
        • Braunstein V.
        • Sprecher C.
        • Shinohara Y.
        • Kirchhoff C.
        • Milz S.
        Attachment sites of the coracoclavicular ligaments are characterized by fibrocartilage differentiation: a study on human cadaveric tissue.
        Scand J Med Sci Sports. 2012; 22: 12-17https://doi.org/10.1111/j.1600-0838.2010.01142.x
        • Ockert B.
        • Wiedemann E.
        • Haasters F.
        [Distal clavicle fractures. Classifications and management].
        Unfallchirurg. 2015; 118: 397-406https://doi.org/10.1007/s00113-015-0003-1
        • Postacchini F.
        • Gumina S.
        • De Santis P.
        • Albo F.
        Epidemiology of clavicle fractures.
        J Shoulder Elbow Surg. 2002; 11: 452-456https://doi.org/10.1067/mse.2002.126613
        • Rieser G.R.
        • Edwards K.
        • Gould G.C.
        • Markert R.J.
        • Goswami T.
        • Rubino L.J.
        Distal-third clavicle fracture fixation: a biomechanical evaluation of fixation.
        Journal of Shoulder and Elbow Surgery. 2013; 22: 848-855https://doi.org/10.1016/j.jse.2012.08.022
        • Rios C.G.
        • Arciero R.A.
        • Mazzocca A.D.
        Anatomy of the clavicle and coracoid process for reconstruction of the coracoclavicular ligaments.
        Am J Sports Med. 2007; 35: 811-817https://doi.org/10.1177/0363546506297536
        • Robinson C.M.
        Fractures of the clavicle in the adult. Epidemiology and classification.
        J Bone Joint Surg Br. 1998; 80: 476-484
        • Sambandam B.
        • Gupta R.
        • Kumar S.
        • Maini L.
        Fracture of distal end clavicle: A review.
        J Clin Orthop Trauma. 2014; 5: 65-73https://doi.org/10.1016/j.jcot.2014.05.007
        • Sheehan S.E.
        • Gaviola G.
        • Sacks A.
        • Gordon R.
        • Shi L.L.
        • Smith S.E.
        Traumatic Shoulder Injuries: A Force Mechanism Analysis of Complex Injuries to the Shoulder Girdle and Proximal Humerus.
        American Journal of Roentgenology. 2013; 201: W409-W424https://doi.org/10.2214/AJR.12.9987
        • Yamada M.
        • Briot J.
        • Pedrono A.
        • Sans N.
        • Mansat P.
        • Mansat M.
        • et al.
        Age- and gender-related distribution of bone tissue of osteoporotic humeral head using computed tomography.
        J Shoulder Elbow Surg. 2007; 16: 596-602https://doi.org/10.1016/j.jse.2007.01.006