Table 1  Summary of methods of bone quality with important outcomes, advantages, and limitations

Radiographs

Tingart, M. J. et al. 2003

The Journal of Bone and Joint Surgery

CTI

19

72 ± 11

Humeri

The cortical thickness of the proximal diaphysis is a reliable predictor of the bone quality of the proximal humerus

Radiographs

Ebraheim N. et al. 2000

Spine

Internal architecture

7

57–78

Sacrum

The strongest part of the sacrum is the anterior cortex above the foramina in S1 and S2. The weakest point of the sacrum was found to lie at the level of the junction of S2 and S3

Radiographs

Huber, M. B. et al. 2009

Medical Physics

BMD, texture information

14

70.8 (66.1–73.2)

Femoral specimens

Texture information contained in trabecular bone structure visualized on radiographs may predict whether an implant anchorage can be used and may determine the local bone quality from preoperative radiographs

Radiographs

Thevenot, J. et al. 2013

Journal of Bone and Mineral Research

BMD, THI

178

79.3 ± 10.4

Femoral bone

Conventional radiography is a low‐cost method for evaluating geometry, structure, and fracture risk of bone

Plain radiographs, DEXA, pQCT

Clavert, P. et al. 2016

Surgical Radiologic Anatomy

BMD, CMI

21

NR

Distal humerus

More than a direct evaluation of the bone density with a CT-scan, the cortio-medullar index (CMI) of the distal humerus diaphysis is a predictor of the bone quality of the distal humerus

DEXA

Tan, J. S. et al. 2010

The Spine Journal

BMD

189

NR

Lumbar specimens

In vitro BMD scan on explanted specimens measured lower DEXA values than in situ BMD scans on full cadavers. A correction factor when used resulted in more accurate measure of the in situ BMD

DEXA

Hua Y. et al. 2009

Clinical Oral Implants Research

Fractal analysis, morphometry

19

NR

Mandibular bone

They investigated the accuracy of fractal analysis and morphometry for bone quality assessment as measured with DEXA

DEXA

Choel, L. et al. 2003

Oral Surgery Oral Medicine Oral Pathology, and Oral Radiology

BMD, BMC

63

80.8 ± 10, 82.7 ± 7.3

Mandibular bone

The intra-alveolar trabecular bone of these 21 mandibles is affected by the same local and systemic influences as cortical bone, whereas the infra-alveolar trabecular bone is mostly sensitive to dental status

DEXA

Yang, J. et al. 2012

Journal of Biomechanical Engineering

BMD, BMC

9

NR

Femurs

The proposed technique is capable of detecting differences in bone quality. The ability to measure site-specific properties without exposure to radiation has the potential to be further developed for clinical applications

DEXA, QCT

Johannesdottir, F. et al. 2017

Bone

BMD, microstructures

76

74 ± 8.8

Proximal femurs

Both cortical and trabecular bone contribute to femoral strength, the contribution of cortical bone being higher in femurs with lower trabecular bone density

pQCT

Chaplais E et al. 2014

BMC Musculoskelet Disord

Material properties of bone

11

75 (59–93)

Leg

This protocol extends the capabilities of pQCT to evaluate bone quality in people who may be at an increased risk of metatarsal insufficiency fractures

HR-pQCT

Kirchhoff C. et al. 2012

BMC Musculoskelet Disord

General morphology

64

72.3 ± 17.4

Humeral head

The presented microarchitectural data measured by HR-pQCT allow for future subtle biomechanical testing comprising knowledge on age- and sex-related changes of the tuberosities of the humeral head

HR-pQCT

de Jong, J. J. et al. 2016

The Journal of Bone and Joint Surgery

Bone parameters

15

62–90

Distal radial

HR-pQCT can be used a promising tool to assess the fracture-healing process in patients with fiberglass cast

HR-pQCT; micro-CT

Liu X.S., Sekhon K.K. et al. 2010

J Bone and Mineral Research

Microstructural of human distal tibia

19

70.6 (55–84)

Tibia

Microstructural measurements and mechanical parameters of distal tibia can be efficiently derived from HR-pQCT images and provide additional information regarding bone fragility

HR-pQCT; micro-CT

Jorgenson, B. L. et al. 2015

Bone

Cortical porosity and density

23

66.3 (55–85)

Mid-shaft region of tibiae

The accuracy of the threshold-based method will improve as new HR-pQCT systems emerge and provide a robust quantitative approach to measure cortical porosity

pQCT

Diederichs, G. et al. 2006

Archives of Orthopaedic and Trauma Surgery

Regional BMD

88

75.8 ± 13.5

Humeri

Bone quality at the humeral head is best predicted by BMD measurements at the contralateral location rather than the ipsilateral distal site

HR-pQCT

Manske, S. L. et al. 2015

Bone

Bone microarchitecture

20

70 (49–95)

Radii

These data support the application of analysis techniques in HR-pQCT that are analogous to those traditionally used for micro-CT to assess trabecular microarchitecture

QCT

Mann, C. et al. 2018

Scientific Reports

BMD

10

80 (59–92)

Lumbar spine

A well-established alternative to DXA is QCT, a three-dimensional method which measures trabecular BMD in milligrams per cubic centimeter by indirectly quantifying hydroxyapatite in comparison with a reference phantom

QCT

Zheng Y et al. 2000

Spine

BMD

13

31 (24–36)

Sacrum

This report detailed BMD variations of the S1 body and ala in a young male group of specimens

pQCT

Lu WW. et al. 2000

Clinical Orthopaedics and Related Research

BMD

13

31 (24–36)

Sacrum

The highest bone mineral density in the lumbosacral spine is found at the pedicles and regions closest to pedicle bases

Micro-CT

Lee, J. H. et al. 2017

Journal of Periodontal &Implant Science

3D-microstructure

60

75.7 (67.3–96)

Hemimaxillae

Bone quality depended on trabecular separation (Tb.Sp) and number—that is, endosteal space architecture—rather than bone surface and trabecular thickness (Tb.Th). Regardless of bone quality, Tb.Th showed little variation

Micro-CT

Chen, R. E. et al. 2019

Clinical Orthopaedics and Related Research

BMD, CTI

10

63 (59–67)

Distal clavicular regions

In the distal clavicle, BMD and cortical thickness are greatest in the conoid tubercle and intertubercle space

Micro-CT

Xie, F. et al. 2018

Archives of Osteoporosis

Microstructural properties

67

NR

Spinous processes

Post-menopausal women and older men with osteoporosis have worse bone quality in autografts than non-osteoporotic men and women. Postmenopausal women with osteoporosis presented serious microarchitectural deterioration in older population

Micro-CT

Ding, M. et al. 2012

Bone

microarchitectural, mechanical, collagen and mineral properties of normal adolescent cancellous bone

23

NR

Left proximal tibiae

Micro-CT can be used to measure various parameters, such as 3D microarchitecture, mechanical properties, collagen and mineral properties of adolescent cancellous bone

Micro-CT, radiography

Rupprecht, M. et al. 2006

Journal of Orthopaedic Research

Bone microarchitecture

60

NR

Calcanei

Bone mass and structure are risk factors in respect to the occurrence and severity of calcaneal fractures, and indicate that calcaneal fractures are at least in part osteoporotic fractures

Micro-CT

Greenwood, C. et al. 2018

Aging and Disease

Bone microarchitecture

164

21–93

Femoral heads

Micro-computed tomography was utilised to investigate the microarchitecture of femoral head trabecular bone from a relatively large cohort of non-fracture and fracture human donors

Micro-CT

Kuhn, G. et al. 2007

Journal Homo of Comparative Human Biology

Bone surface structures, microarchitecture

5

NR

Postcranial

Micro-CT is a tool of high value for the examination of postcranial bone disorders. It cannot replace histological examinations completely because it cannot assess the bone quality (woven or lamellar)

Micro-CT

Arnold, E. L. et al. 2020

Journal of the mechanical behaviour of biomechanical materials

BMD, TMD, microarchitectural parameters

100

20–93

Femoral heads

Properties which are not age dependent are significantly different between age-matched non-fracture and fracture specimens, indicating osteoporosis is a disease, and not just an accelerated aging process

Micro-CT

Ding, M. et al. 2003

The Journal of Bone and Joint Surgery

3D microstructural properties

120

73 (63–81); 72 (58–85)

Proximal tibiae

Using unbiased 3-D methods, we have demonstrated microstructural changes in subchondral cancellous bone in human tibial early OA

Micro-CT

Marinozzi, F. et al. 2012

Ann Ist Super Sanita

3D-structure, morphometric parameters

6

NR

femoral heads

Micro-CT is a promising technique for trabecular bone analysis. Bone morphometric parameters obtained by microtomographic processing allows to completely characterize human bone

Micro-CT

Kim, Y. J. et al. 2015

Clinical Implant Density and Related Research

BMD, 3D-microarchitecture

34

NR

Jaw

Two aspects of bone density using micro-CT, the BV/TV and BMD, are highly correlated with 3D micro-architecture parameters, which represent the quality of trabecular bone. This noninvasive method may adequately enhance evaluation of the alveolar bone

Micro-CT

Kamal, M. et al. 2018

The Journal of Craniofacial Surgery

BMD, structural morphometric

60

69.5 (57.3–81.2)

Calvarium, maxillary tuberosity, mandibular ramus, mandibular symphysis, anterior iliac crest, and tibia

The results show great variation in bone densities and 3D morphometric values across different donor sites

Micro-CT

Thomsen J.S. et al. 2013

Bone

BV/TV, Tb.Th, Tb.N, SMI, CD, DA

79

21.7–96.4; 22.6–94.6

Second lumbar vertebral (L2)

Vertical and horizontal oriented bone density decreases with age in both women and men, and that vertical oriented bone is lost more quickly in women than in men,

NMR

Ni, Q.W. et al. 2007

Measurement Science and Technology

Bound and mobile water

10

65.9 (51–87)

Femurs

Bound to mobile water may be used as a measure of bone quality describing both porosity and water content, both of which may be important determinants of bone strength and fracture resistance

HR-MRI

Link, T. M. et al. 2003

European Radiology

Trabecular bone structure

39

76.9 ± 7.2

Distal radius

High-resolution MR-derived structure parameters, however, performed better in the prediction of trabecular bone structure

MRI (HR-MRI)

Vieth V. et al. 2001

Investigative Radiology

Trabecular bone structure parameters

30

68.5 ± 8.2

Calcaneus

Trabecular bone structure depicted by HR-MRI is significantly correlated with that shown in macro-sections

Micro-MRI

Liu, X. S., Rajapakse C. S. et al. 2010

Journal of Bone and Mineral Research

3D model-independent microstructural measurements

25

70.6 (55–84)

Distal tibias

Most microstructural and mechanical properties of the distal tibia can be derived efficiently from micro-MR images and can provide additional information regarding bone quality

Cyclic compressive loading

Goff, M. G.et al. 2015

Bone

Bone microdamage

32

78 ± 8.8

Vertebral cancellous bone

Microdamage accumulation in fatigue is likely dominated by heterogeneity in tissue material properties rather than stress concentrations caused by micro-scale geometry

Compression-tension loading

Bevill, G. et al. 2006

Bone

Bone volume fraction and architecture, bone strength

54

70 ± 11

Femoral neck, greater trochanter, proximal tibia, vertebral body

Within very low-density bone, the potentially important biomechanical effect of large-deformation failure mechanisms on trabecular bone strength is highly heterogeneous and is not well explained by standard architectural metrics

Compression test

Ding M et al. 2001

Acta Orthop Scand

Mechanical and compositional properties

10

73 (63–81)

Proximal tibiae

Cancellous bone quality is reflected by the amount of bone tissue present, the mechanical properties of the tissue, and its trabecular architecture

Compression test

Kalouche, I. et al. 2010

Clinical biomechanics

Mechanical properties

82

88.9 (76–96)

Cadaveric shoulders

Good correlation between apparent density and elastic modulus was found only in the sagittal planes but not in the coronal and axial plane

Compression test

Bayraktar, H. H. et al. 2004

Journal of Biomechanics

Elastic and yield properties

94

65.5 ± 9.1; 71.8 ± 8.8

Femoral neck

The elastic modulus and yield strains for trabecular tissue are just slightly lower than those of cortical tissue, because of the cumulative effect of these differences, tissue strength is about 25% greater for cortical bone

Micro-indentation

Dall'Ara, E. et al. 2012

Bone

Bone microdamage

35

44–82

Thoracolumbar vertebral bodies (T12-L5)

Micro-indentation was found to discriminate between highly damaged and intact tissue in both trabecular and cortical bone tested in vitro. It remains to be investigated whether this technique would be able to detect also the damage

RPI, bending test

Granke, M. et al. 2014

Journal of the mechanical behaviour of biomechanical materials

Tissue anisotropy, mechanical behaviour

26

25–101

Femoral mid-shaft

With a transverse isotropic behaviour akin to tissue hardness and modulus as determined by micro- and nanoindentation and a significant association with toughness, RPI properties are likely influenced by both elastic and plastic behaviour of bone tissue

RPI

Jenkins, T. et al. 2015

Journal of the mechanical behaviour of biomechanical materials

Maximum load, sample orientation, mode of use, sample preparation and measurement spacing

5

67–89

Femoral heads

RPI users can minimize the potential confounding effects associated with the variables investigated here and reduce the coefficient of variation, hence achieving more consistent testing

Nanoindentation

Albert, C. et al. 2013

Clinical biomechanics

Bone tissue elastic modulus and hardness

11

5–18

Lower extremity long bones

Nanoindentation can be used to measure bone material properties, providing valuable data

Cyclic fatigue loading; Micro-CT

Lambers, F. M.et al. 2013

PLoS One

Mechanical properties, microdamage and bone microarchitecture

32

76 ± 8.8

The third lumbar vertebral bodies

Even small amounts of microscopic tissue damage in human vertebral cancellous bone may have large effects on subsequent biomechanical performance

Micro-CT, compression testing

Charlebois, M. et al. 2010

Journal of Biomechanics Engineering

Volume fraction, compressive behaviour

148

53–100

T12 vertebrae, distal radii, femoral head, calcanei

Reasonable predictions of their compressive mechanical behaviour can be made using the volume fraction and fabric over a broad range of strains

Radiographs, Micro-CT, compressive loading

Yeni, Y. N., Wu B., et al. 2013

Journal of Biomechanics Engineering

Microstructure at various levels of compressive deformation

7

NR

Femoral and tibial cancellous bone cylinders

The heterogeneity of the microstructure is especially sensitive to deformation and these could be good parameters to use to estimate strain history in the tissue

QCT, uniaxial compression test

Wachter NJ. et al. 2001

Clinical Biomechanics

Singh index, mechanical competence

31

68.3 ± 11.7

Femurs

Assessment of bone mineral density by QCT is a reliable and precise method for the estimation of cancellous bone material properties

NMR, three-point bending testing

Nyman, J S. et al. 2008

Bone

Mobile and bound water; Bone strength and toughness

18

66.3 (47–87)

Femurs

Quantifying mobile and bound water with magnetic resonance techniques could potentially serve as indicators of bone quality

Bending test, CT scanner

Lettry, S. et al. 2003

Bone

Mechanical properties, CT numbers

5

85.8 (53–106)

Mandible

A weak correlation was found between the modulus values and the CT number of the mandible. This would not be sufficient for accurate predictions of the bone properties from CT scans

Micro-CT, compression test

Karim, L. et al. 2011

Journal of Orthopaedic Research

Bone microdamage

26

18–97

Tibial plateaus

Low bone volume fraction and increased structure model index have strong influences on microdamage accumulation in bone through altered initiation

Micro-CT, micro-indentation, and bending test

Merlo, K. et al. 2020

Journal of Orthopaedic Research

Microarchitecture, Mechanical Properties, and AGEs

40

73.1 ± 10.9

Tibias

The accumulation of AGEs would cause lower elastic modulus and lower fracture toughness in human cortical bone

Micro-CT, RPI

Beutel, B. G. et al. 2015

Bone

BV/TV, Porosity, Mechanical outputs

6

79 (76–88)

Tibiae

RPI parameters will help to further facilitate its use as a clinical diagnostic tool

RPI, bending test

Krege J.B. et al. 2016

Bone

IDI, TID, bone toughness

4

76–85

Femora

RPI measurements alone, as compared to bending tests, are insufficient to reach conclusions regarding mechanical properties of bone

Indentation testing, CT scanner

Zumstein, V. et al. 2012

Journal of Shoulder and Elbow Surgery

Mechanical strength, subchondral mineralization

32

80.5 (59–95)

Shoulder

Mechanical strength and subchondral mineralization in the humeral head are significantly associated

X-ray radiograms, tensile fracture toughness

Yeni, Y. N. Brown C. U.et al. 2013

Journal of the mechanical behaviour of biomechanical materials

Femoral cortex geometry, tissue mechanical properties

25

53.3 ± 19.7

femurs

Fracture toughness of the tissue was significantly related to radiogram metric indices and that some of these indices explained a greater variability in toughness than porosity, age or gender

Micro-CT, nanoindentation, compressive loading

Li, Z. C. et al. 2012

Arthritis Rheum

Fatigue strength, microarchitecture, mineralization degree, and biomechanical properties

60

53–86; 59–87

Femoral head

The difference in mechanical properties between osteoarthritis and osteoporosis cancellous bone is attributed to different bone mass and bone structure

Compressive loading, microscopic analysis

Hernandez, C. J. et al. 2014

Bone

Mechanical properties, BV/TV and microdamage

47

64–92

Vertebral cancellous bone

Small amounts of microdamage do not necessarily indicate impaired mechanical performance, the presence of modest amounts of microdamage is always indicative of large reductions in cancellous bone stiffness and strength

Bending test, RPI, nanoindentation

Katsamenis, O. L. et al. 2015

Bone

Fracture toughness, crack growth resistance

4

63.25 (43–83)

Femurs

RPI is an emerging technique with the clinical potential for the direct assessment of the mechanical properties of the bone

Bone composition; Compression test

Follet, H. et al. 2004

Bone

DBM, mechanical properties

20

78 ± 8

Calcaneus

The increase in bone strength when DBM is modified in a physiological range without necessary changes of bone matrix volume and bone microarchitecture

Bone composition

Saito, M. et al. 2006

Calcified Tissue International

DBM, collagen crosslinking

50

78 ± 6

77 ± 6

Hip

Detrimental crosslinking in both low and high mineralized bone result in impaired bone quality in osteoporotic patients

Bone composition

Karim, L. et al. 2012

PLoS One

Heterogeneous glycation

42

59.3 ± 22.1

tibial plateaus

The extent of NEG in tibial cancellous bone was the dominant predictor of bone fragility and was associated with changes in microarchitecture and microdamage

Bone composition

Willett, T. L.et al. 2019

Bone

bone collagen integrity parameters, fracture toughness

54

64.4 ± 21.3

Femurs or femur mid-shafts

Bone collagen integrity as measured by thermomechanical methods is a key factor in cortical bone fracture toughness

Bone composition

Poundarik, A. A. et al. 2015

Journal of the mechanical behaviour of biomechanical materials

Glycated collagen

9

34–85

Tibiae

Advanced glycation end-products (AGEs) are predictive of bone quality in aging humans and have diagnostic applications in fracture risk

Bone composition

Ural, A. et al. 2015

Osteoporosis international

NEG

96

60.6 ± 21.0

Proximal end of tibiae

AGEs alter the resorption process and/or accumulate in the tissue as a result of reduced resorption and may lead to bone fragility by adversely affecting fracture resistance through altered bone matrix properties

Bone composition

Wang X et al. 2002

Bone

Collagen molecular structures, mechanical integrity of the collagen network, mechanical properties of bone

30

19–89

Femurs

The adverse changes in the collagen network occur as people age and such changes may lead to the decreased toughness of bone. Also, the results suggest that nonenzymatic glycation may be an important contributing factor causing changes in collagen and, consequently, leading to the age-related deterioration of bone quality