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Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance

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Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance. / Lloyd, Ashley A; Gludovatz, Bernd; Riedel, Christoph; Luengo, Emma A; Saiyed, Rehan; Marty, Eric; Lorich, Dean G; Lane, Joseph M; Ritchie, Robert O; Busse, Björn; Donnelly, Eve.

In: P NATL ACAD SCI USA, Vol. 114, No. 33, 15.08.2017, p. 8722-8727.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lloyd, AA, Gludovatz, B, Riedel, C, Luengo, EA, Saiyed, R, Marty, E, Lorich, DG, Lane, JM, Ritchie, RO, Busse, B & Donnelly, E 2017, 'Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance', P NATL ACAD SCI USA, vol. 114, no. 33, pp. 8722-8727. https://doi.org/10.1073/pnas.1704460114

APA

Lloyd, A. A., Gludovatz, B., Riedel, C., Luengo, E. A., Saiyed, R., Marty, E., Lorich, D. G., Lane, J. M., Ritchie, R. O., Busse, B., & Donnelly, E. (2017). Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance. P NATL ACAD SCI USA, 114(33), 8722-8727. https://doi.org/10.1073/pnas.1704460114

Vancouver

Lloyd AA, Gludovatz B, Riedel C, Luengo EA, Saiyed R, Marty E et al. Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance. P NATL ACAD SCI USA. 2017 Aug 15;114(33):8722-8727. https://doi.org/10.1073/pnas.1704460114

Bibtex

@article{dc10961d1a1b41a1b5ad6eada37b36d7,
title = "Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance",
abstract = "Bisphosphonates are the most widely prescribed pharmacologic treatment for osteoporosis and reduce fracture risk in postmenopausal women by up to 50%. However, in the past decade these drugs have been associated with atypical femoral fractures (AFFs), rare fractures with a transverse, brittle morphology. The unusual fracture morphology suggests that bisphosphonate treatment may impair toughening mechanisms in cortical bone. The objective of this study was to compare the compositional and mechanical properties of bone biopsies from bisphosphonate-treated patients with AFFs to those from patients with typical osteoporotic fractures with and without bisphosphonate treatment. Biopsies of proximal femoral cortical bone adjacent to the fracture site were obtained from postmenopausal women during fracture repair surgery (fracture groups, n = 33) or total hip arthroplasty (nonfracture groups, n = 17). Patients were allocated to five groups based on fracture morphology and history of bisphosphonate treatment [+BIS Atypical: n = 12, BIS duration: 8.2 (3.0) y; +BIS Typical: n = 10, 7.7 (5.0) y; +BIS Nonfx: n = 5, 6.4 (3.5) y; -BIS Typical: n = 11; -BIS Nonfx: n = 12]. Vibrational spectroscopy and nanoindentation showed that tissue from bisphosphonate-treated women with atypical fractures was harder and more mineralized than that from bisphosphonate-treated women with typical osteoporotic fractures. In addition, fracture mechanics measurements showed that tissue from patients treated with bisphosphonates had deficits in fracture toughness, with lower crack-initiation toughness and less crack deflection at osteonal boundaries than that of bisphosphonate-na{\"i}ve patients. Together, these results suggest a deficit in intrinsic and extrinsic toughening mechanisms, which contribute to AFFs in patients treated with long-term bisphosphonates.",
keywords = "Journal Article",
author = "Lloyd, {Ashley A} and Bernd Gludovatz and Christoph Riedel and Luengo, {Emma A} and Rehan Saiyed and Eric Marty and Lorich, {Dean G} and Lane, {Joseph M} and Ritchie, {Robert O} and Bj{\"o}rn Busse and Eve Donnelly",
year = "2017",
month = aug,
day = "15",
doi = "10.1073/pnas.1704460114",
language = "English",
volume = "114",
pages = "8722--8727",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "33",

}

RIS

TY - JOUR

T1 - Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance

AU - Lloyd, Ashley A

AU - Gludovatz, Bernd

AU - Riedel, Christoph

AU - Luengo, Emma A

AU - Saiyed, Rehan

AU - Marty, Eric

AU - Lorich, Dean G

AU - Lane, Joseph M

AU - Ritchie, Robert O

AU - Busse, Björn

AU - Donnelly, Eve

PY - 2017/8/15

Y1 - 2017/8/15

N2 - Bisphosphonates are the most widely prescribed pharmacologic treatment for osteoporosis and reduce fracture risk in postmenopausal women by up to 50%. However, in the past decade these drugs have been associated with atypical femoral fractures (AFFs), rare fractures with a transverse, brittle morphology. The unusual fracture morphology suggests that bisphosphonate treatment may impair toughening mechanisms in cortical bone. The objective of this study was to compare the compositional and mechanical properties of bone biopsies from bisphosphonate-treated patients with AFFs to those from patients with typical osteoporotic fractures with and without bisphosphonate treatment. Biopsies of proximal femoral cortical bone adjacent to the fracture site were obtained from postmenopausal women during fracture repair surgery (fracture groups, n = 33) or total hip arthroplasty (nonfracture groups, n = 17). Patients were allocated to five groups based on fracture morphology and history of bisphosphonate treatment [+BIS Atypical: n = 12, BIS duration: 8.2 (3.0) y; +BIS Typical: n = 10, 7.7 (5.0) y; +BIS Nonfx: n = 5, 6.4 (3.5) y; -BIS Typical: n = 11; -BIS Nonfx: n = 12]. Vibrational spectroscopy and nanoindentation showed that tissue from bisphosphonate-treated women with atypical fractures was harder and more mineralized than that from bisphosphonate-treated women with typical osteoporotic fractures. In addition, fracture mechanics measurements showed that tissue from patients treated with bisphosphonates had deficits in fracture toughness, with lower crack-initiation toughness and less crack deflection at osteonal boundaries than that of bisphosphonate-naïve patients. Together, these results suggest a deficit in intrinsic and extrinsic toughening mechanisms, which contribute to AFFs in patients treated with long-term bisphosphonates.

AB - Bisphosphonates are the most widely prescribed pharmacologic treatment for osteoporosis and reduce fracture risk in postmenopausal women by up to 50%. However, in the past decade these drugs have been associated with atypical femoral fractures (AFFs), rare fractures with a transverse, brittle morphology. The unusual fracture morphology suggests that bisphosphonate treatment may impair toughening mechanisms in cortical bone. The objective of this study was to compare the compositional and mechanical properties of bone biopsies from bisphosphonate-treated patients with AFFs to those from patients with typical osteoporotic fractures with and without bisphosphonate treatment. Biopsies of proximal femoral cortical bone adjacent to the fracture site were obtained from postmenopausal women during fracture repair surgery (fracture groups, n = 33) or total hip arthroplasty (nonfracture groups, n = 17). Patients were allocated to five groups based on fracture morphology and history of bisphosphonate treatment [+BIS Atypical: n = 12, BIS duration: 8.2 (3.0) y; +BIS Typical: n = 10, 7.7 (5.0) y; +BIS Nonfx: n = 5, 6.4 (3.5) y; -BIS Typical: n = 11; -BIS Nonfx: n = 12]. Vibrational spectroscopy and nanoindentation showed that tissue from bisphosphonate-treated women with atypical fractures was harder and more mineralized than that from bisphosphonate-treated women with typical osteoporotic fractures. In addition, fracture mechanics measurements showed that tissue from patients treated with bisphosphonates had deficits in fracture toughness, with lower crack-initiation toughness and less crack deflection at osteonal boundaries than that of bisphosphonate-naïve patients. Together, these results suggest a deficit in intrinsic and extrinsic toughening mechanisms, which contribute to AFFs in patients treated with long-term bisphosphonates.

KW - Journal Article

U2 - 10.1073/pnas.1704460114

DO - 10.1073/pnas.1704460114

M3 - SCORING: Journal article

C2 - 28760963

VL - 114

SP - 8722

EP - 8727

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 33

ER -