Adding Marrow Adiposity and Cortical Porosity to Femoral Neck Areal Bone Mineral Density Improves the Discrimination of Women With Nonvertebral Fractures From Controls

Roger Zebaze, Marit Osima, Minh Bui, Marko Lukic, Xiaofang Wang, Ali Ghasem-Zadeh, Erik F. Eriksen, Angela Vais, Catherine Shore-Lorenti, Peter R. Ebeling, Ego Seeman, Åshild Bjørnerem

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Advancing age is accompanied by a reduction in bone formation and remodeling imbalance, which produces microstructural deterioration. This may be partly caused by a diversion of mesenchymal cells towards adipocytes rather than osteoblast lineage cells. We hypothesized that microstructural deterioration would be associated with an increased marrow adiposity, and each of these traits would be independently associated with nonvertebral fractures and improve discrimination of women with fractures from controls over that achieved by femoral neck (FN) areal bone mineral density (aBMD) alone. The marrow adiposity and bone microstructure were quantified from HR-pQCT images of the distal tibia and distal radius in 77 women aged 40 to 70 years with a recent nonvertebral fracture and 226 controls in Melbourne, Australia. Marrow fat measurement from HR-pQCT images was validated using direct histologic measurement as the gold standard, at the distal radius of 15 sheep, with an agreement (R2 = 0.86, p < 0.0001). Each SD higher distal tibia marrow adiposity was associated with 0.33 SD higher cortical porosity, and 0.60 SD fewer, 0.24 SD thinner, and 0.72 SD more-separated trabeculae (all p < 0.05). Adjusted for age and FN aBMD, odds ratios (ORs) (95% CI) for fracture per SD higher marrow adiposity and cortical porosity were OR, 3.39 (95% CI, 2.14 to 5.38) and OR, 1.79 (95% CI, 1.14 to 2.80), respectively. Discrimination of women with fracture from controls improved when cortical porosity was added to FN aBMD and age (area under the receiver-operating characteristic curve [AUC] 0.778 versus 0.751, p = 0.006) or marrow adiposity was added to FN aBMD and age (AUC 0.825 versus 0.751, p = 0.002). The model including FN aBMD, age, cortical porosity, trabecular thickness, and marrow adiposity had an AUC = 0.888. Results were similar for the distal radius. Whether marrow adiposity and cortical porosity indices improve the identification of women at risk for fractures requires validation in prospective studies.

Original languageEnglish
Number of pages10
JournalJournal of Bone and Mineral Research
DOIs
Publication statusAccepted/In press - 18 Mar 2019

Keywords

  • CORTICAL POROSITY
  • HR-PQCT
  • MARROW ADIPOSITY
  • NONVERTEBRAL FRACTURE
  • WOMEN

Cite this

Zebaze, Roger ; Osima, Marit ; Bui, Minh ; Lukic, Marko ; Wang, Xiaofang ; Ghasem-Zadeh, Ali ; Eriksen, Erik F. ; Vais, Angela ; Shore-Lorenti, Catherine ; Ebeling, Peter R. ; Seeman, Ego ; Bjørnerem, Åshild. / Adding Marrow Adiposity and Cortical Porosity to Femoral Neck Areal Bone Mineral Density Improves the Discrimination of Women With Nonvertebral Fractures From Controls. In: Journal of Bone and Mineral Research. 2019.
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title = "Adding Marrow Adiposity and Cortical Porosity to Femoral Neck Areal Bone Mineral Density Improves the Discrimination of Women With Nonvertebral Fractures From Controls",
abstract = "Advancing age is accompanied by a reduction in bone formation and remodeling imbalance, which produces microstructural deterioration. This may be partly caused by a diversion of mesenchymal cells towards adipocytes rather than osteoblast lineage cells. We hypothesized that microstructural deterioration would be associated with an increased marrow adiposity, and each of these traits would be independently associated with nonvertebral fractures and improve discrimination of women with fractures from controls over that achieved by femoral neck (FN) areal bone mineral density (aBMD) alone. The marrow adiposity and bone microstructure were quantified from HR-pQCT images of the distal tibia and distal radius in 77 women aged 40 to 70 years with a recent nonvertebral fracture and 226 controls in Melbourne, Australia. Marrow fat measurement from HR-pQCT images was validated using direct histologic measurement as the gold standard, at the distal radius of 15 sheep, with an agreement (R2 = 0.86, p < 0.0001). Each SD higher distal tibia marrow adiposity was associated with 0.33 SD higher cortical porosity, and 0.60 SD fewer, 0.24 SD thinner, and 0.72 SD more-separated trabeculae (all p < 0.05). Adjusted for age and FN aBMD, odds ratios (ORs) (95{\%} CI) for fracture per SD higher marrow adiposity and cortical porosity were OR, 3.39 (95{\%} CI, 2.14 to 5.38) and OR, 1.79 (95{\%} CI, 1.14 to 2.80), respectively. Discrimination of women with fracture from controls improved when cortical porosity was added to FN aBMD and age (area under the receiver-operating characteristic curve [AUC] 0.778 versus 0.751, p = 0.006) or marrow adiposity was added to FN aBMD and age (AUC 0.825 versus 0.751, p = 0.002). The model including FN aBMD, age, cortical porosity, trabecular thickness, and marrow adiposity had an AUC = 0.888. Results were similar for the distal radius. Whether marrow adiposity and cortical porosity indices improve the identification of women at risk for fractures requires validation in prospective studies.",
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author = "Roger Zebaze and Marit Osima and Minh Bui and Marko Lukic and Xiaofang Wang and Ali Ghasem-Zadeh and Eriksen, {Erik F.} and Angela Vais and Catherine Shore-Lorenti and Ebeling, {Peter R.} and Ego Seeman and {\AA}shild Bj{\o}rnerem",
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Adding Marrow Adiposity and Cortical Porosity to Femoral Neck Areal Bone Mineral Density Improves the Discrimination of Women With Nonvertebral Fractures From Controls. / Zebaze, Roger; Osima, Marit; Bui, Minh; Lukic, Marko; Wang, Xiaofang; Ghasem-Zadeh, Ali; Eriksen, Erik F.; Vais, Angela; Shore-Lorenti, Catherine; Ebeling, Peter R.; Seeman, Ego; Bjørnerem, Åshild.

In: Journal of Bone and Mineral Research, 18.03.2019.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Adding Marrow Adiposity and Cortical Porosity to Femoral Neck Areal Bone Mineral Density Improves the Discrimination of Women With Nonvertebral Fractures From Controls

AU - Zebaze, Roger

AU - Osima, Marit

AU - Bui, Minh

AU - Lukic, Marko

AU - Wang, Xiaofang

AU - Ghasem-Zadeh, Ali

AU - Eriksen, Erik F.

AU - Vais, Angela

AU - Shore-Lorenti, Catherine

AU - Ebeling, Peter R.

AU - Seeman, Ego

AU - Bjørnerem, Åshild

PY - 2019/3/18

Y1 - 2019/3/18

N2 - Advancing age is accompanied by a reduction in bone formation and remodeling imbalance, which produces microstructural deterioration. This may be partly caused by a diversion of mesenchymal cells towards adipocytes rather than osteoblast lineage cells. We hypothesized that microstructural deterioration would be associated with an increased marrow adiposity, and each of these traits would be independently associated with nonvertebral fractures and improve discrimination of women with fractures from controls over that achieved by femoral neck (FN) areal bone mineral density (aBMD) alone. The marrow adiposity and bone microstructure were quantified from HR-pQCT images of the distal tibia and distal radius in 77 women aged 40 to 70 years with a recent nonvertebral fracture and 226 controls in Melbourne, Australia. Marrow fat measurement from HR-pQCT images was validated using direct histologic measurement as the gold standard, at the distal radius of 15 sheep, with an agreement (R2 = 0.86, p < 0.0001). Each SD higher distal tibia marrow adiposity was associated with 0.33 SD higher cortical porosity, and 0.60 SD fewer, 0.24 SD thinner, and 0.72 SD more-separated trabeculae (all p < 0.05). Adjusted for age and FN aBMD, odds ratios (ORs) (95% CI) for fracture per SD higher marrow adiposity and cortical porosity were OR, 3.39 (95% CI, 2.14 to 5.38) and OR, 1.79 (95% CI, 1.14 to 2.80), respectively. Discrimination of women with fracture from controls improved when cortical porosity was added to FN aBMD and age (area under the receiver-operating characteristic curve [AUC] 0.778 versus 0.751, p = 0.006) or marrow adiposity was added to FN aBMD and age (AUC 0.825 versus 0.751, p = 0.002). The model including FN aBMD, age, cortical porosity, trabecular thickness, and marrow adiposity had an AUC = 0.888. Results were similar for the distal radius. Whether marrow adiposity and cortical porosity indices improve the identification of women at risk for fractures requires validation in prospective studies.

AB - Advancing age is accompanied by a reduction in bone formation and remodeling imbalance, which produces microstructural deterioration. This may be partly caused by a diversion of mesenchymal cells towards adipocytes rather than osteoblast lineage cells. We hypothesized that microstructural deterioration would be associated with an increased marrow adiposity, and each of these traits would be independently associated with nonvertebral fractures and improve discrimination of women with fractures from controls over that achieved by femoral neck (FN) areal bone mineral density (aBMD) alone. The marrow adiposity and bone microstructure were quantified from HR-pQCT images of the distal tibia and distal radius in 77 women aged 40 to 70 years with a recent nonvertebral fracture and 226 controls in Melbourne, Australia. Marrow fat measurement from HR-pQCT images was validated using direct histologic measurement as the gold standard, at the distal radius of 15 sheep, with an agreement (R2 = 0.86, p < 0.0001). Each SD higher distal tibia marrow adiposity was associated with 0.33 SD higher cortical porosity, and 0.60 SD fewer, 0.24 SD thinner, and 0.72 SD more-separated trabeculae (all p < 0.05). Adjusted for age and FN aBMD, odds ratios (ORs) (95% CI) for fracture per SD higher marrow adiposity and cortical porosity were OR, 3.39 (95% CI, 2.14 to 5.38) and OR, 1.79 (95% CI, 1.14 to 2.80), respectively. Discrimination of women with fracture from controls improved when cortical porosity was added to FN aBMD and age (area under the receiver-operating characteristic curve [AUC] 0.778 versus 0.751, p = 0.006) or marrow adiposity was added to FN aBMD and age (AUC 0.825 versus 0.751, p = 0.002). The model including FN aBMD, age, cortical porosity, trabecular thickness, and marrow adiposity had an AUC = 0.888. Results were similar for the distal radius. Whether marrow adiposity and cortical porosity indices improve the identification of women at risk for fractures requires validation in prospective studies.

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KW - HR-PQCT

KW - MARROW ADIPOSITY

KW - NONVERTEBRAL FRACTURE

KW - WOMEN

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DO - 10.1002/jbmr.3721

M3 - Article

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

SN - 0884-0431

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