Cluster analysis of bone microarchitecture from high resolution peripheral quantitative computed tomography demonstrates two separate phenotypes associated with high fracture risk in men and women.

Osteoporosis is a major healthcare problem which is conventionally assessed by dual energy X-ray absorptiometry (DXA). New technologies such as high resolution peripheral quantitative computed tomography (HRpQCT) also predict fracture risk. HRpQCT measures a number of bone characteristics that may inform specific patterns of bone deficits. We used cluster analysis to define different bone phenotypes and their relationships to fracture prevalence and areal bone mineral density (BMD). 177 men and 159 women, in whom fracture history was determined by self-report and vertebral fracture assessment, underwent HRpQCT of the distal radius and femoral neck DXA. Five clusters were derived with two clusters associated with elevated fracture risk. "Cluster 1" contained 26 women (50.0% fractured) and 30 men (50.0% fractured) with a lower mean cortical thickness and cortical volumetric BMD, and in men only, a mean total and trabecular area more than the sex-specific cohort mean. "Cluster 2" contained 20 women (50.0% fractured) and 14 men (35.7% fractured) with a lower mean trabecular density and trabecular number than the sex-specific cohort mean. Logistic regression showed fracture rates in these clusters to be significantly higher than the lowest fracture risk cluster [5] (p<0.05). Mean femoral neck areal BMD was significantly lower than cluster 5 in women in cluster 1 and 2 (p<0.001 for both), and in men, in cluster 2 (p<0.001) but not 1 (p=0.220). In conclusion, this study demonstrates two distinct high risk clusters in both men and women which may differ in etiology and response to treatment. As cluster 1 in men does not have low areal BMD, these men may not be identified as high risk by conventional DXA alone.

[1]  E. Vicaut,et al.  A case-control study of fractures in men with idiopathic osteoporosis: fractures are associated with older age and low cortical bone density. , 2013, Bone.

[2]  Sharmila Majumdar,et al.  Age- and Gender-Related Differences in the Geometric Properties and Biomechanical Significance of Intracortical Porosity in the Distal Radius and Tibia , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[3]  C. Cooper,et al.  Epidemiology of fractures in England and Wales. , 2001, Bone.

[4]  K. Morgan,et al.  Levels of customary physical activity among the old and the very old living at home. , 1988, Journal of epidemiology and community health.

[5]  P. Rüegsegger,et al.  A new method for the model‐independent assessment of thickness in three‐dimensional images , 1997 .

[6]  A. Silman,et al.  Validity of Self-Report of Fractures: Results from a Prospective Study in Men and Women Across Europe , 2000, Osteoporosis International.

[7]  M. Bouxsein,et al.  In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. , 2005, The Journal of clinical endocrinology and metabolism.

[8]  C. Finch,et al.  Patterns of comorbidity in community-dwelling older people hospitalised for fall-related injury: A cluster analysis , 2011, BMC geriatrics.

[9]  M. Nevitt,et al.  Vertebral fracture assessment using a semiquantitative technique , 1993, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[10]  J. Molinero,et al.  Dual energy X-ray absorptimetry: Fundamentals, methodology, and clinical applications , 2012 .

[11]  Sharmila Majumdar,et al.  Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. , 2010, Bone.

[12]  P. Delmas,et al.  Alterations of Cortical and Trabecular Architecture Are Associated With Fractures in Postmenopausal Women, Partially Independent of Decreased BMD Measured by DXA: The OFELY Study , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[13]  O. Johnell,et al.  Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures , 1996 .

[14]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[15]  Ego Seeman,et al.  Pathogenesis of bone fragility in women and men , 2002, The Lancet.

[16]  P. Rüegsegger,et al.  In vivo high resolution 3D-QCT of the human forearm. , 1998, Technology and health care : official journal of the European Society for Engineering and Medicine.

[17]  Bert Van Rietbergen,et al.  Finite element analysis performed on radius and tibia HR-pQCT images and fragility fractures at all sites in postmenopausal women. , 2010, Bone.

[18]  E. Seeman Reduced bone formation and increased bone resorption: rational targets for the treatment of osteoporosis , 2003, Osteoporosis International.

[19]  Hoi-Jeong Lim,et al.  Classification of facial asymmetry by cluster analysis. , 2007, American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics.

[20]  Steven K Boyd,et al.  Automatic segmentation of cortical and trabecular compartments based on a dual threshold technique for in vivo micro-CT bone analysis. , 2007, Bone.

[21]  C. Cooper,et al.  Osteoporosis in the European Union: medical management, epidemiology and economic burden , 2013, Archives of Osteoporosis.

[22]  J. Macneil,et al.  Accuracy of high-resolution peripheral quantitative computed tomography for measurement of bone quality. , 2007, Medical engineering & physics.

[23]  C. Cooper,et al.  Cohort profile: the Hertfordshire cohort study. , 2005, International journal of epidemiology.

[24]  H K Genant,et al.  Structural Adaptation to Changing Skeletal Load in the Progression Toward Hip Fragility: The Study of Osteoporotic Fractures , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[25]  C. Cooper,et al.  Diet and Its Relationship with Grip Strength in Community‐Dwelling Older Men and Women: The Hertfordshire Cohort Study , 2008, Journal of the American Geriatrics Society.

[26]  X. Guo,et al.  Abnormal Microarchitecture and Reduced Stiffness at the Radius and Tibia in Postmenopausal Women With Fractures , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[27]  J. Azpeitia Armán,et al.  Dual energy X-ray absorptimetry: fundamentals, methodology, and clinical applications. , 2012, Radiologia.

[28]  S. Eckstein Ethical principles for medical research involving human subjects. , 2001, European journal of emergency medicine : official journal of the European Society for Emergency Medicine.

[29]  Ann L Oberg,et al.  Effects of Sex and Age on Bone Microstructure at the Ultradistal Radius: A Population‐Based Noninvasive In Vivo Assessment , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[30]  M. Kleerekoper,et al.  Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. , 1983, The Journal of clinical investigation.