FP24-6 Insulin Resistance and BONE Strength. Findings From The Study Of Midlife In The United States

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP24-New Mechanisms in Bone Biology: From Cells to Genetics, & Mice to Men
Basic/Clinical
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:10 AM
Room 121 (Moscone Center)

Poster Board SUN-203
Preethi Srikanthan*1, Carolyn J Crandall1, Dana Miller-Martinez1, Teresa E Seeman1, Gail Greendale1, Neil C Binkley2 and Arun S Karlamangla1
1UCLA, CA, 2Univ of Wisconsin-Madison, Madison, WI
Background:  While several studies have noted increased fracture risk in individuals with type 2 DM (T2DM), the pathophysiologic mechanisms underlying this association are not known; in fact, bone mineral density (BMD) is generally higher in T2DM than in non-diabetics. We hypothesize that insulin resistance (the key pathology in T2DM) negatively influences bone remodeling and leads to reduced bone strength relative to load.

Methods : Data came from 717 participants in the Biomarker Project of the Midlife in the United States Study (MIDUS II). Blood glucose and insulin levels measured from fasting morning blood samples were used to calculate insulin resistance by the Homeostasis model assessment of insulin resistance (HOMA-IR). Projected 2D (areal) BMD was measured in the lumbar spine and left hip using dual-energy X-ray absorptiometry (DXA). Femoral neck axis length and width (FNAL and FNW, respectively) were measured from the hip DXA scans using software provided by the manufacturers.  Body weight and height were measured and used to create composite indices of femoral neck strength relative to load in different failure modes as BMD*FNW/weight for compression strength, BMD*(FNW)2/(FNAL*weight) for bending strength, and BMD*FNW*FNAL/(height*weight) for impact strength. We used multiple linear regression to examine the relationship between HOMA-IR and  the strength indices, adjusted for age, gender, menopausal transition stage (in women),  race, body mass index, and study site. 

Results:  Greater insulin resistance was associated with lower values of all three composite indices of femoral neck strength relative to load. Every doubling of HOMA-IR was associated with 0.10 to 0.14 standard deviations (SD) decrement in the strength indices (p<0.001). On their own, higher levels of fasting insulin (but not of glucose) were independently associated with lower bone strength: each doubling of fasting insulin was associated with 0.08 to 0.16 SD decrement in the three femoral neck composite strength indices.

Conclusions: Our study confirms a negative association between insulin resistance and femoral neck strength relative to load. Further, we note that hyperinsulinemia, rather than hyperglycemia, underlies this relationship. This suggests that insulin resistance and in particular, hyperinsulinemia, may negatively affect bone formation and bone strength relative to load.

Nothing to Disclose: PS, CJC, DM, TES, GG, NCB, ASK

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This research was supported by National Institutes of Health grant numbers 1R01AG033067, R01-AG-032271, and P01-AG-020166. The UCLA GCRC helped support this study (UCLA GCRC Grant # M01- RR000865).
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