Longitudinal associations of insulin resistance with change in bone mineral density in midlife women
Albert Shieh, Gail A. Greendale, Jane A. Cauley, Preethi Srikanthan, Arun S. Karlamangla
Albert Shieh, Gail A. Greendale, Jane A. Cauley, Preethi Srikanthan, Arun S. Karlamangla
View: Text | PDF
Clinical Research and Public Health Bone biology

Longitudinal associations of insulin resistance with change in bone mineral density in midlife women

Abstract

BACKGROUND The effects of insulin resistance on bone mineral density (BMD) are unclear.METHODS In Study of Women’s Health Across the Nation (SWAN) participants, we used multivariable regression to test average insulin resistance (homeostatic model assessment of insulin resistance, HOMA-IR) and rate of change in insulin resistance as predictors of rate of change in lumbar spine (LS) and femoral neck (FN) BMD in 3 stages: premenopause (n = 861), menopause transition (MT) (n = 571), and postmenopause (n = 693). Models controlled for age, average BW, change in BW, cigarette use, race and ethnicity, and study site.RESULTS The relation between HOMA-IR and BMD decline was biphasic. When average log2HOMA-IR was less than 1.5, greater HOMA-IR was associated with slower BMD decline; i.e., each doubling of average HOMA-IR in premenopause was associated with a 0.0032 (P = 0.01, LS) and 0.0041 (P = 0.004, FN) g/cm2 per year slower BMD loss. When greater than or equal to 1.5, average log2HOMA-IR was not associated with BMD change. In women in whom HOMA-IR decreased in premenopause, the association between the HOMA-IR change rate and BMD change rate was positive; i.e, slower HOMA-IR decline was associated with slower BMD loss. In women in whom insulin resistance increased in premenopause, the association was negative; i.e, faster HOMA-IR rise was associated with faster BMD decline. Associations of average HOMA-IR and HOMA-IR change rate with BMD change rate were similar in postmenopause, but weaker during the MT.CONCLUSION When it decreases, insulin resistance is associated with BMD preservation; when it increases, insulin resistance is associated with BMD loss.FUNDING The SWAN has grant support from the NIH of the Department of Health and Human Services (DHHS) through the NIH National Institute on Aging (NIA), National Institute of Nursing Research (NINR), and Office of Research on Women’s Health (ORWH) (grants U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, and U19AG063720).

Authors

Albert Shieh, Gail A. Greendale, Jane A. Cauley, Preethi Srikanthan, Arun S. Karlamangla

×

Figure 2

Annualized change in BMD versus annualized change in insulin resistance.

Options: View larger image (or click on image) Download as PowerPoint
Annualized change in BMD versus annualized change in insulin resistance....
For each midlife stage (premenopause, the MT, and postmenopause), we used LOESS to visualize the relation between annualized change in LS or FN BMD (g/cm2 per year) versus the annualized change in log2HOMA-IR. Annualized rates of change in BMD or log2HOMA-IR were calculated as the difference between the last and first BMD or log2HOMA-IR values in a midlife stage divided by the number of intervening years. A more positive rate of change indicates slower decrease in BMD or log2HOMA-IR, and a more negative rate indicates faster decline in BMD log2HOMA-IR. Here, we show the LOESS plot for change in LS BMD versus the change in log2HOMA-IR from premenopause. LOESS plots for the FN and the other midlife stages (menopause transition, postmenopause) were similar. Note the biphasic relation: when the change in log2HOMA-IR was less than 0 (insulin resistance decreasing), a more positive rate of change in log2HOMA-IR (slower decrease in insulin resistance) correlated with a more positive rate of change in BMD (slower bone loss); when the change in log2HOMA-IR was greater than or equal to 0 (insulin resistance increasing), a more positive rate of change in log2HOMA-IR (faster rise in insulin resistance) related to a more negative rate of change in BMD (faster bone loss).