September 21, 2009 (Denver, Colorado) — Despite having higher levels of bone-mineral density (BMD) prior to menopause, women with diabetes show a substantially greater rate of total hip bone loss as they transition through menopause, compared with women who don't have diabetes. However, bone loss in the spine is slower in people with diabetes than in people without nondiabetes, according to findings presented here at American Society for Bone and Mineral Research 31st Annual Meeting.
The longitudinal study looked at data for 2245 multiethnic women, between the ages of 42 and 52 years, participating in the Study of Women's Health Across the Nation (SWAN) at 5 research centers in the United States between 1996 and 2004.
At baseline, women with diabetes had a total hip mean BMD that was 14% higher (P?< .01) than those without diabetes, and a lumbar spine BMD that was 9% higher (P?< .01); levels of the bone resorption biomarker urinary N-telopeptide of type?1 collagen (NTx/CR) were comparable.
Over an average follow-up period of 3.3 years, the overall rate of decline in hip BMD for women with diabetes throughout menopause was 10-fold greater (P?= .003) than for women without diabetes.
Women without diabetes, however, had a rate of spinal BMD loss that was significantly higher than for women with diabetes (P?= .005).
The number of women with diabetes reporting a fracture over the follow-up period was 2-fold higher (4%) than those without diabetes (2%).
"The study provides evidence that despite higher baseline BMD at all bone sites, rate of total hip bone loss is greater in women with diabetes but [spine-bone loss is lower] as they transition menopause," the researchers conclude.
The mechanisms behind the higher rates of bone loss and fracture risk seen in postmenopausal women remain unclear, but factors such as insulin fluctuations are considered prime culprits, said Naila Khalil, PhD, lead author of the study and postdoctoral research associate with the Department of Community Health, Lifespan Health Research Center, at Wright State University in Kettering, Ohio.
"New bone formation and bone quality, including microarchitectural bone composition and characteristics of bone strength, may be impaired in people with diabetes, leading to lower mechanical strength and a propensity to fracture," she said.
"Bone quality may be affected through multiple pathways, including changes in insulin or insulin-like factors, higher concentrations of advanced glycation end products in collagen, hypercalciuria, nephropathy, microangiopathy, and inflammation," Dr. Khalil said.
The combination of poor bone quality and microstructure could reduce bone strength, she said, adding that another possible explanation for decreased bone strength in diabetes could be accelerated bone loss.
"As observed in our study, more rapid bone loss may cause a decrease in bone strength that cannot be calculated from BMD as measured by [dual-energy x-ray absorptiometry]."
Khalil said the findings shed new light on how early in menopause the acceleration of bone loss begins.
"The 3-fold faster bone loss in hip BMD for diabetic vs nondiabetic women and the incident fractures so early in menopause were surprising to us, and this was seen in relatively healthier women, as we controlled for their baseline health status."
Ann V. Schwartz, PhD, associate professor of epidemiology and biostatistics at the University of California at San Francisco, said the differences in rates of bone loss in the hip and spine among diabetic women are particularly notable.
"I thought it was most interesting that there was more rapid bone loss at the hip for the women with diabetes, but there was an opposite finding at the spine," she said.
Previous reports have also shown more rapid bone loss at the hip, in spite of higher baseline BMD, among women with type?2 diabetes, with the suggestion being that type?2 diabetes has a positive effect on trabecular bone but possibly a negative effect on cortical bone, Dr. Schwartz explained. "That would be consistent with this report of more rapid loss at the hip but relative preservation at the spine."
The findings underscore the need to consider a heightened fracture risk among women with diabetes, she added.
"In assessing fracture risk in women with type?2 diabetes, including in this age range, clinicians have to take into account patients' increased fracture risk at a given BMD," she said. "Usual T-score and FRAX score thresholds will underestimate fracture risk."
The study received financial support from the National Institutes of Health. Dr. Khalil has disclosed no relevant financial relationships. Dr. Schwartz reports receiving research support from Merck, Amgen, and GlaxoSmithKline, and has been a consultant for Merck.
American Society for Bone and Mineral Research (ASBMR) 31st Annual Meeting: Abstract 1205. Presented September 13, 2009.
