糖尿病患的停經後髖骨骨折流失加速

作者：Nancy A. Melville  
出處：WebMD醫學新聞

　　September 21, 2009 (科羅拉多州丹佛) — 根據發表於美國骨質研究協會第31屆年會中的研究報告，即使停經之前的骨質密度(BMD)值高，糖尿病婦女在停經之後的整體髖骨流失速率，明顯比沒有糖尿病者更快。不過，糖尿病患的脊椎骨質流失比沒有糖尿病者慢一些。
　　
　　這篇縱向研究探討年齡在42至52歲間、2,245名各種族婦女的資料，她們在1996至2004年間，於5個研究中心參加「Study of Women's Health Across the Nation (SWAN)」這項研究。
　　
　　開始時，糖尿病婦女的整體髖骨平均BMD值比沒有糖尿病者高14%(P< .01)，腰椎BMD值高9%(P< .01)； 骨骼再吸收生物標記、尿中第1型膠原的氮末端胜肽(N-telopeptide)值相當。
　　
　　平均3.3年的追蹤期間，糖尿病婦女在整個停經期間的髖骨BMD值衰退率，是沒有糖尿病婦女的10倍 (P= .003)。
　　
　　不過，沒有糖尿病婦女的脊椎BMD值流失顯著高於糖尿病婦女(P= .005)。
　　
　　糖尿病婦女在整個追蹤期間的骨折比率(4%)是沒有糖尿病婦女(2%)的2倍。
　　
　　研究者結論表示，該研究提供的證據顯示，轉為停經的過程中，儘管原本在各骨骼處的BMD值較高，糖尿病婦女的整體髖骨骨質流失率高於沒有糖尿病的婦女，但是脊椎骨質流失率較低。
　　
　　該研究的第一作者、俄亥俄萊特州立大學生命健康研究中心社區健康組、博士後研究助理Naila Khalil博士表示，停經婦女骨質流失和骨折比率較高的機轉依舊不清楚，但是胰島素波動等因素被視為首要原因。
　　
　　她表示，新骨形成以及骨骼品質，包括骨骼強度的微細骨組織骨組成和特徵，這些在糖尿病患可能不佳，造成機械強度較低以及容易骨折。
　　
　　Khalil博士表示，骨骼品質受到多種方面因素影響，包括胰島素或類胰島素因素的改變、膠原糖化終產物濃度較高、高尿鈣症、腎病變、小血管病變以及發炎。
　　
　　她表示，骨骼品質與微小結構不佳會降低骨骼強度，指出糖尿病骨骼強度降低的另一個可能解釋是骨骼流失加速。
　　
　　如同我們研究觀察到的，骨骼流失加速會造成骨骼強度降低，這無法用雙能量x光吸收儀測得的BMD值計算得知。
　　
　　Khalil博士表示，研究點出了停經時骨質很早即開始加速流失的新發現。
　　
　　糖尿病婦女的髖骨BMD值流失得比非糖尿病婦女快3倍，以及在停經後很快就發生骨折，這兩個發現令我們感到驚訝，且這在開始時健康狀態相對較健康的控制組婦女也是。
　　
　　加州大學舊金山分校流行病學與生物統計副教授Ann V. Schwartz博士表示，糖尿病婦女的髖骨和脊椎骨質流失速率不同，這一點相當值得注意。
　　
　　她表示，我認為最有趣的是，糖尿病婦女的髖骨骨骼流失較快速，但是脊椎流失率卻相反。
　　
　　Schwartz博士解釋，之前的報告已經顯示，在第2型糖尿病婦女中，不論開始時的BMD值，髖骨的骨質流失較快速，而認為第2型糖尿病對小樑骨有正向效果，對皮質骨有負向效果。這和本研究所指的髖骨流失較快速、脊椎骨相對而言較慢的發現一致。
　　
　　她指出，這些發現強調了考慮糖尿病婦女骨折風險的需要。
　　
　　她表示，在評估第2型糖尿病婦女的骨折風險時，包括年齡範圍在內，醫師必須將病患因為BMD值而增加的骨折風險也納入考量。只有使用骨質密度T-分數以及骨折風險評估FRAX 分數會低估骨折風險。
　　
　　該研究接受國家健康研究中心的財經補助。Khalil博士宣告沒有相關財務關係。Schwartz博士報告接受Merck、Amgen與GlaxoSmithKline等藥廠的研究支持，也擔任Merck藥廠的顧問。
　　
　　美國骨質研究協會第31屆年會：摘要1205。發表於2009年9月13日。

Menopausal Hip Bone Loss Accelerated in Diabetics

By Nancy A. Melville
Medscape Medical News

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.