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Diabetes and change in bone mineral density at the hip, calcaneus, spine, and radius in older women

*, Susan K. Ewing 1, Anne M. Porzig 2, , ,
Teresa A. Hillier 4, Kristine E. Ensrud 5, Dennis M. Black 1, Michael C. Nevitt 1, Steven R. Cummings6 and
1 Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA2 Endocrine Division, Department of Medicine, University of California San Francisco, San Francisco, CA, USA3 Department of Geriatrics, University of Maryland School of Medicine, Baltimore, MD, USA4 Kaiser Permanente Center for Health Research Northwest/Hawaii, Portland, OR, USA5 VA Medical Center, University of Minnesota, Minneapolis, MN, USA6 California Pacific Medical Center, San Francisco, CA, USA7 Division of Endocrinology, Johns Hopkins School of Medicine, Baltimore, MD, USA Older women with type 2 diabetes mellitus (DM) have higher bone mineral density (BMD) Peter Vestergaard, Aarhus University but also have higher rates of fracture compared to those without DM. Limited evidence Hospital, Denmark suggests that DM may also be associated with more rapid bone loss. To determine if bone loss rates differ by DM status in older women, we analyzed BMD data in the Study of Osteo- Jennifer Tickner, University of Western Australia, Australia porotic Fractures (SOF) between 1986 and 1998. SOF participants were women ≥65 years Florent Elefteriou, Vanderbilt at baseline who were recruited from four regions in the U.S. DM was ascertained by self- University, USA report. BMD was measured with dual-energy x-ray absorptiometry (DXA) at baseline and at least one follow-up visit at the hip (N = 6624) and calcaneus (N = 6700) and, on a subset Ann V. Schwartz , Department of of women, at the spine (N = 396) and distal radius (N = 306). Annualized percent change Epidemiology and Biostatistics,University of California San Francisco, in BMD was compared by DM status, using random effects models. Of 6,867 women 185 Berry Street, Suite 5700, 5th with at least one follow-up DXA scan, 409 had DM at baseline. Mean age was 70.8 (SD Floor, San Francisco, CA 94107, USA 4.7) years. Baseline BMD was higher in women with DM at all measured sites. In models adjusted for age and clinic, women with prevalent DM lost bone more rapidly than thosewithout DM at the femoral neck (−0.96 vs. −0.59%/year, p < 0.001), total hip (−0.98 vs.
−0.70%/year, p < 0.001), calcaneus (−1.64 vs. −1.40%/year, p = 0.005), and spine (−0.33vs. +0.33%/year, p = 0.033), but not at the distal radius (−0.97 vs. −0.90%/year, p = 0.91).
These findings suggest that despite higher baseline BMD, older women with DM experi- ence more rapid bone loss than those without DM at the hip, spine, and calcaneus, butnot the radius. Higher rates of bone loss may partially explain higher fracture rates in olderwomen with DM.
Keywords: type 2 diabetes mellitus, bone mineral density, women, older adults, longitudinal studies
than the corresponding risk for non-diabetic patients Type 2 diabetes mellitus (DM) and osteoporosis are two chronic conditions whose prevalence and associated costs continue to Although DM is associated with higher baseline BMD, there is increase, particularly among the elderly. Internationally, over 10% some evidence that people with DM may have more rapid bone of adults age 60 years and older have DM; in the U.S. the prevalence loss. This could partially account for higher fracture risk at a given of DM in this age group is nearly 30% BMD since rapid bone loss contributes to fracture risk indepen- The annual number of hip fractures worldwide was dent of baseline BMD estimated as 1.26 million in 1990, and is projected to approxi- However, previous reports on the rate of mately double by 2025 In older adults, bone loss in older adults with DM have been inconsistent. While considerable overlap in DM and osteoporosis would be expected several studies have reported accelerated bone loss at the hip in simply due to the high prevalence of each condition. In addi- older women with DM, including in the Study of Osteoporotic tion, DM is associated with increased risk of fracture Paradoxically, cross-sectional stud- slower bone loss has also been reported at the spine ies have demonstrated that DM is associated with normal or higher and radius Our goals bone mineral density (BMD) in this study were to clarify the effects of diabetes on the rate Thus, for any given of bone loss and to gain insight into the seemingly paradoxi- BMD T -score, the fracture risk in those with DM tends to be higher cal and poorly understood relationships among diabetes, BMD, Schwartz et al.
Diabetes and change in BMD and fracture. To achieve these goals, we studied the associationsbetween diabetes and rate of bone loss at several skeletal sitesin older women enrolled in the Study of Osteoporotic Fractures(SOF), using longitudinal data from 1986 to 1998.
The Study of Osteoporotic Fractures (SOF) is a prospective cohort
of 9,704 white women aged ≥65 years. Participants were recruited
from the community in four U.S. regions: Portland, Oregon;
Minneapolis, Minnesota; Baltimore County, Maryland; and the
Mononghela Valley near Pittsburgh, Pennsylvania. Enrollment
began in 1986, and the current analyses are based on follow-
up data through 1998 Women were
recruited irrespective of BMD and fracture history; those unable to
walk without assistance and those with bilateral hip replacements
were excluded. All women provided written consent, and SOF was
approved by the Institutional Review Board at each site.
At baseline, participants were asked if a physician had ever told
them that they had diabetes or "sugar diabetes." Women who
answered "yes" to this question were identified as having preva-
lent DM. Twenty-five women did not answer this question and
were excluded. Using the same survey question, incident DM was
defined at years 3.5, 6, 8, and 10 (corresponding to SOF clinic visits
3, 4, 5, and 6) and via medication inventory at years 6, 8, and 10.
Women who did not report diabetes but who were taking diabetic
FIGURE 1 Number of participants in each bone loss analysis by
medications were classified as having DM. Nine women included diabetes status at each visit. N, number of participants included in
in these analyses reported thiazolidinedione (TZD) use at year 10.
analysis of each skeletal site; non-DM, no DM at current or previous visits;PrevDM, DM at baseline; IncDM, new diagnosis of DM between baseline MEASUREMENT OF BONE MINERAL DENSITY
and current visit.
Calcaneal BMD
Peripheral BMD was measured at the calcaneus using single
x-ray absorptiometry (DXA) with Hologic QDR-1000 scanners photon absorptiometry (Osteoanalyzer; Dove Medical Systems) (Hologic, Inc., Bedford, MA, USA). Hip BMD was measured again at the baseline, year 6 and year 8 visits at years 6 and 8 on the same scanners. At year 10, hip BMD was in all women and at the year 10 visit in a subset of participants measured with QDR-1000 scanners for 4,224 women and with Of the 9,679 women with baseline DM data, 6,700 QDR-2000 scanners for 346 women. Of the 9,679 women with women had ≥2 calcaneal measurements and were included in baseline DM data, 6,624 had ≥2 hip BMD measurements and analyses examining the association between DM and change in were included in analyses examining the association between DM calcaneal BMD.
and BMD at the total hip and femoral neck A subset ofthe 9,679 women had spine BMD measured at year 6 (N = 479), with 396 having spine BMD measurements at both years 2 and 6; Distal and proximal radial BMD were measured by single photon these women were included in analyses examining the association absorptiometry. The distal measurement site was just proximal to between DM and spine BMD.
the junction of the ulna and radius, and the proximal site was 25%of the total ulnar length distant from the distal site Radial scans were obtained in all women at baseline Weight was measured on a standard balance beam scale, and weight and in a small subset of women at year 6. Of the 9,679 women with change was calculated by subtracting baseline weight (or year 2 baseline DM data, 306 had distal BMD measurements and 290 had weight for the spine and hip analyses) from current weight. Height proximal BMD measurements at both visits and were included in was measured by a Harpenden stadiometer (Holtain Ltd., Dyved, analyses examining the association between DM and changes in UK). Self-reported height at age 25 was collected at baseline; height distal and proximal radial BMD change was calculated by subtracting height at age 25 from base-line height. Self-reported age at the last menstrual period (LMP) Hip and spine BMD
was collected at baseline, and number of years since menopause Bone mineral density of the total hip, femoral neck, and total lum- was calculated by subtracting age at LMP from baseline age (or bar spine was first measured at year 2 (visit 2) using dual-energy from year 2 age for hip and spine BMD models). Current use Schwartz et al.
Diabetes and change in BMD of vitamin D and calcium supplements, estrogen preparations, Change in BMD is reported as annualized percent change. For thiazide diuretics, and oral steroids was self-reported at baseline hip and calcaneal BMD, the mixed model estimates were used to and year 2. Beginning in year 6, participants were asked to bring estimate BMD at each year of follow-up and plotted to visualize all prescription and non-prescription medications to the clinic changes in BMD over time for each of the DM groups. All analyses visit for a medication inventory. Self-reported use of calcitonin were conducted using SAS version 9.1 (SAS Institute Inc., Cary, injections and fluoride pills started at year 2, and self-reported use of etidronate started at year 6. Tobacco use and walking forexercise were self-reported at each visit. Various aspects of physi- cal performance were assessed by trained examiners at each visit.
Of the 9,679 women at baseline with known diabetes status, 6,867 These included grip strength (measured with a handheld Jamar had ≥2 BMD measurements during the first 10 years of follow-up.
dynamometer using the average of two trials per hand) Of these, 409 (6%) self-reported a physician diagnosis of diabetes gait speed (measured on a at baseline and were categorized as having prevalent DM. Of the 6-m walking course using the time to complete two trials remaining 6,458 women who were not diabetic at baseline, 399 and ability to rise from a chair five times (6%) developed incident DM during follow-up. Characteristics of without using arms the 6,867 women included in one or more of these analyses are Peripheral nerve function was assessed at year 2 using esthesiome- presented in Compared to non-diabetic women, women ter testing on the warmed great toe of both feet, using six filaments with prevalent DM had higher baseline BMD at all six sites. Women of increasing size (3.22–6.10, logarithm of force applied, in 0.1 g).
with prevalent DM had lower grip strength, slower walking speed, Women who felt only the 6.10 filament or no filament on either and were less likely to walk for exercise and to report estrogen use.
toe were identified as having poor light touch discrimination.
Use of alendronate or raloxifene was similar in women with andwithout DM.
Characteristics of participants were examined according to base-
line DM status, using t -tests for continuous variables and chi- Among the 6,624 women with ≥2 hip BMD measurements square tests for categorical variables. Since spine and radial BMD between years 2 and 10, 391 and 303 had prevalent and incident were measured at only two time points, linear regression was used DM, respectively. In age and clinic-adjusted models for the femoral to examine the association between DM and change in BMD at neck, women with prevalent DM, incident DM, and those with- these sites, with results presented as least square means. By con- out DM lost an average of 0.96%, 0.90, and 0.59 BMD %/year, trast, since hip and calcaneal BMD were measured at several time respectively At the total hip, both prevalent and inci- points, random effects models were used to examine the asso- dent DM lost 0.98%/year, while non-DM women lost an average ciation between DM and change in BMD at these sites. These of 0.70%/year. Although bone loss was more rapid in women models account for the between-subject variation and within- with prevalent DM, average BMD remained higher compared with subject correlations among repeated BMD measurements. Time non-DM women throughout 8 years of follow-up was modeled as a continuous covariate, measured as the number In multivariate models, mean BMD loss remained significantly of years between the first BMD and the follow-up BMD scans greater for the women with prevalent DM compared to women for each site. Random effects models included the intercept and without DM at both the femoral neck (−0.86 vs. −0.54%/year, slope of the BMD measurements over time, thereby allowing for p < 0.001) and total hip (−0.86 vs. −0.59%/year, p < 0.001). Addi- individual time trends for each participant.
tional adjustment for concurrent weight change slightly attenu- All models were adjusted for age and clinic site. The following ated, but did not eliminate, the association between prevalent DM covariates were initially considered for inclusion in the multivari- and accelerated BMD loss For incident DM compared to ate models: baseline (or year 2) weight, weight change, baseline (or women without DM, multivariate adjustment attenuated the asso- year 2) height, height loss since age 25, and current use of any of the ciations for femoral neck (−0.79 vs. −0.54%/year, p = 0.06) and following: vitamin D, calcium supplements, estrogen, osteoporosis total hip (−0.77 vs. −0.59%, p = 0.06) BMD, and they were no medications (alendronate, raloxifene, tamoxifen, etidronate, flu- longer statistically significant Further adjustment for oride pills, or calcitonin injections), thiazide, and oral steroids.
concurrent weight change resulted in additional attenuation of Also considered for inclusion in the models were current grip these relationships comparing women with incident DM to those strength, walking speed, ability to rise from chair, walking for exer- cise, years since menopause, current tobacco use, and poor lighttouch discrimination at year 2. These covariates were included in DIABETES AND CHANGE IN CALCANEAL BMD
the multivariate model if they were significantly associated both Of the 6,700 women with ≥2 calcaneal BMD measurements with DM in univariate analyses and with change in BMD in the between baseline and year 10, 387 and 306 had prevalent and age-clinic-adjusted models at p-value < 0.10. Separate multivari- incident DM, respectively. Adjusted for age and clinic, women ate models were constructed for each skeletal site. Weight loss was with prevalent DM lost an average of 1.6%/year, while those with added separately to the multivariate models to assess its role as a incident DM and non-DM women lost 1.4%/year Cal- potential intermediary between DM and change in BMD because caneal BMD was highest among women with prevalent DM, but it is known to predict bone loss from other studies declined more rapidly over time. Although bone loss was more and DM is associated with weight loss in the SOF cohort.
rapid in those with prevalent DM, average BMD remained higher Schwartz et al.
Diabetes and change in BMD Table 1 Characteristicsa of women by diabetes status.
incident DM separately. Results were similar with multivariableadjustment, including adjustment for concurrent weight change.
Prevalent DM
(N = 6458)
(N = 409)
Of the 306 women with distal BMD measurements at baseline
and year 6, 15 had prevalent DM at baseline and 9 women devel- oped incident DM between baseline and year 6. After adjustment Change in weight (V6-BL) for age and clinic site, women with prevalent DM lost an aver- age of 0.97%/year at the distal radius while non-DM women lost 0.90%/year (p = 0.91) Numbers were too small to assess Height loss since age 25 (cm) incident DM separately. Multivariable adjustment did not substan- Years since menopause tially alter these results. Of the 290 women with two proximal BMD measurements, 15 had prevalent DM and 7 developed incident DM. Adjusted for age and clinic site, women with prevalent DM Current vitamin D use gained an average of 0.74%/year at the proximal radius while non- Current calcium use DM women lost 0.33%/year (p = 0.14). Multivariate adjustment Current estrogen use did not substantially alter these results.
Alendronate taken in last Current raloxifene use (V6) Despite their higher baseline BMD, older women with prevalent Current thiazide use DM had more rapid bone loss at the total hip, femoral neck, lum- Current statin use (V4) bar spine, and calcaneus, but not at the distal or proximal radius, Current oral steroid use than their non-diabetic counterparts. These results strengthen the Grip strength (kg) evidence for an association between DM and accelerated bone loss, Walking speed (m/s) but also clarify that this relationship is site-specific. Our findings Inability to rise from chair extend a previous report from the SOF cohort that DM is associ- Walk for exercise ated with accelerated bone loss at the total hip Poor light touch discrimination and are in agreement with previous observations of more rapid bone loss at the hip among postmenopausal women with DM in the Health, Aging, and Body Composition Study (Health ABC) Calcaneus BMD (g/cm2) and in the placebo group of the Fracture Intervention Trial (FIT) Distal radius BMD (g/cm2) In FIT, there was also a Proximal radius BMD (g/cm2) trend toward a faster rate of bone loss at the spine among diabetic Femoral neck BMD (V2) women but the difference was not statistically significant Similarly, the Study of Women's Health Across the Total hip BMD (V2) (g/cm2) Nation (SWAN) found an increased rate of bone loss at the total Total lumbar spine BMD (V2) hip among women with DM in the post menopausal but not per- imenopausal time period However, SWAN, in Mean (SD), or N (%). BMD, bone mineral density; DM, diabetes mellitus. contrast to our findings, reported a slower rate of bone loss at the a Measurement at baseline visit unless otherwise indicated. spine in women with DM. Another study found a slower rate ofbone loss at the radius over 12 years in 19 adults with DM (averageage 52 years), based on BMD z-scores By compared with non-DM women even after 10 years of follow- comparison, we found no differences in the rate of bone loss at the up The difference in mean loss between the preva- lent DM and non-DM groups was significant in the age- and Thiazolidinedione use may contribute to more rapid bone loss clinic-adjusted model, of borderline significance in the multivari- in those with DM. In randomized controlled trials, TZDs have been ate model, and not significant in a model adjusting for weight shown to increase bone loss at the spine and total hip change. There was no difference in BMD loss between women However, our findings with incident DM and those without DM in any of the calcaneal are not explained by TZD use. The vast majority of follow-up of the SOF cohort took place before the introduction of troglitazonein 1997 and of rosiglitazone and pioglitazone in 1999. Indeed, only DIABETES AND CHANGE IN LUMBAR SPINE BMD
nine participants in these analyses reported TZD use at year 10.
Of the 396 women with lumbar spine BMD measurements at Our findings indicate that more rapid bone loss associated with years 2 and 6, 20 had prevalent DM and 9 developed incident DM is a feature of the hip, spine, and calcaneal sites, but not the DM. Adjusted for age and clinic, women with prevalent DM radius. In comparison with the other three sites, the radius has a lost BMD (−0.33%/year), while those without DM gained bone higher proportion of cortical bone and is a non-weight bearing (0.33%/year; p = 0.03) Numbers were too small to assess site. In theory, the lack of effect of DM at the radius could result Schwartz et al.
Diabetes and change in BMD Table 2 Adjusted mean BMD change at the hip and calcaneus by diabetes status.
Site of BMD Change
Prevalent DM
Incident DM
Adjusted for age and site MV without weight changea MV with weight changea TOTAL HIP
Adjusted for age and site MV without weight changea MV with weight change Adjusted for age and site MV without weight changeb MV with weight change * p-Value for differential rate of BMD loss for prevalent DM vs. non-DM. ** p-Value for differential rate of BMD loss for incident DM vs. non-DM. aAdjusted for baseline age, clinic site, baseline height, baseline weight, height change since 25 years since menopause, current vitamin D use, current calcium use, current estrogen use, current use of osteoporosis medications, current thiazide diuretic use, current grip strength, current walking speed, current inability to rise from chair without use of arms, and decreased light touch. bAdjusted for baseline age, clinic site, baseline weight, baseline height, height change since age 25, years since menopause, current vitamin D use, current estrogen use, current thiazide use, current grip strength, current walking speed, current inability to rise from chair without use of arms, and current walking for exercise. FIGURE 2 BMD over time at the femoral neck among older women by diabetes status. Mixed model estimates, adjusted for age and clinic site, were
used to estimate BMD at each year of follow-up.
from a stronger association with loss of trabecular rather than cor- loss in the presence of loading. Other studies indicate that bone tical bone, but cross-sectional studies suggest the opposite geometry, although not bone density, may be negatively affected by DM with a reduction in bone strength relative to load our knowledge, longitudinal studies using quantitative computed DM is associated with higher lev- tomography (QCT) are not currently available to help disentangle els of sclerostin indicating an effect the effect of DM on cortical compared with trabecular bone loss.
on osteocytes, and with reduced bone formation Another possible explanation is a stronger effect of DM on bone DM may inhibit the ability of osteocytes Schwartz et al.
Diabetes and change in BMD FIGURE 3 BMD over time at the calcaneus among older women by diabetes status. Mixed model estimates, adjusted for age and clinic site, were used
to estimate BMD at each year of follow-up.
Table 3 Adjusted mean BMD change at the spine and radius by diabetes status.
Site of BMD Change
Prevalent DM
Adjusted for age and site MV without weight changea MV with weight change Adjusted for age and site MV without weight changeb MV with weight change Adjusted for age and site MV without weight changeb MV with weight change * p-Value compared to non-DM. aAdjusted for age, clinic site, weight, thiazide diuretic use, and vitamin D use. bAdjusted for age, clinic site, weight, walking for exercise, height change since age 25, and vitamin D use. and osteoblasts to respond adequately to load. Thus, at skeletal sites the hip, our results suggest that even at diagnosis, DM has an that experience loading, older women with DM may experience unfavorable impact on BMD. We also found more rapid weight greater net loss of bone.
loss among the diabetic women, despite higher baseline weight.
Our results showing higher BMD at baseline are consistent Previous studies have also reported more rapid weight loss with with meta-analyses reporting higher BMD associated with DM Yet, surprisingly, DM was also While weight loss is a hallmark of poorly controlled DM, more associated with more rapid bone loss at the hip, spine, and cal- rapid weight loss was also observed in those with relatively good caneus. The rate of bone loss was accelerated among those with control Weight loss is a strong risk factor for incident DM at the hip, but not the calcaneus. Thus, at least for bone loss and more rapid bone loss among Schwartz et al.
Diabetes and change in BMD diabetic women appears to account in part for more rapid bone bone strength that cannot be fully captured by DXA. Fracture in loss in our study. However, if weight loss were the only mechanism, diabetic women is associated with increased cortical porosity, a fea- we would expect our models that included concurrent weight loss ture of bone that is not appreciated with DXA scans to abolish the relationship between bone loss and DM. Instead, In our analyses, although DM women had more rapid bone although adjustment for concurrent weight change attenuated the loss, they continued to have higher average hip BMD compared effect of accelerated BMD loss among women with prevalent DM, with non-DM women, even after 8 years of follow-up.
it did not abolish the effect. This indicates that more rapid weight Strengths of our study include up to 10 years of follow-up for loss does not account for the more rapid bone loss that we observed BMD changes and the ability to adjust for multiple potential con- in women with DM.
founders, including use of estrogen and osteoporosis medications.
Other possible mechanisms for accelerated bone loss with DM A limitation of our study is the relatively small number of women include lower levels of insulin-like growth factor 1, changes in cal- with BMD scans of the spine and radius. Another limitation of cium homeostasis, increased advanced glycation end products, and this study is the lack of blood tests for ascertainment of DM. It is decreased blood flow to the lower extremities likely that some participants had undiagnosed diabetes and were Higher levels of inflamma- incorrectly classified as not having diabetes tory cytokines or oxidative stress in those with DM may also drive This misclassification should not have differed by levels of the out- come, changes in BMD. Thus, any misclassification would tend to Reduced exercise in those with DM may increase bias our measures of association between diabetes and change in bone loss but adjustment for physical BMD toward the null. In addition, SOF participants were com- activity in our models did not account for the observed associ- munity dwelling white women, and these results may not apply ation between DM and rate of bone loss. Thus, the mechanisms to other populations. Although analyses were adjusted for multi- underlying the association between DM and accelerated bone loss ple factors, the possibility of residual confounding due to factors merit further exploration.
that were not measured or were measured with error cannot be It has been shown that BMD T -score and FRAX underestimate fracture risk in DM women In conclusion, older women with DM had accelerated bone Accelerated bone loss with DM may be a contribut- loss at the hip, spine, and calcaneus, but not at the radius, com- ing factor as the rate of bone loss predicts fractures independent pared to women without diabetes. Greater concurrent weight loss in the women with DM accounted for some, but not all, of the association between DM and accelerated BMD loss, suggest- The reasons for the association ing that other diabetes-related mechanisms increase bone loss.
between more rapid bone loss and fracture remain controversial.
Despite higher baseline BMD, accelerated bone loss may account, More rapid bone loss may simply be a marker for a lower BMD at least in part, for the increased fracture rate observed with closer to the time of the fracture. In support of this hypothesis, in the Tromso study the rate of bone loss was no longer associatedwith fracture risk when models were adjusted for the final BMD measurement, closer to the time of fracture The Study of Osteoporotic Fractures (SOF) is supported by In contrast, in the Study of Osteoporosis in Men (MrOS) cohort National Institutes of Health funding. The National Institute on the rate of bone loss predicted hip fracture independent of baseline Aging (NIA) provides support under the following grant numbers: BMD and final BMD measurements sug- R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 gesting that more rapid bone loss may be a marker for changes in AG005394, R01 AG027574, and R01 AG027576.
B., and Demirag, N. G. (2007).
the efficacy and safety of Avandamet density in type 1 and 2 diabetic Ahmed, L. A., Emaus, N., Berntsen, Rosiglitazone decreases serum bone- (rosiglitazone/metformin) and met- patients. Diabete Metab. 18, 32–37.
G. K., Bjornerem, A., Fonnebo, V., specific alkaline phosphatase activ- formin on long-term glycaemic Cauley, J. A., Danielson, M.
Jorgensen, L., et al. (2010). Bone ity in postmenopausal diabetic control and bone mineral density Boudreau, R. M., Forrest, K. Y., loss and the risk of non-vertebral women. J. Clin. Endocrinol. Metab. after 80 weeks of treatment in Zmuda, J. M., Pahor, M., et al.
fractures in women and men: 92, 3523–3530. do drug-naive type 2 diabetes mellitus (2007). Inflammatory markers and the Tromso study. Osteoporos. Int. patients. Diabetes Obes. Metab. 13, incident fracture risk in older men 21, 1503–1511. do Berger, C., Langsetmo, L., Joseph, L., and women: the Health Aging Hanley, D. A., Davison, K. S., Bruyere, O., Roux, C., Detilleux, J., Slos- and Body Composition Study. J. Bauer, D. C., Browner, W. S., Cauley, Josse, R. G., et al. (2009). Asso- man, D. O., Spector, T. D., Fardel- Bone Miner. Res. 22, 1088–1095.
J. A., Orwoll, E. S., Scott, J. C., ciation between change in BMD lone, P., et al. (2007). Relation- Black, D. M., et al. (1993). Fac- and fragility fracture in women ship between bone mineral density Cauley, J. A., Lui, L. Y., Barnes, tors associated with appendicular and men. J. Bone Miner. Res. changes and fracture risk reduction D., Ensrud, K. E., Zmuda, J. M., bone mass in older women. The 24, 361–370. do in patients treated with strontium Hillier, T. A., et al. (2009). Suc- Study of Osteoporotic Fractures ranelate. J. Clin. Endocrinol. Metab. cessful skeletal aging: a marker of Research Group. Ann. Intern. Med. Borges, J. L., Bilezikian, J. P., Jones- 92, 3076–3081. do low fracture risk and longevity.
118, 657–665. do Leone, A. R., Acusta, A. P., Ambery, The Study of Osteoporotic Frac- P. D., Nino, A. J., et al. (2011). A Buysschaert, M., Cauwe, F., Jamart, J., tures (SOF). J. Bone Miner. Res. Berberoglu, Z., Gursoy, A., Bayrak- randomized, parallel group, double- Brichant, C., De Coster, P., Magnan, 24, 134–143. do tar, N., Yazici, A. C., Tutuncu, N.
blind, multicentre study comparing A., et al. (1992). Proximal femur Schwartz et al.
Diabetes and change in BMD Cawthon, P. M., Ewing, S. K., Mackey, Grey, A. (2008). Skeletal consequences Ma, L., Oei, L., Jiang, L., Estrada, K., D. C., Fink, H. A., Cummings, S.
Chen, H., Wang, Z., et al. (2012).
Am. J. Epidemiol. 176, 738–743.
R., Ensrud, K. E., et al. (2012).
Association between bone mineral Change in hip bone mineral density density and type 2 diabetes mel- Schwartz, A. V., Garnero, P., Hillier, T.
and risk of subsequent fractures in Gullberg, B., Johnell, O., and Kanis, J.
litus: a meta-analysis of observa- A., Sellmeyer, D. E., Strotmeyer, E.
older men. J. Bone Miner. Res. 27, A. (1997). World-wide projections tional studies. Eur. J. Epidemiol. S., Feingold, K. R., et al. (2009).
for hip fracture. Osteoporos. Int. 7, 27, 319–332. do Pentosidine and increased fracture Clowes, J. A., Riggs, B. L., and risk in older adults with type 2 Khosla, S. (2005). The role of the Hannan, M. T., Felson, D. T., Dawson- Manolagas, S. C., and Almeida, M.
diabetes. J. Clin. Endocrinol. Metab. immune system in the pathophysiol- Hughes, B., Tucker, K. L., Cupples, (2007). Gone with the Wnts: {beta}- 94, 2380–2386. do ogy of osteoporosis. Immunol. Rev. L. A., Wilson, P. W., et al. (2000).
catenin, TCF, FOXO, and oxidative 208, 207–227. do Risk factors for longitudinal bone stress in age-dependent diseases of Schwartz, A. V., Sellmeyer, D. E., Strot- loss in elderly men and women: the bone, lipid, and glucose metabolism.
meyer, E. S., Tylavsky, F. A., Fein- Cowie, C. C., Rust, K. F., Ford, E. S., Framingham Osteoporosis Study.
Mol. Endocrinol. 21, 2605–2614.
gold, K. R., Resnick, H. E., et Eberhardt, M. S., Byrd-Holt, D. D., J. Bone Miner. Res. 15, 710–720.
al. (2005). Diabetes and bone loss Li, C., et al. (2009). Full account- Melton, L. J. III, Riggs, B. L., Leibson, at the hip in older black and ing of diabetes and pre-diabetes in Hillier, T. A., Stone, K. L., Bauer, C. L., Achenbach, S. J., Camp, J. J., white adults. J. Bone Miner. Res. the U.S. population in 1988-1994 D. C., Rizzo, J. H., Pedula, K. L., Bouxsein, M. L., et al. (2008). A bone 20, 596–603. do and 2005-2006. Diabetes Care 32, Cauley, J. A., et al. (2007). Evaluat- structural basis for fracture risk in ing the value of repeat bone min- diabetes. J. Clin. Endocrinol. Metab. Schwartz, A. V., Vittinghoff, E., Bauer, Cummings, S. R., Black, D. M., Nevitt, eral density measurement and pre- 93, 4804–4809. do D. C., Hillier, T. A., Strotmeyer, M. C., Browner, W. S., Cauley, J. A., diction of fractures in older women: Genant, H. K., et al. (1990). Appen- the study of osteoporotic fractures.
Moritz, D. J., Ostfeld, A. M., Blazer, D., (2011). Association of BMD and dicular bone density and age predict Arch. Intern. Med. 167, 155–160.
Curb, D., Taylor, J. O., and Wallace, FRAX score with risk of frac- hip fracture in women. The Study R. B. (1994). The health burden of ture in older adults with type 2 of Osteoporotic Fractures Research Ishii, S., Cauley, J. A., Crandall, C.
diabetes for the elderly in four com- diabetes. JAMA 305, 2184–2192.
J., Srikanthan, P., Greendale, G. A., munities. Public Health Rep. 109, Huang, M. H., et al. (2012). Diabetes Seeley, D. G., Cauley, J. A., Grady, and femoral neck strength: findings Nguyen, T. V., Center, J. R., and Eis- D., Browner, W. S., Nevitt, M.
Cummings, S. R., Nevitt, M. C., from the hip strength across the man, J. A. (2005). Femoral neck C., and Cummings, S. R. (1995).
Browner, W. S., Stone, K., Fox, K.
menopausal transition study. J. Clin. bone loss predicts fracture risk M., Ensrud, K. E., et al. (1995).
Endocrinol. Metab. 97, 190–197.
independent of baseline BMD. J. therapy associated with neuro- Risk factors for hip fracture in Bone Miner. Res. 20, 1195–1201.
muscular function or falling in white women. Study of Osteo- Janghorbani, M., Van Dam, R. M., Wil- elderly women? Study of Osteo- porotic Fractures Research Group.
lett, W. C., and Hu, F. B. (2007).
Orwoll, E. S., Bauer, D. C., Vogt, porotic Fractures Research Group.
N. Engl. J. Med. 332, 767–773.
Systematic review of type 1 and type T. M., and Fox, K. M. (1996).
Arch. Intern. Med. 155, 293–299.
2 diabetes mellitus and risk of frac- Axial bone mass in older women.
ture. Am. J. Epidemiol. 166, 495–505.
Study of Osteoporotic Fractures Ensrud, K. E., Ewing, S. K., Stone, Research Group. Ann. Intern. Med. Shu, A., Yin, M. T., Stein, E., Cre- K. L., Cauley, J. A., Bowman, P.
Keegan, T. H., Schwartz, A. V., Bauer, 124, 187–196. do mers, S., Dworakowski, E., Ives, J., and Cummings, S. R. (2003).
C., Sellmeyer, D.
R., et al. (2012). Bone struc- Kelsey, J. L. (2004). Effect of alen- Patsch, J. M., Burghardt, A. J., Yap, ture and turnover in type 2 dia- weight loss increase bone loss dronate on bone mineral den- S. P., Baum, T., Schwartz, A. V., betes mellitus. Osteoporos. Int. 23, and hip fracture risk in older sity and biochemical markers of Joseph, G. B., et al. (2013). Increased women. J. Am. Geriatr. Soc. 51, bone turnover in type 2 diabetic cortical porosity in type 2 dia- women: the fracture intervention betic postmenopausal women with Sornay-Rendu, E., Munoz, F., Duboeuf, trial. Diabetes Care 27, 1547–1553.
fragility fractures. J. Bone Miner. F., and Delmas, P. D. (2005).
Garcia-Martin, A., Rozas-Moreno, P., Res. 28, 313–324. do Rate of forearm bone loss is Reyes-Garcia, R., Morales-Santana, Khalil, N., Sutton-Tyrrell, K., Strot- meyer, E. S., Greendale, G. A., Petit, M., Paudel, M. L., Taylor, risk of fracture independently of Salcedo, J. A., et al. (2012). Circulat- Vuga, M., Selzer, F., et al. (2011).
B., Hughes, J., Strotmeyer, E. S., ing levels of sclerostin are increased Menopausal bone changes and inci- Schwartz, A. V., et al. (2010). Bone in patients with type 2 diabetes mel- dent fractures in diabetic women: mass and strength in older men Bone Miner. Res. 20, 1929–1935.
litus. J. Clin. Endocrinol. Metab. 97, a cohort study. Osteoporos. Int. with type 2 diabetes: the Osteo- 22, 1367–1376. do porotic Fractures in Men Study.
Vestergaard, P.
Giangregorio, L. M., Leslie, W. D., J. Bone Miner. Res. 25, 285–291.
cies in bone mineral density and Lix, L. M., Johansson, H., Oden, Krakauer, J. C., McKenna, M. J., Bud- A., McCloskey, E., et al. (2012).
erer, N. F., Rao, D. S., White- Raskin, P., Stevenson, M. R., Bar- type 1 and type 2 diabetes-a house, F. W., and Parfitt, A. M.
illa, D. E., and Pak, C. Y. (1978).
meta-analysis. Osteoporos. Int. 18, risk in patients with diabetes. J. (1995). Bone loss and bone turnover Bone Miner. Res. 27, 301–308.
in diabetes. Diabetes 44, 775–782.
insulin. Clin. Endocrinol. (Oxf.) Vogt, M. T., Cauley, J. A., Kuller, Greendale, G. A., Barrett-Connor, E., Looker, H. C., Knowler, W. C., and L. H., and Nevitt, M. C. (1997).
Edelstein, S., Ingles, S., and Haile, Hanson, R. L. (2001). Changes in Bone mineral density and blood R. (1995). Lifetime leisure exer- BMI and weight before and after Schneider, A. L., Pankow, J. S., Heiss, flow to the lower extremities: the cise and osteoporosis. The Rancho the development of type 2 dia- G., and Selvin, E. (2012). Validity study of osteoporotic fractures.
Bernardo study. Am. J. Epidemiol. betes. Diabetes Care 24, 1917–1922.
J. Bone Miner. Res. 12, 283–289.
141, 951–959.
Schwartz et al.
Diabetes and change in BMD Wild, S., Roglic, G., Green, A., Sicree, commercial or financial relationships Cummings SR and Sellmeyer DE (2013) Ensrud, Black, Nevitt , Cummings and R., and King, H. (2004). Global that could be construed as a potential Diabetes and change in bone mineral Sellmeyer. This is an open-access article prevalence of diabetes: estimates for conflict of interest.
density at the hip, calcaneus, spine, and distributed under the terms of the the year 2000 and projections for radius in older women. Front. Endocrinol. 2030. Diabetes Care 27, 1047–1053.
Received: 15 March 2013; accepted: 16 4:62. doi:
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Citation: Schwartz AV, Ewing SK, Porzig ited and subject to any copyright notices authors declare that the research was AM, McCulloch CE, Resnick HE, Hillier Copyright 2013 Schwartz, Ewing , concerning any third-party graphics conducted in the absence of any TA, Ensrud KE, Black DM, Nevitt MC, Porzig , McCulloch, Resnick, Hillier,


Formale Betrachtung von Anfragen auf RDF Datenbanken im Fachbereich Biologie und Informatik an der Johann Wolfgang Goethe Universität Frankfurt am Main bei Herrn Prof. Dott. Ing. Zicari betreut von Dipl. Math. Karsten Tolle Bartholomäus Ende Inhaltsverzeichnis Bartholomäus Ende Matr.-Nr. 2063702 1. Kurzfassung Dieses Dokument befasst sich mit der formalen Analyse von Anfragen auf RDF-Datenbanken. Zu diesem Zweck wird zunächst eine kurze Einführung in das Resource Description Framework (RDF) gegeben.

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Warfarin-Drug Interactions Among Older Adults Andrew Liu, BSc Hon, BScPhm, RPh; Carmine Stumpo, BScPhm, PharmD, RPh Geriatrics Aging. 2007;10(10):643-646. ©2007 1453987 Ontario, Ltd. Posted 12/28/2007 Abstract and Introduction Abstract Warfarin-drug interactions are often encountered in the care of older adults. Interactions may be classified as pharmacokinetic, resulting in changes in serum warfarin concentrations, or pharmacodynamic, resulting in changes in hemostasis or platelet function. Knowledge of these mechanisms of warfarin-drug interactions may help identify warfarin interactions, facilitate prescribing decisions, and assist with appropriate monitoring.