Deborah M. Kado

Prevalent Vertebral Deformities Predict Mortality and Hospitalization in Older Women with Low Bone Mass

OBJECTIVES: To determine the relationship between prevalent vertebral deformities and the risk of mortality and hospitalization in older women with low bone mass.

Rate of bone loss is associated with mortality in older women: a prospective study.

Older women with low bone density have an increased risk of fracture, cardiovascular disease, and mortality. However, it is not known whether this association is caused by ongoing bone loss or by lower bone mass earlier in life. To determine whether rate of bone loss is associated with total and cause‐specific mortality, we prospectively studied 6046 women aged 65 years or older who had serial bone mineral density (BMD) measurements as a part of the Study of Osteoporotic Fractures. Rates (mean ± SD) of loss of BMD at the heel (for a mean of 5.7 years) and hip (for a mean of 3.5 years) were estimated. Cause‐specific mortality was ascertained from death certificates and hospital records. BMD loss at the heel was 5.9 ± 6.0 mg/cm2 per year (1.5 ± 1.5%) and BMD loss at the hip was 4.1 ± 10.2 mg/cm2 per year (0.6 ± 1.4%). During an average follow‐up of 3.2 years after the second measurement of BMD, 371 deaths occurred. Each SD increase in BMD loss at the hip was associated with a 1.3‐fold (95% CI, 1.1‐1.4) increase in total mortality, adjusted for age, baseline BMD, diabetes, hypertension, incident fractures, smoking, physical activity, health status, weight loss, and calcium use. In particular, hip BMD loss was associated with increased mortality from coronary heart disease (relative hazard [RH] = 1.3 per SD; 95% CI, 1.0‐1.8) and pulmonary diseases (RH = 1.6 per SD; 95% CI, 1.1‐2.5). The findings were similar for bone loss at the heel, except there was no significant association with pulmonary mortality. These results raise the possibility that bone loss may share common etiologies with coronary and pulmonary diseases.

Hyperkyphotic Posture Predicts Mortality in Older Community- Dwelling Men and Women: A Prospective Study

Objectives: To determine the association between hyperkyphotic posture and rate of mortality and cause‐specific mortality in older persons.

Hyperkyphotic posture and risk of future osteoporotic fractures : The Rancho Bernardo study

It is unknown whether kyphosis of the thoracic spine is an independent risk factor for future osteoporotic fractures. In 596 community‐dwelling women, we found that with increasing kyphosis, there was a significant trend of increasing fracture risk that was independent of previous history of fractures or BMD.

Narrative Review: Hyperkyphosis in Older Persons

Key Summary Points Hyperkyphosis is a common geriatric condition that affects as many as 20% to 40% of older adults. Hyperkyphosis affects both men and womenthe lay term dowagers hump is a misnomer. Vertebral fractures are present in only about one third of the older adults with the worst degrees of thoracic curvature. Hyperkyphosis may be associated with multiple adverse health outcomes, including impaired pulmonary and physical function, fractures, and possibly increased risk for death. Research about the cause, consequences, and treatment for hyperkyphosis is urgently needed because available evidence is scant and the prevalence of the condition will probably increase as the population ages. With aging, the sagittal convexity of the normal thoracic spine, known as kyphosis, tends to progress (1). Hyperkyphosis, an excess of this process, is often called the dowagers hump. Although not precisely known, the prevalence and incidence of hyperkyphosis in older persons is probably between 20% and 40% (24). The causes and consequences of hyperkyphosis are not well understood. Most clinicians and laypersons assume that hyperkyphosis results from underlying vertebral fractures; however, vertebral fractures are present in only 36% to 37% of the most severe kyphosis cases (5, 6). Furthermore, hyperkyphosis is not simply an undesirable cosmetic consequence of aging. It may be associated with several adverse health outcomes, such as poor pulmonary and physical function. Our narrative review presents evidence that hyperkyphosis cannot be fully explained by osteoporosis and that it is a distinct geriatric syndrome deserving of more attention. With increased clinical awareness informed by continued research, physicians can begin to help prevent and treat hyperkyphosis and may avoid or lessen attendant adverse health consequences. Methods We searched MEDLINE and PubMed (OLDMEDLINE for pre-1966) for studies from 1950 through 28 November 2006 by using the following Medical Subject Heading terms and keywords: kyphosis, hyperkyphosis, and kyphotic posture. We reviewed all citations and available abstracts (4734 for kyphosis, 77 for hyperkyphosis, and 87 for kyphotic posture). We classified 618 abstracts as not relevant (n= 408) or warranting detailed consideration of the original article (n= 210). We also excluded reports that were not in English (n= 1365) and those that addressed the following: 1) primary surgical interventions in children or young adults (n= 1386); 2) trauma-induced hyperkyphosis, such as thoracolumbar burst fractures (n= 107); 3) hyperkyphosis caused by chronic diseases, such as Pott disease (n= 558); and 4) other conditions, such as scoliosis or kyphoscoliosis (n= 1108). As we reviewed the remaining publications, we paid attention to study design and sample size, characteristics of the participants, and whether studies addressed factors other than kyphosis that could have influenced outcomes. How Does One Measure Kyphosis? The normal spine has 3 curves in the sagittal plane: cervical lordosis (anteriorly convex), thoracic kyphosis (anteriorly concave), and lumbar lordosis. Kyphosis can be measured from radiographs or with such devices as the kyphometer (7), goniometer (8), inclinometer (9), and flexible ruler (1) (Figure 1). Developed first to assess scoliosis angles on spinal radiographs, the Cobb angle was modified to measure kyphosis. Considered the current gold standard measurement, it is calculated by drawing a line at the upper border of the vertebral body, marking the beginning of the thoracic curve (commonly T4), and at the inferior border of the vertebral body, representing the interface between the thoracic and lumbar curves (commonly T12). Perpendicular lines are drawn from these 2 lines, and the angle of their intersection is the Cobb angle (Figure 2). Other clinical assessments of kyphosis include qualitative visual measurements (3, 4) and measurement of either the distance from the occiput to wall (10) or the number of 1.7-cm blocks between the head and examination table while the patient is lying flat with the neck in a neutral position (2). Figure 1. The flexicurve: a noninvasive measurement of thoracic kyphosis. Spine Figure 2. The Cobb angle of thoracic kyphosis, calculated from a lateral radiograph. Spine Research has not fully disentangled the differences between clinical and radiologic kyphosis measures. In a study of 26 postmenopausal women (7), independent observers measured kyphosis similarly when they used Debrunner kyphometer, flexicurve-derived kyphosis angle, and radiographic Cobb angle measurements. Intraclass correlation estimates for the measures ranged from 0.87 to 0.92 (7). Traditionally, the Cobb angle is measured from standing lateral spine films. However, in elderly persons, spinal radiography is usually performed with the patient in the supine position for comfort. Because gravitys effect on posture is lost while supine, the kyphosis angle measured in the lying position may underestimate kyphosis. In a study that compared the standing Debrunner kyphometer angle with a supine radiographic Cobb angle measurement in 120 women age 55 to 80 years (11), the mean difference between the 2 measures was only 4. The Debrunner method overestimated the Cobb angle slightly, and the intraclass correlation coefficient for the measures was 0.68 (11). How Does One Define Hyperkyphosis? In younger populations, normal kyphosis angles range between 20 and 40 (12). In older adults, the mean kyphosis angle is about 48 to 50 in women (6, 1315) and about 44 in men (6). We know that the angle increases with age (1, 6, 12, 1626), but we do not have uniformly accepted thresholds for defining either hyperkyphosis or normal thoracic spine changes associated with aging. One longitudinal study of 100 healthy men and women age 50 years or older (mean age, 62 years) reported a mean thoracic angle increase of 3 per decade (27). In a longitudinal study of 10 women (mean age, 77 years) followed for 3 years after a vertebral fracture (24), the mean angle increase was 5.6. Cross-sectional studies reported that the oldest age groups had the most pronounced increases in kyphosis (12, 21, 23). For example, 1 study of men and women reported mean thoracic kyphosis angles of 26 in persons in their 20s, 53 in those 60 to 74 years of age, and 66 in those older than 75 years of age (23). An ongoing large prospective cohort study will soon provide important longitudinal data on rates of progression in older women (28). Potential Causes of Hyperkyphosis Vertebral fractures do not explain all cases of hyperkyphosis (29). Only 36% to 37% of older persons with the worst degrees of kyphosis have underlying vertebral fractures (5, 6). Other postulated causes of hyperkyphosis include postural changes, degenerative disk disease, muscular weakness, ligamentous degeneration, and genetic predisposition (Figure 3). Figure 3. Postulated causes and consequences of hyperkyphosis in older persons. Vertebral Fractures: The Most Cited Cause of Hyperkyphosis In 1963, 2 publications noted an association between vertebral body wedging and kyphosis (30, 31). In the 1970s, Milne and Lauder (1) developed the flexicurve measurement of kyphosis and quantified the vertebral wedging index from lateral chest radiographs. The wedge deformity index increased with age and explained 42% of the variation in kyphosis in men and 48% in women (29). Other studies reported correlations between wedge angles and kyphosis ranging from 0.45 to 0.78 (14, 18, 19). In studies that compared kyphosis between people with and without vertebral fractures, those with vertebral fractures had worse kyphosis (6, 15, 32). Postural Changes Postural changes affecting the cervical, lumbar, and sacral spinal areas and postural flexibility may influence thoracic curvature. For example, investigators have found weak but statistically significant correlations between Cobb angle thoracic kyphosis and cervical lordosis in men (r= 0.27; P < 0.03) and women (r= 0.33; P < 0.009) (23). In 300 volunteers age 20 to 70 years, researchers reported a correlation of 0.35 between radiographic measures of thoracic kyphosis and maximum lumbar lordosis (P= 0.001) (33). In a study involving 51 women (34), those age 66 to 88 years had greater flexicurve kyphosis than those age 21 to 51 years (mean kyphotic index, 11.1 [SD, 3.9] vs. 7.2 [SD, 2.2] during erect stance). The older women were less able to actively correct their posture from a relaxed to an erect position (34). Degenerative Disk Disease A few cross-sectional studies report an association between degenerative disk disease and kyphosis (6, 19, 35). In a study of 100 healthy women age 39 to 91 years (19), investigators found a statistically significant correlation between anterior disk height and kyphosis angle (r = 0.34; P < 0.001). Using measurements of lateral spine radiographs and mid-sagittal computed tomography films of 93 ex vivo spines from men and women age 18 to 94 years, researchers reported a correlation of 0.52 (P < 0.001) between anterior disk wedging and Cobb angle (35). In a third study of 1407 older men and women (6), with each 5-increase in Cobb angle, participants had a 36% (95% CI, 1.26 to 1.48) increased odds of having degenerative disk disease. These cross-sectional studies did not establish whether degenerative disk disease contributed to or was a consequence of hyperkyphosis. Muscle Weakness With 2 exceptions (36, 37), most studies report an inverse correlation between muscle strength and hyperkyphosis (8, 3842). Although not a direct measure of spinal muscle strength, grip strength measured in 151 men and women age 65 to 85 years correlated with worse kyphosis measured from a lateral photograph (r = 0.25; P < 0.005) (38). Similar findings of upper-extremity strength and flexicurve-measured kyphosis include a correlation of 0.32 in 47 women volunteers age 50 to 60 years (P < 0.05) (39). Three studies reported a s

Homocysteine Levels and Decline in Physical Function: MacArthur Studies of Successful Aging

PURPOSE To test whether elevated homocysteine levels are associated with an increased risk of decline in physical function in older persons. METHODS We performed a prospective cohort study of 499 highly functioning men and women aged 70 to 79 years who were enrolled in the MacArthur Studies of Successful Aging. We measured total homocysteine levels and performance-based physical function at baseline; physical function measures were repeated an average of 28 months later. A summary measure of physical performance from tests of balance, gait, lower body strength and coordination, and manual dexterity was developed, and a change score was calculated as the difference in scores from 1988 to 1991. RESULTS The mean (+/-SD) homocysteine level was 11.6 +/- 4.3 micromol/L. With each SD increase in homocysteine, there was an increased risk of being in the worst quartile of decline in physical function (odds ratio = 1.5; 95% confidence interval: 1.2 to 1.9) in analyses that adjusted for age, sex, baseline physical performance, smoking status, vitamin B(12) levels, and incident stroke. Similar results were seen when change in physical performance was treated as a continuous variable. CONCLUSION Older persons with elevated plasma homocysteine levels are at an increased risk of decline in physical function.

Hyperkyphosis Predicts Mortality Independent of Vertebral Osteoporosis in Older Women

Context Whether kyphosis portends poor outcomes for particular groups of women is unclear. Contribution This long-term follow-up study found that, in older white women with previous vertebral fractures, increased kyphosis predicted increased risk for earlier death. The increased risk seemed independent of multiple factors, including age and underlying spinal osteoporosis. Women without vertebral fractures had no obvious increased mortality risk associated with kyphosis. Caution Only white women were studied. Vertebral fractures and kyphosis were not assessed simultaneously. Implication Women with vertebral fractures and hyperkyphosis may have greater risk for mortality than women with only vertebral fractures or only hyperkyphosis. The Editors It is well known that vertebral fractures are associated with an increased risk for death in older persons (14), but the explanation for this is unknown. Our previous work (2) suggested that those with vertebral fractures were more likely to die of a pulmonary cause in particular, possibly because of vertebral fractureinduced changes in the thoracic kyphotic curvature that could detrimentally affect respiratory function. In that study, we performed a subanalysis demonstrating that older women with the worst thoracic hyperkyphosis were more likely to die of a pulmonary cause; however, only one third of those with the greatest kyphotic curvatures had evidence of underlying vertebral fractures (2). Although that study provided a plausible mechanism by which vertebral fractures might lead to death, it also suggested that nonosteoporotic kyphosis may also be associated with adverse health. Some studies have suggested that hyperkyphosis itself may be a risk factor for death (5, 6). However, these studies could not assess whether the increased thoracic curvature or the presence of clinically undetected vertebral fractures were the underlying explanation for the apparent association between hyperkyphosis and increased mortality risk. Therefore, to test whether hyperkyphosis is associated with an increased risk for death independent of vertebral fractures and low bone mineral density, we conducted a prospective cohort study of 610 older women who had measures of kyphosis, bone mineral density, and morphometric vertebral fractures, and we assessed mortality rates over an average follow-up of 13.5 years. Methods Participants were from the Study of Osteoporotic Fractures, an ongoing prospective study of risk factors for fractures and other health outcomes. Between 1986 and 1988, 9704 community-dwelling women age 65 years or older were recruited from various population-based listings in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela Valley, Pennsylvania (7). During the 2-year follow-up visit, 610 women, representing all 4 clinic centers, were consecutively sampled to undergo flexicurve measurements to document the degree of thoracic curvature, known as the kyphosis index. Figure 1 shows the details of the original cohort study design and the sampling of the women for the purposes of the kyphosis study. The institutional review boards at each clinical site approved the study protocol, and written informed consent was obtained from all participants. Figure 1. Study flow diagram. Flexicurve Measurement of Kyphosis An architects flexicurve was used to measure kyphosis during the second clinic examination, a technique first developed in the 1970s. Examiners placed the flexible ruler against the persons back while that person was standing erect, with the upper end placed just below the C7 spinous process and the lower end just at the S2 spinous process. The outline of the curve was then captured by using a handheld digital scanner, and xy coordinates were computed to derive a reference line between curve ends, distance from origin to first intersection of the curve (with the reference line defining the vertical length of the upper back curve), and maximum horizontal distance from the upper back curve to the reference line (Figure 2). The kyphosis index is defined as 100 times the maximum horizontal distance divided by the vertical length of the upper back curve (8). All technicians were taught the measurement technique at the centralized coordinating center. To assess reproducibility, 2 technicians from each clinic site performed the flexicurve measurement in a separate sample comprising 75 women selected from the Study of Osteoporotic Fractures cohort. After the tracings were obtained at the 4 clinical centers, they were sent to the coordinating center for centralized readings. The coefficient of variation for replicate kyphosis index values was 12.6%, and the Pearson correlation coefficient between the paired measurements was 0.66 (8). In addition, as a second check of validity, 20 tracings were selected from the study sample, 2 from each decile of kyphosis index, and 2 independent observers were asked to rank the tracings visually by order of kyphosis severity. The Spearman correlation coefficient between the visual rankings of the tracings by 2 observers was 0.89, and the correlations between the ranking of observers and ranking of kyphosis index were 0.943 (observer 1) and 0.931 (observer 2) (8). Figure 2. Flexicurve measurement calculation. The index of thoracic curvature, or the kyphosis index, is 100 times the maximum horizontal distance divided by the vertical length of the upper back curve (B/E100). Reproduced from Milne and Williamson (5), with permission from Oxford University Press. Vertebral Morphometry Measurements At the baseline visit in 1986 to 1988, radiographs of the thoracic and lumbar spine were obtained in accordance with the 1995 National Osteoporosis Foundation guidelines (9). Using visual triage, trained technicians grouped radiographs as normal, uncertain, or probably fractured on the basis of a semiquantitative grading scheme that categorized a participant by the most abnormal vertebral level (10, 11). The study radiologist further categorized those classified as uncertain as normal or probably fractured. Those classified as probably fractured were then evaluated by morphometry with 6-point digitization to calculate the anterior (Ha), middle (Hm), and posterior (Hp) heights for each vertebral body from T4 to L4. For each vertebral level, 3 height ratios were calculated (Ha/Hp, Hm/Hp, and Hp/Hp1 or Ha/Ha1), and a vertebra was classified as having a prevalent fracture if any of the 3 height ratios were more than 3 SDs less than the study populationspecific mean for that level (12). A vertebra was classified as having a severe prevalent fracture if any of the 3 height ratios were more than 4 SDs below the study populationspecific mean for that level. Incident Vertebral Fracture Assessment A vertebra was classified as having an incident fracture if any of 3 vertebral height ratios decreased by more than 20% and by at least 4 mm compared with the baseline films on repeated radiography done an average of 4.2 years after the initial assessment of prevalent vertebral fractures. The study radiologist reviewed the morphometrically defined incident vertebral fractures to exclude imaging artifacts or such conditions as Scheuermann disease and reclassified 7% as not having an incident fracture. In a random sample of 503 women selected from the original study cohort whose radiographs were triaged and then digitized, triage missed no incident fractures according to the study definition. Questionnaire and Examination All study participants completed a comprehensive baseline and more limited follow-up questionnaire that included questions about demographic characteristics (age and education), medical history, and health behaviors. Whenever possible, data obtained from the second visit were used to best correspond with the timing of the kyphosis index measurement. Baseline measures included a family history of osteoporosis, self-reported spine fractures, stroke, self-reported health status, physical activity, and detailed questions about alcohol use. Information obtained from the second visit questionnaire included data about age and cigarette use. At the baseline and second clinical examination, height and weight were measured, and weight change was calculated as the difference in weight between baseline and the second follow-up visit. Body mass index was also calculated. At the second examination, participants were tested to see whether they could stand from a chair 5 times without using their arms, and they were also asked to perform a tandem stand. Also at the second examination, total hip and spine bone mineral density were measured by using dual-energy x-ray absorptiometry (QDR 1000, Hologic, Waltham, Massachusetts). Details of bone density measurements and quality control procedures are described elsewhere (13). Ascertainment of Death Participants were contacted by mail or telephone every 4 months. The study follow-up for vital statistics was 95% complete as of August 2007. All deaths were confirmed by receipt of death certificates. Statistical Analysis Because kyphosis is strongly associated with vertebral fractures (a known risk factor for death) and because we aim to disentangle the ill health effect of vertebral fractures from kyphosis, we compared the characteristics of women by prevalent vertebral fracture status by using chi-square tests for dichotomous variables or t tests for continuous measures. After confirming the assumption that the hazard rates were proportional, we used Cox proportional hazards models to determine the association between kyphosis index and all-cause mortality. All results are reported as relative hazards with 95% CIs. We first used nonparametric regression modeling with spline transformation to assess the nature of the relation (linear vs. nonlinear) between kyphosis index and mortality by using SAS Macro %Psplinet (SAS Institute, Cary, North Carolina) (14, 15). Because the relationship seemed close to

Association of Spinal Muscle Composition and Prevalence of Hyperkyphosis in Healthy Community-Dwelling Older Men and Women

BACKGROUND Older adults with hyperkyphosis are at increased risk of falls, fractures, and functional decline. Modifiable risk factors for hyperkyphosis have not been well studied. Our objective was to determine whether spinal muscle area and density are associated with hyperkyphosis, independent of age, race, sex, bone mineral density, and trunk fat. METHODS Using data from the Pittsburgh site of the Health, Aging, and Body Composition study, we performed a baseline cross-sectional analysis. Participants were black and white men and women 70-79 years old (N = 1172), independent in activities of daily living and able to walk ¼ mile and up 10 steps without resting. We measured Cobbs angle of kyphosis from supine lateral scout computed tomography scans, and categorized hyperkyphosis as Cobbs angle >40°. Axial images from lateral scout computed tomography scans assessed spinal extensor muscle cross-sectional area and density (proxy for fat infiltration). RESULTS In our sample, 21% had hyperkyphosis. Prevalence in black men was 11%; in white men, 17%; in black women, 26%; and in white women, 30%. In multivariate analysis, each standard deviation increase in muscle density was associated with a 29% reduction in the odds of hyperkyphosis, independent of covariates. Muscle area was not significantly associated with hyperkyphosis. CONCLUSIONS Lower spinal muscle density is associated with hyperkyphosis in healthy community-dwelling older adults. This potentially modifiable risk factor could be targeted in exercise interventions. Randomized trials are needed to determine whether an exercise program targeting spinal muscle density reduces hyperkyphosis and in turn improves health outcomes.

Factors associated with kyphosis progression in older women: 15 years' experience in the study of osteoporotic fractures.

Age‐related hyperkyphosis is thought to be a result of underlying vertebral fractures, but studies suggest that among the most hyperkyphotic women, only one in three have underlying radiographic vertebral fractures. Although commonly observed, there is no widely accepted definition of hyperkyphosis in older persons, and other than vertebral fracture, no major causes have been identified. To identify important correlates of kyphosis and risk factors for its progression over time, we conducted a 15‐year retrospective cohort study of 1196 women, aged 65 years and older at baseline (1986 to 1988), from four communities across the United States: Baltimore County, MD; Minneapolis, MN; Portland, OR; and the Monongahela Valley, PA. Cobb angle kyphosis was measured from radiographs obtained at baseline and an average of 3.7 and 15 years later. Repeated measures, mixed effects analyses were performed. At baseline, the mean kyphosis angle was 44.7 degrees (SE = 0.4, SD = 11.9) and significant correlates included a family history of hyperkyphosis, prevalent vertebral fracture, low bone mineral density, greater body weight, degenerative disc disease, and smoking. Over an average of 15 years, the mean increase in kyphosis was 7.1 degrees (SE = 0.25). Independent determinants of greater kyphosis progression were prevalent and incident vertebral fractures, low bone mineral density and concurrent bone density loss, low body weight, and concurrent weight loss. Thus, age‐related kyphosis progression may be best prevented by slowing bone density loss and avoiding weight loss.

Diffuse Idiopathic Skeletal Hyperostosis and Its Relation to Back Pain Among Older Men: The MrOS Study

OBJECTIVES To estimate the prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in a cross-sectional study of elderly men age 65 to 100 years and to examine back and neck pain as possible correlates of DISH. METHODS DISH was defined using Resnicks criteria and scored according to Mata on lateral spine radiographs of 298 randomly selected participants from the MrOS Study. Standardized self-reported questionnaires were used to assess the frequency and severity of back and neck pain, and the relation of these to DISH status was estimated with χ(2) tests, as well as prevalence ratios and 95% confidence intervals using log-binomial regression models. RESULTS DISH was observed in 126 older men (42%), increased with age (30%, 39%, 48%, and 56% for ages 65-69, 70-74, 75-79, and ≥80 respectively), and was positively associated with body mass index (BMI) (P = 0.04) and blood pressure (P = 0.02). Significantly less back pain in the past 12 months was reported among men with DISH as compared to men without (59% vs 71%, P = 0.03), which remained after adjustment for age, BMI, and blood pressure (prevalence ratios = 0.73, 95% confidence interval = 0.57-0.95). Back pain severity (P = 0.07) and frequency (P = 0.06) were also less frequent among men with DISH compared to men without, whereas reported neck pain was similar between groups (P = 0.39). CONCLUSIONS Among community-dwelling elderly men, DISH prevalence is high, increases with age, and is positively associated with BMI and blood pressure. Frequency of self-reported back pain over the past 12 months was lower in older men with DISH as compared to those without DISH.