INTRODUCTION:Hyperkyphosis commonly affects older people but is not widely acknowledged as a clinically actionable problem, especially in men. There are several techniques to quantify kyphosis including the blocks and Cobb angle measurements. This study includes both kyphosis measures to investigate whether older men with accentuated kyphosis may be at increased mortality risk. METHODS:Men aged ≥65 years (N = 5994) were recruited to participate in the MrOS prospective cohort study from 2000 to 2002 (baseline). Our primary cohort included 2931 enrollees (mean age 79.3 years; SD 5.2) who underwent blocks-measured kyphosis from 2006 to 2009. Our secondary cohort included 2351 participants who underwent radiographic Cobb angle measurements at baseline. Cox proportional hazards analyses were used to determine association between kyphosis and all-cause mortality while adjusting for prevalent radiographic vertebral fractures, bone mineral density, incident fractures, gait speed, timed chair stands, self-reported health, alcohol use, medical co-morbidities, and physical activity. RESULTS:During a mean follow-up of 8.3 (SD 3.2) years, 1393 participants died in the primary cohort. In this group, compared to men with 0-1 block kyphosis, increasing blocks-measured kyphosis was associated with increased mortality (HR: 1.26-1.53, p trend <0.001). With addition of prevalent vertebral fracture to adjusted models, the association remained significant in participants with severe kyphosis (3+ blocks-measured). Similarly, with addition of chair stand performance the association remained significant for 4+ blocks kyphosis. Walking speed did not attenuate the association of kyphosis and mortality. In the secondary cohort, there were no significant associations between radiographic Cobb angle kyphosis and mortality. CONCLUSIONS:Increasing blocks-measured kyphosis was associated with a greater risk of mortality in older men, indicating that hyperkyphosis identified on physical exam should be considered a clinically significant finding that may warrant further evaluation and treatment.

Selective estrogen receptor modulators (SERMs) hold the promise of an ideal estrogenic compound. Moderate efficacy for the prevention of osteoporotic vertebral fractures has now been found after 5 years of treatment with the SERM bazedoxifene; however, expectations for one SERM to provide multiple benefits for postmenopausal women might be a pipe dream.

The incidence of osteoporotic fractures increases with advancing age and is associated with significant health care expenditures, particularly related to hip fractures and loss of quality of life. Unfortunately, few studies have included subjects 80 years of age and older to help guide management of elderly patients who are living in the community or in long-term care facilities. Treating this age group encompasses the same general measures and pharmacologic therapies as in younger adults. Focusing on fall prevention and adequate vitamin D is essential. All prevention strategies in the elderly for fracture risk reduction should include simple vitamin D and calcium supplementation. However, for those at high risk of fracture, adding pharmacologic therapy should be considered. This article reviews recent research findings of general measures and pharmacologic therapy that are applicable to managing osteoporosis in the elderly.

Purpose of reviewVitamin D is an important determinant of bone health and neuromuscular function. This article discusses recent research findings about the association of vitamin D and skeletal health with respect to parathyroid hormone, bone mineral density, physical performance, falls, and fracture. Recent findingsThe critical threshold to maximize adequate calcium absorption and suppress excess parathyroid hormone secretion is a 25-hydroxyvitamin D level of 30 ng/ml or 75 nmol/l. In a study of postmenopausal women on osteoporosis therapy, 45% of women taking 400 IU or more of vitamin D daily had serum 25-hydroxyvitamin D levels lower than 30 ng/ml compared with 63% taking less than 400 IU of vitamin D supplementation daily. In community-dwelling adults, a significant positive association was shown between 25-hydroxyvitamin D levels and total hip bone mineral density and lower extremity function. A meta-analysis of hip fractures demonstrated a 26% lowering of risk with doses of greater than 700 IU of vitamin D supplementation. Subsequent clinical trials showed similar reductions but were not statistically significant. SummaryThe inexpensive and simple practice of maintaining adequate vitamin D can contribute to decreasing fracture risk through skeletal and neuromuscular effects. Prevention strategies for fracture risk reduction should include vitamin D supplementation, particularly in the elderly.

UNLABELLED:Many physicians remain uncertain about prescribing hormone therapy for symptomatic women at the onset of menopause. The American Society for Reproductive Medicine (ASRM) convened a multidisciplinary group of healthcare providers to discuss the efficacy and risks of hormone therapy for symptomatic women, and to determine whether it would be appropriate to treat women at the onset of menopause who were complaining of menopausal symptoms.MAJOR FINDINGS:Numerous controlled clinical trials consistently demonstrate that hormone therapy, administered via oral, transdermal, or vaginal routes, is the most effective treatment for vasomotor symptoms. Topical vaginal formulations of hormone therapy should be preferred when prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy. Data from the Women's Health Initiative indicate that the overall attributable risk of invasive breast cancer in women receiving estrogen plus progestin was 8 more cases per 10,000 women-years. No increased risk for invasive breast cancer was detected for women who never used hormone therapy in the past or for those receiving estrogen only. Hormone therapy is not effective for the treatment of cardiovascular disease and that the risk of cardiovascular disease with hormone therapy is principally in older women who are considerably postmenopause.CONCLUSIONS:Healthy symptomatic women should be offered the option of hormone therapy for menopausal symptoms. Symptom relief with hormone therapy for many younger women (at the onset of menopause) with menopausal symptoms outweighs the risks and may provide an overall improvement in quality of life. Hormone therapy should be individualized for symptomatic women. This involves tailoring the regimen and dose to individual needs.

Drs Mikhail and Cope raise an interesting statistical issue regarding the principle of reporting P values for subgroup analyses. Unfortunately, this principle is violated in many publications. Our cohort of interest was women with a BMD score between −1.6 and −2.5 at the femoral neck, regardless of fracture status at baseline. The statistical significance, or lack thereof, within the 2 subgroups defined by fracture status (present vs absent) at baseline considered in this article should not change the overall inference to be made from our analysis. Our findings apply equally to patients with or without prevalent vertebral fracture. In such an analysis, the inference within subgroups should focus on the P values for the interaction and not on the P values within the subgroups.1Pocock SJ Hughes MD Lee RJ Statistical problems in the reporting of clinical trials: a survey of three medical journals.N Engl J Med. 1987; 317: 426-432Crossref PubMed Scopus (513) Google Scholar, 2Peto R Misleading subgroup analyses in GISSI [letter].Am J Cardiol. 1990; 66: 771-772Abstract Full Text PDF PubMed Scopus (8) Google Scholar, 3Brookes ST Whitely E Egger M Smith GD Mulheran PA Peters TJ Subgroup analyses in randomized trials: risk of subgroup-specific analyses: power and sample size for the interaction test.J Clin Epidemiol. 2004; 57: 229-236Abstract Full Text Full Text PDF PubMed Scopus (480) Google Scholar In our analysis, the interaction (baseline fracture status × treatment group) was not significant: P=.44 for clinical vertebral fracture and P=.54 for radiographic vertebral fracture. To elucidate this point, it is easy to conceive of a hypothetical trial in which the overall treatment effect is positive, but inappropriate subgroup analyses report nonsignificant findings for 2 subgroups (eg, sex) when analyzed separately. We would arrive at the interesting conclusion that the drug is effective in the whole population but not effective in men or in women! If the treatment effect is independent (statistically) of the subgroup assignment, it is not appropriate to focus on P values within the subgroups. Hence, treatment decisions cannot be broken down into specific subgroups either. Thus, we stand by our conclusion that the effect of alendronate on clinical or radiographic vertebral fracture is independent of fracture status at baseline. To address the second issue, we first need to note that there is no uniform definition of nonvertebral fracture. The most liberal definition (hereafter called definition 1) has been used in alendronate studies4Black DM Cummings SR Karpf DB Fracture Intervention Trial Research Group et al.Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures.Lancet. 1996; 348: 1535-1541Abstract Full Text Full Text PDF PubMed Scopus (3433) Google Scholar, 5Black DM Thompson DE Bauer DC FIT Research Group et al.Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial [published correction appears in J Clin Endocrinol Metab. 2001;86:938].J Clin Endocrinol Metab. 2000; 85: 4118-4124Crossref PubMed Scopus (753) Google Scholar, 6Cummings SR Black DM Thompson DE Fracture Intervention Trial Research Group et al.Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.JAMA. 1998; 280: 2077-2082Crossref PubMed Scopus (2093) Google Scholar, 7Pols HA Felsenberg D Hanley DA Foxamax International Trial Study Group et al.Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study.Osteoporos Int. 1999; 9: 461-468Crossref PubMed Scopus (551) Google Scholar in which nonvertebral fracture was defined as any fracture except a vertebral fracture. The most conservative definition (hereafter called definition 2), which includes only fracture of the hip, clavicle, humerus, wrist, pelvis, or leg, was used in the risedronate studies.8Harris ST Watts NB Genant HK Vertebral Efficacy With Risedronate Therapy (VERT) Study Group et al.Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial.JAMA. 1999; 282: 1344-1352Crossref PubMed Scopus (2289) Google Scholar, 9Reginster J Minne HW Sorensen OH Vertebral Efficacy with Risedronate Therapy (VERT) Study Group et al.Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis.Osteoporos Int. 2000; 11: 83-91Crossref PubMed Scopus (1427) Google Scholar The effect of alendronate on nonvertebral fracture (definition 1) was not statistically significant among patients with existing vertebral fracture.4Black DM Cummings SR Karpf DB Fracture Intervention Trial Research Group et al.Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures.Lancet. 1996; 348: 1535-1541Abstract Full Text Full Text PDF PubMed Scopus (3433) Google Scholar When definition 2 of nonvertebral fractures is used, alendronate reduced the risk of nonvertebral fracture by 36% (P=.002). In both cases, the results were not dependent on baseline BMD. Specifically, the study included patients with existing vertebral fracture and T scores between −1.6 and −2.5 at the femoral neck. Among patients without existing vertebral fracture at baseline, we reported an important statistical interaction of the effect of alendronate on nonvertebral fracture using definition 1.6Cummings SR Black DM Thompson DE Fracture Intervention Trial Research Group et al.Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.JAMA. 1998; 280: 2077-2082Crossref PubMed Scopus (2093) Google Scholar Thus, we concluded that among patients without existing vertebral fracture, alendronate was effective for those with T scores less than −2.5 but not effective for those with T scores between −1.6 and −2.5. The same is true if definition 2 is used. We also reported5Black DM Thompson DE Bauer DC FIT Research Group et al.Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial [published correction appears in J Clin Endocrinol Metab. 2001;86:938].J Clin Endocrinol Metab. 2000; 85: 4118-4124Crossref PubMed Scopus (753) Google Scholar that alendronate was effective in reducing nonvertebral (definitions 1 and 2) fracture among patients with T scores less than −2.5 and without existing vertebral fracture. Thus, it would not be prudent from a statistical viewpoint to combine subgroups when the responses were different. It is for this very reason, even though the analysis was prespecified, that we have not reported on the effect of alendronate on nonvertebral fracture in any cohort in the FIT study that included patients with T scores between −1.6 and −2.5 from both arms of FIT. However, it is should be noted that in the Fosamax International Trial (FOSIT), which included patients with BMD T scores less than −1.0 at the femoral neck, alendronate reduced the risk of nonvertebral fracture (definition 1) by 47% after 1 year.7Pols HA Felsenberg D Hanley DA Foxamax International Trial Study Group et al.Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study.Osteoporos Int. 1999; 9: 461-468Crossref PubMed Scopus (551) Google Scholar This reduction was independent of baseline BMD. The baseline vertebral fracture status of these patients was not known. To address the questions from Dr Seeman, please note that our study used the T score at the femoral neck to define the cutoff for BMD. However, in clinical practice, the cutoff is based also on the T score from other sites. The standard of care for those who measure BMD by using a central measurement is to measure both spine and hip BMD and to use the lowest values of the sites (spine, hip neck, hip trochanter, or total hip) to diagnose osteoporosis. Thus, a patient may have a World Health Organization-defined osteoporotic spine BMD T score of −2.6 and yet have nonosteoporotic hip BMD measurements (eg, T score of −1.8) and be correctly described as “osteoporotic.” In our cohort, in which osteopenia was defined according to the World Health Organization's definition of a femoral neck BMD T score of −1.6 or less but greater than −2.5, 77% of patients had osteopenic spine. If we used a cohort of patients for whom all T scores (spine, hip neck, or total hip) were greater than −2.5, the findings would be somewhat different. The relative risk (RR) reductions would be 80% (RR, 0.20; 95% confidence interval [CI], 0.05–0.63) and 57% (RR, 0.43; 95% CI, 0.26–0.72) for clinical and radiographic vertebral fracture, respectively. If we limited the cohort to those with spinal osteopenia, then the RR reductions would be 41% (RR, 0.59; 95% CI, 0.32–1.00) and 46% (RR, 0.54; 95% CI, 0.39–0.76) for clinical and radiographic vertebral fracture, respectively. Finally, to address Dr Seeman's question regarding the computation of a valid number needed to treat, we need a good estimate of the baseline risk. Rates in placebo groups in clinical trials are not surrogates for the true baseline risk for individual patients. Alendronate and Vertebral Fracture RiskMayo Clinic ProceedingsVol. 80Issue 9PreviewTo the Editor: Women with osteopenia without fractures are at modest risk of fracture but contribute to more than half of all fragility fractures in the community because of their large numbers. An important unmet need is to provide evidence of antifracture efficacy of a drug for these women. Full-Text PDF

Insomnia is a problem in all stages of life but is particularly common after age 65. A number of factors--including advanced age, psychosocial influences, medical illness, and the use of medications and alcohol--may disturb sleep architecture. Evaluation of insomnia in the older patient requires a careful history and physical examination, supplemented by a sleep diary. Treatment of underlying conditions and nonpharmacologic improvements in sleep hygiene are first-line therapy, but pharmacologic agents such as benzodiazepines, nonbenzodiazepine hypnotics, or antidepressants may be needed. Nonbenzodiazepines with rapid elimination may offer a lower side-effect profile than other hypnotic agents when used for insomnia in the older population.

BACKGROUND:Many elderly female residents of long-term care facilities have osteoporosis and could benefit from intervention to increase bone density.OBJECTIVE:To examine the efficacy and safety of alendronate for treatment of osteoporosis in elderly female residents of long-term care facilities.DESIGN:Multicenter, randomized, double-blind, placebo-controlled 2-year study.SETTING:25 long-term care facilities.PATIENTS:327 elderly women with osteoporosis.INTERVENTION:Patients were randomly assigned to receive alendronate, 10 mg/d, or placebo. All patients also received vitamin D, 400 IU/d, and some patients received supplemental calcium (total intake, approximately 1500 mg/d).MEASUREMENTS:Bone mineral density (BMD) of the spine and hip and biochemical markers of bone turnover.RESULTS:Alendronate produced significantly greater increases in BMD than did placebo (24-month differences: spine, 4.4% [95% CI, 3.3% to 5.5%]; femoral neck, 3.4% [CI, 2.3% to 4.4%]). Alendronate produced greater decreases from baseline in biochemical markers of bone turnover than did placebo (P < 0.001).CONCLUSION:Alendronate increased BMD at both the spine and hip in elderly female residents of long-term care facilities.

OBJECTIVE:To evaluate vaginal bleeding profiles with lower doses of conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA) as continuous combined therapy.DESIGN:The Women's Health, Osteoporosis, Progestin, Estrogen (Women's HOPE) study, a randomized, double-blind, placebo-controlled trial.SETTING:Study centers across the United States.PATIENT(S):Two thousand six hundred seventy-three healthy, postmenopausal women.INTERVENTION(S):Women received CEE, 0.625 mg/d; CEE, 0.625 mg/d, plus MPA 2.5 mg/d; CEE, 0.45 mg/d; CEE, 0.45 mg/d, plus MPA, 2.5 mg/d; CEE 0.45 mg/d, plus MPA, 1.5 mg/d; CEE, 0.3 mg/d; CEE, 0.3 mg/d, plus MPA, 1.5 mg/d; or placebo for 1 year.MAIN OUTCOME MEASURE(S):Bleeding data were analyzed in efficacy-evaluable and intention-to-treat populations.RESULT(S):Cumulative amenorrhea and no bleeding rates were higher with lower doses of CEE/MPA than with CEE 0.625/MPA 2.5. A linear trend between time since menopause and cumulative amenorrhea was observed (P<.05) in all CEE/MPA groups except the CEE 0.45/MPA 1.5 group. The proportion of patients who experienced no bleeding in cycle 1 was 89%, 82%, and 80% in the CEE 0.3/MPA 1.5, CEE 0.45/MPA 1.5, and CEE 0.45/MPA 2.5 groups, respectively. These values were significantly greater than the incidence of no bleeding in the CEE 0.625/MPA 2.5 group (P<.05).CONCLUSION(S):Lower-dose regimens of CEE and MPA produce higher rates of amenorrhea and no bleeding compared with CEE 0.625/MPA 2.5 and may be appropriate for newly menopausal patients.

Osteoporosis is a common disease in postmenopausal women and can result in considerable morbidity and mortality as a consequence of spontaneous fractures. Fortunately, effective therapeutic agents that prevent or slow bone resorption are now available for the prevention and treatment of osteoporosis. Most patients treated with antiresorptive agents gain bone mass and have a reduced risk of fractures. There are few studies that compare different antiresorptive agents, and those evaluate bone density not fractures. Antifracture efficacy has been established in separate randomized, placebo-controlled studies and results of studies using raloxifene and risedronate have been published this year. Current advances with alendronate include different dosing regimens, combination with other drugs, and extension to other patient populations. Advances with estrogen involve the effect of lower dosages. In choosing an agent for osteoporosis prevention or treatment, the variable effects on bone and nonskeletal sites must be taken into consideration.

Background Mortality increases after hip fractures in women and more so in men. Little is known, however, about mortality after other fractures. We investigated the mortality associated with all fracture types in elderly women and men.Methods We did a 5-year prospective cohort study in the semi-urban city of Dubbo, Australia, of all residents aged 60 years and older (2413 women and 1898 men). Low-trauma osteoporotic fractures that occurred between 1989 and 1994, confirmed by radiography and personal interview, were classified as proximal femur, vertebral, and groupings of other major and minor fractures. We calculated standardised mortality rates from death certificates for people with fractures compared with the Dubbo population.Findings 356 women and 137 men had low-trauma fractures. In women and men, mortality was increased in the first year after all major fractures. In women, age-standardised mortality ratios were 2.18(95% CI 2.03-2.32) for proximal femur, 1.66 (1.51-1.80) for vertebral, 1.92 (1.70-2.14) for other major, and 0.75 (0.66-0.84) for minor fractures. In men, these ratios were 3.17 (2.90-3.44) for proximal femur, 2.38 (2.17-2.59) for vertebral, 2.22 (1.91-2.52) for other major, and 1.45 (1.25-1.65) for minor fractures. There were excess deaths (excluding minor fractures in women) in all age-groups.Interpretation All major fractures were associated with increased mortality, especially in men. The loss of potential years of life in the younger age-group shows that preventative strategies for fracture should not focus on older patients at the expense of younger women and of men.

The time required to decide to seek medical care for acute chest pain is the major modifiable component in the process of care delivery. This study demonstrates that prehospital delay in the setting of acute chest pain was related to the type of health insurance.

This is a 65-yr-old woman with dermatomyositis and extensive calcinosis. On physical examination subcutaneous nodules were widely distributed on her chest and extremities. Her current CPK is 163 IU/L (normal range 0-175); however, with a recent flare of her symptoms, the CPK peaked at 411 IU/L. Her current medications are Imuran 25 mg/d, Prednisone 4 mg/d, and conjugated equine estrogen 0.625 mg/d.

This is a 65-yr-old woman with dermatomyositis and extensive calcinosis. On physical examination subcutaneous nodules were widely distributed on her chest and extremities. Her current CPK is 163 IU/L (normal range 0-175); however, with a recent flare of her symptoms, the CPK peaked at 411 IU/L. Her current medications are Imuran 25 mg/d, Prednisone 4 mg/d, and conjugated equine estrogen 0.625 mg/d.