Biomedical subjects

Anne M Kenny

Publications and source records attributed to Anne M Kenny.

16 recordsLinked to original sources

PubMed2006

Association between level of frailty and bone mineral density in community-dwelling men.

The goal of this study is to determine the associations between the components of a frailty definition and bone mineral density (BMD) in older men. A total of 392 community dwelling men (age range: 58-95 yr) with a mean age of 73+/-8 yr were evaluated. Femoral neck BMD T-scores ranged from -5.78 to +2.50, with 48.7% who had T-scores between -1 and -2.5 (low bone mass) and 8.7% who had T scores < or = -2.5 (osteoporosis). Participants were characterized as normal (39%), intermediate (55%), or frail (6%). Hand grip strength was 31.5+/-9.1 kg in those with normal BMD compared with 26.5+/-7.9 kg in those with osteoporotic BMD (p=0.0026). Walk speed (8 ft) was 2.32+/-0.49 s in those with normal BMD compared with 2.87+/-1.30 s with osteoporotic BMD (p=0.0015). Femoral neck T-score declined significantly with increasing level of frailty (p=0.014), but significance of decline was lost when corrected for age. Increasing frailty was associated with lower femoral neck BMD, although the association was not independent of age. Two components of the frailty model (i.e., hand grip strength and walking speed) were independently associated with lower femoral neck BMD, a finding that has not previously been reported in men.

Absorptiometry, Photon↗

PubMed2005

Role of endocrine-immune dysregulation in osteoporosis, sarcopenia, frailty and fracture risk.

Osteoporosis, a key predictor of hip fractures can be treated using a variety of safe and effective interventions. Nevertheless, optimally effective strategies for the prevention of hip fractures must also incorporate efforts to address a broad range of other potentially reversible factors. Hyperthyroidism, anticonvulsants, caffeine and smoking may decrease bone mass and increase fracture risk at any age. In older individuals it is important to also consider additional risk factors, including long-acting benzodiazepines, poor vision and sarcopenia. The presence of sarcopenia, an age-related decline in muscle bulk and quality enhances the risk of frailty and possibly also hip fracture, particularly if associated with diminished functional mobility, lower quadriceps strength and poor balance or body sway. In this review we examine evidence which indicates the presence of endocrine-immune dysregulation in both osteoporosis and sarcopenia. Post-menopausal declines in serum estrogen and androgen levels contribute to increases in local bone levels of cytoclastic cytokines, followed by increased osteoclastogenesis and bone loss. Similarly, the presence of decreased gonadal hormones and IGF-1, combined with unusually high peripheral levels of cytokines, inflammatory mediators and coagulation markers all enhance the risk of sarcopenia and frailty. We propose that a translational research approach which emphasizes common pathophysiologic mechanisms in osteoporosis and sarcopenia could accelerate the speed of discovery of effective strategies for both frailty and hip fracture prevention.

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PubMed2005

Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials.

BACKGROUND: We performed a meta-analysis of randomized clinical trials to determine the risks of adverse events associated with testosterone replacement in older men. METHODS: The MEDLINE database was searched from 1966 to April 2004, using testosterone as the indexing term; limits included human, male, > or =45 years old, and randomized controlled trial. Of the 417 studies thus identified, 19 met the inclusion criteria: testosterone replacement for at least 90 days, men > or =45 years old with low or low-normal testosterone level, randomized controlled trial, and medically stable men. Odds ratios (ORs) were pooled using a random effects model, assuming heterogeneous results across studies, and were weighted for sample size. RESULTS: In the 19 studies that met eligibility criteria, 651 men were treated with testosterone and 433 with placebo. The combined rate of all prostate events was significantly greater in testosterone-treated men than in placebo-treated men (OR = 1.78, 95% confidence interval [CI], 1.07-2.95). Rates of prostate cancer, prostate-specific antigen (PSA) >4 ng/ml, and prostate biopsies were numerically higher in the testosterone group than in the placebo group, although differences between the groups were not individually statistically significant. Testosterone-treated men were nearly four times as likely to have hematocrit >50% as placebo-treated men (OR = 3.69, 95% CI, 1.82-7.51). The frequency of cardiovascular events, sleep apnea or death was not significantly different between the two groups. CONCLUSIONS: Testosterone replacement in older men was associated with a significantly higher risk of detection of prostate events and of hematocrit >50% than was placebo; hematocrit increase was the most frequent adverse event associated with testosterone replacement. These data reaffirm the need to monitor hematocrit, PSA, and digital examination of the prostate during testosterone replacement in older men.

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PubMed2005

Effects of ultra-low-dose estrogen therapy on muscle and physical function in older women.

OBJECTIVES: To determine the effects of ultra-low-dose hormone therapy on muscle mass and physical function in community-dwelling women. DESIGN: Double-blind, placebo-controlled trial. SETTING: Clinical research center in Connecticut. PARTICIPANTS: Healthy, community-dwelling women aged 65 and older (n=167). INTERVENTION: Eligible women were randomly assigned to treatment with 0.25 mg 17-beta estradiol or placebo for 36 months. All women (estradiol or placebo) with an intact uterus received micronized progesterone 100 mg/d for 2 weeks every 6 months. All participants received 1,300 mg elemental calcium with 1,000 IU vitamin D per day. MEASUREMENTS: Appendicular skeletal muscle mass (ASM), lean body mass (LBM), and percentage body fat were measured using dual x-ray absorptiometry. Sarcopenia was defined as skeletal muscle mass (ASM/height2) 2 standard deviations or less than young, healthy reference population mean. Physical activity (Physical Activity Scale in the Elderly (PASE)) and performance were measured. Serum estrone, estradiol, and sex hormone-binding globulin were measured. RESULTS: The prevalence of sarcopenia at baseline was 13%. There were no baseline differences between groups except for PASE score and chair rise time, in which the estrogen group had better performance. No changes in ASM, LBM, percentage of body fat, or physical performance were found after 3 years of estrogen therapy. CONCLUSION: Sarcopenia was present in 13% of this group of community-dwelling, postmenopausal older women. Ultra-low-dose estrogen therapy neither improves nor harms ASM. Similarly, no changes in body fat or physical performance were detected.

Absorptiometry, Photon↗

PubMed2004

Comparison of the effects of calcium loading with calcium citrate or calcium carbonate on bone turnover in postmenopausal women.

Calcium supplementation is known to increase bone mineral density and decrease fractures, but the relative efficacy of different forms of calcium supplementation is not established. We compared the effects of calcium carbonate and calcium citrate on markers of bone resorption in older postmenopausal women in an open-labeled crossover study. Forty women were randomized to receive 1000 mg/day of either calcium citrate or calcium carbonate for 12 weeks, followed by a 2-week washout without calcium supplements and 12 weeks treatment with the alternate calcium supplement. All women received vitamin D (900 IU/day). Thirty-four women (25 Caucasian, nine Hispanic) completed the study. No significant differences in the decrease in parathyroid hormone (PTH) or bone specific alkaline phosphatase or the increase in urinary calcium/creatinine were detected between the two treatments. However, calcium citrate supplementation decreased the collagen cross-link resorption markers, urinary N-telopeptide (-30%), C-telopeptide (-31%), free deoxypyridinoline (19%) and serum N-telopeptide (-8%), compared to no significant change following calcium carbonate supplementation (+2%, +3%, +2% and +2%, respectively; P<0.05). Calcium citrate decreased markers of bone resorption significantly more than calcium carbonate in postmenopausal women, although no differences in their effects in calcium excretion or PTH were detected.

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PubMed2004

Effects of testosterone on behavior, depression, and cognitive function in older men with mild cognitive loss.

BACKGROUND: The role of sex hormones in the prevention of cognitive decline is uncertain. Animal studies suggest mechanisms for sex hormones including testosterone to maintain optimal cognitive function. But, there are studies to suggest that endogenous testosterone levels are associated with aggression in men with cognitive impairment. METHODS: In this pilot study, 11 men (mean age 80 +/- 5 years, range 73-87 years) with early cognitive decline and bioavailable testosterone levels below 128 ng/dl (lower limit for adult normal range) were randomized to receive intramuscular testosterone (200 mg every 3 weeks) or placebo for 12 weeks. Outcome measures included sex hormones (testosterone, bioavailable testosterone, sex hormone binding globulin, estradiol, and estrone), Behave AD Questionnaire, Katz Activities of Daily Living, Geriatric Depression Scale, Digit Span, Clock Face Drawing, Clock Face Perception, Verbal Fluency, Trail-Making B, and International Prostate Symptom Score at baseline, 4 weeks, and 10 weeks. RESULTS: All men completed the study. Total and bioavailable testosterone, estrone, and estradiol levels increased in men receiving testosterone, but no changes were detected in men receiving placebo. No significant changes were found in behavior following testosterone supplementation, nor was there evidence of change in depression or activities of daily living. No discernable changes were found in any of the cognitive tests. Symptoms of prostate hyperplasia remained unchanged in the testosterone (6.6 + 5.8 to 5.2 + 3.6; p =.39) and placebo (8.8 + 6.4 to 6.4 + 3.8; p =.15) groups, and prostate-specific antigen levels did not change significantly. CONCLUSION: No significant changes in behavior, function, depression, or cognitive performance occurred following 12 weeks of testosterone replacement in men with low testosterone levels and early-to-moderate cognitive impairment. This pilot work suggests that testosterone can be given to men with early cognitive impairment without significant concern about worsening aggressive or unwanted behaviors.

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PubMed2003

Ultralow-dose micronized 17beta-estradiol and bone density and bone metabolism in older women: a randomized controlled trial.

CONTEXT: Estrogen therapy is known to prevent osteoporosis, but studies have shown that conventional doses increase adverse events. Whether lower doses, one quarter of standard treatment, prevent bone loss is not known. OBJECTIVE: To examine the effect of 3 years of treatment with 0.25 mg/d of micronized 17beta-estradiol on bone mineral density (BMD) and bone turnover in healthy older postmenopausal women. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted from July 24, 1998, through June 14, 2002, at a university general clinical research center in the United States. Healthy, community-dwelling women (N = 167) who were older than 65 years at enrollment. INTERVENTION: Dosage of 0.25 mg/d of micronized 17beta-estradiol (n = 83) or placebo (n = 84); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months. MAIN OUTCOME MEASURES: The BMD of the hip, spine, wrist, and total body measured annually for 3 years. Serum and urine biochemical markers of bone resorption and formation and sex hormones were measured at baseline, 3 months, and during years 1 and 3 of treatment. RESULTS: Mean BMD increased at all sites for participants taking low-dose estrogen (17beta-estradiol) compared with placebo (P<.001). Compared with participants receiving placebo, participants taking low-dose estrogen had BMD increases of 2.6% for the femoral neck; 3.6%, total hip; 2.8%, spine; and 1.2%, total body. Markers of bone turnover, N-telopeptides of type 1 collagen, and bone alkaline phosphatase decreased significantly (P<.001) in participants taking low-dose estrogen compared with placebo. Estradiol, estrone, and sex hormone-binding globulin levels increased in the estrogen-treated group compared with placebo. The adverse effect profile was similar; specifically, there were no statistically significant differences in breast tenderness, changes in endometrial thickness or pathological effects, or annual mammographic results between the 2 groups. The number of abnormal mammograms over 3 years was 15 for the low-dose estrogen group and 10 for the placebo group (8 occurred at baseline) (P =.26). There were no reports of breast cancer during the study. CONCLUSIONS: In older women, a dosage of 0.25 mg/d of 17beta-estradiol increased bone density of the hip, spine, and total body, and reduced bone turnover, with minimal adverse effects. Future studies evaluating the effect of low-dose estrogen on fractures are indicated.

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PubMed2003

Effects of vitamin D supplementation on strength, physical function, and health perception in older, community-dwelling men.

OBJECTIVES: To study the effects of vitamin D supplementation in healthier populations of men. DESIGN: : Randomized, controlled trial. SETTING: General clinical research center. PARTICIPANTS: Sixty-five healthy, community-dwelling men (mean age+/-standard deviation=76+/-4, range 65-87). INTERVENTION: Cholecalciferol (1,000 IU/d) or placebo supplementation for 6 months; all received 500 mg supplemental calcium. MEASUREMENTS: Upper and lower extremity muscle strength and power, physical performance and activity, health perception, calcium and vitamin D intake, and biochemical assessment, including 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), and ionized calcium levels. RESULTS: The levels of 25OHD increased and PTH decreased in the cholecalciferol group, whereas there were no significant changes in the control group (P<.001). Baseline 25OHD levels correlated with baseline single-leg stance time and physical activity score. Baseline PTH levels correlated with baseline 8-foot walk time and physical activity score. No significant difference in strength, power, physical performance, or health perception was found between groups. CONCLUSION: The 25OHD or PTH levels correlated with physical activity and physical performance in older, community-dwelling men with normal 25OHD status. Vitamin D supplementation increased 25OHD levels and decreased PTH levels but did not increase muscle strength or improve physical performance or health perception in this group of healthy, older men. Further investigations of the effects of vitamin D supplementation should focus on individuals with low levels of vitamin D.

25-Hydroxyvitamin D 2↗

PubMed2003

Prevalence of sarcopenia and predictors of skeletal muscle mass in nonobese women who are long-term users of estrogen-replacement therapy.

BACKGROUND: Sarcopenia refers to the loss of skeletal muscle mass with age. We have found a prevalence of sarcopenia of 22.6% in older postmenopausal women not receiving estrogen. The objective of this study was to determine the prevalence of sarcopenia in a population of older, nonobese, community-dwelling women who had been long-term users of estrogen replacement therapy (ERT). METHODS: We measured appendicular skeletal muscle mass by dual x-ray absorptiometry (DXA) in 189 women aged 59 to 78 years old who had been using ERT for at least 2 years (mean +/- SD duration, 12.7 +/- 8.2 years). We defined sarcopenia as an adjusted appendicular skeletal muscle mass (ASM) (mass divided by height squared) more than 2 SDs below the mean for a young healthy reference population. Health and menopause history were obtained. Body mass index (BMI) was calculated, and physical activity and performance were measured using the Physical Activity Scale in the Elderly, the chair rise time, the 6-minute walk, and measures of lower extremity strength and power. Serum estrone, estradiol, testosterone, and sex hormone binding globulin were measured. RESULTS: The prevalence of sarcopenia in nonobese, community-dwelling women who were long-term ERT users was 23.8%. Skeletal muscle mass correlated significantly with BMI, age at the time of starting ERT, hand grip strength, lower extremity strength and power, and testosterone level, but not with estradiol level. In linear regression analysis, BMI, leg press strength, and testosterone level contributed to adjusted ASM, accounting for 48.7% of the variance (p <.001). CONCLUSIONS: Sarcopenia is as common in nonobese women who are long-term ERT users as in community-dwelling women not using ERT, suggesting that ERT does not protect against the muscle loss of aging. BMI, strength, and testosterone level contributed to appendicular skeletal mass in women. These data suggest that interventions to target nutrition, strength training, and testosterone replacement should be further investigated for their role in preventing muscle loss with age.

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PubMed2003

Understanding the components of publication success: a survey of academic award recipients.

PURPOSE: This study examines predictors of publication number in career development awardees. We examined whether daily writing predicted publication number among junior faculty. DESIGN AND METHODS: We surveyed 94 career development awardees; the survey consisted of 28 questions in four domains: characteristics, environment, writing practices, and attitudes about writing. RESULTS: Variables that contributed positively to publication number included male gender and those with a negative effect were clinical research and perceiving the need to write as a requirement for advancement. In subgroup analysis of junior faculty, a habit of writing daily was predictive of greater publication numbers. IMPLICATIONS: Career development awardees published more first-authored manuscripts if they were male, were involved in nonclinical research, and did not perceive writing as a requirement for advancement. These factors highlight the need to explore the lower overall publication productivity in women and in clinical investigators. Junior faculty members that write daily publish more manuscripts, regardless of gender, research type, or motivators. The benefits of daily writing warrant direct study if not empiric implementation.

Awards and Prizes↗

PubMed2003

Exercise in older adults.

Physical activity and exercise are beneficial to overall health and delay disability, even in the oldest old. We present data on exercise in older adults and its various benefits. Furthermore, we describe exercise programs suitable for adults over 65 and identify resources available to both patient and physician.

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PubMed2003

Osteoporosis in older men and women.

Hip fracture incidence accelerates approximately 10 years following the menopause in women and after age 70 in men. Approximately one million Americans suffer fragility fractures each year at a cost of over 14 billion dollars. The disability, mortality and cost of hip and vertebral fractures are substantial in the rapidly growing aging population so that prevention of osteoporosis is a major public health concern. Bone mineral density (BMD) measurement is used to make the diagnosis of osteoporosis prior to incident fracture, and to predict fracture risk. Recommendations for treatment and prevention of osteoporosis based on bone mineral density score published by the World Health Organization and the National Osteoporosis Foundation are outlined.

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PubMed2002

Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women.

BACKGROUND: Sarcopenia refers to the loss of skeletal muscle mass with age. The objective of this study was to determine the prevalence of sarcopenia in a population of older, community-dwelling research volunteers. METHODS: Appendicular skeletal muscle mass was measured by dual x-ray absorptiometry in 195 women aged 64 to 93 years and 142 men aged 64 to 92 years. We defined sarcopenia as appendicular skeletal muscle mass/height(2) (square meters) less than 2 standard deviations below the mean for young, healthy reference populations. We used two different reference populations and compared prevalence in our population to that reported in previous studies. Body mass index (BMI) was calculated and physical activity and performance were measured with the Physical Activity Scale for the Elderly, the Short Physical Performance Battery, and the Physical Performance Test. We measured health-related quality of life by using the SF-36 general health survey. Serum estrone, estradiol, sex hormone-binding globulin, parathyroid hormone, and 25-hydroxy vitamin D were measured in all participants and bioavailable testosterone was measured only in men. Leg press strength and leg press power were determined in men. RESULTS: The prevalence of sarcopenia in our cohort was 22.6% in women and 26.8% in men. A subgroup analysis of women and men 80 years or older revealed prevalence rates of 31.0% and 52.9%, respectively. In women, skeletal muscle mass correlated significantly with BMI and levels of serum estrone, estradiol, and 25-hydroxy vitamin D; in men, it correlated significantly with BMI, single leg stance time, leg press strength, leg press power, SF-36 general health score, Physical Performance Test total score, and bioavailable testosterone levels. With the use of linear regression analysis, BMI was the only predictor of appendicular skeletal muscle mass in women, accounting for 47.9% of the variance (p <.05). In men, BMI accounted for 50.1%, mean strength accounted for 10.3%, mean power accounted for 4.1%, and bioavailable testosterone accounted for 2.6% of the variance in appendicular skeletal muscle mass (p <.05). CONCLUSIONS: Sarcopenia is common in adults over the age of 65 years and increases with age. BMI is a strong predictor of skeletal muscle mass in women and men. Strength, power, and bioavailable testosterone are further contributors in men. These data suggest that interventions to target nutrition, strength training, and testosterone replacement therapy should be further investigated for their role in preventing muscle loss with age.

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PubMed2002

Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels.

BACKGROUND: Many men older than 50 years have bioavailable testosterone levels below the reference range for young adult men. The impact of the decreased androgen levels on cognition and health perception has received little attention. METHODS: Sixty-seven men (mean age 76 +/- 4 years, range 65-87) with bioavailable testosterone levels below 128 ng/dl (lower limit for adult normal range) were randomized to receive transdermal testosterone (2-2.5 mg patches/d) or placebo patches for 1 year. All men received 500 mg supplemental calcium and 400 IU vitamin D. Outcome measures included sex hormones [testosterone, bioavailable testosterone, sex hormone binding globulin (SHBG), estradiol, and estrone], cognitive tests (Digit Symbol, Digit Span, Trailmaking A and B), health perception (Medical Outcome Survey Short-form 36 or SF-36), lower extremity muscle strength and power, and calcium intake. RESULTS: Twenty-three men (34%) withdrew from the study; 44 men completed the trial. Bioavailable testosterone levels increased from 93 +/- 34 (SD) to 162 +/- 100 ng/dl (p <.002) at 12 months in the testosterone group (n = 24) while no change occurred in the control group (n = 20). While there was no change in estradiol levels in either group, estrone levels increased in the testosterone group (28 +/- 7 to 32 +/- 9 pg/dl, p =.017). Scores on the Digit Symbol test improved in both the testosterone and placebo groups. Scores on Trailmaking B improved in men treated with testosterone (p <.005), although the changes were not statistically different from the changes seen in the placebo group. Twelve-month scores on Trailmaking B for the entire group were correlated with 12-month testosterone levels (p =.016). Scores for health perception measured by SF-36 did not change significantly, though scores of mental and general health declined in both groups during the 12-month intervention. Twelve-month bioavailable testosterone scores were directly correlated with scores for physical role (p =.022), vitality (p =.036), and the physical composite score (p =.010). CONCLUSIONS: Transdermal testosterone treatment in men with low bioavailable testosterone levels does not impair and may improve cognitive function. Treatment did not improve health perception but this may have been due to the side effects of skin irritation suggested by similar reactions in both the testosterone and placebo groups.

Administration, Cutaneous↗

PubMed2002

Effects of transdermal testosterone on lipids and vascular reactivity in older men with low bioavailable testosterone levels.

BACKGROUND: Sex hormones are known to affect cholesterol levels and vascular tone in women. The effects of testosterone on cholesterol and vascular tone in men are less well understood. Low testosterone levels have been associated with higher cholesterol levels in epidemiologic studies, but testosterone replacement has resulted in variable changes in cholesterol levels. Similarly, clinical studies suggest that testosterone may be vasodilatory, but few studies have directly evaluated the effects of testosterone on vascular tone. METHODS: Sixty-seven men (mean age 76 +/- 4 years, range 65-87) with bioavailable testosterone levels below 4.44 nmol/l (lower limit for adult normal range) were randomized to receive transdermal testosterone (2-2.5 mg patches/d) or placebo patches for 1 year. Twenty-three men (34%) withdrew from the study; 44 men completed the trial. RESULTS: While total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels did not significantly change during the year of therapy, high-density lipoprotein (HDL) levels (p =.004) and, specifically, HDL(2) subfraction (p =.02) decreased in men receiving testosterone supplementation. Vascular tone was measured by brachial artery reactivity in 36 men. Endothelium-dependent brachial artery reactivity did not change from baseline measurements in men receiving transdermal testosterone (0.3 +/- 6.7% to 1.6 +/- 4.6%; p =.58) or in the placebo group (3.2 +/- 5.5% to 0.7 +/- 5.5%; p =.23). CONCLUSIONS: Transdermal testosterone decreased HDL(2) cholesterol but did not affect vascular reactivity in men older than 65 years selected for low testosterone levels. No study to date has addressed the direct relationship between testosterone replacement and cardiovascular events.

Administration, Cutaneous↗

PubMed2002

Mechanisms of bone remodeling: implications for clinical practice.

The adult skeleton undergoes continuous remodeling. The remodeling cycle involves the interaction of cells of osteoblastic and osteoclastic lineage and is regulated by both systemic hormones and local factors. In addition to the systemic calcium-regulating hormones, parathyroid hormone, 1,25-dihydroxy vitamin D and calcitonin, sex hormones play an important role. Estrogen has been identified as the major inhibitor of bone resorption in both men and women. Androgen is important not only as a source of estrogen, through the action of aromatase, but also for its direct effect in stimulating bone formation. The effects of sex hormones may be mediated by their ability to alter the secretion of local cytokines, prostaglandins and growth factors. Sex hormone action is also modulated by the level of sex hormone-binding globulin in the circulation. A more precise analysis of these effects has been made possible by the development of new methods of measuring not only bone mineral density, but also relative rates of bone formation and resorption using biochemical markers. These new approaches have allowed us to define more precisely the specific roles of androgens, estrogens and other regulatory hormones in human skeletal physiology and pathophysiology.

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