Karen M. Prestwood

How Well Are Community-Living Women Treated for Osteoporosis after Hip Fracture?

To examine whether women with recent hip fracture are receiving adequate treatment for osteoporosis. To examine patient and physician characteristics associated with adequate treatment for osteoporosis.

Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial

BACKGROUND Soy foods contain several components (isoflavones and amino acids) that potentially affect bone. Few long-term, large clinical trials of soy as a means of improving bone mineral density (BMD) in late postmenopausal women have been conducted. OBJECTIVE Our goal was to evaluate the long-term effect of dietary soy protein and/or soy isoflavone consumption on skeletal health in late postmenopausal women. DESIGN We conducted a randomized, double-blind, placebo-controlled clinical trial in 131 healthy ambulatory women aged >60 y. Ninety-seven women completed the trial. After a 1-mo baseline period, subjects were randomly assigned into 1 of 4 intervention groups: soy protein (18 g) + isoflavone tablets (105 mg isoflavone aglycone equivalents), soy protein + placebo tablets, control protein + isoflavone tablets, and control protein + placebo tablets. RESULTS Consumption of protein powder and isoflavone pills did not differ between groups, and compliance with the study powder and pills was 80-90%. No significant differences in BMD were observed between groups from baseline to 1 y after the intervention or in BMD change between equol and non-equol producers. However, there were significant negative correlations between total dietary protein (per kg) and markers of bone turnover (P < 0.05). CONCLUSIONS Because soy protein and isoflavones (either alone or together) did not affect BMD, they should not be considered as effective interventions for preserving skeletal health in older women. The negative correlation between dietary protein and bone turnover suggests that increasing protein intakes may suppress skeletal turnover. This trial was registered at ClinicalTrials.gov as NCT00668447.

OSTEOPOROSIS: Pathogenesis, Diagnosis, and Treatment in Older Adults

Prevention of osteoporosis is a major health concern. Bone loss occurs throughout life in both women and men due to calcium deficiency, hormonal deficiency, and changes in bone formation. The diagnosis of osteoporosis can now be made prior to fragility fracture, allowing for prevention as well as treatment. Criteria for diagnosis of osteoporosis are reviewed, and a plan for the evaluation of secondary causes of osteoporosis is discussed. Also reviewed are prevention and treatment options such as exercise, calcium supplementation, hormone replacement, and new and investigational drugs.

The effect of a short course of calcium and vitamin D on bone turnover in older women.

Calcium and vitamin D (1200 mg/day + 800 IU) has been shown to reduce hip fracture incidence in older women living in long-term care facilities who had borderline low vitamin D levels. We examined the effect of a short course of calcium and vitamin D on biochemical markers of bone turnover in older community-living women. Twelve community-living women (mean age 75 years) in good general health, without diseases or on medications known to affect bone, were entered into the study. All women were treated with calcium citrate (1500 mg/day of elemental calcium) and vitamin D3 (1000 IU/day) (Ca + D) for 6 weeks. Biochemical markers of bone turnover were measured in serum and urine collected at baseline (two samples), 5 and 6 weeks on Ca + D, and 5 and 6 weeks after termination of Ca + D. Markers of bone formation were osteocalcin, bone alkaline phosphatase and type I procollagen peptide. Markers of bone resorption were urinary hydroxyproline, free pyridinoline and deoxypyridinoline crosslinks, and N-telopeptides of type I collagen. Parathyroid hormone (PTH) and 25-hydroxyvitamin D were also measured at baseline, 6 weeks on treatment and 6 weeks after termination of treatment. All markers of bone resorption decreased on Ca + D and returned to baseline after termination of Ca + D (p<0.05). Markers of bone formation did not change with Ca + D treatment. PTH decreased on Ca + D and returned to baseline after treatment, and 25-hydroxyvitamin D increased with treatment and remained elevated 6 weeks after the end of treatment. We conclude that Ca + D reduces bone resorption in older women, possibly by suppressing PTH levels.

Effects of smoking cessation or reduction on hormone profiles and bone turnover in postmenopausal women.

The purpose of this study was to prospectively evaluate the impact of smoking cessation on hormonal concentrations, sex hormone-binding globulin (SHBG) and markers of bone turnover in postmenopausal women. Sixty-six women who were either users or non-users of estrogen replacement therapy (ERT) were randomly assigned, using a weighted randomization scheme, to smoking cessation (SC) or to smoking cessation after 6 weeks of monitoring (wait-list control group, WLC). We measured hormones [estrone, estradiol, testosterone, parathyroid hormone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS) and androstenedione] and SHBG, markers of bone turnover [procollagen peptide (PINP), bone alkaline phosphatase (BAP), and osteocalcin (OC), N- and C-terminal collagen cross-links (NTx and CTx)], and cotinine, at baseline and again at 6 weeks in women who reported smoking cessation and in women randomized to the WLC group. Analyses included 20 subjects who quit or significantly reduced their smoking and 18 subjects in the WLC group. After controlling for differences in age and ERT use between groups, we found a significant change in SHBG in the SC vs. the WLC group (-8% vs. +5%, respectively; p = 0.01), and in DHEA (-18% vs. -5%, respectively; p = 0.04), but not in other hormonal concentrations. We also noted a significant change in NTx in the SC vs. WLC group (-5% vs. +56%, respectively, p = 0.01), but not in other markers of bone turnover. Percentage changes in SHBG and NTx were correlated with changes in plasma cotinine (r = 0.48; p = 0.004 and r = 0.36; p = 0.04, respectively). Six weeks of smoking abstinence produces reductions in SHBG and NTx. This may partly explain how smoking contributes to osteoporosis in postmenopausal women.

Short-Term Effects of Intramuscular and Transdermal Testosterone on Bone Turnover, Prostate Symptoms, Cholesterol, and Hematocrit in Men Over Age 70 with Low Testosterone Levels

The objective of the study was to determine whether short-term testosterone administration to older men with low bioavailable testosterone would have any immediate adverse effects, especially on the symptoms of benign prostate hyperplasia, preliminary to embarking on a long-term study of testosterone treatment. Transdermal and intramuscular testosterone were compared to determine whether there were any rapid changes in markers of bone formation or resorption with either testosterone administration. We undertook a non-randomized trial of 9 weeks intervention with either intramuscular testosterone, transdermal testosterone or neither followed by a 9-week observation period. Twenty-seven men over age 70 years with no medical conditions known to affect bone turnover and total testosterone levels below 350 ng/dl (normal range 350–1230 ng/dl) or bioavailable testosterone levels below 128 ng/dl (normal range 128–430 ng/dl) received either testosterone via transdermal patch (TP; two 2.5 mg patches/d), intramuscular testosterone enanthate (IM; 200 mg every 3 weeks) or no testosterone for 9 weeks of treatment followed by a 9 week observation period. Nine men were enrolled in each group. The mean age of the men was 74 ± 3 years (range 70–83 years). While all men receiving testosterone treatment increased levels above their own baseline, only 6 of 9 men receiving transdermal testosterone achieved bioavailable testosterone levels in the normal range for young men. Neither treatment group demonstrated changes in estradiol levels. No side effects were reported using the intramuscular testosterone while 5/9 men using transdermal testosterone developed a rash. There were no significant changes in markers of bone resorption or formation in either testosterone treatment group. There were no ill effects on prostate size, symptoms or prostate specific antigen level. PSA levels of 1.5 ± 0.7 ng/dl and 1.6 ± 0.7 ng/dl in the TP and IM groups, respectively, were 2.0 ± 1.0 ng/dl and 1.8 ± 0.9 ng/dl following treatment. Cholesterol profiles were also not affected by either transdermal or intramuscular testosterone. Similarly hemoglobin and hematocrit remained unchanged in men receiving either testosterone preparation.

The effect of raloxifene on markers of bone turnover in older women living in long-term care facilities.

Objectives: To examine the effect of raloxifene on bone turnover in elderly women.

The Effect of 3-Year Treatment with 0.25 mg/day of Micronized 17β-Estradiol on Cognitive Function in Older Postmenopausal Women

OBJECTIVES: To evaluate the effect of ultra‐low‐dose (0.25 mg/d) micronized 17β‐estradiol on cognitive function in older postmenopausal women.

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.

Low-dose estradiol alters brain activity

Although several studies have examined the effects of estrogen replacement therapy (ERT) on neural activity associated with tasks of learning and memory, no study has examined such effects on a sustained attention task. This study examined the effect of low-dose estrogen replacement therapy on hemodynamic activity elicited by a visual three-stimulus oddball task recorded using event-related functional magnetic resonance imaging (fMRI). Participants included 16 women between the ages of 73 and 84 who were part of a randomized controlled double-blind study to evaluate the effect of an ultralow dose micronized estradiol on bone. No significant differences in behavioral performance were found with ERT. However, there was evidence that ERT group participants had both reductions and increases in the amplitude of hemodynamic response in a variety of subcortical and cortical brain regions. These included regions involved in perception and attention such as the occipital and parietal lobes, motor cortex, anterior cingulate and prefrontal cortex. These findings suggest that estrogen may facilitate the efficiency of brain function during the performance of sustained attention tasks in post-menopausal elderly women.