PubMed Health⌕ Search

Biomedical subjects

Paul D Miller

Publications and source records attributed to Paul D Miller.

At least 37 records · Page 2Linked to original sources
PubMed2005

Ibandronate produces significant, similar antifracture efficacy in North American and European women: new clinical findings from BONE.

OBJECTIVES: BONE (oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe) determined whether less frequent dosing of ibandronate (dose-free interval > 2 months) provided similar antifracture efficacy to daily dosing. As osteoporosis medications must be effective across different populations, an additional objective of BONE was to investigate and report the effect of oral ibandronate in North American and European women, as described here. PATIENTS AND METHODS: BONE was a randomized, double-blind, placebo-controlled, fractureprevention study in 2946 postmenopausal women (age 55 years-80 years; > or = 5 years since menopause) with osteoporosis (low lumbar spine bone mineral density and one to four prevalent vertebral fractures [T4-L4]). Participants received daily calcium (500 mg) and vitamin D (400 IU) plus either placebo, oral daily ibandronate (2.5 mg) or oral intermittent ibandronate (20 mg every other day for 12 doses every 3 months). The efficacy and tolerability of ibandronate were assessed independently in both North American and European populations. RESULTS: Consistent, significant efficacy was observed in the North American (new vertebral fracture risk reduction: 60% and 54% with daily and intermittent ibandronate, respectively) and European patient populations (50% and 48%, respectively). Both ibandronate regimens also significantly reduced the incidence of new, worsening, and acute clinical, vertebral fractures. Daily and intermittent ibandronate significantly increased bone density at the spine in both North American (5.4% and 4.4% vs. baseline with daily and intermittent ibandronate, respectively) and European (7.1% and 6.3% vs. baseline, respectively) populations. Significant increases were also observed for total hip bone density (2.6% and 3.7% vs. baseline for daily, and 2.5% and 3.1% for intermittent; North American and European populations, respectively). Comparable, significant decreases in biochemical markers of bone turnover (reductions in urinary excretion of C-telopeptide levels of 53.5% and 67.1% vs. baseline for daily, and 50.0% and 53.8% for intermittent; North American and European populations, respectively) were also observed in both populations (p < 0.004 for all cited measurements in each ibandronate group vs. placebo). Oral ibandronate was well tolerated in both North American and European patients, with a safety profile similar to placebo. CONCLUSIONS: Oral ibandronate, administered daily or intermittently, effectively reduced vertebral fracture risk in North American and European women with postmenopausal osteoporosis. These results demonstrate the efficacy of ibandronate administered with extended dose-free intervals, regardless of patients' geographical origin. Research investigating other less frequent ibandronate regimens, such as once-monthly oral administration, is underway.

Administration, Oral↗
PubMed2005

How useful are measures of BMD and bone turnover?

Measurements of bone mineral density (BMD) and biochemical markers of bone turnover are useful in the diagnosis and management of osteoporosis, as well as in research relating to the pathogenesis and treatment of the disease. Recent challenges to the utility of these measures have resulted in some confusion among both researchers and clinicians. BMD accounts for the great majority of bone strength and is the current gold standard for the diagnosis of osteoporosis, as well as for prediction of fracture risk. Although bone turnover increases sharply after menopause, biochemical markers of bone turnover have limited usefulness in fracture risk prediction. Persistently elevated bone turnover throughout the menopause is associated with structural decrements, cannot be measured routinely and non-invasively. In research applications, both BMD and markers of bone turnover are used to identify candidate agents in preclinical and clinical studies. In addition, head-to-head comparisons of treatments utilize these measures, because fracture endpoint trials would need to be extraordinarily large and complex. Analyses that have suggested that change in BMD or bone turnover 'explains' little of change in fracture risk with treatment appear to be flawed. Although neither can perfectly predict fracture, they are our current best alternatives.

Bone Density↗
PubMed2005

Longterm reduction of back pain risk in women with osteoporosis treated with teriparatide compared with alendronate.

OBJECTIVE: To compare the effects on back pain of teriparatide versus alendronate, we analyzed the reporting of back pain in a head to head comparator trial and a followup study. METHODS: In the comparator trial, women were randomized to receive either daily self-injected teriparatide 40 microg plus an oral placebo (n = 73), or daily oral alendronate 10 mg plus self-injected placebo (n = 73). Treatment was for a median 14 months. After completion of the comparator trial, 72% of these patients enrolled in a nontreatment followup study. Adverse events were recorded at each comparator trial visit and followup study visit, and the incidence of new or worsening back pain in each group was compared. RESULTS: During the comparator trial, compared with women randomized to alendronate 10 mg, women randomized to teriparatide 40 microg had reduced risk for any back pain (relative risk 0.27, 95% CI 0.09-0.82) and moderate or severe back pain (relative risk 0.19, 95% CI 0.04-0.86). The differences in the reporting of back pain between the teriparatide treated women and the alendronate treated women were sustained during an interval including the comparator trial plus 18 additional months. During an interval including the comparator trial plus 30 additional months, teriparatide treated patients had numerically fewer occurrences of back pain and moderate or severe back pain. CONCLUSION: Compared with women randomized to alendronate 10 mg, women randomized to teriparatide 40 microg had reduced risk of back pain during the trial and 2.5 years of followup.

Aged↗
PubMed2005

Safety and tolerability of oral daily and intermittent ibandronate are not influenced by age.

OBJECTIVE: The risk of osteoporosis increases exponentially with age. Elderly patients, who are often frail, have declining functional status and take multiple medications, and require osteoporosis therapies that are not only effective, but also very well tolerated. Ibandronate is a potent nitrogen-containing bisphosphonate that can be given intermittently with extended between-dose intervals. Oral daily and intermittent ibandronate (interval between doses > 2 mo) was found to significantly reduce the risk of new morphometric vertebral fractures by 62% and 50%, respectively, compared with calcium and vitamin D supplementation alone. We investigated the effect of age on the safety profile of oral daily and intermittent ibandronate, with particular emphasis on the upper gastrointestinal (GI) safety profile of ibandronate. METHODS: A predefined subgroup analysis examined the tolerability of oral ibandronate in women aged < 70 and > or = 70 years. RESULTS: The incidence of adverse events in patients aged > or = 70 years receiving oral daily and intermittent ibandronate was similar and comparable to placebo. The incidence of upper GI adverse events, including dyspepsia and esophagitis, was also similar between the 2 treatment groups and placebo. CONCLUSION: Older patients (> or = 70 yrs) receiving oral daily and intermittent ibandronate are at no greater risk of adverse events than older patients receiving placebo. Older patients were at no greater risk of upper GI adverse events than younger patients or patients receiving placebo. As a result of the good efficacy and tolerability observed in this trial, a once-monthly oral regimen of ibandronate is in late-stage clinical development.

Administration, Oral↗
PubMed2004

Recalculation of the NHANES database SD improves T-score agreement and reduces osteoporosis prevalence.

UNLABELLED: In attempt to improve diagnostic agreement between manufacturers, a recent software update incorporated NHANES III data in GE Lunar densitometers. As a result, the femur neck and trochanter T-scores were lowered, and osteoporosis prevalence was increased. Use of a recalculated young-normal SD for the GE Lunar-adjusted NHANES III database improved diagnostic agreement and is recommended. INTRODUCTION: Use of manufacturer-specific normative databases for T-score derivation leads to discordance in T-score values and differences in diagnostic classification. To address this issue, the International Committee for Standards in Bone Measurement (ICSBM) recommended the NHANES III database for femur T-score derivation. Acquired on Hologic (Hol) instruments, this database requires conversion equations for application to other DXA systems. NHANES III total femur (TF) conversions for GE Lunar (GE) have previously been available, and femoral neck (FN) and trochanter (TR) equations were reported recently. Per the ICSBM recommendation, GE Lunar incorporated these values into their female database. This should produce T-score and diagnostic agreement between Hol and GE instruments; however, this has not been evaluated. MATERIALS AND METHODS: We compared GE femur scans in 115 postmenopausal women using software before and after the NHANES III software update. Subsequently, T-scores derived from femur scans obtained on GE and Hol densitometers were compared in a different group of 89 postmenopausal women. RESULTS: The NHANES III software update had no effect on measured BMD (g/cm2) at any femur region. However, because of changes in values used for T-score calculation (increase in the mean young-normal BMD at the FN and TR and a reduction in SD at the TR), the T-scores were lower (mean, 0.48 and 0.68, respectively) at the FN and TR using post-NHANES III software. Consequently, this update increased femur osteoporosis prevalence in these 115 women from 7.8% to 18.3%. Comparison of GE with Hol total proximal femur T-scores revealed a minimal difference (<0.1) and equal diagnoses of osteoporosis. FN and TR differences were larger, with mean GE T-scores lower than Hol (p < 0.001) by 0.17 and 0.50, respectively, thereby introducing osteoporosis diagnostic disagreement (13 [GE] versus 9 [Hol]). Our evaluation suggested that this disparity resulted from direct application of published NHANES III SDs at the FN and TR. As such, we applied the conversion formulae to the NHANES III published Hologic data and found the FN and TR SDs were greater than assumed by GE. Using our recalculated SD to derive T-scores reduced the mean GE/Hol T-score difference to 0.03 at the FN and 0.32 at the TR and resolved osteoporosis diagnostic disagreement. CONCLUSION: The GE NHANES III software update leads to lower FN and TR T-scores than obtained with Hol or prior GE software. Recalculation of the young-normal SD reduces this difference and is recommended. Clinicians are advised to avoid using the TR for diagnosis or, at a minimum, use caution when making treatment decisions based solely on T-score at this site.

Absorptiometry, Photon↗
PubMed2004

Osteoporosis and fracture risk in women of different ethnic groups.

UNLABELLED: Osteoporosis and 1-year fracture risk were studied in 197,848 postmenopausal American women from five ethnic groups. Weight explained differences in BMD, except among blacks, who had the highest BMD. One SD decrease in BMD predicted a 50% increased fracture risk in each group. Despite similar relative risks, absolute fracture rates differed. INTRODUCTION: Most information about osteoporosis comes from studies of white women. This study describes the frequency of osteoporosis and the association between BMD and fracture in women from five ethnic groups. MATERIALS AND METHODS: This study was made up of a cohort of 197,848 community-dwelling postmenopausal women (7784 blacks, 1912 Asians, 6973 Hispanics, and 1708 Native Americans) from the United States, without known osteoporosis or a recent BMD test. Heel, forearm, or finger BMD was measured, and risk factor information was obtained; 82% were followed for 1 year for new fractures. BMD and fracture rates were compared, adjusting for differences in covariates. RESULTS: By age 80, more than one-fifth of women in each ethnic group had peripheral BMD T scores <-2.5. Black women had the highest BMD; Asian women had the lowest. Only the BMD differences for blacks were not explained by differences in weight. After 1 year, 2414 new fractures of the spine, hip, forearm, wrist, or rib were reported. BMD at each site predicted fractures equally well within each ethnic group. After adjusting for BMD, weight, and other covariates, white and Hispanic women had the highest risk for fracture (relative risk [RR] 1.0 [referent group] and 0.95, 95% CI, 0.76, 1.20, respectively), followed by Native Americans (RR, 0.87; 95% CI, 0.57, 1.32), blacks (RR, 0.52; 95% CI, 0.38, 0.70), and Asian Americans (RR, 0.32; 95% CI, 0.15, 0.66). In age- and weight-adjusted models, each SD decrease in peripheral BMD predicted a 1.54 times increased risk of fracture in each ethnic group (95% CI, 1.48-1.61). Excluding wrist fractures, the most common fracture, did not materially change associations. CONCLUSIONS: Ethnic differences in BMD are strongly influenced by body weight; fracture risk is strongly influenced by BMD in each group. Ethnic differences in absolute fracture risk remain, which may warrant ethnic-specific clinical recommendations.

Aged↗
PubMed2004

Bone mineral density thresholds for pharmacological intervention to prevent fractures.

BACKGROUND: Treatment intervention thresholds for prevention of osteoporotic fractures can be derived from reports from the World Health Organization (diagnostic criteria) and National Osteoporosis Foundation (treatment criteria). It is not known how well these thresholds work to identify women who will fracture and are therefore candidates for treatment interventions. We used data from the National Osteoporosis Risk Assessment (NORA) to examine the effect of different treatment thresholds on fracture incidence and numbers of women with fractures within the year following bone mineral density measurement. METHODS: The study comprised 149 524 white postmenopausal women aged 50 to 104 years (mean age, 64.5 years). At baseline, bone mineral density was assessed by peripheral bone densitometry at the heel, finger, or forearm. New fractures during the next 12 months were self-reported. RESULTS: New fractures were reported by 2259 women, including 393 hip fractures; only 6.4% had baseline T scores of -2.5 or less (World Health Organization definition for osteoporosis). Although fracture rates were highest in these women, they experienced only 18% of the osteoporotic fractures and 26% of the hip fractures. By National Osteoporosis Foundation treatment guidelines, 22.6% of the women had T scores of 2.0 or less, or -1.5 or less with 1 or more clinical risk factors. Fracture rates were lower, but 45% of osteoporotic fractures and 53% of hip fractures occurred in these women. CONCLUSIONS: Using peripheral measurement devices, 82% of postmenopausal women with fractures had T scores better than -2.5. A strategy to reduce overall fracture incidence will likely require lifestyle changes and a targeted effort to identify and develop treatment protocols for women with less severe low bone mass who are nonetheless at increased risk for future fractures.

Age Distribution↗
PubMed2004

An approach to identifying osteopenic women at increased short-term risk of fracture.

BACKGROUND: Identification and management of women to reduce fractures is often limited to T scores less than -2.5, although many fractures occur with higher T scores. We developed a classification algorithm that identifies women with osteopenia (T scores of -2.5 to -1.0) who are at increased risk of fracture within 12 months of peripheral bone density testing. METHODS: A total of 57 421 postmenopausal white women with baseline peripheral T scores of -2.5 to -1.0 and 1-year information on new fractures were included. Thirty-two risk factors for fracture were entered into a classification and regression tree analysis to build an algorithm that best predicted future fracture events. RESULTS: A total of 1130 women had new fractures in 1 year. Previous fracture, T score at a peripheral site of -1.8 or less, self-rated poor health status, and poor mobility were identified as the most important determinants of short-term fracture. Fifty-five percent of the women were identified as being at increased fracture risk. Women with previous fracture, regardless of T score, had a risk of 4.1%, followed by 2.2% in women with T scores of -1.8 or less or with poor health status, and 1.9% for women with poor mobility. The algorithm correctly classified 74% of the women who experienced a fracture. CONCLUSIONS: This classification tool accurately identified postmenopausal women with peripheral T scores of -2.5 to -1.0 who are at increased risk of fracture within 12 months. It can be used in clinical practice to guide assessment and treatment decisions.

Age Distribution↗
PubMed2004

Predictive value of low BMD for 1-year fracture outcomes is similar for postmenopausal women ages 50-64 and 65 and Older: results from the National Osteoporosis Risk Assessment (NORA).

UNLABELLED: The relationship of low bone mass and fracture in younger postmenopausal women has not been extensively studied. In a large cohort of postmenopausal women > or =50 years of age, we found the relationship of BMD measured at peripheral sites and subsequent 1-year fracture risk to be similar between women <65 and those > or =65 years of age. INTRODUCTION: Low bone mass and fractures are prevalent in older postmenopausal women. However, the frequency of low bone mass and fracture in younger postmenopausal women has not been studied extensively. There are very limited data regarding the association between BMD measurements and fractures in postmenopausal women who are between the ages of 50 and 64. MATERIALS AND METHODS: In the National Osteoporosis Risk Assessment (NORA) we studied the frequency of low bone mass and its association with fracture in women 50-64 years of age in comparison with women > or =65 of age. NORA enrolled 200,160 postmenopausal women > or =50 years of age who had no prior diagnosis of osteoporosis. Baseline BMD was measured at the heel, forearm, or finger. A 1-year follow-up survey requesting incident fractures since baseline was completed by 163,935 women, 87,594 (53%) of whom were 50-64 years of age. The association between BMD and fracture was assessed using logistic regression, adjusted for important covariates. RESULTS: Thirty-one percent of women 50-64 years of age had low bone mass (T scores < or = -1.0) compared to 62% of women > or =65 years of age. During the first year of follow-up, 2440 women reported fractures of wrist/forearm, rib, spine, or hip, including 440 hip fractures. Nine hundred four women 50-64 years of age reported fractures, including 86 hip fractures, accounting for 37% of fractures and 20% of hip fractures reported in the entire NORA cohort. Relative risk for osteoporotic fracture was 1.5 for each SD decrease in BMD for both the younger and older groups of women. CONCLUSION: Low BMD in younger postmenopausal women 50-64 years of age showed a 1-year relative risk of fracture similar to that found in women > or =65 years of age.

Age Factors↗
PubMed2004

Pitfalls in bone mineral density measurements.

Bone mineral density (BMD) measurements have been the single greatest advancement for osteoporosis. BMD measurements have helped define a prefracture diagnosis of osteoporosis, predict fracture risk in postmenopausal women and elderly men, and monitor the course of disease processes that negatively affect bone or therapeutic agents that can improve bone strength. Despite the large amount of clinical, epidemiologic, and basic science data that has advanced our understanding of BMD performance and interpretation, many pitfalls in BMD performance and interpretation pervade the practice of bone densitometry. However, all of these pitfalls can be overcome. Proper quality control and clinical interpretation of BMD computer printout reports are paramount for correct diagnosis, risk assessment, and serial BMD measurements. Though BMD application(s) are a clinical tool that can and should be used by many different primary care and specialty physicians, the performances and interpretations are not simple processes. Proper education and training in the use of BMD technologies provides the means of achieving the great intent that BMD measurements are capable of providing.

Absorptiometry, Photon↗
PubMed2004

Osteoporosis in men: epidemiology, diagnosis, prevention, and treatment.

BACKGROUND: Osteoporosis and fragility fractures in men account for substantial health care expenditures and decreased quality of life. OBJECTIVE: This article reviews the most current information about the epidemiology, diagnosis, prevention, and treatment of osteoporosis in men. METHODS: Relevant literature was identified through a search of MEDLINE (1966-June 2003) limited to English-language studies in men. The search terms included fractures, bone density, or osteoporosis plus either epidemiology, diagnosis, prevention, control, or therapy. Additional search terms included specific subtopics (eg, bisphosphonates, calcium, exercise, parathyroid hormone). The authors contributed additional relevant publications. RESULTS: Morbidity after fragility fracture is at least as high in men as in women, and the rate of fracture-related mortality 1 year hip fracture is approximately double in men compared with women. The bioavailable fraction of testosterone slowly declines into the ninth decade in men. There is evidence that the effect of estrogen on bone is greater than that of testosterone in men. Diagnosing osteoporosis in men is complicated by a lack of consensus on how it should be defined. Significant risk factors for osteoporosis or fracture include low bone mineral density, previous fragility fracture, maternal history of fracture, marked hypogonadism, smoking, heavy alcohol intake or alcoholism, low calcium intake, low body mass or body mass index, low physical activity, use of bone-resorbing medication such as glucocorticoids, and the presence of such conditions as hyperthyroidism, hyperparathyroidism, and hypercalciuria. Prevention is paramount and should begin in childhood. During adulthood, calcium (1000-1500 mg/d), vitamin D (400-800 IU/d), and adequate physical activity play crucial preventive roles. When treatment is indicated, the bisphosphonates are the first choice, whereas there is less support for the use of calcitonin or androgen therapy. Parathyroid hormone (1-34) is a promising anabolic therapy. There is also strong evidence for the use of bisphosphonates for the treatment of glucocorticoid-induced osteoporosis.

Androgens↗
PubMed2004

Rapid loss of hip fracture protection after estrogen cessation: evidence from the National Osteoporosis Risk Assessment.

OBJECTIVE: Since the findings from the Women's Health Initiative became available in July 2002, millions of women have discontinued postmenopausal hormone therapy (HT). The objective of this study was to evaluate the association between HT cessation and hip fracture risk. METHODS: Women who participated in the National Osteoporosis Risk Assessment and completed the 12-month follow-up survey were studied. All participants were aged at least 50 years, were postmenopausal, and had no previous diagnosis of osteoporosis. Baseline and 12-month follow-up questionnaires assessed use of HT and incident fractures. Of the 140,584 women in this study, 269 reported an incident hip fracture. A logistic regression model was used to assess association between HT use and incident hip fracture, controlling for potential confounders. RESULTS: Consistent with the Women's Health Initiative, women in National Osteoporosis Risk Assessment who were currently on HT had a 40% lower incidence of hip fractures compared with those who never used HT. Women who stopped using HT more than 5 years earlier had similar hip fracture risk to never users, as expected. However, surprisingly, women who had discontinued HT within the previous 5 years had an increased hip fracture odds ratio of 1.65 (95% confidence interval 1.05, 2.59) relative to never users of HT. CONCLUSION: Postmenopausal women who have discontinued HT within the past 5 years have a risk for hip fracture that is at least as high as that in women who have never used HT. LEVEL OF EVIDENCE: II-2

Aged↗
PubMed2004

Upper tract surveillance in primary bladder cancer follow-up.

OBJECTIVE: To determine if there is national variation in regimens of upper urinary tract surveillance in patients with primary bladder cancer. METHODS: A questionnaire was sent to 470 consultant urologists from a British Association of Urological Surgeons list in the UK; 301 anonymous replies were received. Two replies were incomplete and therefore the results of 299 questionnaires (64%) were analysed. RESULTS: Of the 299 surgeons, 19 (6%) use no form of upper urinary tract surveillance; 162 (54%) use surveillance in selected patients, i.e. those with carcinoma in situ (47%), multiple bladder tumours at first presentation (39%) and after cystectomy (70%), and 118 (39%) use upper tract surveillance on all patients with a history of bladder cancer. The median (range) screening interval was 24 (12-60) months and surveillance continued for a median of 10 (2 to indefinite) years, continuing for an indefinite period in 33%. CONCLUSIONS: Most urologists use upper tract surveillance in patients with bladder cancer but there is wide variation in the duration and interval for which it continues, and in the type of patient selected for surveillance. Some patients at high risk of upper tract tumour are not being screened. Asymptomatic upper tract tumours may not be diagnosed because the intervals between surveillance are too long, and the duration for which it continues inadequate. There is a need for multidisciplinary national guidelines to reduce variation in practice.

Carcinoma in Situ↗
PubMed2004

Standards and guidelines for performing central dual-energy x-ray absorptiometry in premenopausal women, men, and children.

The Canadian Panel of the International Society for Clinical Densitometry has developed standards in order to establish the minimum level of acceptable performance for the practice of bone densitometry in Canada. Previously, this group addressed the performance of densitometry in postmenopausal women. This report addresses the use of densitometry in men, premenopausal women, and children with a focus on dual-energy X-ray absorptiometry.

Absorptiometry, Photon↗
PubMed2003

Cooled thermotherapy for the treatment of benign prostatic hyperplasia: durability of results obtained with the Targis System.

OBJECTIVES: To evaluate the durability of benefit associated with cooled high-energy thermotherapy (cooled thermotherapy) using the Targis System with data extending to 5 years after treatment. METHODS: At three centers in Canada and the United Kingdom, 150 patients with benign prostatic hyperplasia underwent cooled thermotherapy with the Targis System. This was an outpatient procedure performed without general or regional anesthesia. Patients were followed up at 1 and 6 weeks, 3, 6, and 12 months, and yearly to 5 years. RESULTS: Patients were evaluated at 1, 2, 3, 4, and 5 years after treatment (n = 132, 111, 90, 77, and 59, respectively). At these intervals, the American Urological Association symptom scores improved by 11.7 (57%), 12.1 (58%), 11.5 (53%), 10.1 (47%), and 10.6 (47%) points (P <0.0001 for each), the peak flow rates improved by a mean of 4.0 (57%), 4.0 (56%), 3.4 (48%), 3.3 (47%) and 2.4 (37%) mL/s (P <0.0001 for each), and quality-of-life scores improved by 2.6, 2.6, 2.5, 2.3, and 2.3 points (P <0.0001 for each). At least a 50% improvement in the American Urological Association symptom score was observed in 63% to 68% of patients available for follow-up at years 1, 2, and 3 and 50% and 51% of patients available for follow-up at years 4 and 5, respectively. Four patients required repeated microwave thermotherapy, 27 required subsequent invasive treatments, 1 permanent catheterization, 11 required alpha-blockers, and 1 antiandrogen therapy. CONCLUSIONS: Cooled thermotherapy with the Targis System produces durable improvements in symptoms, quality of life, and flow rates to at least 5 years after treatment.

Aged↗