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E Michael Lewiecki

Publications and source records attributed to E Michael Lewiecki.

At least 19 recordsLinked to original sources
PubMed2006

Comparative effects of raloxifene and alendronate on fracture outcomes in postmenopausal women with low bone mass.

UNLABELLED: The double-blind, randomized raloxifene alendronate comparison trial was the first study designed to compare two osteoporosis therapies head-to-head for fracture risk reduction. The original protocol planned to treat 3000 postmenopausal women with alendronate 10 mg/day (ALN) or raloxifene 60 mg/day (RLX) for 5 years, and to recruit women (50-80 years old) with a femoral neck bone mineral density (BMD) T-score between -2.5 and -4.0, inclusive, no prevalent vertebral fractures, and no prior bone-active agent use. The trial was stopped early, due to difficulty in finding treatment-naïve women to meet enrollment goals within the planned timeline, resulting in insufficient power to show non-inferiority between therapies in the primary endpoint (number of women with >or=1 new osteoporotic vertebral or nonvertebral fracture). Except for vertebral fractures, fracture analyses were based upon 1412 of the 1423 women randomized (mean age of 66 years). After 312+/-254 days (mean+/-SD), 22 women in the ALN group and 20 in the RLX group had new vertebral or nonvertebral fractures. Four women in the ALN group and none in the RLX group had moderate/severe vertebral fractures, a pre-specified endpoint (P=0.04). Lumbar spine, femoral neck, and total hip BMD were increased from baseline at 2 years in each group (P<0.001), with greater increases in the ALN group (each P<0.05). Similar numbers of women in each group had >or=1 adverse event and discontinued due to an adverse event. The only adverse events with an incidence that differed between groups were colonoscopy, diarrhea, and nausea; each was more common with ALN treatment (each P<0.05). One woman in each group had a venous thromboembolic event. One case of breast cancer occurred in each group. In summary, as this trial was terminated early, there was insufficient power to compare the fracture risks between alendronate and raloxifene. Safety profiles were as expected from clinical trial and post-marketing reports. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00035971.

Aged↗
PubMed2006

Clinical review: Clinical applications of vertebral fracture assessment by dual-energy x-ray absorptiometry.

CONTEXT: Vertebral fracture (VF) is the most common type of fragility fracture, yet most VFs are not clinically apparent. VFs are associated with a significant increase in morbidity, mortality, and risk of future fracture. Many patients with VFs do not have T-scores classified as osteoporosis. Knowledge of VFs may change diagnostic classification, estimation of future fracture risk, and clinical management. VF assessment (VFA) by dual-energy x-ray absorptiometry is a method for imaging the spine to diagnose VFs. EVIDENCE ACQUISITION: Background information and medical evidence on the technology and clinical applications of VFA was acquired by electronic searching of PubMed for appropriate terms that included vertebral fracture, imaging, diagnosis, dual-energy x-ray absorptiometry, and cost effectiveness. Matches with the highest levels of medical evidence were selected for review, recognizing that the new and evolving nature of the field required inclusion of some material that relied partly on expert opinion. EVIDENCE SYNTHESIS: The sensitivity and specificity of VFA compare favorably with spine radiographs in the ability to diagnose grade 2 and 3 VFs. VFA involves less radiation, lower cost, and often greater patient convenience than spine radiography. Cost effectiveness modeling suggests that imaging of the spine in selected patients provides essential diagnostic and therapeutic information at a nominal cost. Patients with T-scores that are classified as low bone mass (osteopenia) who are selected for pharmacological therapy based on the presence of a VF benefit by reduction in fracture risk. Guidelines for the clinical application of VFA have been developed by the International Society for Clinical Densitometry. CONCLUSIONS: VFA is a technology for diagnosing VFs that may alter diagnostic classification, improve fracture risk stratification, and identify patients likely to benefit from pharmacological therapy who otherwise might not be treated.

Absorptiometry, Photon↗
PubMed2006

Official positions of the International Society for Clinical Densitometry and Executive Summary of the 2005 Position Development Conference.

The International Society for Clinical Densitometry (ISCD) convenes a Position Development Conference (PDC) every two years for the purpose of making recommendations on clinically relevant issues in bone densitometry. Topics for consideration are developed by the ISCD Scientific Advisory Committee and the PDC Steering Committee. Clinically relevant questions related to each topic area are assigned to subcommittees for a comprehensive medical literature review and presentation of a report to an international panel of experts. The expert panel includes representatives of the American Society for Bone and Mineral Research (ASBMR) and the International Osteoporosis Foundation (IOF). The recommendations of the PDC expert panel are evaluated by the ISCD Board of Directors, and those that are approved become Official Positions of the ISCD. The Official Positions have subsequently been endorsed by the ASBMR and IOF. The most recent PDC was held July 15-17, 2005, in Vancouver, BC, Canada. Topics considered included technical standardization, vertebral fracture assessment, and application of the 1994 World Health Organization (WHO) criteria to various skeletal sites and to populations other than postmenopausal white women. This report describes the methodology of the 2005 PDC and presents a summary of all ISCD Official Positions.

Absorptiometry, Photon↗
PubMed2006

Vertebral fracture assessment: the 2005 ISCD Official Positions.

Vertebral Fracture Assessment (VFA) is a low radiation method for imaging the thoraco-lumbar spine using bone densitometers. VFA can easily be performed at the time of bone mineral density (BMD) measurement, allowing integration of BMD and vertebral fracture information into clinical patient care. As VFA is a relatively new procedure, it has received limited study and heretofore has not had widespread clinical application. Consequently, the International Society for Clinical Densitometry (ISCD) considered the following VFA issues at the 2005 Position Development Conference: (1) indications for VFA; (2) methodology for the diagnosis of vertebral fractures using VFA; and (3) indications for additional imaging after VFA. The ISCD Official Positions with respect to the above issues, as well as the rationale and evidence used to derive these positions, are presented here.

Absorptiometry, Photon↗
PubMed2006

Standards for performing DXA in individuals with secondary causes of osteoporosis.

This document addresses skeletal health assessment in individuals with secondary causes of osteoporosis. Recommendations are based on consensus of the Canadian Panel of the International Society for Clinical Densitometry and invited international experts. Bone mineral density (BMD) testing in these populations is performed in conjunction with careful evaluation of the disease state contributing to bone loss and increased fragility fracture risk, as well as assessment of other contributing risk factors for fracture. The presence of secondary causes of bone loss may further increase the risk of fracture independently of BMD and may necessitate earlier pharmacologic intervention. Dual-energy X-ray absorptiometry is indicated in the initial workup of secondary causes of osteoporosis. The BMD fracture risk relationship is not known for individuals with chronic renal failure (CRF). The BMD testing in this population may be normal in the presence of skeletal fragility, and quantitative bone histomorphometry is better at evaluating skeletal status than BMD in CRF. Dual-energy X-ray absorptiometry is a valuable tool in assessing skeletal health in individuals with secondary causes of osteoporosis.

Absorptiometry, Photon↗
PubMed2006

Denosumab in postmenopausal women with low bone mineral density.

BACKGROUND: Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162) binds RANKL with high affinity and specificity and inhibits RANKL action. METHODS: The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase. RESULTS: Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent. CONCLUSIONS: In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis. (ClinicalTrials.gov number, NCT00043186.).

Alendronate↗
PubMed2006

RANK ligand inhibition with denosumab for the management of osteoporosis.

Receptor activator of nuclear factor-kappaB ligand (RANKL) is a cytokine member of the tumour necrosis factor family that is the principal final mediator of osteoclastic bone resorption. It plays a major role in the pathogenesis of postmenopausal osteoporosis, as well bone loss associated with rheumatoid arthritis, metastatic cancer, multiple myeloma, aromatase inhibitor therapy and androgen deprivation therapy. Denosumab (AMG 162) is an investigational fully human monoclonal antibody with a high affinity and specificity for RANKL. By inhibiting the action of RANKL, denosumab reduces the differentiation, activity and survival of osteoclasts, thereby slowing the rate of bone resorption. Denosumab has been shown to increase bone mineral density (BMD) and reduce bone turnover in postmenopausal women with low BMD. Denosumab is a potential treatment for osteoporosis and other skeletal disorders.

Animals↗
PubMed2006

Bone density testing in clinical practice.

The diagnosis of osteoporosis and monitoring of treatment is a challenge for physicians due to the large number of available tests and complexities of interpretation. Bone mineral density (BMD) testing is a non-invasive measurement to assess skeletal health. The "gold-standard" technology for diagnosis and monitoring is dual-energy X-ray absorptiometry (DXA) of the spine, hip, or forearm. Fracture risk can be predicted using DXA and other technologies at many skeletal sites. Despite guidelines for selecting patients for BMD testing and identifying those most likely to benefit from treatment, many patients are not being tested or receiving therapy. Even patients with very high risk of fracture, such as those on long-term glucocorticoid therapy or with prevalent fragility fractures, are often not managed appropriately. The optimal testing strategy varies according to local availability and affordability of BMD testing. The role of BMD testing to monitor therapy is still being defined, and interpretation of serial studies requires special attention to instrument calibration, acquisition technique, analysis, and precision assessment. BMD is usually reported as a T-score, the standard deviation variance of the patient's BMD compared to a normal young-adult reference population. BMD in postmenopausal women is classified as normal, osteopenia, or osteoporosis according to criteria established by the World Health Organization. Standardized methodologies are being developed to establish cost-effective intervention thresholds for pharmacological therapy based on T-score combined with clinical risk factors for fracture.

Absorptiometry, Photon↗
PubMed2006

Peripheral bone densitometry: Clinical applications.

Technologies for the measurement of bone mineral density and other parameters of bone strength at peripheral skeletal sites have been studied since the 1960s. Single-energy Photon Absorptiometry (SPA), Radiographic Absorptiometry (RA), Radiogrametry (RG), Single-energy X-ray Absorptiometry (SXA), Peripheral Dual-energy X-ray Absorptiometry (pDXA), and Quantitative Ultrasonometry (QUS) have been successively evaluated. These technologies and their clinical applications are discussed in this article. The available scientific evidence supports the clinical use of these technologies at peripheral skeletal for assessment of fracture risk. Peripheral measurements other than the 33% (one-third) radius by DXA cannot be used to diagnose osteoporosis according to current standards. Peripheral skeletal sites are not clinically useful for monitoring changes in BMD with natural evolution of the disease and its treatment. Peripheral BMD measurement can theoretically be used to screen patients for selection to central DXA testing, although device-specific cut-points should be developed before this is implemented. When central DXA testing is not available, peripheral BMD testing may be considered to identify individuals who might benefit from pharmacological intervention.

Absorptiometry, Photon↗
PubMed2006

Redefining osteoporosis treatment: Who to treat and how long to treat.

Osteoporosis is a common disease that is associated with increased risk of fractures and serious clinical consequences. Bone mineral density (BMD) testing is used to diagnose osteoporosis, estimate the risk of fracture, and monitor changes in BMD over time. Combining clinical risk factors for fracture with BMD is a better predictor of fracture risk than BMD or clinical risk factors alone. Methodologies are being developed to use BMD and validated risk factors to estimate the 10-year probability of fracture, and then combine fracture probability with country-specific economic assumptions to determine cost-effective intervention thresholds. The decision to treat is based on factors that also include availability of therapy, patient preferences, and co-morbidities. All patients benefit from nonpharmacological lifestyle treatments such a weight-bearing exercise, adequate intake of calcium and vitamin D, fall prevention, avoidance of cigarette smoking and bone-toxic drugs, and moderation of alcohol intake. Patients at high risk for fracture should be considered for pharmacological therapy, which can reduce fracture risk by about 50%.

Accidental Falls↗
PubMed2006

Uses and misuses of quantitative ultrasonography in managing osteoporosis.

Quantitative ultrasonography is attractive as a test for osteoporosis, being precise, radiation-free, portable, and inexpensive, but it is still no substitute for the gold-standard test, dual-energy x-ray absorptiometry (DXA). At present, it cannot be used to diagnose osteoporosis or to monitor the effects of medications on bone density. As more data become available, however, it may play a larger role. A thorough understanding of the utility and limitations of this test is necessary for using it effectively in clinical practice.

Absorptiometry, Photon↗
PubMed2006

Position Development Conference of the International Society for Clinical Densitometry. Vancouver, BC, July 15-17, 2005.

Every 2 years the International Society for Clinical Densitometry (ISCD) organizes a position development conference at which a panel of experts reviews topics of interest in the field of bone densitometry and proposes Official Positions of the ISCD. In July 2005, the most recent conference was held in Vancouver, Canada, during which 4 topics were discussed: (1) Cross-calibration of dual energy x-ray absorptiometry (DXA) systems, (2) Vertebral fracture assessment, (3) World Health Organization (WHO) classification of bone density for populations other than postmenopausal women, and (4) WHO classification for varying skeletal sites. The Official Positions reached at this conference enumerated in this report have been published in The Journal of Clinical Densitometry, and can be found at www.iscd.org.

Absorptiometry, Photon↗
PubMed2005

Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study.

UNLABELLED: Once-monthly (50/50, 100, and 150 mg) and daily (2.5 mg; 3-year vertebral fracture risk reduction: 52%) oral ibandronate regimens were compared in 1609 women with postmenopausal osteoporosis. At least equivalent efficacy and similar safety and tolerability were shown after 1 year. INTRODUCTION: Suboptimal adherence to daily and weekly oral bisphosphonates can potentially compromise therapeutic outcomes in postmenopausal osteoporosis. Although yet to be prospectively shown in osteoporosis, evidence from randomized clinical trials in several other chronic conditions shows that reducing dosing frequency enhances therapeutic adherence. Ibandronate is a new and potent bisphosphonate with antifracture efficacy proven for daily administration and also intermittent administration with a dose-free interval of >2 months. This report presents comparative data on the efficacy and safety of monthly and daily oral ibandronate regimens. MATERIALS AND METHODS: MOBILE is a 2-year, randomized, double-blind, phase III, noninferiority trial. A total of 1609 women with postmenopausal osteoporosis were assigned to one of four oral ibandronate regimens: 2.5 mg daily, 50 mg/50 mg monthly (single doses, consecutive days), 100 mg monthly, or 150 mg monthly. RESULTS: After 1 year, lumbar spine BMD increased by 3.9%, 4.3%, 4.1%, and 4.9% in the 2.5, 50 /50, 100, and 150 mg arms, respectively. All monthly regimens were proven noninferior, and the 150 mg regimen superior, to the daily regimen. All monthly regimens produced similar hip BMD gains, which were larger than those with the daily regimen. All regimens similarly decreased serum levels of C-telopeptide, a biochemical marker of bone resorption. Compared with the daily regimen, a significantly larger proportion of women receiving the 100 and 150 mg monthly regimens achieved predefined threshold levels for percent change from baseline in lumbar spine (6%) or total hip BMD (3%). All regimens were similarly well tolerated. CONCLUSIONS: Monthly ibandronate is at least as effective and well tolerated as the currently approved daily ibandronate regimen in postmenopausal osteoporosis.

Absorptiometry, Photon↗
PubMed2005

Early changes in biochemical markers of bone formation predict BMD response to teriparatide in postmenopausal women with osteoporosis.

UNLABELLED: The relationship between early changes in biochemical markers of bone turnover and the subsequent BMD response to daily teriparatide therapy in women with postmenopausal osteoporosis was studied. Changes in five biochemical markers, obtained from a subset of women enrolled in the Fracture Prevention Trial, were examined. Early increases in the PICP and the PINP were the best predictors of BMD response to teriparatide in this analysis. INTRODUCTION: Early reductions in biochemical markers of bone turnover with antiresorptive therapy negatively correlate with subsequent increases in BMD. We undertook this analysis to determine if early changes in biochemical markers with teriparatide therapy predict subsequent increases in BMD. MATERIALS AND METHODS: In the Fracture Prevention Trial, 1637 postmenopausal women with osteoporosis were randomized to receive daily, self-administered, subcutaneous injections of placebo, teriparatide 20 microg/day, or teriparatide 40 microg/day. Serum concentrations of two bone formation markers (bone-specific alkaline phosphatase [bone ALP] and the carboxy-terminal extension peptide of procollagen type 1 [PICP]) and urinary concentrations of two bone resorption markers (free deoxypyridinoline [DPD] and N-terminal telopeptide [NTX]) were assessed in a trial population subset (n = 520) at baseline and at 1, 3, 6, and 12 months. We also assessed serum concentrations of another bone formation marker, the amino-terminal extension peptide of procollagen type 1 (PINP), in a subset of 771 women at baseline and 3 months. Lumbar spine (LS) BMD was measured by DXA at baseline and 18 months. Femoral neck BMD was measured at baseline and 12 months. RESULTS AND CONCLUSION: Baseline bone turnover status correlated positively and significantly with BMD response. The highest correlations occurred for the LS BMD response to teriparatide 20 microg/day. Among all studied biochemical markers, increases in PICP at 1 month and PINP at 3 months correlated best with increases in LS BMD at 18 months (0.65 and 0.61, respectively; p < 0.05). The relationships between these two biochemical markers and the LS BMD response were stronger than the corresponding relationships for the femoral neck BMD response. Using receiver operator curve analysis, we determined that the increases in PICP at 1 month and PINP at 3 months were the most sensitive and accurate predictors of the LS BMD response.

Adult↗
PubMed2005

Review of guidelines for bone mineral density testing and treatment of osteoporosis.

Clinical practice guidelines (CPGs) are systematically developed statements intended to influence the behavior of health care providers and improve patient care. There are many CPGs with recommendations for selection of patients for bone mineral density testing and pharmacologic treatment of osteoporosis. Health care provider adherence rates for these CPGs are low. The multiplicity of osteoporosis CPGs directed to the same health care providers may play a role in their limited utilization in clinical practice. Similarities, differences, and conflicts in osteoporosis CPGs with wide distribution in the United States were examined. The analysis showed similarities as well as substantial variation in the patient populations addressed, inconsistency of some recommendations, differences in clinical risk factors identified, and sometimes limitations in clinical applications. If the number and diversity of osteoporosis CPGs is adversely affecting their use in clinical practice, then collaboration of stakeholder organizations to develop more consistent CPGs, in combination with systems-based approaches for their implementation, may improve patient care and reduce the burden of osteoporotic fractures.

Bone Density↗