Biomedical subjects

Jacques P Brown

Publications and source records attributed to Jacques P Brown.

At least 19 recordsLinked to original sources

PubMed2007

Long-term control of bone turnover in Paget's disease with zoledronic acid and risedronate.

UNLABELLED: A single 5-mg infusion of zoledronic acid restores biochemical markers of bone turnover into the reference range in the majority of patients with Paget's disease and maintains biochemical remission for at least 2 years. This effect is largely independent of pretreatment disease activity and prior bisphosphonate therapy. INTRODUCTION: Zoledronic acid (ZOL) is a potent bisphosphonate that produces a rapid and complete control of the increased bone turnover of Paget's disease. Long-term control of disease activity is an important aim of treatment in the hope that this will reduce the risk of complications such as deformity, fracture, and degenerative joint disease. MATERIALS AND METHODS: This study compares the ability of ZOL 5 mg given as a 15-minute intravenous infusion with risedronate (RIS) 30 mg daily by mouth for 60 days to maintain long-term control of bone turnover. No bisphosphonate was given during the extension study. All patients (n = 296) who achieved a therapeutic response, defined as normalization or a >75% reduction in the total alkaline phosphatase (total ALP) excess above the midpoint of the reference range, were eligible for inclusion. RESULTS: ZOL maintained the mean level of total ALP at the middle of the reference range, whereas those treated with risedronate showed a linear increase in total ALP from the 6-month post-treatment time-point. Both treatments resulted in a linear relationship between the 6-month nadir and 24-month total ALP. The relationship for RIS was shifted upward, showing that for a given level of post-treatment biochemical activity, bone turnover increased with time. This was in contrast to the ZOL-treated patients where total ALP generally remained unchanged over this 18-month extension period. A similar pattern of response was seen with the other bone turnover markers. CONCLUSIONS: ZOL maintains bone turnover within the reference range over 24 months from the initiation of treatment. A reduction in the incidence and severity of long-term complications may require persistent normalization of bone turnover over many years, and this now seems a realistic possibility with ZOL.

Administration, Oral↗

PubMed2007

Changes to osteoporosis prevalence according to method of risk assessment.

UNLABELLED: The impact of clinical risk factor-based absolute risk methods on the prevalence of high risk for osteoporotic fracture is unknown. We applied absolute risk methods to 6646 subjects and found that the prevalence of elderly women deemed to be at high risk increased substantially, whereas the overall prevalence was highly dependent on the threshold used to designate high risk. INTRODUCTION: Many groups have advocated using absolute risk methods that incorporate clinical risk factors to target patients for osteoporosis therapy. We examined how the application of such absolute risk classification systems influences the prevalence of those considered to be at high risk for osteoporotic fracture and compared these systems to one based solely on BMD. MATERIALS AND METHODS: Using 6646 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, randomly selected, population-based cohort, we assessed three different systems for determining prevalence of high risk for osteoporotic fracture: a BMD-based system; a simplified risk factor system incorporating age, sex, BMD, and two clinical risk factors; and a comprehensive system, incorporating age, sex, BMD, and seven clinical risk factors. The 10-year absolute risks of incident fragility fracture were compared across systems using three different high-risk thresholds. RESULTS: The prevalence of a T score < or = -2.5 was 18.8% (95% CI: 17.7-19.9%) in women and 3.9% (95% CI: 3.0-4.7%) in men. Using a 15% 10-year risk of fracture threshold, the prevalence of women at high risk increased to 46.9% (95% CI: 45.4-48.4) and 42.5% (95% CI: 41.1-43.9) when the comprehensive and simplified risk factor classification systems were used, respectively. Using a 25% 10-year absolute risk threshold, the prevalence of high risk was similar to that of the BMD-based system, whereas the 20% threshold gave intermediate rates. All thresholds analyzed resulted in an increased prevalence of older women at high risk for fracture, whereas only the 15% 10-year risk of fracture threshold resulted in an increase in the prevalence of men at high risk. CONCLUSIONS: The application of risk factor-based systems results in an increased prevalence of older women at high risk. The prevalence of individuals at high risk may increase with changes to the methods used to determine those who are eligible for therapy. These data have important implications for the pattern of care and costs of treating osteoporotic fractures.

Absorptiometry, Photon↗

PubMed2006

Clinical trial of a leucotriene B4 receptor antagonist, BIIL 284, in patients with rheumatoid arthritis.

BACKGROUND: Several clinical and experimental lines of evidence suggest that leucotriene B4 (LTB4), an arachidonic acid derivative with potent proinflammatory properties, plays a key role in the pathophysiology of rheumatoid arthritis (RA). OBJECTIVE: To evaluate the efficacy and safety of BIIL 284, an oral long-acting LTB4 receptor antagonist, as monotherapy for the treatment of patients with active RA. METHODS: This was a multi-centre, randomised, double-blind, placebo-controlled trial of patients with active RA of 3 months' duration. A total of 342 patients were randomised to receive 5 mg, 25 mg or 75 mg of BIIL 284 or placebo. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR) 20. RESULTS: Although a higher percentage of ACR 20 responders was observed in the groups treated with 25 mg and 75 mg of BIIL 284 compared with those treated with placebo, no statistically significant differences were found between any of the three active treatment groups compared with the placebo group with regard to the primary or secondary end points. All trial treatments were safe and well tolerated. CONCLUSIONS: This clinical trial demonstrates that treatment of patients with active RA with a potent oral long-acting LTB4 receptor antagonist produced only modest improvements in disease activity. The results of this trial support the conclusion that LTB4 is not a major contributor to the inflammatory process in RA.

Administration, Oral↗

PubMed2006

The effects of antifracture therapies on the components of bone strength: assessment of fracture risk today and in the future.

OBJECTIVE: To summarize the current knowledge regarding the impact of the most common antifracture medications on the various determinants of bone strength. METHODS: Relevant English-language articles acquired from Medline from 1966 to January 2005 were reviewed. Searches included the keywords bone AND 1 of the following: strength, remodeling, microcrack, structure, mineralization, collagen, organic, crystallinity, osteocyte, porosity, diameter, anisotropy, stress risers, or connectivity AND alendronate, estrogen, etidronate, hormone replacement therapy, parathyroid hormone, risedronate, OR teriparatide. Abstracts from relevant conference proceedings were also reviewed for pertinent information. RESULTS: Antiresorptive therapies increase bone strength through decreasing bone turnover. This lower bone turnover results in a higher mean mineralization and decreases the number of active resorption pits within bone at any given time. These resorption pits are speculated to be areas of focal weakness and a higher number of them would, if all other things were equal, result in greater fragility. Parathyroid hormone therapy increases the rate of bone remodeling, which introduces many resorption pits, but this source of strength loss is thought to be compensated by rapid increases in bone mass. CONCLUSIONS: Both the antiresorptives, particularly bisphosphonates, and the parathyroid hormone therapy increase bone strength; however, the changes that are elicited to achieve this differ significantly.

Bone Density↗

PubMed2006

Bone strength: the whole is greater than the sum of its parts.

OBJECTIVE: To summarize the current knowledge regarding the various determinants of bone strength. METHODS: Relevant English-language articles acquired from Medline from 1966 up to January 2005 were reviewed. Searches included the keywords bone AND 1 of the following: strength, remodeling, microcrack, structur*, mineralization, collagen, organic, crystallinity, osteocyte, porosity, diameter, anisotropy, stress risers, or connectivity. Abstracts from applicable conference proceedings were also reviewed for pertinent information. RESULTS: Bone strength is determined from both its material and its structural properties. Material properties such as its degree of mineralization, crystallinity, collagen characteristics, and osteocyte viability have substantial impacts on bone strength. Structural properties such as the diameter and thickness of the cortices, the porosity of the cortical shell, the connectivity and anisotropy of the trabecular network, the thickness of trabeculae, and the presence of trabecular stress risers and microcracks impact bone strength in diverse manners. Remodeling activity either directly or indirectly impacts all of these processes. CONCLUSIONS: Bone strength is dependent on numerous, interrelated factors. Remodeling activity has a direct impact on almost all of the components of bone strength and requires further investigation as to its impact on these factors in isolation and in unison.

Bone Density↗

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

The natural progression of health-related quality of life: results of a five-year prospective study of SF-36 scores in a normative population.

BACKGROUND: Limited information exists regarding the natural progression of health-related quality of life (HRQOL) in the general population, as most research has been cross-sectional or has followed populations with specific medical conditions. Such norms are important to establish, because the effect of any intervention may be confounded by changes due to the natural progression of HRQOL over time. METHODS: Participants were randomly selected from 9 Canadian cities and surrounding rural areas. Changes in the eight domains and 2 summary component scores of the Medical Outcomes Study 36-item short form (SF-36) were examined over a 5 year period (1996/1997-2001/2002). Mean changes were calculated for men and women within 10 year age categories. Multiple imputation was used to adjust for potential selection bias due to missing data. RESULTS: The baseline sample included 6539 women and 2884 men. Loss to follow-up was 17% for women and 23% for men. Mean changes tended to be small, but there was an overall trend towards decreasing HRQOL over time. Changes were more pronounced in the older age groups and in the physically oriented domains. Younger age groups tended towards small mean improvements, particularly in the mentally oriented domains. Large standard errors suggest that on an individual level, large improvements in some participants are balanced by large declines in others. CONCLUSION: In general, the HRQOL of Canadians appears relatively stable over a 5 year period. However, care should be taken when assessing HRQOL longitudinally in certain age or gender groups, as changes associated with an intervention can potentially be confounded by the natural progression of HRQOL.

Adult↗

PubMed2006

Canadian Consensus Conference on osteoporosis, 2006 update.

OBJECTIVE: To provide guidelines for the health care provider on the diagnosis and clinical management of postmenopausal osteoporosis. OUTCOMES: Strategies for identifying and evaluating high-risk individuals, the use of bone mineral density (BMD) and bone turnover markers in assessing diagnosis and response to management, and recommendations regarding nutrition, physical activity, and the selection of pharmacologic therapy to prevent and manage osteoporosis. EVIDENCE: MEDLINE and the Cochrane database were searched for articles in English on subjects related to osteoporosis diagnosis, prevention, and management from March 2001 to April 2005. The authors critically reviewed the evidence and developed the recommendations according to the Journal of Obstetrics and Gynaecology Canada's methodology and consensus development process. VALUES: The quality of evidence is rated using the criteria described in the report of the Canadian Task Force on the Periodic Health Examination. Recommendations for practice are ranked according to the method described in this report. SPONSORS: The development of this consensus guideline was supported by unrestricted educational grants from Berlex Canada Inc., Lilly Canada, Merck Frosst, Novartis, Novogen, Novo Nordisk, Proctor and Gamble, Schering Canada, and Wyeth Canada.

Female↗

PubMed2006

Sequestosome 1: mutation frequencies, haplotypes, and phenotypes in familial Paget's disease of bone.

UNLABELLED: Mutations of the SQSTM1/p62 gene are commonly observed in PDB. Screening an updated sample from Quebec and using previously published data from other populations, we compared frequency estimates for SQSTM1/p62 mutations and haplotype distribution. The P392L mutation was the most prevalent, embedded in two different haplotypes, possibly shared by other populations. We also examined the phenotype and penetrance of P392L. INTRODUCTION: There is accumulating evidence that supports a contribution of genetic factors in the etiology of Paget's disease of bone (PDB), and several genetic loci have been suggested for the disorder. The sequestosome1/p62 (SQSTM1/p62) gene was the first gene identified to have a role in PDB, with 14 mutations reported to date. MATERIAL AND METHODS: To evaluate the importance of the SQSTM1/p62 mutations in PDB, we recruited, sequenced, and genotyped a total of 123 carriers from 20 families in addition to 214 unrelated PDB patients. We compared the frequency of SQSTM1/p62 mutations in familial and unrelated cases among different populations. Finally, we examined the phenotypic expression and penetrance of the P392L mutation in the Quebecois families. RESULTS AND CONCLUSIONS: The 14 mutations reported in SQSTM1/p62 all affect the ubiquitin-associated domain of the protein. The P392L mutation is the most commonly observed mutation in PDB patients and was consistently found in unrelated and familial PDB cases in the populations tested. Analysis of adjacent polymorphisms suggests that P392L is associated with two different haplotypes in the Quebecois patients, similar to what has been observed in European populations. In Quebec, both haplotypes had similar frequencies in unrelated P392L carriers, whereas one haplotype was predominant in the other populations studied. These data suggest that these two haplotypes, possibly introduced by European founders in the Quebecois population, were equally distributed in the succeeding generations. Finally, the P392L mutation is transmitted as an autosomal dominant trait in the Quebecois families, with a high but incomplete penetrance peaking after age 60. The large phenotypic variability and similarity between unrelated and familial cases, respectively, remain unexplained and require further research.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Determinants of health-related quality of life in women with vertebral fractures.

Health-related quality of life (HRQL) is an important consideration in the management of patients with vertebral fractures. The purpose of this study was to examine patient-related factors that contribute to HRQL after vertebral fractures, including co-morbidities, medications, fracture history, family disease history, demographics, exercise, education and living environment. A total of 1,129 post-menopausal women (mean age 67.2, SD 11.9 years) was studied from the Canadian Database of Osteoporosis and Osteopenia (CANDOO). HRQL was measured using the mini-osteoporosis quality of life questionnaire (mini-OQLQ). Separate multivariable linear regression analyses [parameter estimates and corresponding 95% confidence intervals (CI)] were performed for each of the five mini-OQLQ domains: symptoms, physical functioning, emotional functioning, activities of daily living and leisure domains. A strong positive association was found between HRQL and post-secondary education, a family history of osteoporosis, working and thiazide therapy. Exercise improved HRQL; however, several hours a week were required to be meaningful. Living in long-term care had the most marked negative effect on HRQL. Smoking, past surgery of the hip or spine, sedatives, anticonvulsants, atherosclerotic disease and hypertension were also associated with a substantially decreased HRQL across several domains. Calcium channel-blockers, chemotherapy, corticosteroids, diabetes, migraines, the number of non-vertebral fractures and falls had a negative impact on selected domains. We demonstrated that several modifiable factors influence HRQL in patients with vertebral fractures, and physicians should be aware of these and other markers of reduced HRQL to enhance patient care.

Activities of Daily Living↗

PubMed2005

Evaluation of easily measured risk factors in the prediction of osteoporotic fractures.

BACKGROUND: Fracture represents the single most important clinical event in patients with osteoporosis, yet remains under-predicted. As few premonitory symptoms for fracture exist, it is of critical importance that physicians effectively and efficiently identify individuals at increased fracture risk. METHODS: Of 3426 postmenopausal women in CANDOO, 40, 158, 99, and 64 women developed a new hip, vertebral, wrist or rib fracture, respectively. Seven easily measured risk factors predictive of fracture in research trials were examined in clinical practice including: age (< 65, 65-69, 70-74, 75-79, 80+ years), rising from a chair with arms (yes, no), weight (< 57, > or = 57 kg), maternal history of hip fracture (yes, no), prior fracture after age 50 (yes, no), hip T-score (> -1, -1 to > -2.5, < or = -2.5), and current smoking status (yes, no). Multivariable logistic regression analysis was conducted. RESULTS: The inability to rise from a chair without the use of arms (3.58; 95% CI: 1.17, 10.93) was the most significant risk factor for new hip fracture. Notable risk factors for predicting new vertebral fractures were: low body weight (1.57; 95% CI: 1.04, 2.37), current smoking (1.95; 95% CI: 1.20, 3.18) and age between 75-79 years (1.96; 95% CI: 1.10, 3.51). New wrist fractures were significantly identified by low body weight (1.71, 95% CI: 1.01, 2.90) and prior fracture after 50 years (1.96; 95% CI: 1.19, 3.22). Predictors of new rib fractures include a maternal history of a hip fracture (2.89; 95% CI: 1.04, 8.08) and a prior fracture after 50 years (2.16; 95% CI: 1.20, 3.87). CONCLUSION: This study has shown that there exists a variety of predictors of future fracture, besides BMD, that can be easily assessed by a physician. The significance of each variable depends on the site of incident fracture. Of greatest interest is that an inability to rise from a chair is perhaps the most readily identifiable significant risk factor for hip fracture and can be easily incorporated into routine clinical practice.

Aged↗

PubMed2005

Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease.

BACKGROUND: The advent of bisphosphonates advanced therapy for Paget's disease, but more effective and convenient agents are needed to increase adherence. Zoledronic acid, a bisphosphonate administered as a single intravenous infusion, might meet these needs. METHODS: In two identical, randomized, double-blind, actively controlled trials of 6 months' duration, we compared one 15-minute infusion of 5 mg of zoledronic acid with 60 days of oral risedronate (30 mg per day). The primary efficacy end point was the rate of therapeutic response at six months, defined as a normalization of alkaline phosphatase levels or a reduction of at least 75 percent in the total alkaline phosphatase excess. The results of the studies were pooled. RESULTS: At six months, 96.0 percent of patients receiving zoledronic acid had a therapeutic response (169 of 176), as compared with 74.3 percent of patients receiving risedronate (127 of 171, P<0.001). Alkaline phosphatase levels normalized in 88.6 percent of patients in the zoledronic acid group and 57.9 percent of patients in the risedronate group (P<0.001). Zoledronic acid was associated with a shorter median time to a first therapeutic response (64 vs. 89 days, P<0.001). Higher response rates in the zoledronic acid group were consistent across all demographic, disease-severity, and treatment-history subgroups and with changes in other bone-turnover markers. The physical-component summary score of the Medical Outcomes Study 36-item Short-Form General Health Survey, a measure of the quality of life, increased significantly from baseline at both three and six months in the zoledronic acid group and differed significantly from those in the risedronate group at three months. Pain scores improved in both groups. During post-trial follow-up (median, 190 days), 21 of 82 patients in the risedronate group had a loss of therapeutic response, as compared with 1 of 113 patients in the zoledronic acid group (P<0.001). CONCLUSIONS: A single infusion of zoledronic acid produces more rapid, more complete, and more sustained responses in Paget's disease than does daily treatment with risedronate.

Administration, Oral↗

PubMed2005

Are oral bisphosphonates effective in improving lumbar bone mineral density in breast cancer survivors with osteopenia or osteoporosis?

OBJECTIVE: Breast cancer survivors with osteoporosis or osteopenia are commonly encountered in primary care and gynaecology practices. Our objective was to determine whether treatment with oral bisphosphonates (alendronate or cyclic etidronate) was more effective than calcium with vitamin D in improving lumbar spine bone mineral density (BMD) within one year in breast cancer survivors. METHODS: Breast cancer survivors with at least one year of clinical follow-up were identified from the prospective observational Canadian Database of Osteoporosis and Osteopenia (CANDOO). Analysis of covariance was used to examine the effects of bisphosphonate therapy on change in lumbar spine BMD at one year compared with the effects of calcium with vitamin D (analysis adjusted for baseline L2-L4 BMD, current tamoxifen use, number of prevalent vertebral fractures [VFs], and time since diagnosis of breast cancer, and age). RESULTS: Eighteen patients took calcium and vitamin D, 25 took cyclic etidronate, and 27 took oral alendronate. Adjusted one-year BMD increases for alendronate and cyclic etidronate compared to calcium and vitamin D were as follows: alendronate 4.53% (95% confidence interval [CI] 1.26%, 7.81%, P = 0.008), and cyclic etidronate 1.85% (-1.55%, 5.25%, P = 0.280). BMD increases were significantly greater in patients with prevalent VF compared to those without VF (P = 0.025). In contrast, time since diagnosis of breast cancer was significantly associated with a decrease in BMD (P = 0.002). We were unable to detect any effect of current tamoxifen use, baseline lumbar spine BMD, or age on changes in BMD at one year. CONCLUSION: Treatment with alendronate was associated with significantly greater improvements in lumbar spine BMD within one year in breast cancer survivors when compared with treatment with cyclic etidronate or calcium and vitamin D.

Aged↗

PubMed2005

Recommendations for bone mineral density reporting in Canada.

OBJECTIVE: To propose a set of recommendations for optimal bone mineral density (BMD) reporting in postmenopausal women and older men and to provide clinicians with both a BMD diagnostic category and a useful tool to assess an individual's risk of osteoporotic fracture. OPTIONS: The current methods of BMD reporting were reviewed. In this document, we propose that an individual's 10-year absolute fracture risk, rather than BMD alone, be used for fracture risk categorization. Consequently, age, sex, BMD, fragility fracture history, and glucocorticoid use are the basis for the approach outlined in this document. OUTCOMES: An optimal BMD report as proposed in this document will provide clinicians with both a BMD diagnostic category and a useful tool to assess an individual's risk of osteoporotic fracture. A BMD report format, a checklist, and a patient questionnaire are meant to further encourage its use. EVIDENCE: All recommendations were developed using a consensus from clinicians and experts in the field of BMD testing and a standard method for the evaluation and citation of the supporting evidence. VALUES: These recommendations were developed by a multidisciplinary working group under the auspices of the Scientific Advisory Council of the Osteoporosis Society of Canada and the Canadian Association of Radiologists. BENEFITS, HARM, AND COSTS: Optimal BMD reports help the practitioner to assess an individual's risk for osteoporotic fracture and to decide whether medical therapy is warranted. RECOMMENDATIONS: The BMD report should include: patient identifiers. Dual-energy X-ray absorptiometry (DXA) scanner identifier. BMD results expressed in absolute values (g/cm2; 3 decimal places) and T-score (1 decimal place) for lumbar spine; proximal femur (total hip, femoral neck, and trochanter); and an alternate site (forearm BMD preferred: 1/3 radius, 33% radius or proximal radius) if either hip or spine is not valid. A statement about any limitations due to artifacts, if present. The fracture risk category (low, moderate, or high) as determined by using Tables 3 and 4 and by including major clinical factors that modify absolute fracture risk probability (with an indication of the corresponding absolute 10-year fracture risk of <10%, 10-20%, or >20%). A statement as to whether the change is statistically significant or not for serial measurements. The BMD centre's least significant change for each skeletal site (in g/cm2) should be included. VALIDATION: Recommendations were based on consensus opinion. Since these are the first Canadian recommendations integrating clinical risk factors in a quantitative fracture risk assessment, it is anticipated that these "Recommendations for BMD Reporting in Canada" will be a work in progress and will be updated periodically to accommodate advances in this field.

Absorptiometry, Photon↗

PubMed2004

Risk factors associated with incident clinical vertebral and nonvertebral fractures in postmenopausal women: the Canadian Multicentre Osteoporosis Study (CaMos).

Utilizing data from the Canadian Multicentre Osteoporosis Study (CaMos), we examined the association between potential risk factors and incident vertebral and nonvertebral fractures. A total of 5,143 postmenopausal women were enrolled. Information collected during the study included data from the CaMos baseline and annually mailed fracture questionnaires, the Short Form 36 (SF-36), the Health Utilities Index, and physical measurements. Participants were followed for 3 years. Postmenopausal women were classified into four groups according to their incident fracture status since baseline: those without a new fracture; those with a new clinically recognized vertebral fracture; those with an incident nonvertebral fracture at the wrist, hip, humerus, pelvis, or ribs (main nonvertebral fracture group); and those with any new nonvertebral fracture (any-nonvertebral-fracture group). We performed multivariate Cox proportional hazard analysis using all possible risk factors to determine the association between risk factors and the time to the first minimal trauma fracture. Best predictive models were also determined using variables that were included in the full models. The Bayesian information criterion was used for model selection. For all analyses, relative risks and associated 95% confidence intervals were calculated. During the follow-up period, 34, 163, and 280 women developed a vertebral, a main nonvertebral, or any nonvertebral fracture, respectively. The best predictive models indicated that a five point lower quality of life as measured by the SF-36 physical component summary score was associated with relative risks of 1.21 (95% CI, 1.02 to 1.44), 1.17 (95% CI, 1.07 to 1.28), and 1.19 (95% CI, 1.11 to 1.27) for incident vertebral, main nonvertebral, and all nonvertebral fractures, respectively. In addition, for a one standard deviation (SD=0.12) lower femoral neck BMD, the relative risks for incident vertebral, main nonvertebral, and any nonvertebral fractures increased by 2.73 (95% CI, 1.74 to 4.28), 1.39 (95% CI, 1.06 to 1.82), and 1.34 (95% CI, 1.09 to 1.65), respectively. Furthermore, various anthropometric measures, disease conditions, and medications are associated with a new fracture. Identifying postmenopausal women at risk is important given that fracture prevention therapies are now available.

Adult↗

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

The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis.

The atypical PKCs (aPKCs) have been implicated genetically in at least two independent signaling cascades that control NF-kappa B and cell polarity, through the interaction with the adapters p62 and Par-6, respectively. P62 binds TRAF6, which plays an essential role in osteoclastogenesis and bone remodeling. Recently, p62 mutations have been shown to be the cause of the 5q35-linked Paget's disease of bone, a genetic disorder characterized by aberrant osteoclastic activity. Here we show that p62, like TRAF6, is upregulated during RANK-L-induced osteoclastogenesis and that the genetic inactivation of p62 in mice leads to impaired osteoclastogenesis in vitro and in vivo, as well as inhibition of IKK activation and NF-kappa B nuclear translocation. In addition, RANK-L stimulation leads to the inducible formation of a ternary complex involving TRAF6, p62, and the aPKCs. These observations demonstrate that p62 is an important mediator during osteoclastogenesis and induced bone remodeling.

Animals↗

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↗