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PubMed2005

Possible participation of advanced glycation end products in the pathogenesis of osteoporosis in diabetic patients.

Osteoporosis, one of the most prevalent metabolic bone diseases in developed countries, is a major public health problem through its association with fragility fractures. Several epidemiological studies have reported moderately increased risks of osteoporotic bone fractures in diabetic patients compared with general population. However, the underlying molecular link between diabetes and osteoporosis remains to be elucidated. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress. There is a growing body of evidence to show that AGEs-their receptor (RAGE) interactions are involved in the development of atherosclerosis and diabetic microangiopathy. AGEs enhance osteoclast-induced bone resorption in cultured mouse unfractionated bone cells. Furthermore, we have recently found that AGEs-RAGE interactions induced human mesenchymal stem cell apoptosis and subsequently prevented cognate differentiation into adipose tissue, cartilage, and bone. In vivo, serum levels of AGEs are elevated in patients with osteoporosis as well. These observations let us to hypothesize that AGEs could explain the molecular link between diabetes and osteoporosis. In this paper, we would like to propose the possible ways of testing our hypotheses. Does treatment with metformin, which has a potential effect on the inhibition of glycation reactions in vivo, decrease the risk for osteoporotic bone fractures in diabetic patients? If the answer is yes, is this beneficial effect of metformin superior to that of other anti-diabetic agents with equihypoglycemic properties? Does treatment with pyridoxamine, a post-Amadori inhibitor (so-called Amadorins) of AGE formation, reduce the risk for osteoporotic bone fractures as well? Furthermore, are increased levels of AGEs and RAGE in bone tissues associated with high risk for bone fractures in patients with diabetes? These clinical studies could clarify whether the AGEs-RAGE interactions serve as a causal link between diabetes and osteoporosis.

Animals↗

PubMed2005

Pharmacological studies of the large-scaled purified genistein from Huaijiao (Sophora japonica-Leguminosae) on anti-osteoporosis.

In this report, we used genistein that was extracted from a Chinese herbal medicine Huaijiao (Sophora japonica-Leguminosae) to evaluate its pharmacological function on anti-osteoporosis. This genistein is purified in a large-scale production from Huaijiao by a state-of-art method as described by Tian et al. [2004. The preparation of genistein and LC-MS/MS on-line analysis. Drug Devel. Res. 61, 6-12]. Chemical structure of the isolated genistein was examined by using various techniques including nuclear magnetic resonant spectrum, infrared absorption spectrum, ultraviolet absorption spectrum and mass spectrum, and was proved to be identical to those purified from soybean in a small scale as previously reported. We randomly divided female SD rats into 6 groups, including control, ovariectomized model, Nilestriol-treated, and three level of dosages of genistein-treated. We evaluated the pharmacological effects of genistein against osteoporosis by measuring the bone density of femur and bone mineral group including calcium, phosphorous, and magnesium. The consequences of genistein treatment on bone histology and morphology were also determined by measuring the trabcular area, thickness and number. Our results indicated that treatment with a 4.5 or 9 mg/kg dosage of genistein could also prevent osteoporosis significantly at the 4th week after treatment. In comparison with the anti-osteoporosis effects of soybean genistein, the genistein extracted from Huaijiao has the same beneficial effect on anti-osteoporosis.

Animals↗

PubMed2006

Preferred skeletal site for osteoporosis screening in high-risk populations.

OBJECTIVES: The current World Health Organization (WHO) definition of osteoporosis, which is based on densitometry of lumbar and femoral regions, is extensively used for decision-making in clinical practice. Discordance in diagnosis of osteoporosis using this definition is a known phenomenon. The aim of this study was to evaluate the impact of such discordance and to assess the diagnostic value of using one skeletal site for screening purposes as opposed to the two sites required in the WHO criteria. STUDY DESIGN: Data was collected from 4188 individuals (3848 female); mean age=53.4 years (standard deviation 11.8) referred to a community-based outpatient osteoporosis testing centre in Tehran, Iran. METHODS: Dual-energy X-ray absorptiometry (DXA) was performed on L1-L4 lumbar spine and total hip for all cases. The DXA results were categorized according to WHO criteria. Sensitivity for each site was calculated as number of cases with T-score < -2.5 at that site divided by the total number of cases with T-score < -2.5 at any site. RESULTS: Prevalence of osteoporosis diagnosis using lumbar DXA, femoral DXA, and WHO criteria (either of the sites) were 24.7%, 12.4%, and 27.8%, respectively. Sensitivity of lumbar DXA for diagnosis of osteoporosis (88.9%) was significantly higher than femoral DXA (44.6%, P<0.001); but this difference became non-significant for men > or = 60 and women > or = 70 (P=0.615 and P=0.077, respectively). Agreement of the procedures in different sites (kappa) was 0.40 (0.37 to 0.43). When proximal femur was considered as the reference, positive likelihood ratios of lumbar DXA to detect cases were 4.7 and 2.0 in younger and older groups, respectively. CONCLUSIONS: Concerning the high rate of discordance and low agreement between DXA results, the data obtained from each anatomical site cannot predict the condition of the other site. However, if use of a single assessment is intended for screening programs, public health authorities can develop different strategies for different age groups of their population. We propose lumbar DXA for the younger group (men < 60 and women < 70) and femoral densitometry for the older.

Absorptiometry, Photon↗

PubMed2006

[Pregnancy-associated osteoporosis. A new case].

INTRODUCTION: Pregnancy-associated osteoporosis is a rare disorder and its pathophysiology remains unknown. EXEGISIS: We report a case of pregnancy-associated osteoporosis in a 27-year-old primiparous patient, revealed by acute lumbar pain and a right costal pain during the last month of pregnancy. The standard radiographs showed multiple vertebral compression fracture and a 10th rib fracture. The diagnosis of osteoporosis was established by osteodensitometry. Diagnostic work-up excluded a secondary osteoporosis, and the outcome was favourable with an increase of bone mineral density after 2 years of treatment with calcium, vitamin D and alendronate 10 mg/j. CONCLUSION: Although rare, diagnosis of pregnancy-associated osteoporosis should be suspected when thoracic or lumbar spine pain occur during pregnancy or in the post-partum period as it can lead to vertebral or peripheral fractures.

Adult↗

PubMed2005

Risk factors for osteoporosis in young renal transplant recipients.

Osteoporosis is a frequent complication after renal transplantation. Although several risk factors have been defined in its pathogenesis, the parameters influencing this complication in young patients with functioning grafts have not been well defined. We sought to determine the possible risk factors for osteoporosis among 55 male and 27 female renal transplant patients of mean age 35.5 +/- 11.7 years with 68.8% recipients of living-related grafts. Bone mineral densitometry was performed in all patients at 1 year after transplantation. The study utilized the World Health Organization recommendations that define normal (group 1, n = 19), osteopenic (group 2, n = 24), or osteoporotic (group 3, n = 39) patients according to T-score values. Pre- and posttransplant data included gender, age at dialysis onset; age at transplantation; pretransplant dialysis duration; body mass index (BMI); serum calcium, albumin, phosphorus, parathyroid hormone (PTH), and C-reactive protein levels; lipid profile, cumulative doses of immunosuppressive drugs, and pulse steroid dose. Differences between groups 1 and 3 showed that patients with osteoporosis were younger (P < .003) and had started dialysis and underwent transplantation at a younger age than those without osteoporosis (P < .01, P < .003). In addition, pretransplant body weight (P < .02), posttransplant BMI (P < .01), and pretransplant PTH (P < .04), posttransplant total cholesterol, and high-density lipoprotein cholesterol levels were lower among group 3 (P < .004, P < .003). Young adults who started dialysis and underwent transplantation at a younger age were prone to osteoporosis. Additionally, high BMI and cholesterol levels seemed to be preventative for bone loss after transplantation.

Adult↗

PubMed1997

Medical nutrition therapy for patients with osteoporosis.

Osteoporosis is a disease of bone fragility that afflicts more than 25 million Americans and costs the economy of the United States approximately $13.8 billion per year. In addition to direct economic costs, osteoporosis frequently costs patients their independence and a decrease in quality of life. Patients with osteoporosis, particularly those with hip fractures, are often older, malnourished persons in need of nutrition assessment and intervention. Such intervention in persons with hip fractures has been shown to be effective in reducing medical costs by decreasing hospital stays and morbidity. We review here a working practice of care at our osteoporosis research center for the medical nutrition therapy of patients with osteoporosis. Medical nutrition therapy includes an evaluation of the patient's health history, social status, and nutrient, intake. On the basis of the assessment, a nutrition care plan can be developed and implemented with the goals of improving clinical outcomes and the quality of life for patients and saving health care dollars.

Anthropometry↗

PubMed1997

Update on primary osteoporosis.

Osteoporosis is the most common bone disorder encountered in clinical practice. It is also one of the most important diseases facing our aging population. In the United States alone, an estimated 1.5 million fractures that occur annually are attributed to osteoporosis, and they account for an estimated $13 billion annually. With the projected increase in life expectancy for the global population, osteoporosis and osteoporosis-related fractures have the potential to become an even larger health-care problem in the future. This article focuses on the evaluation and treatment of primary osteoporosis in women.

Diagnosis, Differential↗

PubMed1999

A simple system to determine who needs osteoporosis screening.

OBJECTIVE: To define factors that identify patients at highest risk for osteoporosis who should be screened. METHODS: We gave a questionnaire we developed for osteoporosis risk factors to 1346 menopausal women who were being screened by bone densitometry at the spine, hip, and femoral neck. Chi-square analysis using the one-tailed test was done on all categoric variables to determine differences or patterns in bone mineral density at specific sites. Multivariate logistic regression analysis was done on each of the three sites scanned to determine which combination of independent variables was a significant predictor of the presence or absence of osteoporosis. RESULTS: Factors identified that were significant for the presence of osteoporosis were age 61 years or older, weight 165 pounds or less, or lack of any use of estrogen, either oral contraceptives or estrogen replacement therapy. CONCLUSION: We devised a simple system to identify which patients should be screened for osteoporosis.

Absorptiometry, Photon↗

PubMed2000

Association of a Leu(10)-->Pro polymorphism of the transforming growth factor-beta1 with genetic susceptibility to osteoporosis and spinal osteoarthritis.

Osteoporosis and osteoarthritis each exhibit a strong genetic component. Although polymorphisms of a variety of genes have been associated with bone mineral density and genetic susceptibility to osteoporosis or to osteoarthritis, the genes responsible for these conditions have not been definitively identified. We have shown that a T(869)-->C polymorphism of the transforming growth factor-beta1 (TGF-beta1) gene, which results in a Leu-->Pro substitution at amino acid 10, is associated with bone mineral density in Japanese adolescents and postmenopausal women, with genetic susceptibility to osteoporosis or spinal osteoarthritis, and with the outcome of treatment for osteoporosis with active vitamin D. I here review our recent studies, which have provided insight into the function of TGF-beta1 as well as into the role of genetic factors in the development of osteoporosis and osteoarthritis.

Animals↗

PubMed2003

Osteoporosis management in the new millennium.

The prevalence of osteoporosis in all US postmenopausal women is 17%, and it is as high as 30% in women older than 65. All postmenopausal women should be encouraged to have adequate daily calcium and vitamin D intake, to exercise regularly, and to avoid tobacco and excessive alcohol use. Although the clinical impact and cost-effectiveness of osteoporosis screening tools remain to be established, a rational approach based on current evidence involves using National Osteoporosis Foundation guidelines, Simple Calculated Osteoporosis Risk Estimation, or Osteoporosis Risk Assessment Instrument clinical decision rules to decide when a postmenopausal woman should undergo further evaluation.

Alendronate↗

PubMed1999

Role of polypeptides in the treatment and diagnosis of osteoporosis.

Osteoporosis is a common disorder characterized by reduced bone mineral density, deterioration of the microarchitecture of bone tissue and increased risk of fracture. The aim of treatment of osteoporosis is to maintain and, ideally, to restore bone strength safely. In recent years the role of polypeptide growth factors in bone metabolism has begun to appear. It has been proposed that alterations in the expression or production of growth factor can modulate the proliferation and activity of bone forming cells. In this direction, the role of structurally diverse peptides for the management and diagnosis of osteoporosis has attracted the attention of many investigators. This paper reviews numerous findings concerning the use of polypeptides, hormones, and growth factors, for the management of osteoporosis. Many of the compounds mentioned here are experimental prototypes of new therapeutic classes. Though it is unlikely that some of the compounds may ever be used clinically, development of safe and efficacious agents in each class will define the future course of therapy for osteoporosis.

Aged↗

PubMedDate not supplied

[Cortisone-induced osteoporosis: from physiopathology to treatment].

Corticosteroid-induced osteoporosis, the principal cause of "secondary" osteoporosis, is usually observed in patients under prolonged systemic corticosteroid therapy and results from the multiple effects exerted by these drugs on bone cell metabolism. Corticosteroids reduce the intestinal absorption of calcium and its tubular reabsorption, thereby negativating the calcium balance and inducing a parathyroid reaction. This reaction is responsible for an increase in bone cell remodelling, but the main manifestation of the direct effect of corticosteroids on bone is osteoblast depression, so that there is disparity between bone resorption and formation, which in turn is responsible for bone tissue deficit. Sex hormone deficiency (due to menopause or treatment) and lack of physical activities (due to the causal disease or to iatrogenic myopathy) amplify bone rarefaction. By quantifying the bone loss, modern densitometry methods provide an early risk evaluation. Osteoporosis of varying intensity exposes some 20% of patients to fractures, vertebral collapse and rib fractures. Preventive measures are always recommended, including minimal effective dose corticosteroid therapy, sodium-free diet, calcium and vitamin D supplement, sex hormone replacement and pursuance of physical activities. Once the stage of fractures by osteoporosis has been reached, the "curative" treatment aims at reducing the incidence of new fractures, either by slowing down osteoclast resorption, or by restoring the bone tissue reserve through stimulation of the osteoblasts. The usefulness of these therapeutic measures in the preventive treatment of corticosteroid-induced osteoporosis remains controverted.

Adrenal Cortex Hormones↗

PubMed1997

Hormone replacement therapy and prevention of osteoporosis: risk assessment and practical advice.

A review of the Debrecen Regional Osteoporosis Program (DROP) in Hungary is given, with special reference to the detection of postmenopausal osteoporosis (PMOP) and its treatment by hormone replacement therapy (HRT). The new definition of osteoporosis by focusing on bone mineral density (BMD) measurements has the major advantage of practical usefulness. The algorithm of managing osteoporotic patients can be easily constructed from the result of bone densitometry as the primary diagnostic tool. The DROP serves a total population of 550,000, is equipped with a DXA bone densitometer, a bone metabolism laboratory and backed by a multidisciplinary team of clinicians from gynecology, radiology, rheumatology, internal medicine, and orthopedic surgery. In 1995 the total number of patients undergoing densitometry was 3170. In 2045 patients T scores of -1 or below were found. From this total number, 348 patients received HRT for 1 year or longer. The results of the treatment showed a positive response (i.e. no bone loss, or net gain) in 65%, while half of the 'non responders' proved in fact non compliant. The contradiction between risk assessment and early diagnosis is explained and replacing 'risk assessment' by 'selection criteria for bone densitometry' is proposed. 'Prevention of osteoporosis' is also to be replaced by 'prevention of complications', i.e. osteoporotic fractures. One of these measures is HRT. Its rational use in the prevention and treatment of osteoporosis and its relation to other treatment methods in the authors' own experience is discussed.

Bone Density↗

PubMed2004

Maldaptation of the link between inflammation and bone turnover may be a key determinant of osteoporosis.

Currently the etiology of osteoporosis is attributed to various endocrine, metabolic, and mechanical factors. We hypothesize that many cases of osteoporosis are also partially attributable to a maladaptation of the link between inflammation and bone turnover. We explore the spatial and temporal link between inflammation and osteoporosis in conditions such as aging, menopause, reflex sympathetic dystrophy, HIV, pregnancy, transplantation, and steroid administration. While nutritional and mechanical factors clearly play a role in many of these situations, the spatial and temporal concordance of osteoporosis and inflammation is buttressed by emerging molecular evidence. Modern bone biology of humans may reflect dual functional legacies of mineral storage and structural support. Osteoporosis may result from disequilibrium between structural demand for key minerals and their biologic demand during maladaptive states of inflammation.

Bone Remodeling↗

PubMed1992

The value of simple morphometric techniques in the diagnosis of osteoporosis.

In order to assess the value of simple morphometric methods in the diagnosis of osteoporosis we measured trabecular bone volume (TBV), trabecular number per unit area and relative osteoid volume in two separate iliac crest biopsies in 20 patients with conclusive autopsy evidence of osteoporosis and 20 controls. In osteoporotic patients trabecular bone volume ranged between 3.0-19.2% (median 10.7%) in the anterior and 3.0-14.3% (median 9.7%) in the posterior biopsy and in controls between 2.5-24.8% (median 13.5%) in the anterior and 5.8-25% (median 12.4%) in the posterior. Trabecular numbers in osteoporotic patients ranged from 1.7-8.3/10 mm2 (median 3.5) and in controls 1.6-17/10 mm2 (median 5.63). Relative osteoid volume showed a similarly wide range. In adjacent biopsies trabecular bone volume and trabecular number could differ by as much as 100% and this casts doubt on the value of sequential bone biopsies in the management of individual patients. We conclude that simple morphometric techniques cannot accurately diagnose osteoporosis. However, if the TBV is greater than 18% osteoporosis is unlikely to be present (upper 95% confidence limit = 17.8%). However, a low value for TBV is not diagnostic for osteoporosis because of a large overlap between control and osteoporotic groups.

Aged↗

PubMed2001

Relation of the estrogen receptor alpha gene microsatellite polymorphism to bone mineral density and the susceptibility to osteoporosis in postmenopausal Chinese women in Taiwan.

OBJECTIVE: Osteoporosis is a common disorder with a strong genetic component. Our aim was to investigate the correlation of the estrogen receptor alpha gene microsatellite polymorphism (TA dinucleotide repeat polymorphism 5' upstream of exon 1) with bone mineral density and their relationship to osteoporosis. METHODS: We determined the estrogen receptor alpha gene microsatellite polymorphism using polymerase chain reaction-based microsatellite analysis in postmenopausal Chinese women in Taiwan. Bone mineral density of the lumbar spine and proximal femur were measured using dual-energy X-ray absorptiometry. RESULTS: The ERalpha genotype was classified into '12' through '27' according to the number of TA dinucleotide repeats they contained, as a 'signpost'. After adjustment for potential confounding factors including age, height, and weight, subjects with genotype 18+ (n=4) had lower bone mineral density values and a 54.5 times greater risk for osteoporosis when compared with subjects with genotype 18- (n=170) at the lumbar spine. This should be interpreted with caution because of the small number of subjects with the unfavorable genotype 18+. According to mean number of TA dinucleotide repeats, women with a high number of repeats (TA > or =20) (n=38) had the lowest bone mineral density and a 6.1 times greater risk for osteoporosis than women with a low number of repeats (TA < or =15) (n=61) at the femoral neck, after adjustment for potential confounding factors such as age, height, and weight. CONCLUSION: The present study suggests that the estrogen receptor alpha gene microsatellite polymorphism may be a candidate genetic marker for risk of osteoporosis in postmenopausal Chinese women in Taiwan.

Absorptiometry, Photon↗

PubMed2003

Bisphosphonate treatment of osteoporosis.

Bisphosphonates represent the agents of choice for most patients with osteoporosis. They are the best studied of all agents for the prevention of bone loss and reduction in fractures. They increase BMD, primarily at the lumbar spine, but also at the proximal femur. In patients who have established osteoporosis, bisphosphonates reduce the risk of vertebral fractures, and are the only agents in prospective trials to reduce the risk of hip fractures and other nonvertebral fractures. Bisphosphonates reduce the risk of fracture quickly. The risk of radiographic vertebral deformities is reduced after 1 year of treatment with risedronate [68]. The risk of clinical vertebral fractures is reduced after 1 year of treatment with alendronate [69] and just 6 months' treatment with risedronate [157]. The antifracture effect of risedronate has been shown to continue through 5 years of treatment [158]. Alendronate and risedronate are approved by the FDA for prevention of bone loss in recently menopausal women, for treatment of postmenopausal osteoporosis, and for prevention (risedronate) and treatment (alendronate and risedronate) of glucocorticoid-induced osteoporosis. Alendronate is also approved for treatment of osteoporosis in men. Other bisphosphonates (etidronate for oral use, pamidronate and zoledronate for intravenous infusion) are also available and can be used off label for patients who cannot tolerate approved agents. Although bisphosphonates combined with estrogen or raloxifene produce greater gains in bone mass compared with single-agent treatment, the use of two antiresorptive agents in combination cannot be recommended because the benefit on fracture risk has not been demonstrated and because of increased cost and side effects.

Bone Density↗

PubMed1998

Women's knowledge of osteoporosis.

Osteoporosis affects one in four women over the age of 65 and is a major cause of hip fractures that place women in nursing homes. In this study of 247 women, their knowledge of osteoporosis was assessed with the Facts on Osteoporosis Quiz. The instrument measured their responses to questions about self-care practices related to risk factors and preventive behavior associated with osteoporosis. Respondents came from occupational and primary health care settings and a health fair. The women ranged in age from 22 to 84 years. Findings indicated that the majority of women had inadequate knowledge of osteoporosis risk factors and preventive behavior.

Adult↗