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PubMed2006

The cost-effectiveness of risedronate in the treatment of osteoporosis: an international perspective.

INTRODUCTION: Risedronate, a bisphosphonate for treatment and prevention of osteoporosis, has been shown in several clinical trials to reduce the risk of fractures in postmenopausal women with osteoporosis. The cost-effectiveness of risedronate treatment has previously been evaluated within different country settings using different model and analysis approaches. The objective of this study was to assess the cost-effectiveness of risedronate in postmenopausal women in four European countries -- Sweden, Finland, Spain, and Belgium -- by making use of the same modelling framework and analysis setup. METHODS: A previously developed Markov cohort model for the evaluation of osteoporosis treatments was used to estimate the cost-effectiveness of risedronate treatment. For each country, the model was populated with local mortality, fracture incidence, and cost data. Hip fractures, clinical vertebral fractures, and wrist fractures were included in the model. RESULTS: The incremental cost per quality-adjusted life years (QALY) gained from a 5-year intervention with risedronate compared to "no intervention" in 70-year-old women at the threshold of osteoporosis [T-score = -2.5 based on National Health and Nutrition Examination Survey (NHANES) III data] and previous vertebral fracture was estimated to be euro 860, euro 19,532, euro 11,782, and euro 32,515 in Sweden, Finland, Belgium, and Spain, respectively. Among 70-year-old women at the threshold of osteoporosis without previous fracture the estimated cost per QALY gained ranged from euro 21,148 (Sweden) to euro 80,100 (Spain). The differences in cost-effectiveness between countries are mainly explained by different costs (fracture and treatment costs), fracture risks, and discount rates. Based on cost per QALY gained threshold values found in the literature, the study results indicated risedronate to be cost effective in the treatment of elderly women with established osteoporosis in all the included countries. CONCLUSIONS: At a hypothetical threshold value of euro 40,000 per QALY gained, the results in this study indicate that risedronate is a cost-effective treatment in elderly women at the threshold of osteoporosis (i.e., a T-score of -2.5) with prevalent vertebral fractures in Sweden, Finland, Belgium, and Spain.

Age Factors↗
PubMed2006

Risk factors of osteoporosis in institutionalized older Thai people.

INTRODUCTION: There are very few published studies on osteoporosis among the institutionalized elderly in Asian countries, where the incidence of osteoporosis is increasing rapidly. Our objectives were to determine both the prevalence and risk factors of osteoporosis, as assessed by calcaneal bone mineral density (BMD) measurements, in a Thai nursing home. METHODS: Activities of daily living, the Mini-Mental State Examination, blood chemistry, body composition analysis, calcaneal quantitative ultrasound (QUS) and serum C-terminal telopeptides of type I collagen (serum beta-CTx) were assessed in 108 older people living in the largest nursing home for the elderly in Bangkok. Calcaneal BMD was measured by dual-energy X-ray absorptiometry (DXA). RESULTS: The prevalence of osteoporosis, as defined by a calcaneal BMD T-score <1.6, was 79.6%. The prevalence of low bone mass, as defined by a T-score of broadband ultrasound attenuation <1.0, was 80.6%. The prevalence of osteoporosis detected by these two methods was not significantly different (p=1.00). The prevalence of increased bone turnover [with the cutoff point being the mean + 2 standard deviation (SD) of the serum beta-CTx level of a sex- and age-matched control group] was 13.9%. In multiple linear regression analysis, five risk factors -- serum beta-CTx, mental health, mobility index, height and lean body mass -- were able to predict calcaneal BMD at a coefficient of determination R(2)) of 0.54. CONCLUSIONS: These results indicate the importance of mental health and self-care ability as factors associated with osteoporosis. Increased bone turnover was also a significant risk factor of low bone mass. Calcaneal QUS was a useful screening tool for diagnosing osteoporosis in this population and was comparable to calcaneal DXA.

Aged↗
PubMed2006

The population burden of fractures originates in women with osteopenia, not osteoporosis.

INTRODUCTION: Osteoporosis is associated with increased risk for fracture. However, most postmenopausal women have bone mineral density (BMD) within the normal or osteopenic range. The aim of this study was to determine the proportion of the population burden of fragility fractures arising from women at modest risk for fracture. METHODS: We measured baseline BMD in a population-based random sample of 616 postmenopausal women aged 60-94 years and followed these individuals for a median of 5.6 years (IQR 3.9-6.5) to determine the incidence of fractures according to age, BMD and the presence of a prior fracture. RESULTS: Based on WHO criteria, 37.6% of the women had normal total hip BMD, 48.0% had osteopenia and 14.5% had osteoporosis. The incidence of fracture during follow-up was highest in women with osteoporosis, but only 26.9% of all fractures arose from this group; 73.1% occurred in women without osteoporosis (56.5% in women with osteopenia, 16.6% in women with normal BMD). Decreasing BMD, increasing age and prior fracture contributed independently to increased fracture risk; in a multivariate model, the relative risk for fracture increased 65% for each SD decrease in BMD (RR=1.65, 95%CI 1.32-2.05), increased 3% for every year of age (RR=1.03, 95%CI 1.01-1.06) and doubled with prevalent fracture (RR=2.01, 95% CI 1.40-2.88). A prevalent fracture increased the risk for fractures such that women with osteopenia and prevalent fracture had the same, if not greater, risk as women with osteoporosis alone. CONCLUSIONS: Reducing the population burden of fractures requires attention to women with osteopenia, as well as osteoporosis, because over half of the fragility fractures in the population arise in these individuals, and women with osteopenia plus a prevalent fracture have the same fracture risk as women with osteoporosis.

Aged↗
PubMed2006

Compliance with osteoporosis drug therapy and risk of fracture.

INTRODUCTION: Patient compliance with osteoporosis drug therapy is often poor in clinical practice and may be associated with higher risk of fracture. METHODS: A nested case-control study was undertaken using a US health insurance claims database. The source population included all women aged >or=45 years who began drug therapy for osteoporosis. Cases consisted of those who experienced an osteoporosis-related fracture; they were matched to controls without osteoporosis-related fracture. Compliance with osteoporosis drug treatment was assessed in terms of the number of therapy-days received and medication possession ratio (MPR). Conditional logistic regression was employed to examine the relationship between compliance and fracture risk. RESULTS: A total of 453 women with osteoporosis-related fracture were identified and matched to 2,160 controls. Fracture risk was significantly lower for patients with >180 days of therapy [181-360 days: odds ratio (OR) = 0.70, 95% CI = 0.49-0.99; >360 days: OR = 0.65, 95% CI = 0.43-0.99) versus those with or=90% (OR = 0.70, 95% CI = 0.52-0.93) versus those with MPR <30%. Fracture risk decreased as compliance increased (p(trend) < 0.05). CONCLUSION: Among women initiating drug therapy for osteoporosis, better compliance is associated with reduced risk of fracture.

Aged↗
PubMed2001

A prospective evaluation of the awareness, knowledge, risk factors and current treatment of osteoporosis in a cohort of elderly subjects.

This was a prospective cohort study of 145 seniors attending a senior's clinic and social day program using a self-administered questionnaire. Its objective was to evaluate the awareness, knowledge, risk factors and current treatment of osteoporosis in our two patient groups. A secondary objective was to determine differences between the two cohorts, and between men and women. Participants included 39 men and 106 women, with an average age of 76 years. Of these, 89% were aware of osteoporosis and 61% gave the correct definition. Awareness and accurate definition were less in men compared with women (p < 0.01, and p < 0.05) and clinic compared to day program groups (p < 0.01). Only 54% of men knew osteoporosis could affect them. Television, newspapers and friends were identified as the main source of information. Physicians ranked as fifth as a source of information. In all, 84% knew diet was important. Prevalence of risk factors other than age were < 20%, except for senescence (38%) and alcohol use (40%). Utilization of specific therapies for osteoporosis was only 18% overall with a rate of 3% in men (p < 0.01). In women, 50% and were taking calcium supplements compared with 15% men (p < 0.001) and for multivitamins the figures were 57% and 33% respectively (p < 0.05). These results show a high level of awareness and correct definition of osteoporosis in this cohort of patients. Specific therapy for prevention or treatment of osteoporosis was inappropriately low in the face of high risk. This study highlights the care gap in osteoporosis in seniors and the need for increased physician involvement in patient education and treatment. Proactive treatment requests from patients need to be encouraged, especially with the future demographic shift.

Absorptiometry, Photon↗
PubMed2001

Bone mineral density of the spine, hip and distal forearm in representative samples of the Japanese female population: Japanese Population-Based Osteoporosis (JPOS) Study.

Low bone mineral density (BMD) is one of the most important elements for the diagnosis of osteoporosis and screening people with higher risk of fractures. To establish the criterion value of BMD for the diagnosis of osteoporosis and to estimate the prevalence rate of osteoporosis in Japanese women, we performed a Japanese population-based osteoporosis (JPOS) study. The subjects were 4550 women aged 15 through 79 years randomly selected from seven municipalities throughout Japan. The sample size was determined to ensure that the observed mean BMD would remain within 2.5% from the real value with a probability of 0.95 in each of the 5-year age groups. The study comprised bone mass measurements by dual-energy X-ray absorptiometry at the spine (L2-4), hip and distal forearm, body size measurements and detailed interviews on medical and gynecologic history. After excluding those subjects with apparent or suggested abnormalities affecting bone mass from 3985 women (87.6%) who completed the study, 3465 women remained and served as the subjects. We present 5-year age-specific mean values of BMD and cut-off values for the diagnosis of osteoporosis according to World Health Organization (WHO) and the Japanese Society of Bone and Mineral Research (JSBMR) criteria. The cut-off levels at the spine and the distal radius proposed in this study were similar to those proposed by the JSBMR but the cut-off level at the femoral neck in this study was 4.7% higher than that of the JSBMR. The prevalence rates of osteoporosis according to WHO criteria in the present subjects aged 50 through 79 years were calculated as 38.0% at the spine, 11.6% at the femoral neck and 56.8% at the distal one-third site of the radius, and those in the Japanese female population of the same age were estimated to be 35.1%, 9.4% and 51.2%, respectively. A fivefold difference was observed among the prevalence rates at different skeletal sites, which suggests that the different definitions of osteoporosis should be established for the different skeletal sites. The prevalence rate diagnosed at the femoral neck seemed to be lower in the present study than those reported for Caucasians. This might account for a lower incidence rate of hip fracture in Japanese women.

Absorptiometry, Photon↗
PubMed2002

Evaluation of osteoporosis treatment in seniors after hip fracture.

A retrospective chart review was carried out on all consecutive patients over 65 years of age admitted to a tertiary care teaching hospital with a diagnosis of a new hip fracture. A further chart review occurred after discharge from post-surgery rehabilitation. The primary objective was to evaluate the prevalence of osteoporosis diagnosis and treatment in both phases of the study. Secondary objectives included evaluation of the mortality rates, length of stay, prevalence of osteoporosis investigation, and prevalence of osteoporosis diagnosis based on the clinical subspecialty involved. There were 311 patients evaluated in the initial phase, and 226 after rehabilitation. The mortality rate was 5.8% (10% for men, 4% for women; p<0.005) in the acute care hospital and 9.3% (8% men, 10% women) during rehabilitation. Previous hip fracture occurred in 17.4%, and 1.5% were readmitted during the study period with fracture of the opposite hip. Osteoporosis was diagnosed in the acute care hospital on admission in 11.9% and on discharge in 15.4%. In the rehabilitation hospital it was diagnosed in 9.7% on admission and 11.2% on discharge (p=NS). Osteoporosis treatment (including calcium or vitamin D therapy) was instituted in 13% on admission to acute care and in 9.7% at the time of discharge. For the rehabilitation hospital, treatment occurred in 12.8% on admission and 10.2% on discharge. The diagnosis of osteoporosis significantly increased the prevalence of treatment (p<0.001). Use of specific agents (hormone replacement therapy, bisphosphonates or calcitonin) occurred in <66% of all patients. Osteoporosis is under-diagnosed and under-treated in this group of elderly hip fracture patients. It is associated with significant mortality and morbidity and every effort should be made to prevent future fractures. Physicians in the 'front line' of hip fracture treatment are missing this key aspect of management in their patients. Education of these physicians, as well as the public, may be the key to addressing this care gap.

Aged↗
PubMed2002

Age-related bone mineral density, accumulated bone loss rate and prevalence of osteoporosis at multiple skeletal sites in chinese women.

We investigated the age-related bone mineral density (BMD), accumulated bone loss rate (ABLR) and the prevalence of osteoporosis at different skeletal sites in Chinese women. BMD was measured at the anteroposterior (AP) spine, supine lateral spine (areal BMD at the midarea [mLat] and the whole region [Lat], volumetric BMD at the middle region [MVD] and total region [TVD]), hip (femoral neck [FN], trochanter [Troc] and Ward's triangle [Ward's]) and forearm (radius + ulna ultradistal [RUUD], 1/3 region [RU1/3] and total region [RUT]) using a dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) in 2702 females aged from 5 to 96 years old. Data were analyzed by eight different regression models. We found that the cubic regression model was the best for describing age-related changes in BMD. The coefficients of determination ( R(2)) of the fitting curve were 0.398 to 0.612 ( p = 0.000). The data were then analyzed by 5-year age groups. This showed that the earliest peak BMD was at the age of 20-24 years at Troc and Ward's, and the latest at the age of 40-44 years at RU1/3 and RUT of the distal forearm. Compared with BMD, the ABLRs were highest at Ward's (-66.2%) and the lowest at RU1/3 of the distal forearm (-31.3%) in subjects over 80 years old. The prevalence of osteoporosis at at least one site in these women was 0.5 +/- 0.4% in those 30-39, 4.6 +/- 4.4% in those 40-49, 23.9 +/- 13.3% in those 50-59, 56.3 +/- 20.3% in those 60-69, 71.8 +/- 16.7% in those 70-79 and 83.2 +/- 12.1% those over 80 years of age, respectively. The prevalence of osteoporosis in these women was 8.6-11.1% at the age of 40-49 and 36.5-40.6% at the age of 50-59 at the lateral spine regions (mLat, Lat, MVD and TVD), and 0.5-3.7% at the age of 40-49 and and 3.9-21.7% at the age of 50-59 years at the other skeletal sites (AP, FN, Troc, Ward's, RUUD, RU1/3 and RUT). Significant differences were found in the prevalence of osteoporosis between the lateral spine regions and other skeletal sites ( p<0.001) at the age of 40-59 years. In summary, we demonstrated significant age-related differences in peak BMD, ABLR and osteoporosis prevalence among various skeletal sites. Our data suggest that the supine lateral spine is the most sensitive site for the diagnosis of osteoporosis, especially in the early menopausal period, although the prevalence of osteoporosis varied with age and with different sites measured.

Absorptiometry, Photon↗
PubMed1997

Correlation between vitamin D receptor genotypes and bone mineral density in Japanese patients with osteoporosis.

In order to better understand the pathogenesis of osteoporosis, we investigated the correlation between the vitamin D receptor (VDR) genotypes defined by BsmI restriction enzyme, as well as other related factors, and the bone mineral density (BMD) at the lumbar spine in 90 Japanese patients with osteoporosis. The same study was performed in 36 patients with osteoarthrosis of the hip joint and 92 healthy volunteers. The majority of the VDR genotypes were bb, and a few of the population showed either the BB or Bb genotype in all three groups. There was no statistical difference in the frequencies of these VDR genotypes in the three groups. The mean age-matched value of BMD (Z scores) at the lumbar spine in patients with osteoporosis was significantly lower than that in patients with osteoarthrosis or healthy volunteers. The mean Z scores of the healthy volunteers with bb genotype were significantly higher than those with BB genotype, whereas those of the osteoporosis patients with BB genotype were significantly higher than those with Bb genotype. There was no significant difference in the mean Z scores between bb and Bb genotypes in patients with osteoporosis and healthy volunteers. No significant difference was seen in the mean Z scores in patients with osteoarthrosis regardless of genotype. On the other hand, body weight significantly correlated with BMD in patients with osteoporosis by simple- and multiple-regression analysis. These results indicate that the BMD at the lumbar spine in Japanese patients with osteoporosis is affected by body weight, and might be affected partially by the VDR genotypes defined by BsmI.

Adult↗
PubMed1998

Osteoporosis and coronary atherosclerosis in asymptomatic postmenopausal women.

Estrogen deficiency is a risk factor for osteoporosis and coronary artery disease. Osteoporosis can be evaluated by measuring bone mineral density (BMD). Coronary atherosclerotic burden can be evaluated by measuring coronary calcium using electron beam computed tomography (EBT) of the heart. We compared coronary calcium scores in 45 asymptomatic postmenopausal women with normal and low BMD. BMD of the lumbar spine and proximal femur was measured by dual X-ray absorptiometry (DXA), and coronary calcium was measured quantitatively by EBT. Women were divided into control, osteopenia, and osteoporosis groups based on the T score of the lumbar spine. Women were similar in age, years since menopause, height, weight, and body mass index (BMI). BMD +/- SD (g/cm2) of L1-L4 was 0.96 +/- 0.11, 0.83 +/- 0.03, and 0.73 +/- 0.05, in control, osteopenia, and osteoporosis group, respectively. The total coronary calcium score +/- SD (relative units) was 41.9 +/- 83.1, 115.1 +/- 181.9, and 221.7 +/- 355.4 for control, osteopenia, and osteoporosis group, respectively; the score was significantly higher in the osteoporosis than in the control group. This study provides initial data suggesting that women with osteoporosis may have a higher risk of developing coronary atherosclerosis.

Absorptiometry, Photon↗
PubMed2001

Treatment of osteoporosis among older adults discharged from hospital in Italy.

OBJECTIVE: Osteoporosis and its complications represent one of the most important causes of morbidity and mortality among the elderly. Despite the availability of several drugs deemed effective at reducing the incidence of fractures, only a minority of patients receive pharmacological treatment. We studied patients with a diagnosis of osteoporosis at discharge from hospital in Italy to identify predictors of receiving specific pharmacological treatment and to analyse how the pattern of drug prescription has changed in the last decade. METHODS: We analysed data from a multicentre pharmacoepidemiology study that collected data on hospitalised patients throughout Italy. Patients with a diagnosis of osteoporosis admitted during five different surveys in 1988, 1991, 1993, 1995 and 1997 were considered for the present study. RESULTS: Of 863 patients with a diagnosis of osteoporosis, 461 (53.4%) received treatment. Age [odds ratio (OR) 0.86 for each decade of increment, 95% confidence interval (CI) 0.73, 0.99], male gender (OR 0.67, 95% CI 0.44, 0.99), number of comorbid conditions (4-5 vs. 0-3 conditions: OR 0.66, 95% CI 0.47, 0.91; 6 or more vs. 0-3 conditions: OR 0.47, 95% CI 0.31, 0.72) and number of medications (OR 0.92 for each drug increase, 95% CI 0.85, 0.99) were all associated with a reduced likelihood of receiving pharmacological treatment for osteoporosis. In contrast, concomitant corticosteroid use (OR 2.00, 95% CI 1.05, 3.80), admission for hip or vertebral fracture (OR 2.10, 95% Cl 1.12, 3.93) and year of survey (OR 1.11, 95% CI 1.01, 1.24) were independent predictors of a higher treatment rate. Among individual drugs, calcitonin use remarkably declined from 42.1% in 1988 to 0.8% in 1997 (P for trend <0.001), while bisphosphonate prescriptions increased from 1.3% in 1988 to 34.9% in 1997 (P for trend <0.001). Prescription of calcium did not change significantly throughout the decade examined, while vitamin D had a twofold increase (14.2% in 1988 to 26.2% in 1997, P for trend <0.001). CONCLUSIONS: Among patients discharged from hospital in Italy, osteoporosis is an uncommon diagnosis. Even when the diagnosis is made, osteoporosis is often undertreated, and treatment is reserved for younger and less medically complex patients.

Aftercare↗
PubMed2004

Development and validation of the osteoporosis prescreening risk assessment (OPERA) tool to facilitate identification of women likely to have low bone density.

Osteoporosis and its consequent increase in fracture risk is a major health concern for postmenopausal women and older men and has the potential to reach epidemic proportions. The "gold standard" for osteoporosis diagnosis is bone densitometry. However, economic issues or availability of the technology may prevent the possibility of mass screening. The goal of this study was to develop and validate a clinical scoring index designed as a prescreening tool to help clinicians identify which women are at increased risk of osteoporosis [bone mineral density (BMD) T-score -2.5 or less] and should therefore undergo further testing with bone densitometry. Records were analyzed for 1522 postmenopausal females over 50 years of age who had undergone testing with dual-energy X-ray absorptiometry (DXA). Osteoporosis risk index scores were compared to bone density T-scores. Hologic QDR 4500 technology was used to measure BMD at the femoral neck and lumbar spine (L1-L4). Participants who had a previous diagnosis of osteoporosis or were taking bone-active medication were excluded. Receiver-operating characteristic (ROC) analysis was used to identify the specific cutpoint value that would identify women at increased risk of low BMD. A simple algorithm based on age, weight, history of previous low impact fracture, early menopause, and corticosteroid therapy was developed. Validation of this five-item osteoporosis prescreening risk assessment (OPERA) index showed that the tool, at the recommended threshold (or cutoff value) of two, had a sensitivity that ranged from 88.1 [95% confidence interval (CI) for the mean: 86.2-91.9%] at the femoral neck to 90% (95% CI for the mean: 86.1-93.1%) at the lumbar spine area. Corresponding specificity values were 60.6 (95% CI for the mean: 57.9-63.3%) and 64.2% (95% CI for the mean: 61.4-66.9%), respectively. The positive predictive value (PPV) ranged from 29 at the femoral neck to 39.2% at the lumbar spine, while the corresponding negative predictive values (NPVs) reached 96.5 and 96.2%, respectively. Based on this cutoff value, the area under the ROC curve was 0.866 (95% CI for the mean: 0.847-0.882) for the lumbar spine and 0.814 (95% CI for the mean: 0.793-0.833) for the femoral neck. We conclude that the OPERA is a free and effective method for identifying Italian postmenopausal women at increased risk of osteoporosis. Its use could facilitate the appropriate and more cost-effective use of bone densitometry in developing countries.

Absorptiometry, Photon↗
PubMed1985

Prevention and treatment of sciatic denervation disuse osteoporosis in the rat tibia with capacitively coupled electrical stimulation.

Osteoporosis in the sciatic-denervated rat tibia was both prevented and reversed with a capacitively coupled electrical field. In both the prevention of the development of osteoporosis and the reversal of a previously established osteoporosis, a statistically significant enhancement of wet weight, dry weight, ashed weight, ultimate strength, cortical area, cortical thickness, and a concomitant decrease in cortical porosity occurred in the stimulated, denervated tibiae of the experimental animals compared with the nonstimulated, denervated tibiae of the control animals. These effects exhibited dose-response characteristics. A 60 kHz symmetrical sinewave signal was effective in preventing osteoporosis at a range of 5-10 peak-to-peak, and it was effective in reversing osteoporosis at 10 V peak-to-peak. Reversal of a well-established osteoporosis in laboratory animals has not been reported previously. Continued investigation into the use of a capacitively coupled electrical field in the prevention and treatment of osteoporosis seems warranted from these studies.

Animals↗
PubMed1988

The direct medical costs of osteoporosis for American women aged 45 and older, 1986.

Annual direct medical costs of osteoporosis incurred by American women aged 45 and older are estimated at $5.2 billion in 1986. Costs are stratified by type of care (inpatient hospital, nursing home and outpatient) and by age group (ages 45 to 59, 60 to 74 and 75 and older). Survey data from the National Center for Health Statistics are combined with census data to project utilization estimates from the survey years to 1986. A portion of all health care encounters for diagnoses secondary to osteoporosis are considered to be caused by osteoporosis according to age- and diagnosis-specific attribution weights. These weights are derived from the opinion of a panel of osteoporosis experts. For inpatient hospitalization, the assigned diagnosis related group (DRG) is used to further specify osteoporosis as the cause of hospitalization. The cost components of osteoporosis care for American women in 1986 are inpatient care, $2.8 billion; nursing home care, $2.1 billion; and outpatient care, $0.2 billion. Study results suggest considerable potential future cost-savings of osteoporosis prevention and abatement.

Age Factors↗
PubMed2004

Sex hormone-binding globulin, estradiol, and bone turnover markers in male osteoporosis.

The role of estrogen deficiency in male osteoporosis is still under discussion. One hundred five subjects, 65 of them suffering from osteoporosis (mean age, 53.9 years) and 40 age-matched controls were studied. Osteoporosis was defined by a T score < -2.5 in the lumbar spine or at the femoral neck. Forty-one (63.1%) of the subjects had a history of low-energy fractures, involving vertebrae in 33 cases (50.8%). Osteoporosis was considered to be idiopathic in 33 subjects (50.8%) for whom no etiology could be found. We measured levels of total estradiol (pg/ml, with a detection threshold of 4 pg/ml), total testosterone (ng/ml), and their carrier protein, that is, sex hormone-binding globulin (SHBG, pmol/ml). Various markers of bone remodeling were also measured. Two of them provide an estimate of bone formation-osteocalcin (OC) and bone alkaline phosphatase (BAP). Two others evaluate bone resorption-procollagen type I C-terminal telopeptide (ICTP) and serum C-telopeptide of type I collagen (sCTX). There was no significant difference in estradiol levels between controls and osteroporosis patients. We did not find any significant correlation between estradiol levels and spinal bone mineral density (BMD) (r = 0.15, P > 0.05), and the relationship between estradiol levels and BMD at the femoral neck was weak (r = 0.25, P < 0.05). On the other hand, SHBG was significantly higher in the osteoporotic patients than in controls (P < 0.01). This difference persisted after adjustment for body mass index (BMI) and after exclusion of patients with a condition known to increase SHBG levels. Moreover, this carrier protein was negatively correlated with BMD at the femoral neck (r = -0.37, P < 0.01) and at the lumbar spine (r = -0.27, P < 0.05). SHBG also correlates strongly with sCTX (r = 0.37, P < 0.01). Finally, logistic regression analysis showed that serum SHBG concentration was significantly associated with the presence of fractures; the odds ratio of having a fracture was 2.04 [95% confidence interval (CI) 1.2-3.4, P < 0.01] for each increase of 1 standard deviation (SD) in the patient's SHBG level. The stronger relationship was nearly the same for the whole group and for patients with idiopathic osteoporosis. This study therefore suggests that SHBG may play a key role in male patients with idiopathic or secondary osteoporosis. It shows that serum SHBG concentration is increased in middle-aged men with osteoporosis and is correlated with hip, spine BMD, and sCTX levels. Finally, our findings are in agreement with previous studies which suggest that serum SHBG is a new biological marker of fracture risk in men.

Adult↗
PubMed2006

Multilocus analysis of estrogen-related genes in Spanish postmenopausal women suggests an interactive role of ESR1, ESR2 and NRIP1 genes in the pathogenesis of osteoporosis.

Osteoporosis is a common disease with multiple environmental and genetic risk factors involved. Using a marker-by-marker approach, the role of different estrogen-related genes has been analyzed in different populations, but most of these studies ignore the complex multigenic nature of human osteoporosis. Looking for markers related to osteoporosis, we have analyzed five single nucleotide polymorphisms located in genes related to the estrogen pathway, Follicle Stimulating Hormone Receptor (FSHR) gene, the CYP19 aromatase (CYP19A1) gene, the Estrogen Receptor alpha (ESR1) gene, the Estrogen Receptor beta (ESR2) gene and the Nuclear Receptor Interacting Protein 1 (NRIP1) gene in 265 unrelated postmenopausal women. We have obtained nominal P values for the NRIP1 Gly75Gly and ESR2 *39A>G markers (P=0.013 and P=0.02 respectively), but no gene seems to be associated after multiple test corrections. Reanalysis of this study using 437 postmenopausal women confirmed our results and only detect marginal effects for ESR2 marker (P=0.045). By contrast, multilocus analysis predicted epistatic interactions between ESR1, ESR2 and NRIP1 loci and its involvement in postmenopausal osteoporosis (P=0.003). We detected two digenic genotypes involving ESR2-NRIP1 and ESR2-ESR1 genes strongly associated with osteoporosis (P=0.007). Replication of multilocus studies using 437 patients confirmed the detected interactions (P<0.01). We proposed a non-additive non-multiplicative oligogenic model including ESR2 AG genotype modulated by NRIP1 A+ or ESR1 TT genotypes involved in osteoporosis. Our results reaffirm the polygenic nature and the genetic complexity of osteoporosis trait adding a new candidate gene (NRIP1) for association studies of bone-related traits.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Gene expression profiling of bone marrow stromal cells from juvenile, adult, aged and osteoporotic rats: with an emphasis on osteoporosis.

PURPOSE: Osteoporosis is a multi-factorial, age-related disease with a complex etiology and mode of regulation involving a large numbers of genes. To better understand the possible relationships among genes, we fingerprinted genes in a rat model induced by ovariectomy to determine differences among osteoporotic, non-osteoporotic, aged and juvenile rats. METHODS: We applied genome wide cDNA microarray technology to analyze genes expressed in bone marrow mesenchymal stromal cells (BMSC) and compared non-osteoporotic adult vs. osteoporotic, non-osteoporotic adult vs. aged, and non-osteoporotic adult vs. juvenile. Rigorous statistical analysis of functional annotation (EASE program) identified over-represented biological and molecular functions with significant group wide changes (p< or =0.05). Some of the expressed genes were further confirmed by quantitative RT-PCR (reverse transcription-polymerase chain reaction). RESULTS: Differences in gene expression were observed by identifying transcripts selected by t-test that were consistently changed by a minimum of two-fold. There were 195 transcripts that showed an increased expression and 109 transcripts that showed decreased expression relative to the osteoporotic condition. Of these, 75% transcripts were unknown gene products or ESTs (expressed sequence tag). A number of genes found in the aged and juvenile groups were not present in the osteoporotic rats. Functional clustering of the genes using the EASE bioinformatics program revealed that transcripts in osteoporosis were associated with signal transduction, lipid metabolism, protein metabolism, ionic and protein transport, neuropeptide and G protein signaling pathways. Although some of the genes have previously been shown to play a key role in osteoporosis, several genes were uniquely identified in this study and likely play a role in developing aged related osteoporosis that could have compelling implications in the development of new diagnostic strategies and therapeutics for osteoporosis. CONCLUSIONS: These data suggest that osteoporosis is associated with changes of multiple novel gene expression and that numerous pathways could play important roles in osteoporosis pathogenesis.

Age Factors↗
PubMed2005

Prevention of osteoporosis in glucocorticoid-treated neurology patients.

OBJECTIVES: Iatrogenic, including corticosteroid-induced osteoporosis is preventable with administration of osteoprotective biphosphonates. The best medical practice is published in the National Guidelines: UK Osteoporosis Consensus Group (1998, update 2002). We conducted an audit in prednisolone-treated general neurology patients, to assess compliance to national guidelines, raise awareness of osteoporosis prevention, and improve clinical practice in a tertiary neurology referral centre. METHODS AND RESULTS: Preintervention: Of the 48 cases (21 male) identified twenty-nine (61%) received osteoporosis prophylaxis. Nineteen (40%) were given biphosphonates, while 10 (21%) hormone replacement therapy or calcium and Vitamin D. INTERVENTION: Results were presented to the consultant body. Postintervention: Data were collected prospectively on 48 patients (30 male) in year 2001. Thirty-eight (79%) received prophylaxis: 35 (73%) were started on biphosphonates, while 3 (6%) on calcium and Vitamin D. This process was repeated 2 years later to assess sustainability. Of the 48 patients, 44 (92%) received prophylaxis: 41 (86%) were taking biphosphonates, while 3 (6%) calcium and Vitamin D. CONCLUSION: We present an original and complete audit on osteoporosis prophylaxis in a typical population of neurology patients. Though initial results were similar to previous reports, our audit led to significant improvement in clinical practice. National guidelines could not be followed meticulously, as our centre has no regular access to bone densitometry. Our patient population had other risk factors for osteoporosis apart from steroid use. Therefore, we recommend that neurologists in this setting use osteoporosis prophylaxis for all their patients on long-term corticosteroids.

Adult↗