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Biomedical subjects

D Felsenberg

Publications and source records attributed to D Felsenberg.

At least 19 recordsLinked to original sources
PubMed2006

Geographic and other determinants of BMD change in European men and women at the hip and spine. a population-based study from the Network in Europe for Male Osteoporosis (NEMO).

INTRODUCTION: While the determinants of BMD change have been studied in women, there have been few longitudinal studies in men. As part of the Network in Europe for Male Osteoporosis (NEMO) study, data were analysed from 1337 men and 1722 women aged 50-86y (mean=67 years) from 13 centres across Europe to assess determinants of BMD change and between-gender contrasts. METHODS: BMD was measured at the femoral neck, trochanter and/or L2-L4 spine on 2 occasions 0.8-8 years apart (mean=3.5 years) using DXA densitometers manufactured by Hologic (n=6), Lunar (n=5) and Norland (n=2). Each was cross-calibrated using the European Spine Phantom and annual rates of BMD change (g/cm(2)/year) were calculated from the standardised paired BMD values. The EPOS risk factor questionnaire was administered at baseline. RESULTS: In multivariate linear regression models, there were large between centre differences in the mean rates of BMD change in all 3 sites for both genders (P<0.0001) with the standard deviation of the between centre heterogeneity in the adjusted means being 0.005 g/cm(2)/year at the femoral neck. The overall adjusted mean annual rates of BMD change in g/cm(2)/year (95% CI) pooled across centres by random effects meta-analysis in men were: femoral neck -0.005 (-0.009, -0.001); trochanter -0.003 (-0.006, -0.001); and spine 0.000 (-0.004, 0.004). In women the respective estimates were: -0.007 (-0.009, -0.005); -0.004 (-0.006, -0.003); and -0.005 (-0.008, -0.001). The I(2) statistic for heterogeneity was between 81% and 94%, indicating strong evidence of between centre heterogeneity. Higher baseline BMD value was associated with subsequent greater decline in BMD (P<0.001). Preserved BMD was associated with higher baseline body weight in all 3 sites in men (P<0.012) but not in women. Weight gain preserved BMD (P<0.039) in all 3 sites for both genders, except the male spine. Increasing age was associated with faster BMD decline at the trochanter in both genders (P<0.026) and with a slower rate of decline at the female spine (P=0.002). Effects of lifestyle, physical activity, medications, and reproductive factors were not consistent across sites or between genders. CONCLUSION: These results show major geographic variations in rates of BMD change in men and women over 50 years of age across diverse European populations and demonstrate that body weight and weight gain are key determinants of BMD change in men.

Absorptiometry, Photon↗
PubMed2006

Epidemiology, treatment and costs of osteoporosis in Germany--the BoneEVA Study.

INTRODUCTION: In Germany, accurate data on the prevalence and treatment of osteoporosis, as well as the cost of this illness, are not available. The aim of this study is to give a valid estimation of these items for the year 2003. METHODS: Routine data from a German sickness fund covering 1.5 million beneficiaries and billing data for outpatient visits were used to obtain estimates of prevalence for osteoporosis. Claims data for patients with osteoporosis (M80, M81) or an osteoporosis-related fracture diagnosis (S22, S32, S42, S52, S72, S82) or treatment with anti-osteoporosis drugs were examined. Costs were calculated from the perspective of the German health insurance system and the German nursing care insurance system, respectively. Only direct costs of osteoporosis were considered. RESULTS: In 2003, 7.8 million Germans (6.5 million women) were affected by osteoporosis. Of them, 4.3% experienced at least one clinical fracture. Only 21.7% were treated with an anti-osteoporosis drug. The total direct costs attributable to osteoporosis amounted to euros 5.4 billion. CONCLUSION: This study confirms that osteoporosis is underdiagnosed, undertreated and imposes a considerable economic burden on the health system in Germany. Effective strategies for the prevention and management of this disease are needed.

Age Distribution↗
PubMed2006

Whom to treat? The contribution of vertebral X-rays to risk-based algorithms for fracture prediction. Results from the European Prospective Osteoporosis Study.

INTRODUCTION: Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5-20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age. METHODS: Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models. RESULTS: In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010). CONCLUSION: We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.

Age Factors↗
PubMed2006

Strength, size and activation of knee extensors followed during 8 weeks of horizontal bed rest and the influence of a countermeasure.

Changes in the quadriceps femoris muscle with respect to anatomical cross sectional area (CSA), neural activation level and muscle strength were determined in 18 healthy men subjected to 8 weeks of horizontal bed rest (BR) with (n = 9) and without (n = 9) resistive vibration exercise (RVE). CSA of the knee extensor muscle group was measured with magnetic resonance imaging every 2 weeks during bed rest. In the control subjects (Ctrl), quadriceps femoris CSA decreased linearly over the 8 weeks of bed rest to -14.1 +/- 5.2% (P < 0.05). This reduction was significantly (P < 0.001) mitigated by the exercise paradigm (-3.5 +/- 4.2%; P < 0.05). Prior to and seven times during bed rest, maximal unilateral voluntary torque (MVT) values of the right leg were measured together with neural activation levels by means of a superimposed stimulation technique. For Ctrl, MVT decreased also linearly over time to -16.8 +/- 7.4% after 8 weeks of bed rest (P < 0.01), whereas the exercise paradigm fully maintained MVT during bed rest. In contrast to previous reports, the maximal voluntary activation remained unaltered for both groups throughout the study. For Ctrl, the absence of deterioration of the activation level might have been related to the repeated testing of muscle function during the bed rest. This notion was supported by the observation that for a subset of Ctrl subjects (n = 5) the MVT of the left leg, which was not tested during BR, was reduced by 20.5 +/- 10.1%, (P < 0.01) which was for those five subjects significantly (P < 0.05) more than the 11.1 +/- 9.2% (P < 0.01) reduction for the right, regularly tested leg.

Adult↗
PubMed2006

Relationship between risk factors and QUS in a European Population: The OPUS study.

There are many risk factors associated with low bone mineral density. Quantitative ultrasound (QUS) is a generally accepted method for measurement of bone and has been shown to be strongly associated with future fracture risk. The Osteoporosis and Ultrasound Study (OPUS) is a multi-centre European wide study examining 5 different QUS scanners (4 calcaneal, 1 finger device). The aim of this paper was to examine the relationship between risk factors (as assessed by questionnaire) and QUS measurements. 449 younger women (aged 20 to 39 years) and 2283 older women (aged 55 to 79 years) were included in this analysis. As expected, those with a self-reported previous fracture had lower QUS measurements than those without (P < 0.001). However, no significant difference was seen between those reporting a maternal hip fracture and those who did not report such an event. Differences were found for smokers vs. non-smokers for SOS but not for BUA measurements. Weight was positively correlated with all BUA variables but only with some SOS variables. We determined which risk factors were most strongly associated with QUS measurements by using step-wise multiple regression. Models for each QUS measurement were calculated, and the R2 values ranged from 0.18 to 0.28 for SOS, 0.27 to 0.32 for BUA and 0.31 to 0.42 for the finger QUS device. The most common risk factors across all models were age, use of hormone replacement therapy, self-reported previous fracture, self-reported diagnosis of osteoporosis, current weight, pulse rate and self-reported estimated height at age 20 years. We analysed relationships across the 5 centres and detected some geographical differences in the prevalence of the risk factors. In conclusion, similar relationships are seen with QUS measurements as are found for bone mineral density. However, the strength of the association is dependent on the type of QUS device and variable measured.

Adult↗
PubMed2006

Highly demanding resistive vibration exercise program is tolerated during 56 days of strict bed-rest.

Several studies have tried to find countermeasures against musculoskeletal de-conditioning during bed-rest, but none of them yielded decisive results. We hypothesised that resistive vibration exercise (RVE) might be a suitable training modality. We have therefore carried out a bed-rest study to evaluate its feasibility and efficacy during 56 days of bed-rest. Twenty healthy male volunteers aged 24 to 43 years were recruited and, after medical check-ups, randomised to a non-exercising control (Ctrl) group or a group that performed RVE 11 times per week. Strict bed-rest was controlled by video surveillance. The diet was controlled. RVE was performed in supine position, with a static force component of about twice the body weight and a smaller dynamic force component. RVE comprised four different units (squats, heel raises, toe raises, kicks), each of which lasted 60 - 100 seconds. Pre and post exercise levels of lactate were measured once weekly. Body weight was measured daily on a bed scale. Pain questionnaires were obtained in regular intervals during and after the bed-rest. Vibration frequency was set to 19 Hz at the beginning and progressed to 25.9 Hz (SD 1.9) at the end of the study, suggesting that the dynamic force component increased by 90 %. The maximum sustainable exercise time for squat exercise increased from 86 s (SD 21) on day 11 of the BR to 176 s (SD 73) on day 53 (p = 0.006). On the same days, post-exercise lactate levels increased from 6.9 mmol/l (SD2.3) to 9.2 mmol/l (SD 3.5, p = 0.01). On average, body weight was unchanged in both groups during bed-rest, but single individuals in both groups depicted significant weight changes ranging from - 10 % to + 10 % (p < 0.001). Lower limb pain was more frequent during bed-rest in the RVE subjects than in Ctrl (p = 0.035). During early recovery, subjects of both groups suffered from muscle pain to a comparable extent, but foot pain was more common in Ctrl than in RVE (p = 0.013 for plantar pain, p = 0.074 for dorsal foot pain). Our results indicate that RVE is feasible twice daily during bed-rest in young healthy males, provided that one afternoon and one entire day per week are free. Exercise progression, mainly by progression of vibration frequency, yielded increases in maximum sustainable exercise time and blood lactate. In conclusion, RVE as performed in this study, appears to be safe.

Adult↗
PubMed2005

Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study.

BACKGROUND: Reducing bisphosphonate dosing frequency may improve suboptimal adherence to treatment and therefore therapeutic outcomes in postmenopausal osteoporosis. Once-monthly oral ibandronate has been developed to overcome this problem. OBJECTIVE: To confirm the 1 year results and provide more extensive safety and tolerability information for once-monthly dosing by a 2 year analysis. METHODS: MOBILE, a randomised, phase III, non-inferiority study, compared the efficacy and safety of once-monthly ibandronate with daily ibandronate, which has previously been shown to reduce vertebral fracture risk in comparison with placebo. RESULTS: 1609 postmenopausal women were randomised. Substantial increases in lumbar spine bone mineral density (BMD) were seen in all treatment arms: 5.0%, 5.3%, 5.6%, and 6.6% in the daily and once-monthly groups (50 + 50 mg, 100 mg, and 150 mg), respectively. It was confirmed that all once-monthly regimens were at least as effective as daily treatment, and in addition, 150 mg was found to be better (p<0.001). Substantial increases in proximal femur (total hip, femoral neck, trochanter) BMD were seen; 150 mg produced the most pronounced effect (p<0.05 versus daily treatment). Independent of the regimen, most participants (70.5-93.5%) achieved increases above baseline in lumbar spine or total hip BMD, or both. Pronounced decreases in the biochemical marker of bone resorption, sCTX, observed in all arms after 3 months, were maintained throughout. The 150 mg regimen consistently produced greater increases in BMD and sCTX suppression than the 100 mg and daily regimens. Ibandronate was well tolerated, with a similar incidence of adverse events across groups. CONCLUSIONS: Once-monthly oral ibandronate is at least as effective and well tolerated as daily treatment. Once-monthly administration may be more convenient for patients and improve therapeutic adherence, thereby optimising outcomes.

Administration, Oral↗
PubMed2005

Oral ibandronate significantly reduces the risk of vertebral fractures of greater severity after 1, 2, and 3 years in postmenopausal women with osteoporosis.

In a recent multinational, double-blind, placebo-controlled, randomized, phase III study (BONE: IBandronate Osteoporosis Vertebral Fracture trial in North America and Europe), oral daily ibandronate (2.5 mg) significantly and substantially reduced the risk of new vertebral fractures by 62% relative to placebo after 3 years of treatment. The objective of the present study was to retrospectively analyze data from the BONE study to examine the efficacy of oral ibandronate in preventing incident vertebral fractures of greater severity. This analysis was conducted on the placebo and oral daily ibandronate (2.5 mg) arms of the BONE study, comprising a total of 1964 women (aged 55-80 years, >or=5 years postmenopause) with osteoporosis. Vertebral fractures on annual lateral radiographs of the spine were graded as mild, moderate, or severe, using criteria derived from an established semiquantitative technique. The findings demonstrate that in addition to being effective in significantly reducing the risk of new vertebral fractures of all severities, oral daily ibandronate has a pronounced effect on the more severe, most clinically relevant, vertebral fractures: a significant and sustained reduction of 59% in the relative risk of combined new moderate and severe vertebral fractures was observed at years 1 (P = 0.0164), 2 (P = 0.0004), and 3 (P < 0.0001).

Administration, Oral↗
PubMed2005

Low grip strength is associated with bone mineral density and vertebral fracture in women.

OBJECTIVES: Grip strength has been reported to be associated with bone mass locally at the forearm and also at distant skeletal sites, including the spine and hip. Less is known about the association between low grip strength and risk of vertebral fracture. The aim of this study was to examine the association between low grip strength, bone mineral density at the hip and spine, and vertebral fracture in middle-aged and elderly European men and women. METHODS: Men and women aged 50 yr and over were recruited for participation in a screening survey of vertebral osteoporosis across Europe. Subjects who agreed to take part had an interviewer-administered questionnaire and lateral spinal radiographs performed. Subjects were assessed also for grip strength using a handgrip dynamometer (range 0-300 mmHg). A subsample of those recruited had bone mineral density measurements performed at the spine and femoral neck. Subjects had repeat lateral spine radiographs performed a mean of 3.8 yr following the baseline survey. Linear regression analysis was used to determine the association between low grip strength and bone mineral density at the hip and spine. Logistic regression was used to determine the association between grip strength and both prevalent and incident vertebral fracture. RESULTS: One thousand two hundred and sixty-five men and 1380 women with data concerning grip strength and bone mineral density were included in the analysis. In women, after age adjustment, compared with those with 'normal' grip, those with 'impaired' (231-299 mmHg) and low grip (<231 mmHg) had significantly lower bone mass at the spine and femoral neck. In men, those with low grip strength had a lower BMD at the spine and hip than those in the normal group. However, because of the small numbers with submaximal grip strength, the confidence intervals around all estimates included zero. Adjustment for body size and levels of physical activity had little effect on the results. In addition, among women, after adjustment for age, body mass index and physical activity levels, compared with those with normal grip, those with low grip strength had an increased risk of developing incident vertebral fracture (odds ratio = 2.67; 95% confidence interval 1.13, 6.30). Further adjustment for spine bone density had little influence on the association (odds ratio = 2.60). CONCLUSIONS: In women, low grip strength is associated with low bone mineral density at both the spine and hip and an increased risk of incident vertebral fracture. These associations cannot be explained by differences in body size or lifestyle.

Absorptiometry, Photon↗
PubMed2005

Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study.

BACKGROUND: Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) study to assess its efficacy and safety in preventing nonvertebral fractures also. METHODS: Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment. FINDINGS: In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture (age > or = 74 yr and femoral neck bone mineral density T score < or = -3, corresponding to -2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture. Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip). Incidence of adverse events (AEs) was similar in both groups. CONCLUSION: This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis.

Aged↗
PubMed2005

Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study.

We have previously shown that center- and sex-specific fall rates explained one-third of between-center variation in upper limb fractures across Europe. In this current analysis, our aim was to determine how much of the between-center variation in fractures could be attributed to repeated falling, bone mineral density (BMD), and other risk factors in individuals, and to compare the relative contributions of center-specific BMD vs. center-specific fall rates. A clinical history of fracture was assessed prospectively in 2451 men and 2919 women aged 50-80 from 20 centers participating in the European Prospective Osteoporosis Study (EPOS) using standardized questionnaires (mean follow-up = 3 years). Bone mineral density (BMD, femoral neck, trochanter, and/or spine) was measured in 2103 men and 2565 women at these centers. Cox regression was used to model the risk of incident fracture as a function of the person-specific covariates: age, BMD, personal fracture history (PFH), family hip fracture history (FAMHIP), time spent walking/cycling, number of 'all falls' and falls not causing fracture ('fracture-free') during follow-up, alcohol consumption, and body mass index. Center effects were modeled by inclusion of multiplicative gamma-distributed random effects, termed center-shared frailty (CSF), with mean 1 and finite variance theta (theta) acting on the hazard rate. The relative contributions of center-specific fall risk and center-specific BMD on the incidence of limb fractures were evaluated as components of CSF. In women, the risk of any incident nonspine fracture (n = 190) increased with age, PFH, FAMHIP, > or =1 h/day walking/cycling, and number of 'all falls' during follow-up (all P < 0.074). 'Fracture-free' falls (P = 0.726) and femoral neck BMD did not have a significant effect at the individual level, but there was a significant center-shared frailty effect (theta = 0.271, P = 0.001) that was reduced by 4% after adjusting for mean center BMD and reduced by 19% when adjusted for mean center fall rate. Femoral trochanter BMD was a significant determinant of lower limb fractures (n = 53, P = 0.014) and the center-shared frailty effect was significant for upper limb fractures (theta = 0.271, P = 0.011). This upper limb fracture center effect was unchanged after adjusting for mean center BMD but was reduced by 36% after adjusting for center mean fall rates. In men, risk of any nonspine fracture (n = 75) increased with PFH, fall during follow-up (P < 0.026), and with a decrease in trochanteric BMD [RR 1.38 (1.08, 1.79) per 1 SD decrease]. There was no center effect evident (theta = 0.081, P = 0.096). We conclude that BMD alone cannot be validly used to discriminate between the risk of upper limb fractures across populations without taking account of population-specific variations in fall risk and other factors. These variations might reflect shared environmental or possibly genetic factors that contribute quite substantially to the risk of upper limb fractures in women.

Accidental Falls↗
PubMed2004

Back pain, disability, and radiographic vertebral fracture in European women: a prospective study.

Vertebral fractures are associated with back pain and disability. There are, however, few prospective data looking at back pain and disability following identification of radiographic vertebral fracture. The aim of this analysis was to determine the impact of radiographically identified vertebral fracture on the subsequent occurrence of back pain and disability. Women aged 50 years and over were recruited from population registers in 18 European centers for participation in the European Prospective Osteoporosis Study. Participants completed an interviewer-administered questionnaire which included questions about back pain in the past year and various activities of daily living, and they had lateral spine radiographs performed. Participants in these centers were followed prospectively and had repeat spine radiographs performed a mean of 3.7 years later. In addition they completed a questionnaire with the same baseline questions concerning back pain and activities of daily living. The presence of prevalent and incident vertebral fracture was defined using established morphometric criteria. The data were analyzed using logistic regression with back pain or disability (present or absent) at follow-up as the outcome variable with adjustment made for the baseline value of the variable. The study included 2,260 women, mean age 62.2 years. The mean time between baseline and follow-up survey was 5.0 years. Two hundred and forty participants had prevalent fractures at the baseline survey, and 85 developed incident fractures during follow-up. After adjustment for age, center, and the baseline level of disability, compared with those without baseline prevalent fracture, those with a prevalent fracture (odds ratio [OR] = 1.4; 95% confidence interval [CI] 1.0 to 2.0) or an incident fracture (OR = 1.7; 95% CI, 0.9 to 3.2) were more likely to report disability at follow-up, though the confidence intervals embraced unity. Those with both a prevalent and incident fracture, however, were significantly more likely to report disability at follow-up (OR = 3.1; 95% CI, 1.4 to 7.0). After adjustment for age, center, and frequency of back pain at baseline, compared with those without baseline vertebral fracture, those with a prevalent fracture were no more likely to report back pain at follow-up (OR = 1.2; 95% CI, 0.8 to 1.7). There was a small increased risk among those with a preexisting fracture who had sustained an incident fracture during follow-up (OR = 1.6; 95% CI, 0.6 to 4.1) though the confidence intervals embraced unity. In conclusion, although there was no significant increase in the level of back pain an average of 5 years following identification of radiographic vertebral fracture, women who suffered a further fracture during follow-up experienced substantial levels of disability with impairment in key physical functions of independent living.

Activities of Daily Living↗
PubMed2004

Efficacy and safety of ibandronate given by intravenous injection once every 3 months.

Oral bisphosphonates are established therapeutics for postmenopausal osteoporosis. Alternative, simplified dosing regimens that improve tolerability and promote convenience may be advantageous. Ibandronate is a highly potent, nitrogen-containing bisphosphonate that can be administered as a convenient intravenous (i.v.) injection (over 15-30 s) in schedules featuring extended between-dose intervals. In a recent fracture prevention study, 1 and 0.5 mg i.v. ibandronate injections, given once every 3 months, were shown to dose-dependently increase lumbar spine and hip bone mineral density (BMD) and decrease biochemical markers of bone turnover in women with postmenopausal osteoporosis, but the overall magnitude of efficacy provided by both doses was suboptimal. In the present study (Intermittent Regimen intravenous Ibandronate Study: the IRIS study), the dose-response relationship with intermittent intravenous ibandronate injections was further evaluated in 520 postmenopausal osteoporotic women (aged 55-75 years, time since menopause >or= 5 years, lumbar spine [L1-L4] BMD T score < -2.5). At enrolment, participants were randomized to receive either 2 mg (n = 261) or 1 mg (n = 131) ibandronate or placebo (n = 128) intravenous injections, given once every 3 months. After 1 year, ibandronate therapy produced substantial and dose-dependent increases in lumbar spine and hip BMD, and decreases in biochemical markers of bone turnover, with the 2 mg dose providing significantly greater efficacy than the 1 mg dose. Most notably, lumbar spine BMD increased by 5.0% and 2.8% in the 2 and 1 mg groups, respectively, and decreased by 0.04% in the placebo group. Furthermore, total hip BMD increased by 2.9%, 2.2%, and 0.6%, respectively. Serum and urinary CTX, reflecting bone resorption, were decreased by 62.5% and 61%, respectively, with the 2 mg dose, and by 43.5% and 42%, respectively, with the 1 mg dose. Intravenous ibandronate was well tolerated with a similar incidence of adverse events to placebo. Importantly, no indicators of renal toxicity were reported. In summary, the 2 mg ibandronate regimen provides significantly greater BMD increases and significantly greater suppression of bone resorption markers than the 1 mg dose used in this study and in the previous fracture prevention study. Ongoing studies aim to further establish the efficacy and convenience of intermittent intravenous ibandronate injections in postmenopausal osteoporosis.

Aged↗
PubMed2004

A 3-year double-blind, randomized, controlled study on the influence of two oral contraceptives containing either 20 microg or 30 microg ethinylestradiol in combination with levonorgestrel on bone mineral density.

In this first prospective, double-blind, randomized, parallel-group study we evaluated the influence of two combined oral contraceptives on bone mineral density (BMD) and metabolic bone parameters. One dose-reduced preparation contained 20 microg ethinylestradiol (EE) in combination with 100 microg levonorgestrel (LNG) (20/100) was compared with the reference preparation which contained 30 microg EE in combination with 150 microg LNG (30/150). Data from 48 volunteers aged 20-35 years were obtained over an observation period of 36 treatment cycles. The direction of the change (increase or decrease) in all investigated bone-related variables was similar in both treatment groups. As compared to baseline, bone mineral density decreased by 0.4% in the 20/100 group and by 0.8% in the 30/150 group after 36 treatment cycles. These changes were not significantly different between the two treatment groups (p = 0.902). For bone-specific alkaline phosphatase, we measured a mean increase of 55.4% (20/100 group) and of 113.2% (30/150 group) after 36 treatment cycles. The two treatments did not differ statistically significantly (p = 0.522). With respect to cross-linked N-telopeptides (NTx), we detected a decrease of the mean NTx urine concentrations of 21.1% (20/100) and of 13.4% (30/150). These changes also did not significantly differ between the two treatments (p = 0.613). Both study treatments were safe and well-tolerated by all volunteers participating in the study. In conclusion, BMD did not change during the 3-year observation period. Thus, both trial preparations containing either 20 or 30 microg EE in combination with LNG were capable of maintaining BMD in young fertile women. There is no reason to assume that the EE dose reduction had any negative impact on BMD. Because there were no differences in BMD between the treatment groups, it can be assumed that even lower dosages than 20 microg EE might be sufficient for bone protection. Biochemical markers provided evidence for a reduced bone resorption.

Adult↗
PubMed2004

Adjusting for the partial volume effect in cortical bone analyses of pQCT images.

Quantitative analyses of computed tomography images are prone to errors due to the partial volume effect which affects objects (e.g., bones) that have a different size or are assessed with different resolution. We have developed a set of equations suitable for both modeling the partial volume effect in cortical bone and for performing the corresponding adjustment. Seven hollow cylinders and 2 cuboid phantoms were made out of Al with 1% Si. The specimens were scanned with a pQCT machine (XCT2002, Stratec Medizintechnik, Pforzheim, Germany) and analyzed with the integrated software, version 5.50. Measurements were performed at different resolutions (voxel size=0.20 to 0.75 mm), both in air and in Ringer solution, and analyses were performed at different detection thresholds. Applying the correcting equations set we could reduce the errors in cortical density by about 80%. The cortical area was assessed with a negligible error at a threshold (theta0) that is equivalent to the mean of the cortical bone density and of the background density. On choosing theta0 as the detection threshold the error in density was lowered to less than 2%. We propose to assess cortical area and cortical density in several steps, first assessing the area and density thereafter. Applying this method should be beneficial whenever "true world" values are required, or objects of different size are compared.

Absorptiometry, Photon↗
PubMed2003

Health-related quality of life and radiographic vertebral fracture.

BACKGROUND: Vertebral fractures are associated with back pain and disability; however, relatively little is known about the impact of radiographic vertebral fractures on quality of life in population samples. The aim of this study was to determine the impact of a recent radiographic vertebral fracture on health-related quality of life (HRQoL). METHODS: Men and women aged 50 years and over were recruited from population registers in 12 European centers. Subjects completed an interviewer-administered questionnaire and had lateral spine radiographs performed. Subjects in these centers were followed prospectively and had repeat spinal radiographs performed a mean of 3.8 years later. Prevalent deformities were defined using established morphometric criteria, and incident vertebral fractures by both morphometric criteria and qualitative assessment. For each incident fracture case, three controls matched for age, gender, and center were selected: one with a prevalent deformity (at baseline) and two without prevalent deformities. All subjects were interviewed or completed a postal questionnaire instrument which included Short Form 12 (SF-12), the EQ-5D (former EuroQol), and the quality of life questionnaire of the International Osteoporosis Foundation (QUALEFFO). The median time from the second spinal radiograph until the quality of life survey was 1.9 years. Comparison between cases and their matched controls was undertaken using the signed rank test. RESULTS: 73 subjects with incident vertebral fracture (cases), mean age 64.8 years (of whom 23 had a baseline deformity), and 196 controls, mean age 63.9 years (of whom 60 had a baseline deformity), were studied. There were strong correlations between the domain scores for each of the three instruments. There was no statistically significant difference in any of the domain scores between cases and those controls with a prevalent deformity. However, compared with the controls without a prevalent deformity the cases had significantly impaired quality of life as determined using the total QUALEFFO score (38.2 vs 33.7), the physical component score of the SF-12 (39.9 vs 43.7) and the health status score of the EQ-5D (62.3 vs 69.9). When the analysis was repeated after stratification of the cases by baseline deformity status (i.e., cases with and without a prevalent deformity at baseline), cases with a prevalent deformity had impaired quality of life compared with their matched controls, both with and without a prevalent deformity. In contrast there was no significant difference in quality of life among the cases without a prevalent deformity and either control group. CONCLUSIONS: In this population-based study a recent vertebral fracture was associated with impairment in quality of life, though this was mainly among those who had sustained a previous vertebral deformity.

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PubMed2003

Determinants of incident vertebral fracture in men and women: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50-79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR = 1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR = 0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies.

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