Showing papers in "Osteoporosis International in 2000"

Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis

Abstract: The purpose of this randomized, double-masked, placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis. The study was conducted at 80 study centers in Europe and Australia. Postmenopausal women (n= 1226) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo; all subjects also received elemental calcium 1000 mg/day, and up to 500 IU/day vitamin D if baseline levels were low. The study duration was 3 years; however, the 2.5 mg group was discontinued by protocol amendment after 2 years. Lateral spinal radiographs were taken annually for assessment of vertebral fractures, and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals. Risedronate 5 mg reduced the risk of new vertebral fractures by 49% over 3 years compared with control (p<0.001). A significant reduction of 61% was seen within the first year (p= 0.001). The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years. The risk of nonvertebral fractures was reduced by 33% compared with control over 3 years (p= 0.06). Risedronate significantly increased bone mineral density at the spine and hip within 6 months. The adverse-event profile of risedronate, including gastrointestinal adverse events, was similar to that of control. Risedronate 5 mg provides effective and well-tolerated therapy for severe postmenopausal osteoporosis, reducing the incidence of vertebral fractures and improving bone density in women with established disease.

Long-Term Risk of Osteoporotic Fracture in Malmö

Abstract: The objectives of the present study were to estimate long-term risks of osteoporotic fractures. The incidence of hip, distal forearm, proximal humerus and vertebral fracture were obtained from patient records in Malmo, Sweden. Vertebral fractures were confined to those coming to clinical attention, either as an inpatient or an outpatient case. Patient records were examined to exclude individuals with prior fractures at the same site. Future mortality rates were computed for each year of age from Poisson models using the Swedish Patient Register and the Statistical Year Book. The incidence and lifetime risk of any fracture were determined from the proportion of individuals fracture-free from the age of 45 years. Lifetime risk of shoulder, forearm, hip and spine fracture were 13.3%, 21.5%, 23.3% and 15.4% respectively in women at the age of 45 years. Corresponding values for men at the age of 45 years were 4.4%, 5.2%, 11.2% and 8.6%. The risk of any of these fractures was 47.3% and 23.8% in women and men respectively. Remaining lifetime risk was stable with age for hip fracture, but decreased by 20-30% by the age of 70 years in the case of other fractures. Ten and 15 year risks for all types of fractures increased with age until the age of 80 years, when they approached lifetime risks because of the competing probabilities of fracture and death. We conclude that fractures of the hip and spine carry higher risks than fractures at other sites, and that lifetime risks of fracture of the hip in particular have been underestimated.

Risk of mortality following clinical fractures

Abstract: To examine the risk of mortality following all clinical fractures, we followed 6459 women age 55-81 years participating in the Fracture Intervention Trial for an average of 3.8 years. All fractures and deaths were confirmed by medical record or death certificate. Clinical fractures were fractures that came to medical attention. Fracture status was used as a time-dependent covariate in proportional hazards models. The 907 women who experienced a fracture were older, had lower bone mineral density and were more likely to report a positive fracture history. A total of 122 women died over the course of the study with 23 of these deaths occurring after a clinical fracture. The age-adjusted relative risk (95% confidence intervals) of dying following a clinical fracture was 2.15 (1.36, 3.42). This primarily reflected the higher mortality following a hip fracture, 6.68 (3.08, 14.52); and clinical vertebral fracture, 8.64 (4.45, 16.74). Results were similar after adjusting for treatment assignment, health status and specific common comorbidities. There was no increase in mortality following a forearm or other fracture (non-hip, non-wrist, nonvertebral fracture). In conclusion, clinical vertebral fractures and hip fractures are associated with a substantial increase in mortality among a group of relatively healthy older women.

An Update on the Diagnosis and Assessment of Osteoporosis with Densitometry

Abstract: In 1994 the WHO proposed guidelines for the diagnosis of osteoporosis based on measurement of bone mineral density. They have been widely used for epidemiological studies, clinical research and for treatment strategies. Despite the widespread acceptance of the diagnostic criteria, several problems remain with their use. Uncertainties concern the optimal site for assessment, thresholds for men and diagnostic inaccuracies at different sites. In addition, the development of many new technologies to assess the amount or quality of bone poses problems in placing these new tools within a diagnostic and assessment setting. This review considers the recent literature that has highlighted the strengths and weaknesses of diagnostic thresholds and their use in the assessment of fracture risk, and makes recommendations for actions to resolve these difficulties.

Recognition of vertebral fracture in a clinical setting.

Abstract: Osteoporosis-related vertebral fractures have important health consequences for older individuals, including disability and increased mortality. Because these fractures can be prevented with appropriate medications, recognition and treatment of high-risk patients is warranted. A cross-sectional survey was carried out in a large, regional hospital in New England to examine the frequency with which vertebral fractures are identified and treated by clinicians in a population of hospitalized older women who have radiographic evidence of fractures. The study population consisted of 934 women aged 60 years and older who were hospitalized between October 1, 1995 and March 31, 1997, and who had a chest radiograph obtained. Vertebral fractures in the thoracic region were identified by two radiologists. Discharge diagnoses, medical record notes and radiology reports were compared with the results of the radiologists’ readings to determine the frequency with which fractures were identified and appropriate, osteoporosis-preventing medications prescribed. Moderate or severe vertebral fractures were identified for 132 (14.1%) study subjects, but only 17 (1.8%) of the 934 participants had a discharge diagnosis of vertebral fracture. Of these 132, only 17% had fracture noted in the medical record or discharge summary; 50% of contemporaneous radiology reports identified a fracture as present; and 23% of the time it was found in the radiologist’s summary impression. Only 18% of medical records indicated that fracture patients had been prescribed calcium, vitamin D, estrogen replacement or an antiresorptive agent. Relatively few hospitalized older women with radiographically demonstrated vertebral fractures were thus identified or treated by clinicians, suggesting a need for improved recognition.

Biochemical Measurements of Bone Turnover in Children and Adolescents

Abstract: Biochemical measurements of bone turnover are helpful in the study of the pathophysiology of skeletal metabolism and growth. However, interpretation of their results is difficult because they depend on age, pubertal stage, growth velocity, mineral accrual, hormonal regulation, nutritional status, circadian variation, day-to-day variation, method of expression of results of urinary markers, specificity for bone tissue, sensitivity and specificity of assays. Three markers of bone formation have been described including their bone specificity and age-related changes: osteocalcin, alkaline phosphatase and its skeletal isoenzyme, procollagen I extension peptides. Bone resorption markers (hydroxyproline; deoxypyridinoline; pyridinoline; peptides containing these crosslinks such as N-telopeptide to helix in urine (NTX), C-telopeptide-1 to helix in serum (ICTP) and C-telopeptide-2 in urine and serum (CTX); tartrate-resistant acid phosphatase; hydroxylysine and its glycosides) are described with special attention to methodologic issues, mainly ways of expression of their results. Changes of bone turnover during growth are described during four periods: infancy, prepubertal period, puberty and the postpubertal period. Pubertal changes of bone markers are described with special attention to gender differences and hormonal mechanisms of the growth spurt which determine differences related to the pubertal stage. Disturbances of bone turnover in four conditions are described to illustrate the impact of such diseases on growth and formation of peak bone mass: prematurity, malnutrition, growth hormone deficiency and corticosteroid-treated bronchial asthma. Available data suggest biochemical markers of bone remodeling may be useful in the clinical investigation of bone turnover in children in health and disease. However, their use in everyday clinical practice is not advised at present.

Estimation of the Prevalence of Low Bone Density in Canadian Women and Men Using a Population-Specific DXA Reference Standard: The Canadian Multicentre Osteoporosis Study (CaMos)

Abstract: The Canadian Multicentre Osteoporosis Study (CaMos) is a prospective cohort study which will measure the incidence and prevalence of osteoporosis and fractures, and the effect of putative risk factors, in a random sample of 10 061 women and men aged ≥25 years recruited in approximately equal numbers in nine centers across Canada. In this paper we report the results of studies to establish peak bone mass (PBM) which would be appropriate reference data for use in Canada. These reference data are used to estimate the prevalence of osteoporosis and osteopenia in Canadian women and men aged ≥50 years. Participants were recruited via randomly selected household telephone listings. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry using Hologic QDR 1000 or 2000 or Lunar DPX densitometers. BMD results for lumbar spine and femoral neck were converted to a Hologic base. BMD of the lumbar spine in 578 women and 467 men was constant to age 39 years giving a PBM of 1.042 ± 0.121 g/cm2 for women and 1.058 ± 0.127 g/cm2 for men. BMD at the femoral neck declined from age 29 years. The mean femoral neck BMD between 25 and 29 years was taken as PBM and was found to be 0.857 ± 0.125 g/cm2 for women and 0.910 ± 0.125 g/cm2 for men. Prevalence of osteoporosis, as defined by WHO criteria, in Canadian women aged ≥50 years was 12.1% at the lumbar spine and 7.9% at the femoral neck with a combined prevalence of 15.8%. In men it was 2.9% at the lumbar spine and 4.8% at the femoral neck with a combined prevalence of 6.6%.

Osteoprotegerin and its ligand: A new paradigm for regulation of osteoclastogenesis and bone resorption.

Abstract: In just 3 years, striking new advances have been made in understanding the molecular mechanisms that govern the crosstalk between osteoblasts/stromal cells and hematopoietic osteoclast precursor cells that leads to osteoclastogenesis. Led first by the discovery of osteoprotegerin (OPG), a naturally occurring protein with potent osteoclastogenesis inhibitory activity, rapid progress was made to the isolation of RANKL, a transmembrane ligand expressed on osteoblasts/stromal cells that binds to RANK, a transmembrane receptor on hematopoietic osteoclast precursor cells. The interaction of RANK and RANKL initiates a signaling and gene expression cascade that results in differentiation and maturation of osteoclast precursor cells to active osteoclasts capable of resorbing bone. OPG acts as a decoy receptor, binding to RANKL and blocking its interaction with RANK, inhibiting osteoclast development. Many of the calciotropic hormones and cytokines, including 1,25(OH)2D3, PTH, PGE2 and IL-11, appear to act through a dual capacity to inhibit production of OPG and stimulate production of RANKL. Estrogen, on the other hand, appears to inhibit production of RANKL and RANKL-stimulated osteoclastogenesis. Recently, the results of the first clinical trial with OPG supported its potential as a therapeutic agent for diseases such as osteoporosis. The new understanding provided by the RANK/RANKL/OPG paradigm for both differentiation of osteoclasts and their activation has had tremendous impact on the field and opened new avenues for development of possible treatments of diseases characterized by excessive bone resorption.

Deterioration in Quality of Life Following Hip Fracture: A Prospective Study

Abstract: To examine longitudinal change in health- related quality of life (HRQoL) following hip fracture in elderly subjects, 32 patients with hip fractures and 29 sex-matched non-fracture control subjects (mean ± SD age 82 ± 8 and 86 ± 6 years respectively) were enrolled in a prospective, case–control study. Fracture subjects completed a generic questionnaire, Short Form 36 (SF-36), and a disease-targeted measure, the revised Osteoporosis Assessment Questionnaire (OPAQ2), on two separate occasions, within 1 week of fracture and 12–15 weeks after fracture. Controls completed both questionnaires on two occasions 12 weeks apart. SF-36 scores were significantly correlated with OPAQ2 in comparable domains of Physical Function (r= 0.76), General Health (r= 0.70) and Mental Health/Tension (r = 0.86). Control subjects had stable scores with the OPAQ2 and SF-36. At 3 months after fracture there was a significant reduction in HRQoL in the SF-36 domains Physical Function (–51%), Vitality (–24%) and Social Function (–26%) and in the OPAQ2 domains Physical Function (–20%), Social Activity (–49%) and General Health (–24%). Hip fracture patients thus had a lower baseline HRQoL and experienced a significant deterioration in HRQoL after hip fracture on both the SF-36 and OPAQ2. HRQoL should be part of a comprehensive assessment of the costs of osteoporosis including fracture-associated morbidity.

Clinical use of biochemical markers of bone remodeling: current status and future directions.

Abstract: Biochemical markers of bone turnover provide a means of evaluating skeletal dynamics that complements static measurements of bone mineral density (BMD). This review evaluates the use of commercially available bone turnover markers as aids in diagnosis and monitoring response to treatment in patients with osteoporosis. High within-person variability complicates but does not preclude their use. Elevated bone resorption markers appear to be associated with increased fracture risk in elderly women, but there is less evidence of a relationship between bone formation markers and fracture risk. The critical question of predicting fracture efficacy with treatment has not been answered. Changes in bone markers as currently determined do not predict BMD response to either bisphosphonates or hormone replacement therapy. Single measurements of markers do not predict BMD cross-sectionally (except possibly in the very elderly), or change in BMD in individual patients, either treated or untreated. On the other hand, research applications of bone turnover markers are of value in investigating the pathogenesis and treatment of bone diseases. Markers have potential in the clinical management of osteoporosis, but their use in this regard is not established. Additional studies with fracture endpoints and information on negative and positive predictive value are needed to evaluate fully the utility of bone turnover markers in individual patients.

Vertebral fracture definition from population-based data: preliminary results from the Canadian Multicenter Osteoporosis Study (CaMos).

Abstract: The Canadian Multicenter Osteoporosis Study is a large population-based prospective study of osteoporosis in the Canadian population. The study involves 9424 subjects, both male and female, from nine centers and seven regions of Canada. Each subject completed an extensive interview to obtain medical, demographic and lifestyle information, and was examined by dual-energy X-ray absorptiometry of the spine and hip, ultrasound of the heel and, for subjects over 50 years of age, lateral spine radiographs. Spinal morphometry of the initial radiographs was performed to determine the prevalence of vertebral deformity. A method is utilized to extract reference norms for vertebral shape from a subset of the population data, which is then used to categorize any deformity within the whole data set. Using 3 standard deviations (SD) as a limit of normality, the male prevalence of 21.5% was similar to the female prevalence of 23.5%. Using 4 SD this reduced to 7.3% and 9.3% respectively. The younger men (50–59 years) showed a higher prevalence of deformity than the women and a lower increase of prevalence with age. In the older age group (over 80 years) the female prevalence of 45% compared with 36% for the men using 3 SD (grade 1) to define the limit of normality. The female group presented with more severe deformities on average than the male group. This continuing study will provide longitudinal information regarding the development of osteoporosis and associated risk factors which will eventually be of use to develop public health policies.

The injury mechanisms of osteoporotic upper extremity fractures among older adults: a controlled study of 287 consecutive patients and their 108 controls.

Abstract: The risk factors for falls in older adults are well known but knowledge on the direct injury mechanisms that result in various osteoporotic fractures has been very sparse. The purpose of this study was therefore to clarify the injury mechanisms of osteoporotic upper extremity fractures of older adults and to compare these mechanisms with those of the control fallers, and in this way to obtain reliable insight into the etiology and pathogenesis of upper extremity fractures and thus to enable fracture prevention. One hundred and twelve patients with a fresh fracture of the proximal humerus, 65 patients with an elbow fracture, 110 patients with a wrist fracture and 108 controls (no fracture, or a fracture other than the case fracture) were interviewed and examined between September 1995 and December 1997. The inclusion criteria of the subjects were that the patient was 50 years of age or older at the time of the accident, and that the fracture/injury had occurred as a result of low-energy trauma (typically a fall from standing height or less) within a week before the interview and examination. In 97% of patients with a proximal humerus or elbow fracture, and in all patients (100%) with a wrist fracture, the fracture was a result of a fall. In the control group this figure was 93%. In a polychotomous logistic regression analysis the intergroup differences in the fall directions (adjusted by gender, age and functional capacity) were statistically highly significant (χ2= 43.6, d.f. = 15, p<0.001). Most of the patients with a proximal humerus fracture or elbow fracture reported that they had fallen “obliquely forward” (43% and 38%) or “to the side” (29% and 26%), whereas in the wrist fracture group the main fall direction was also “obliquely forward” (34%) but the other fall directions (i.e., “forward”, “to the side”, “obliquely backward” and “backward”) were quite equally represented (13–19%). The odds ratio (OR) for an obliquely forward fall resulting in a proximal humerus fracture was 3.5 [95% confidence interval (CI) 1.4–9.2), as compared with the fall directions of the controls and the “obliquely backward” fall direction. In a logistic regression analysis the patients with a wrist fracture managed to break their fall (e.g., with an outstretched arm) more frequently than the patients in the other groups (OR 3.9; 95% CI 2.0–7.3). The patients with a proximal humerus fracture, in turn, managed to break their fall less frequently than the controls (OR 0.33; 95% CI 0.14–0.80). The same was true of the patients with an elbow fracture, although the difference was not significant (OR 0.49%; 95% CI 0.19–1.3). As objective evidence for a direct fall-induced impact on the fracture site, 68% of patients with a proximal humerus fracture revealed a fresh subcutaneous hematoma on the shoulder/upper arm, while such a hematoma was rare in the controls (2%) (p<0.001). Correspondingly, 62% of patients with an elbow fracture showed a similar hematoma on the elbow area, while this was seen in none of the controls (p<0.001). In patients with a wrist fracture a hand/wrist hematoma was seen in 58% of the victims, as compared with 18% of the controls (p<0.001). The study shows that the most typical osteoporotic upper extremity fractures of older adults have their specific injury mechanisms. A great majority of these fractures occur as a result of a fall and a subsequent direct impact of the fractured site. Effective fracture prevention could be achieved by minimizing the obvious risk factors of falling and reducing the fall-induced impact force with injury site protection.

Epidemiology of osteoporotic pelvic fractures in elderly people in Finland: sharp increase in 1970-1997 and alarming projections for the new millennium.

Abstract: The purpose of our epidemiologic study was to determine the current trend in the number and incidence of osteoporotic pelvic fractures in Finland, a country with a Caucasian population of 5 million. Thus, all Finns 60 years of age or older who were admitted to hospitals in 1970-1997 for primary treatment of a first osteoporotic pelvic fracture were selected from The National Hospital Discharge Register. In each year of the study, the number and the age-specific and age-adjusted incidences of fractures were expressed as the number of. patients per 100,000 individuals. The total number of osteoporotic pelvic fractures increased considerably in Finland during the study period, from 128 in 1970 to 913 in 1997, an average increase of 23% a year. The corresponding fracture incidence (per 100,000 persons 60 years of age or older) was 20 in 1970 and 92 in 1997. The mean age of the patients also increased, from 74 years (1970) to 80 years (1997). Despite this, the age-adjusted incidence of osteoporotic pelvic fractures also showed a steady increase from 1970 to 1997: in women, from 31 to 103, and in men, from 13 to 38 (relative increases were 232% and 192%, respectively). If this trend continues, the current number of osteoporotic pelvic fractures in this country (about 900 fractures per year) may treble by the year 2030 (about 2,700 fractures per year). We conclude that the number of osteoporotic pelvic fractures in elderly Finns is increasing at a rate that cannot be explained simply by demographic changes and therefore effective preventive measures should be urgently initiated to control the increasing burden of these age-related fractures.

Femoral Bone Mineral Density, Neck-Shaft Angle and Mean Femoral Neck Width as Predictors of Hip Fracture in Men and Women.

Abstract: The effect of femoral bone mineral density (BMD) and several parameters of femoral neck geometry (hip axis length, neck-shaft angle and mean femoral neck width) on hip fracture risk in a Spanish population was assessed in a cross-sectional study. All parameters were determined by dual-energy X-ray absorptiometry. There were 411 patients (116 men, 295 women; aged 60-90 years) with hip fractures in whom measurements were taken in the contralateral hip. Controls were 545 persons (235 men, 310 women; aged 60-90 years) who participated in a previous study on BMD in a healthy Spanish population. Femoral neck BMD was significantly lower, and neck-shaft angle and mean femoral neck width significantly higher, in fracture cases than in controls. The logistic regression analysis adjusted by age, height and weight showed that a decrease of 1 standard deviation (SD) in femoral neck BMD was associated with an odds ratio of hip fracture of 4.52 [95% confidence interval (CI) 2.93 to 6.96] in men and 4.45 (95% CI 3.11 to 6.36) in women; an increase of 1 SD in neck-shaft angle of 2.45 (95% CI 1.73 to 3.45) in men and 3.48 (95% CI 2.61 to 4.65) in women; and an increase of 1 SD in mean femoral neck width of 2.15 (95% CI 1.55 to 2.98) in men and 2.40 (95% CI 1.79 to 3.22) in women. The use of a combination of femoral BMD and geometric parameters of the femoral neck except for hip axis length may improve hip fracture risk prediction allowing a better therapeutic strategy for hip fracture prevention.

Intensive Insulin Therapy and Bone Mineral Density in Type 1 Diabetes Mellitus: A Prospective Study

Abstract: To determine the effect of metabolic control on bone mineral density (BMD) in type 1 diabetes mellitus (type 1 DM), we studied BMD (by dual-energy X-ray energy absorptiometry) and bone remodeling parameters in 62 patients with type 1 DM both before and 7 years after commencement of intensive insulin therapy. Overall outcomes after the 7-year treatment included the stabilization of BMD at all sites, as well as a significant decrease in tartrate-resistant acid phosphatase (TRAP) (4.302 +/- 2.62 vs 2.65 +/- 0.97 IU/I; p=0.0001) and increase in intact parathyroid hormone (PTHi) (28.05 +/- 15.7 vs 39.78 +/- 22.41 ng/l; p=0.005). Presence of diabetic retinopathy (RTP) versus its absence (non-RTP) was associated with lower BMD in femoral neck (FN) (0.831 +/- 0.142 vs 0.756 +/- 0.153 mg/ cm2; p = 0.03) and Ward's triangle (WT) (0.736 +/- 0.165 vs 0.632 +/- 0.172 mg/cm2; p=0.03), and with a lower T-score in FN (-0.93 +/- 1.34 vs -1.70 +/- 1.46; p = 0.04) and WT (-0.72 +/- 1.42 vs -1.540 +/- 1.55; p = 0.04) and Z-score in FN (-0.591 +/- 1.23 vs -1.132 +/- 1.46; p=0.01). The percentage of patients with osteopenia or osteoporosis in the RTP group was significantly higher than in the non-RTP group (72% vs 53%, p=0.05; RR= 3.2) and the glycosylated hemoglobin (HbA1c) levels of the RTP group were also higher (8.53 +/- 1.6% vs 7.1+/- 1.1%; p=0.05). The improvement in metabolic control, increase in body mass index and decrease in resorption parameters could contribute to the stabilization of bone mass in type I DM but the presence of retinopathy is a critical factor in the progression of diabetic osteopenia.

Validity of self-report of fractures : Results from a prospective study in men and women across Europe

Abstract: In population-based studies of osteoporosis, ascertainment of fractures is typically based on self-report, with subsequent verification by medical records. The aim of this analysis was to assess the validity of self-report of incident nonspine fractures using a postal questionnaire. The degree of overreporting of fracture (false positives) was assessed by comparing self-reports of new fracture from respondents in the multicenter European Prospective Osteoporosis Study with data from other sources including radiographs and medical records. In the analysis, 563 subjects reported nonspine fractures. Verification of the presence of fracture was possible in 510 subjects. Of these, fractures were not confirmed in 11% (false positives). The percentage of false positives was greater in men than in women (15% vs 9%, p=0.04), and less for fractures of the distal forearm and hip than for fractures at other sites. In a separate study, the degree of underreporting (false negatives) was assessed by follow-up of 251 individuals with confirmed fracture ascertained from the records of fracture clinics in three European centers (Lubeck, Oviedo, Warsaw). Questionnaire responses were received from 174 (69%) subjects. Of these, 12 (7%) did not recall sustaining a fracture (false negatives). The percentage of false negatives was lower for hip and distal forearm fractures with only 3 of 90 (3%) such fractures not recalled. Using the combined data from both studies, of those who reported a ‘date’ of fracture on the questionnaire, 91% of subjects were correct to within 1 month of the actual date of the fracture. A postal questionnaire is a relatively simple and accurate method for obtaining information about the occurrence of hip and distal forearm fractures, including their timing. Accuracy of ascertainment of fractures at other sites is less good and where possible self-reported fractures at such sites should be verified from other sources.

Serum bone alkaline phosphatase and calcaneus bone density predict fractures: a prospective study.

Abstract: The aim of this study was to assess the ability of serum bone-specific alkaline phosphatase (bone ALP), creatinine-corrected urinary collagen crosslinks (CTx) and calcaneus bone mineral density (BMD) to identify postmenopausal women who have an increased risk of osteoporotic fractures. Calcaneus BMD and biochemical markers of bone turnover (serum bone ALP and urinary CTx) were measured in 512 community-dwelling postmenopausal women (mean age at baseline 69 years) participating in the Hawaii Osteoporosis Study. New spine and nonspine fractures subsequent to the BMD and biochemical bone markers measurements were recorded over an average of 2.7 years. Lateral spinal radiographs were used to identify spine fractures. Nonspine fractures were identified by self-report at the time of each examination. During the 2.7-year follow-up, at least one osteoporotic fracture occurred in 55 (10.7%) of the 512 women. Mean baseline serum bone ALP and urinary CTx were significantly higher among women who experienced an osteoporotic fracture compared with those women who did not fracture. In separate age-adjusted logistic regression models, serum bone ALP, urinary CTx and calcaneus BMD were each significantly associated with new fractures (odds ratios of 1.53, 1.54 and 1.61 per SD, respectively). Multiple variable logistic regression analysis identified BMD and serum bone ALP as significant predictors of fracture (p = 0.002 and 0.017, respectively). The results from this investigation indicate that increased bone turnover is significantly associated with an increased risk of osteoporotic fracture in postmenopausal women. This association is similar in magnitude and independent of that observed for BMD.

Factors associated with mortality after hip fracture.

Abstract: There is a well-known excess mortality subsequent to hip fracture, which is probably restricted to subgroups of hip fracture patients with reduced health status. We studied the association between risk factors and death in 248 hip fracture patients and 248 controls originally enrolled in a population-based case–control study. This cohort was followed for 3 1/2 years with respect to total mortality. A markedly increased mortality was found in hip fracture patients passing a mental status test at a low score [relative risk (RR) = 2.3, 95% confidence interval (CI) 1.4-3.7], in hip fracture patients reporting two or more selected chronic diseases (RR = 3.3, 95% CI 1.8–6.1), in hip fracture patients not walking outdoors before the fracture (RR = 3.2, 95% CI 2.0–5.1) and in hip fracture patients in the lower half of handgrip strength distribution (RR = 2.3, 95% CI 1.6–3.4), all compared with the control group. In contrast, hip fracture patients without these risk factors did not have increased mortality compared with the control group. This study suggests that otherwise healthy and fit patients do not have increased mortality subsequent to hip fracture. The excess mortality is restricted to persons with reduced mental status, reduced somatic health and low physical ability. Special attention should be paid to patients with such risk factors in the treatment and rehabilitation period.

Can the WHO Criteria for Diagnosing Osteoporosis be Applied to Calcaneal Quantitative Ultrasound

Abstract: With the increasing number of quantitative ultrasound (QUS) devices in use worldwide it is important to develop strategies for the clinical use of QUS. The aims of this study were to examine the age-dependence of T-scores and the prevalence of osteoporosis using the World Health Organization Study Group criteria for diagnosing osteoporosis and to examine the T-score threshold that would be appropriate to identify women at risk of osteoporosis using QUS. Two groups of women were studied: (i) 420 healthy women aged 20–79 years with no known risk factors associated with osteoporosis; (ii) 97 postmenopausal women with vertebral fractures. All subjects had dual-energy X-ray absorptiometry (DXA) measurements of the spine and hip and QUS measurements on three calcaneal ultrasound devices (Hologic Sahara, Hologic UBA575+, Osteometer DTUone). A subgroup of 102 (76 on the DTUone) healthy women aged 20–40 years was used to estimate the young adult mean and SD for each QUS and DXA measurement parameter to calculate T-scores. The age-related decline in T-scores for QUS measurement parameters was half the rate observed for the bone mineral density (BMD) measurements. The average T-score for a woman aged 65 years was –1.2 for QUS measurements and –1.75 for the BMD measurements. When osteoporosis was defined by a T-score ≤–2.5 the prevalence of osteoporosis in healthy postmenopausal women was 17%, 16% and 12% for lumbar spine, femoral neck and total hip BMD respectively. When the same definition was used for QUS measurements the prevalence of osteoporosis ranged from 2% to 8% depending on which ultrasound device and measurement parameter was used. Four different approaches, based on DXA-equivalent prevalence rates of osteoporosis, were utilized to examine which T-score threshold would be appropriate for identifying postmenopausal women at risk of osteoporosis using QUS measurements. These ranged from –1.05 to –2.12 depending upon the approach used to estimate the threshold and on which QUS device the measurements were performed, but all were significantly lower than the threshold of –2.5 used for BMD measurements. In conclusion, the WHO threshold of T=–2.5 for diagnosing osteoporosis requires modification when using QUS to assess skeletal status. For the three QUS devices used in this study, a T-score threshold of –1.80 would result in the same percentage of postmenopausal women classified as osteoporotic as the WHO threshold for BMD measurements. Corresponding T-score thresholds for individual measurement parameters on the two commercially available devices were –1.61, –1.94 and –1.90 for Sahara BUA, SOS and estimated heel BMD respectively and –1.45 and –2.10 for DTU BUA and SOS respectively Additional studies are needed to determine suitable T-score thresholds for other commercial QUS devices.

Loss of bone density and lean body mass after hip fracture.

Abstract: Few studies of bone loss have assessed the amount of loss directly after a hip fracture. The present prospective study was conducted to determine changes in bone mineral density (BMD) and muscle mass shortly after fracture and through 1 year to assess short-term loss and related factors. The setting was two acute care teaching hospitals in Baltimore, Maryland, and subjects were 205 community-dwelling women with a new fracture of the proximal femur between 1992 and 1995. Bone density of the nonfractured hip and whole-body and body composition were measured by dual-energy X-ray absorptiometry at 3 and 10 days and 2, 6 and 12 months after admission. Mean BMD of the femoral neck was 0.546 +/- 0.007 g/cm(2) at baseline. Average loss of femoral neck BMD from baseline was 2.1% at 2 months, 2.5% at 6 months and 4.6% at 12 months. The average loss of BMD in the intertrochanteric region was 2.1% at 12 months. Total lean body mass decreased by 6% while fat mass increased by 3. 6% by 1 year after the fracture. These findings indicate that significant loss in BMD and lean body mass occur shortly after hip fracture while body fat increases. Continued loss was evident throughout the 1 year of follow-up. This loss of both bone density and muscle mass may lead to new fractures.

Costs induced by hip fractures: a prospective controlled study in Belgium. Belgian Hip Fracture Study Group.

Abstract: The economic burden of hip fractures is thought to be important, but the excess medical costs they induce remain largely unknown We assessed the direct medical costs induced by hip fractures during and after hospitalization Hospital costs of 170 consecutive Belgian women with hip fracture were gathered During the year following discharge, all medical costs were collected for the 159 hip fracture women who survived the acute hospitalization stay A similar collection of data was performed on a comparison group of 159 age-and residence-matched women without a history of hip fracture The mean cost of the acute hospital stay was 8,667 Belgian francs and the mean 1-year hip-fracture-related extra costs after hospitalization was 6,636 Belgian francs During the year following the acute hospital stay, 19% of the hip fracture women and 4% of the comparison women were newly admitted to nursing homes (p<0001) Although health care costs increased with age, hip-fracture-related extra costs after hospitalization seemed similar in those below or above 81 years old These extra costs amounted to 7,710 Belgian francs in women not living in nursing homes at the time of fracture, and to 3,479 Belgian francs in women who lived in nursing homes Health or mental status before hip fracture seemed not to affect extra costs Taking into account the higher mortality of women with hip fracture, the extra costs during the acute hospital stay and during the 1-year follow-up amounted to a mean 15,151 Belgian francs In conclusion, both acute hospital stays and subsequent medical care contribute significantly to medical costs induced by hip fractures

Pregnancy-associated osteoporosis: does the skeleton recover?

Abstract: Osteoporosis in pregnancy is a rare clinical problem of unknown cause. If the bone loss results from the pregnancy alone it should improve toward normal after delivery; in contrast, where bone density was low before pregnancy, due to some other secondary cause, significant postpartum improvement might not be expected. Thirteen women (age 23-37 years) with pregnancy-associated osteoporosis presenting with either pain in the back and vertebral collapse (8 subjects) or pain in the hip (5 subjects) had consecutive dual-energy X-ray absorptiometry measurements of bone mineral density (BMD) for up to 8 years after an affected pregnancy. The BMD results were expressed as a Z-score in relation to an age-matched mean. The mean initial (0-6 months postpartum) BMD was low in both groups and at both sites. In the back pain group the mean spine Z-score (Ll-L4) was -3.34 (range -2.25 to -4.66) and mean total hip Z-score was -2.41 (range -1.44 to -3.82). In the hip pain group the mean spine Z-score was -2.00 (range -1.48 to -2.65) and mean hip Z-score was -2.19 (range -1.12 to -3.26). Subsequent mean hip and spine BMD increased significantly toward the lower end of the normal range. We conclude that a reversible part of the bone loss is related to the pregnancy itself. A low BMD before pregnancy cannot be excluded. Knowledge that the bone density increases after an affected pregnancy, combined with the known rarity of recurrent symptoms in subsequent pregnancies, is important in prognosis.

Walking after stroke: does it matter? Changes in bone mineral density within the first 12 months after stroke. A longitudinal study.

Abstract: Stroke patients have increased risk of hip fractures. Nearly all fractures occur on the hemiplegic side, and reduced bone mineral density (BMD) may be an important predisposing factor. The aim of this study was to investigate the degree of demineralization within the first year after stroke, and to elucidate a possible difference in patients with high versus low ambulatory levels. Forty acute stroke patients were followed (17 initially wheelchair-bound and 23 initially ambulatory). BMD was measured in the proximal femur bilaterally at a mean 6 days, 7 months and 1 year after stroke onset using dual-energy X-ray absorptiometry. Ambulatory status was independently associated with changes in BMD (p≤0.005) 1 year after stroke. The 17 initially wheelchair-bound patients had a significant 10% reduction in BMD at the paretic side and 5% reduction at the non-paretic side (p<0.001), while the 23 patients initially able to walk had a significant loss (3%) only at the paretic side (p = 0.01). The analysis also indicated that the major reduction in BMD took place within the first 7 months. Two months after stroke 12 of the wheelchair-bound patients had relearned to walk. At the paretic side the 1 year changes in BMD in the patients who stayed wheelchair-bound, the patients who relearned to walk within the first 2 months and the patients who were able to walk throughout the study were 13%, 8% and 3%, respectively, and a statistically significant trend with ambulatory level was found (p = 0.007). This study provides clear evidence that lack of mobility and weight-bearing early after stroke is an important factor for the greater bone loss in the paretic leg, but that relearning to walk within the first 2 months after stroke, even with the support of another person, may reduce the bone loss after immobilization.

Effect of Soy Protein on Bone Metabolism in Postmenopausal Japanese Women

Abstract: We conducted a cross-sectional study of the effects of soybean protein intake on bone mineral density and biochemical markers in 85 postmenopausal Japanese women. Nutrients in the diet of postmenopausal Japanese women visiting the osteoporosis unit, including subjects with normal lumbar spine bone mineral density (L2–4 BMD), were investigated by questionnaire, and the calculated daily energy, protein, soy protein and calcium intake were obtained. L2–4 BMD was measured with dual-energy X-ray absorptiometry, and assays done of serum alkaline phosphatase (ALP) and serum intact osteocalcin (IOC) as bone formation markers and urinary pyridinoline (UPYR) and urinary deoxypyridinoline (UDPYR) as bone resorption markers. Soy protein intake was significantly associated with the Z-score for L2–4 BMD (r= 0.23, p = 0.038) and UDPYR (r =−0.23, p = 0.034). Stepwise multiple regression analyses showed that soy protein intake is significantly associated with the Z-score for L2–4 BMD (β= 0.225, p = 0.04) and UDPYR (β=−0.08, p = 0.03) among four nutritional factors. These results suggest that high soy protein intake is associated with a higher bone mineral density and a lower level of bone resorption, but further studies are needed to confirm the causal dynamic mechanisms.

Visual assessment of vertebral deformity by X-ray absorptiometry: a highly predictive method to exclude vertebral deformity.

Abstract: The accurate identification of prevalent vertebral fractures is important in both the clinical and research setting as they are associated with increased risk of further fracture and irreversible clinical consequences. This study reports a direct comparison of prevalent vertebral deformity identification using X-ray absorptiometry (XA) scans, acquired on a dual-energy X-ray absorptiometry (DXA) machine, and conventional radiographs in a diverse group of 161 postmenopausal women, ranging from healthy subjects with normal bone mineral density (BMD) to osteoporotic subjects with multiple vertebral deformities. Deformities were identified by a trained operator by visual assessment of the XA scans (VXA) and semiquantitatively by an experienced radiologist on the conventional radiographs (XSQ). Subjects were recruited prospectively and were triaged according to their VXA results into normal, equivocal and definite deformity groups. VXA and XSQ demonstrated good agreement (96.3%, K = 0.79) in classifying vertebrae as normal or deformed in the 1978 of 2093 vertebrae deemed analyzable on both the XA scans and conventional radiographs. VXA showed good sensitivity (91.9%) in the identification of moderate/severe XSQ deformities and an excellent negative predictive value (98.0%) was produced when VXA was used to distinguish subjects without vertebral deformities from those with possible or definite deformities on a per subject basis. The majority of disagreement between the two methods resulted from different classification of mild wedge and endplate deformities and the poor visualization of upper thoracic vertebrae on the XA scans. Agreement improved, particularly on a per subject basis, when analysis was restricted to the vertebral levels from L4 to T7. Visual triage of XA scans by a trained operator would seem to be swift, convenient and cost-effective method, with excellent negative predictive value, to distinguish subjects with very low risk of vertebral deformities from those with possible deformities. These 'normal' subjects can then be excluded prior to performing conventional radiographs and further time-consuming and costly methods of vertebral deformity assessment such as XSQ by an experienced radiologist and/or quantitative morphometry. VXA may prove useful in the clinical evaluation of patients at risk of osteoporosis as an adjunct to BMD scans or in the selection of subjects for osteoporosis-related clinical trials.

Prevention of bone loss with risedronate in glucocorticoid-treated rheumatoid arthritis patients.

Abstract: The aim of the study was to assess risedronate's effect on bone mineral density in postmenopausal women with rheumatoid arthritis receiving glucocorticoids. We carried out a two center, 2 year, double-masked, placebo-controlled trial with a third year of nontreatment follow-up. We studied 120 women requiring long-term glucocorticoid therapy at > 2.5 mg/day prednisolone randomized to treatment with daily placebo; daily 2.5 mg risedronate; or cyclical 15 mg risedronate (2 out of 12 weeks). At 97 weeks, bone mineral density was maintained at the lumbar spine (+1.4%) and trochanter (+0.4%) in the daily 2.5 mg risedronate group, while significant bone loss occurred in the placebo group (-1.6%, p = 0.03; and 4.0%, p < 0.005, respectively). At the femoral neck, there was a nonsignificant bone loss in the daily 2.5 mg risedronate group (-1.0%) while in the placebo group bone mass decreased significantly (-3.6%, p < 0.001). The difference between placebo and daily 2.5 mg risedronate groups was significant at the lumbar spine (p = 0.009) and trochanter (p = 0.02) but did not reach statistical significance at the femoral neck. Although not significantly different from placebo at the lumbar spine, the overall effect of the cyclical regimen was similar to that of the daily 2.5 mg risedronate regimen. Treatment withdrawal led to bone loss in the risedronate groups that was significant at the lumbar spine. A similar number of patients experienced adverse events (including upper gastrointestinal events) across treatment groups and risedronate was generally well tolerated. Thus risedronate preserves bone mass in postmenopausal women with rheumatoid arthritis receiving glucocorticoids while patients receiving a placebo have significant bone loss.