Showing papers in "Osteoporosis International in 2004"

An estimate of the worldwide prevalence, mortality and disability associated with hip fracture

Abstract: The aim of this study was to quantify the global burden of osteoporosis as judged by hip fracture and the burden in different socio-economic regions of the world. The population mortality in 1990 and the incidence of hip fracture in different regions were identified, where possible in 1990. Excess mortality from hip fracture used data for Sweden, and disability weights were assigned to survivors from hip fracture. In 1990 there were an estimated 1.31 million new hip fractures, and the prevalence of hip fractures with disability was 4.48 million. There were 740,000 deaths estimated to be associated with hip fracture. There were 1.75 million disability adjusted life-years lost, representing 0.1% of the global burden of disease world-wide and 1.4% of the burden amongst women from the established market economies. We conclude that hip fracture is a significant cause of morbidity and mortality worldwide.

Mortality after osteoporotic fractures

Abstract: The aim of this study was to examine the pattern of mortality following osteoporotic fractures at the spine, shoulder, hip, and forearm. We studied 2,847 patients with fractures at these sites identified from the radiology department in Malmo, Sweden. Poisson regression was used to compute mortality immediately after the fracture and with time. Mortality immediately after fracture was significantly higher in fracture cases than in the general population except for forearm fractures in both men and women. Mortality was higher in men than in women, but not different when adjusted for sex-specific population risks. For spine, shoulder, and hip fracture, mortality fell after the 1st year, an effect that was most marked for patients with spine fractures. The decrease in mortality risk with time was significant for hip, vertebral, and shoulder fracture. We conclude that the risk of death is increased in patients with osteoporotic fractures and that the highest risk is found immediately after the fracture event. The decreasing mortality with time after fracture may be due in part to a decrease in deaths causally related to the fracture. The extent to which early intervention for osteoporosis might avoid some of these deaths is unknown.

The impact of compliance with osteoporosis therapy on fracture rates in actual practice

Abstract: Background: Clinical trials have demonstrated that drug therapy can reduce osteoporosis-related fracture risk in women over 50 years of age. Noncompliance could considerably limit the effectiveness observed in actual practice, however. The objective of this study was therefore to estimate fracture risk in relation to compliance with osteoporosis medication in actual practice. Methods: Demographic, prescription drug use, physician services, and hospitalization information for women with osteoporosis who were dispensed an osteoporosis medication between 1996 and 2001 was obtained from the Saskatchewan health data files. Compliance to treatment was defined as drug available to cover 80% of the time. Subsequent fractures were identified via hospitalizations or physician contacts with a relevant diagnostic or procedure code. The risk of fractures in relation to compliance was examined using a Cox proportional hazards model with time-dependent covariates. The impact of other patient characteristics, including age, having suffered a prior fracture, and prior use of osteoporosis medication and steroids, was also examined. Results: 11,249 women suffering from osteoporosis were identified with a mean age at the time of the index prescription of 68.4 years and average follow-up of 2 years. The overall fracture rate was 4.5% per year. Patients who complied experienced a 16% lower fracture rate. This association was maintained within subgroups and after controlling for other patient characteristics that independently predict the fracture rate. Conclusion: These results indicate that improving compliance in actual practice may significantly decrease osteoporosis-related fracture risk.

Fracture risk following an osteoporotic fracture.

Abstract: The aim of this study was to examine the pattern of fracture risk following a prior fracture at the spine, shoulder or hip. We studied 1918 patients with fractures at these sites identified from the Department of Radiology in Malmo who were followed for 5 years. Poisson regression was used to compute fracture rates immediately after the initial fracture and at 5 years thereafter in men and women aged 60 or 80 years. Immediate fracture risk was higher than that of the general population, more markedly so at the age of 60 than at 80 years. At the age of 60 years, the risk of hip, forearm and spine fractures were significantly increased following a prior spine, hip or shoulder fracture in men. A similar pattern was seen in women, except that the increase in risk of forearm fracture following a spine or hip fracture was not statistically significant. The incidence of further fractures at the shoulder, spine or hip fell with time after the first fracture, a fall that was significant for all fractures after a shoulder fracture, hip fracture after a spine fracture, and hip and spine fractures after a hip fracture. We conclude that the risk of a subsequent fracture immediately after an osteoporotic fracture is highest immediately after the event. This provides a rationale for very early intervention immediately after fractures to avoid recurrent fractures.

Practice patterns in the diagnosis and treatment of osteoporosis after a fragility fracture: a systematic review.

Abstract: Fragility fractures are a strong indicator of underlying osteoporosis (OP) With the risk of future fracture being increased 15- to 95-fold following a fragility fracture, the diagnosis and treatment of OP in men and women with fragility fractures provides the opportunity to prevent future fragility fractures This review describes the current status of practice in investigation and diagnosis of OP in men and women with fragility fractures, the rates and types of postfracture treatment in patients with fragility fractures and OP, interventions undertaken in this population, and the barriers to OP identification and treatment A literature search performed in Medline, Healthstar, CINAHL, EMBASE, PreMedline, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews identified 37 studies on OP diagnosis, treatment, and interventions The studies varied in design methodology, study facilities, types of fractures, and pharmacological treatments Some studies revealed that no patients with fragility fractures received investigation or treatment for underlying OP Investigation of OP by bone mineral density was low: 14 of 16 studies reported investigation of less than 32% of patients Investigation by bone mineral density resulted in high rates of OP diagnosis (35-100%), but only moderate use of calcium and vitamin D (8-62%, median 18%) and bisphosphates (05-38%) in patients investigated postfracture Studies on barriers to OP identification and treatment focused on various groups of health practitioners Barriers included the cost of therapies, time and cost of resources for diagnosis, concerns about medications, and the lack of clarity regarding the responsibility to undertake this care

Functional outcome and quality of life following hip fracture in elderly women: a prospective controlled study

Abstract: The aim of this prospective study was to document the functional outcome and quality of life (QoL) over 1 year following hip fracture in elderly women. A total of 159 unselected elderly women with a first hip fracture were matched for age and residence with an equal number of control women. Functional status was measured by completing a Rapid Disability Rating Scale version 2 (RDRS-2) questionnaire [score ranging from 0 (best) to 54 (worse)], before hospital discharge and 12 months later. To examine longitudinal change in health-related QoL, fracture subjects and controls completed the Short Form 36 (SF-36) questionnaire. For the 134 women still alive at 1 year, the mean RDRS-2 score before hospital discharge was 16.2 (95% CI: 15.0-18.0) and 3.5 (2.6-4.3) in patients and controls, respectively ( P<0.001). During the year following hospital discharge, the mean RDRS-2 score improved to 13.0 (11.1-14.1) in hip-fracture women and worsened to 4.3 (3.3-5.0) in the control group (differences with initial scores: P<0.001 in both groups). After adjustment for potential confounders (including age and comorbidity), the estimated functional decline attributable to a hip fracture was 24% in the first year. Poor functional status upon discharge was the strongest predictor of a poor functional status at 1 year. Overall, similar trends were observed when using SF-36 scores as compared with RDRS-2 scores. However, only 51% of the study population was able to complete the SF-36 questionnaire at discharge and after 1 year, and these subjects were considerably younger ( P<0.001), had less cognitive impairment ( P<0.001), and had better functional status ( P<0.001) than those who were unable to complete the SF-36. For those women able to complete the SF-36 questionnaires, the mean SF-36 score before hospital discharge was 56.4 (95% CI: 51.9-60.9) and 71.1 (67.5-74.8) in patients and controls, respectively ( P<0.001). During the year following hospital discharge, the mean SF-36 score improved significantly to 61.1 (56.5-65.7) in hip-fracture patients ( P=0.03), but remained unchanged in the control group ( P=0.23). Overall, the results of this study indicate that women who sustain a hip fracture continue to suffer from substantial functional impairment and loss in QoL at 1 year, despite a significant recovery during this 12-month period. Function upon hospital discharge is the strongest predictor of functional status 1 year later. Assessing QoL in hip fracture women through self-administered questionnaires is subject to considerable bias due to non-response.

Excess mortality after hospitalisation for vertebral fracture

Abstract: An excess mortality is well described after vertebral fracture. Deaths are in part related to co-morbidity, but could also be due to the fracture event itself, either directly or indirectly. The aim of this study was to examine the quantum and pattern of mortality following vertebral fracture. We identified 16,051 men and women aged 50 years or more with a vertebral fracture that required hospitalization in 28.8 million person years from the patient register of Sweden. Mortality after vertebral fracture was examined using Poisson models applied to fracture patients and compared to that of the general population. At all ages, the risk of death was markedly increased immediately after the event. After a short period of declining risk, the risk increased with age at a rate that was higher than that of the general population and comparable to that 1 year after hip fracture. The latter function was assumed to be due to deaths related to co-morbidity and the residuum assumed to be due to the vertebral fracture. Causally related deaths comprised 28% of all deaths associated with vertebral fracture (depending on age). We conclude that a minority of deaths following hospitalization for vertebral fracture are attributable to the fracture itself under the assumptions we used.

Health-related quality of life after osteoporotic fractures.

Abstract: Objective: To estimate the impact of osteoporosis fractures on health-related quality of life (HRQOL) in postmenopausal women. Methods: To compare the impact on HRQOL of different osteoporotic fractures, 600 consecutive women 55–75 years old with a new fracture (inclusion fracture) were invited by mail. After exclusions by preset criteria (high-energy fractures, ongoing osteoporosis treatment, or unwillingness to participate), 303 women were included, 171 (56%) of whom had a forearm, 37 (12%) proximal humerus, 40 (13%) hip, and 55 (18%) vertebral fracture, respectively, and all were investigated and treated according to the current local consensus program for osteoporosis. In addition, HRQOL was evaluated by the SF-36 questionnaire and compared with local, age-matched reference material. Examinations were performed 82 days (median) after the fracture and 2 years later. Results: HRQOL was significantly reduced at baseline regarding all SF-36 domains after vertebral fractures and most after hip fractures, but only regarding some domains after forearm and humerus fracture. After 2 years, improvements had occurred after all types of fractures, and after forearm or humerus fracture, HRQOL was completely normalized in all domains. However, 2 years after hip fracture, HRQOL was still below normal regarding physical function, role-physical and social function, while after vertebral fracture, scores were still significantly lower for all domains, physical as well as mental. Patients with one or more previous fractures before the inclusion fracture had lower HRQOL at baseline and after 2 years, compared with those with no previous fracture. Patients with osteoporosis (T-score <−2.5 in hip or spine) had lower HRQOL than those with normal BMD. Conclusion: Vertebral and hip fractures have a considerably greater and more prolonged impact on HRQOL than forearm and humerus fractures. The number of fractures was inversely correlated to HRQOL. These differences should be taken into account when making priorities in health care programs.

Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE study.

Abstract: Increasing evidence suggests that a high rate of bone turnover is associated with low bone mineral density (BMD) and is strongly linked to fracture risk. Measurement of biochemical markers of bone turnover is therefore becoming a more widely used endpoint in clinical trials in postmenopausal osteoporosis. This multinational double-blind, fracture-prevention study enrolled 2946 postmenopausal women with osteoporosis. Patients were randomized to receive placebo or oral ibandronate administered daily (2.5 mg/day) or intermittently (20 mg every other day for 12 doses every 3 months). The primary endpoint was the incidence of new vertebral fractures after 3 years. Secondary outcome measures included changes in the rate of bone turnover as assessed by biochemical markers and increases in spinal and hip BMD. Daily and intermittent oral ibandronate significantly reduced the risk of vertebral fractures by 62% and 50%, respectively, and produced significant and sustained reductions in all the measured biochemical markers of bone turnover. By 3 months, the rate of bone turnover was reduced by approximately 50–60%, and this level of suppression was sustained throughout the remainder of the study. In summary, oral ibandronate, given daily or with a between-dose interval of >2 months, normalizes the rate of bone turnover, provides significant increases in BMD and a marked reduction in the incidence of vertebral fractures. Thus, intermittent ibandronate has potential to become an important alternative to currently licensed bisphosphonates in postmenopausal osteoporosis.

Long-term changes in bone metabolism, bone mineral density, quantitative ultrasound parameters, and fracture incidence after spinal cord injury: a cross-sectional observational study in 100 paraplegic men.

Abstract: To study the time course of demineralization and fracture incidence after spinal cord injury (SCI), 100 paraplegic men with complete motor loss were investigated in a cross-sectional study 3 months to 30 years after their traumatic SCI. Fracture history was assessed and verified using patients’ files and X-rays. BMD of the lumbar spine (LS), femoral neck (FN), distal forearm (ultradistal part = UDR, 1/3 distal part = 1/3R), distal tibial diaphysis (TDIA), and distal tibial epiphysis (TEPI) was measured using DXA. Stiffness of the calcaneus (QUI.CALC), speed of sound of the tibia (SOS.TIB), and amplitude-dependent SOS across the proximal phalanges (adSOS.PHAL) were measured using QUS. Z-Scores of BMD and quantitative ultrasound (QUS) were plotted against time-since-injury and compared among four groups of paraplegics stratified according to time-since-injury ( 20 years (p 10 years. In paraplegic men early (trabecular) and persistent (cortical) bone loss occurs at the lower limbs and leads to an increasing fracture incidence with time-after-SCI.

Vitamin D status and its relationship with bone mineral density in healthy Asian Indians

Abstract: Synthesis of vitamin D takes place in the skin under the effect of sunlight. The Indian subcontinent is situated between 8.4° N and 37.6° N latitudes and has adequate sunshine throughout the year. Thus, it has been presumed that Indians are vitamin D sufficient. We measured serum 25-hydroxy vitamin D [25(OH)D] (n=92) and 1,25-dihydroxy vitamin D [1, 25(OH)2D] (n=65) levels in healthy hospital staff, using 125I radioimmunoassay. Serum intact parathyroid hormone (PTH) concentration was estimated by immunoradiometric assay. Bone mineral density was estimated using a dual energy X-ray absorptiometer (HologicR QDR 4500A). Using a serum 25(OH)D level of 15 ng/ml as a cutoff, 66.3% (61/92) of the subjects were found to be vitamin D deficient. Of these, 20.6% (19/92) subjects had severe vitamin D deficiency (<5 ng/ml), 27.2% (25/92) had moderate vitamin D deficiency (5–9.9 ng/ml), while 18.5% (17/92) had mild vitamin D deficiency (10–14.9 ng/ml). When a serum 25(OH)D level of 20 ng/ml was used as a cutoff, 78.3% subjects were diagnosed to be vitamin D deficient/insufficient. The serum 1,25(OH)2D level was within the normal range (40.6±20.1 pg/ml; mean ± SD). Mean (±SD) serum intact PTH, estimated in a limited number of subjects (n=15), was 72.3 (±21.0) pg/ml (range 36–100 pg/ml). There was a significant correlation between daily sun exposure and 25(OH)D levels (r=0.731, P<0.001). The serum 25(OH)D level correlated with BMD at the femoral neck and Ward's triangle (r=0.50, P=0.020 and r=0.46, P=0.037, respectively). Our findings show that vitamin D deficiency is common in urban north Indian hospital staff. The possible reasons include inadequate sunlight exposure and skin pigmentation in Indians. The serum 1,25(OH)2D level is not a good indicator of vitamin D deficiency. A low serum 25(OH)D level is possibly one of the reasons for lower bone mineral density among Indians.

Comparison of methods for the visual identification of prevalent vertebral fracture in osteoporosis

Abstract: The identification of vertebral fracture in osteoporosis is based mainly on the identification of abnormal variation in vertebral shape, but this can be misleading in the presence of a non-fracture deformity or normal variant of vertebral shape. Qualitative identification of vertebral fracture (Qual) is influenced by the subjectivity of the approach, and although more objective, the semiquantitative method (SQ) can be difficult to apply. In addition, there has been little independent evaluation of SQ in relation to other approaches. We aimed to evaluate a new algorithm-based approach for the qualitative identification of vertebral fracture (ABQ) and to compare it with SQ and Qual. Two radiologists reported spinal radiographs for 372 postmenopausal women using Qual (reader 1), and SQ and ABQ (reader 2). Non-fracture deformities and normal variants were also reported using Qual and ABQ. The prevalence of vertebral fracture by subjects was higher for SQ (24%) than for Qual (11%) and ABQ (7%). Agreement was poor between SQ and the other methods, and moderate between Qual and ABQ. Twenty-two women with vertebral fracture were agreed by all three methods, similar to the total identified by ABQ (25 women). Seventeen women diagnosed with fracture by Qual, had non-fracture deformity or normal variant (but no fracture) according to ABQ. Of the women with SQ fractures, 53% and 70% were identified negative for fracture but positive for non-fracture deformity or normal variant by ABQ and Qual. The main sources of discrepancy between SQ and the other methods were Scheuermann's disease, normal variation, and degenerative change accompanied by short anterior vertebral height. For all methods, bone mineral density (BMD) and BMD Z-scores were lower in women with vertebral fractures than in those with no fractures. Bone mineral density and BMD Z-scores were also lower at the lumbar spine and total body in women with vertebral fractures according to Qual and ABQ than they were for SQ, and were lower in women with SQ fractures agreed by Qual and ABQ, compared with those diagnosed negative for fracture by Qual and ABQ (p<0.01). We conclude that poor agreement between methods arises mainly from difficulties in differentiating true fracture from non-fracture deformity. Our new approach attempts to address this problem but requires further testing in a larger study population.

The risk and burden of vertebral fractures in Sweden

Abstract: The aim of this study was to determine the risk and burden of vertebral fractures judged as those coming to clinical attention and as morphometric fractures. Incidence and utility loss were computed from data from Malmo, Sweden. Clinical fractures accounted for 23% of all vertebral deformities in women and for 42% in men. The average 10-year fracture probability for morphometric fractures increased with age in men from 2.9% at the age of 50 years (7.2% in women) to 8.4 at the age of 85 years (26.7% in women). As expected, probabilities increased with decreasing T-score for hip BMD. Cumulative utility loss from a clinical vertebral fracture was substantial and was 50-62% of that due to a hip fracture depending on age. When incidence of fractures in the population was weighted by disutility, all spine fractures accounted for more morbidity than hip fracture up to the age of 75 years. We conclude that vertebral fractures have a major personal and societal impact that needs to be recognised in algorithms for assessment of risk and in health economic strategies for osteoporosis.

Oral glucocorticoid use is associated with an increased risk of fracture

Abstract: Oral glucocorticoids (GCs) are widely used and despite their adverse effects on bone mineral density, the risk of sustaining osteoporotic fractures is not well addressed. The objective of this retrospective, cohort study was to assess fracture risk in patients exposed to oral GCs. Patients from an administrative claims database who were prescribed oral GCs and were enrolled 1 year before and 1 year after the initial oral GC claim were matched with a comparison population on age, sex, and date of first claim. Measurements of exposure included amount, duration, and pattern of oral GC use. The osteoporosis-related risk of fracture was based on the ratio of hazard functions estimated using a Cox proportional hazards model. The adjusted relative risk (RR) estimates (and 95% CI) for fractures were hip 1.87 (95% CI, 1.2 to 2.9), vertebral 2.92 (95% CI, 2.0 to 4.3), wrist/forearm 1.03 (95% CI, 0.8 to 1.4), nonvertebral 1.68 (95% CI, 1.5 to 1.9), any fracture 1.75 (95% CI, 1.6 to 1.9). A dose dependence of fracture risk was observed for hip, vertebral, nonvertebral, and any fractures. Long duration and continuous pattern of GC use demonstrated a significant 5-fold increased risk of hip and 5.9-fold increased risk of vertebral fracture. The combined effect of higher dose, longer duration, and continuous pattern further increased RR estimates to 7-fold for hip and 17-fold for vertebral fractures. This study confirms previous observations that suggest oral GCs have a rapid deleterious effect on trabecular-rich bone. The emerging relationship between amount, duration, and pattern of oral GC exposure and fracture risk should be considered in clinical practice and managed care settings to avoid the debilitating effects of fractures in patients.

Consequences of hip fracture on activities of daily life and residential needs

Abstract: The aim of this study was to describe the consequences of hip fracture with respect to changes in residential needs and the ability to perform activities of daily life. Patients 50 years and older admitted to the two largest hospitals of Oslo with a hip fracture during the period May 1996 through April 1997 were identified. In November 1997 a questionnaire on residential needs, activities of daily life, hip pain and health status was sent to the patients still alive (n = 767). After reminders, the questionnaires of 593 patients (77%) were included. Logistic regression analysis was applied to assess items associated with functional limitation and need for residential care. The proportion of patients living in nursing homes increased from 15% before to 30% after the hip fracture, and men were twice as likely to move into a nursing home than women. Of the patients living in their own homes before the hip fracture, 6% of those 85 years had to move to nursing home after hip fracture. The proportion of patients walking without any aid decreased from 76 to 36%, and 43% of the patients lost their prefracture ability to move outside on their own. More than a fourth of the patients (28%) lost their ability to cook their own dinner after sustaining hip fracture. The probability of these events increased with increasing age. The probability of reporting inferior health status and for having hip pain that affected sleep after the fracture was unrelated to age. Many patients sustaining a hip fracture, and in particular the oldest patients, have reduced ability to perform activities of daily life.

Fundamentals and pitfalls of bone densitometry using dual-energy X-ray absorptiometry (DXA).

Abstract: Measurement of bone mineral density (BMD) with central dual-energy X-ray absorptiometry (DXA) is the current "gold standard" for diagnosing osteoporosis and for monitoring patients. Errors in demographic information, improper patient positioning, incorrect scan analysis, and mistakes in interpretation can all lead to a wrong clinical decision or action. This paper reviews the fundamentals of positioning, scan analysis, and interpretation for central DXA and highlights some of the common pitfalls that may lead to erroneous results.

Attainment of peak bone mass at the lumbar spine, femoral neck and radius in men and women: relative contributions of bone size and volumetric bone mineral density

Abstract: The age at which peak bone mineral content (peak BMC) is reached remains controversial and the mechanism underlying bone mass "consolidation" is still undefined. The aims of this study were to investigate; (1) the timing of peak BMC by studying bone size and volumetric BMD (vBMD) as separate entities and (2) to determine the relative contributions of bone size and vBMD to bone mass "consolidation". A total of 132 healthy Caucasian children (63 boys and 69 girls, ages 11-19 years) and 134 healthy Caucasian adults (66 men and 68 women, ages 20-50 years) were studied. BMC was measured by DXA at the AP and lateral lumbar spine (LS) femoral neck (FN) and ultradistal radius (UDR). vBMD and bone volume (size) were estimated. Bone mass "consolidation" was examined between age 16 years to the age peak bone values were attained. During growth, BMC and bone size increased steeply with age and approximately 80-90% of peak values were achieved by late adolescence. vBMD at the spine and UDR (in women) increased gradually, but vBMD at the FN and UDR in men remained almost constant. During "consolidation", bone size continued to increase with little change in vBMD. Peak vBMD at the lumbar spine was reached at 22 and 29 years in men and women, respectively, but earlier at the FN at 12 years. At the UDR peak vBMD was achieved at age 19 years in women, with little change in men. In conclusion, peak vBMD and bone size are almost fully attained during late adolescence. Although speculative, the lack of change in vBMD during consolidation implies that the continued increase in bone mass may primarily be due to increases in bone size rather than increases in either trabecular volume, cortical thickness or the degree of mineralisation of existing bone matrix (vBMD). Skeletal growth and maturation is heterogeneous, but crucial in understanding how the origins of osteoporosis may begin during childhood and young adulthood.

Health-related quality of life and radiographic vertebral fracture

Abstract: 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. Conclusion: 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.

Long-term fracture risk following renal transplantation: a population-based study

Abstract: Abnormal bone metabolism is a recognized complication of end-stage renal disease, but fracture risk following renal transplantation has not been well quantified. We followed the 86 Olmsted County, Minnesota, residents who underwent initial renal transplantation in 1965–1995 for 911 person-years (median, 10.6 years per subject) in a retrospective cohort study. Fractures, and possible risk factors, were assessed through review of each subject’s complete community medical records. Altogether, 117 fractures were observed during follow-up extending to 33 years. The cumulative incidence of any fracture at 15 years was 60% versus 20% expected (P<0.001). There was a significantly increased risk of fractures generally [standardized incidence ratio (SIR), 4.8; 95% CI, 3.6–6.4] and vertebral (SIR, 23.1; 95% CI, 12.3–39.6) and foot fractures (SIR, 8.4; 95% CI, 5.1–12.9) especially. Age at first transplantation, renal failure due to diabetes, pancreas transplantation, peripheral neuropathy, peripheral vascular disease and blindness were all associated with overall fracture risk. In a multivariate analysis, however, only age and diabetic nephropathy were independent predictors of fracture risk generally, while higher activity status was protective. Diabetes was the only independent predictor of lower limb fractures, whereas age and osteoporosis history predicted vertebral fractures. Cumulative corticosteroid dosage was not associated with increased fracture risk in this analysis. Despite the fact that our patients had few risk factors for preexisting bone disease attendant to postmenopausal osteoporosis, prior corticosteroid use or renal osteodystrophy, these data indicate that renal transplantation is associated with a significant increase in fracture risk among unselected patients in the community. Diabetic patients, particularly, experience excess lower limb fractures. Patients and their care providers should be aware of this elevated fracture risk, which continues long-term.

Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels.

Abstract: Patients with vascular calcifications often have low bone mineral density (BMD), but it is still uncertain if osteoporosis and peripheral vascular disease (VD) are interrelated and linked by a common pathomechanism. Moreover, data on bone turnover in patients with advanced atherosclerosis are lacking. We measured BMD by dual-energy X-ray absorptiometry (DXA) and quantitative bone ultrasound (QUS), as well as the serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), osteoprotegerin (OPG) and its ligand RANKL, and the urinary concentration of the C-terminal telopeptides of type I collagen (CrossLaps), in 36 patient (20 male and 16 female) with serious atherosclerotic involvement of the carotid and/or femoral artery to investigate the underlying mechanism of vascular and osseous disorders. Thirty age-matched and gender matched healthy individuals served as controls. After adjustment for age, BMD was significantly reduced at the lumbar spine in 23/36 (63%) patients (mean T score −1.71±1.42) and at the proximal femur in 34/36 (93%) patients (neck mean T score −2.5±0.88). Ten patients (27%) had abnormal QUS parameters. Gender and diabetes had no effect on the relationship between vascular calcification and bone density at any site measured. VD subjects had OC and BAP serum levels lower than controls (13.3±3.1 vs 27.7±3.3 ng/ml, P<0.01, and 8.4±2.3 vs 12.5±1.4 μg/l, P<0.01, respectively). Urinary CrossLaps excretion was not significantly different in patients with VD and in controls (257.9±138.9 vs 272.2±79.4 µg/mmol Cr, respectively). Serum OPG and RANKL levels were similar in patients and in controls (3.5±1.07 vs 3.4±1.05 pmol/l, and 0.37±0.07 vs 0.36±0.06 pmol/l, respectively). We proved high occurrence of osteoporosis in VD, with evidence of age and gender independence. Negative bone remodelling balance would be a consequence of reduced bone formation, with no apparent increased activation of the OPG–RANKL system.

Combination of bone mineral density and upper femur geometry improves the prediction of hip fracture

Abstract: Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) is the main determinant of the clinical evaluation of hip fracture risk. However, it has been shown that BMD is not the only predictive factor for hip fracture, but that bone geometry is also important. We studied whether the combination of bone geometry and BMD could further improve the determination of hip fracture risk and fracture type. Seventy-four postmenopausal females (mean age 74 years) with a non-pathologic cervical or trochanteric hip fracture without previous hip fracture or hip surgery constituted the study group. Forty-nine had a cervical fracture (mean age 73 years) and 25 had a trochanteric fracture (mean age 76 years). The control group consisted of 40 age-matched females (mean age 74 years). The geometrical parameters were defined from plain anteroposterior radiographs, and the potential sources of inaccuracy were eliminated as far as possible by using a standardized patient position and calibrated dimension measurements with digital image analysis. BMD was measured at the femoral neck (FEBMD), Ward’s triangle (WABMD), and the trochanter (TRBMD). Stepwise linear regression analysis showed that the best predictor of hip fracture was the combination of medial calcar femoral cortex width (CFC), TRBMD, neck/shaft angle (NSA), and WABMD (r=0.72, r 2=0.52, P<0.001). The area under the receiver operating characteristic curve (ROC) for this model was 0.93, while the area under ROC for TRBMD alone was 0.81. At a specificity of 80%, sensitivity improved from 52.5% to 92.5% with this combination compared with TRBMD alone. The combined predictors of cervical and trochanteric fracture differed, being NSA, CFC, TRBMD, and WABMD for cervical and TRBMD and femoral shaft cortical thickness for trochanteric fracture. In addition, we found a statistically significant correlation between FEBMD and femoral shaft and femoral neck cortex width (r=0.40, P<0.01 and r=0.30, P<0.01, respectively). The results confirm that the combination of BMD and radiological measures of upper femur geometry improve the assessment of the risk of hip fracture and fracture type compared to BMD alone, and that bone geometry plays an important role in the evaluation of bone strength.

The burden of osteoporosis in Latin America.

Abstract: Osteoporosis causes considerable morbidity, mortality and resource utilization in industrialized nations. Its burden is relatively well known in United States and Canada, but poorly studied in the rest of America. This study aimed to discover the burden of osteoporosis in Latin America through a review of literature and publicly available information. In this transversal and descriptive study, information from 20 countries in Latin American region was collected from diverse published and electronic sources. Rheumatologists and bone specialists were asked for additional information through a questionnaire created by consensus. In the year 2000, the population of the Latin America and Caribbean region was 524 million from diverse ethnic origins. On average, 5.5% of the population is 65 years and older. However, with life expectancy higher than 70 years in most countries, a significant growth in the elderly population is anticipated. Studies using World Health Organization's criteria for osteoporosis report 12-18% of women 50 years and older with vertebral osteoporosis and 8-22% with proximal femur osteoporosis. Community based studies in Argentina reported between 263 and 331 hip fractures per 100,000 people 50 years and older. Hospital based studies in Colombia, Chile, Brazil, Mexico, Panama, Peru and Venezuela reported between 40 and 362 hip fractures per 100,000 persons aged 50 and more. Between 17 and 37% of hip fracture sufferers die in the year following fracture. Prevalence of vertebral fractures in community-dwelling women aged 50 and more in Mexico is 19.35%. Data on other fractures are rare. Direct costs of a hip fracture ranged from $4500 to $6000. National gross income per capita in the region ranges from $410 to $7550. The burden of osteoporosis varies across countries with differences in populations and health resources. Considerable support for research is required, since numerous gaps in knowledge need to be filled to face the anticipated explosive growth in osteoporotic fractures.

The importance of bisphosphonate therapy in maintaining bone mass in men after therapy with teriparatide [human parathyroid hormone(1-34)].

Abstract: Teriparatide, the active fragment of human parathyroid hormone (hPTH 1–34), is an anabolic agent for the treatment of osteoporosis. Important questions remain regarding management strategy beyond the recommended 18- to 24-month course of teriparatide treatment. We followed 21 men for up to 2 years after discontinuing teriparatide. Twelve men (57%) chose treatment with bisphosphonate immediately after teriparatide withdrawal, while 9 (43%) opted for no pharmacologic agent. At the end of 1 year lumbar spine bone density increased an additional 5.1±1.0% in the bisphosphonate group, while it declined by 3.7±1.7% in those on no medication (P<0.002). In six men who delayed initiation of bisphosphonate until 1 year after teriparatide withdrawal, their subsequent gains in the second year, 2.6±1.7%, still placed them below the peak gains they achieved on teriparatide. In contrast, the 12 men who began bisphosphonates immediately and continued treatment for the entire 2-year post-PTH period had continued gains at the lumbar spine, 8.9±1.5% above their post-PTH values (P=0.002). For the 4-year period, including 2 years of teriparatide and 2 years of bisphosphonate, the total gains at the lumbar spine were 23.6±2.9%. Men, who received bisphosphonate in only the 2nd year post-teriparatide, had cumulative gains of 11.1±3.4%. Three men who did not receive any bisphosphonate at any time during the post-PTH period had cumulative gains of only 5.5±3.7%. These findings suggest that the use of bisphosphonates following teriparatide is an important component of any strategy utilizing this anabolic drug for osteoporosis in men. The immediate use of bisphosphonates after teriparatide withdrawal may help to optimize gains in bone density at the lumbar spine.

The need for clinical guidance in the use of calcium and vitamin D in the management of osteoporosis: a consensus report

Abstract: A European Union (EU) directive on vitamins and minerals used as ingredients of food supplements with a nutritional or physiological effect (2002/46/EC) was introduced in 2003. Its implications for the use of oral supplements of calcium and vitamin D in the prevention and treatment of osteoporosis were discussed at a meeting organized with the help of the World Health Organization (WHO) Collaborating Center for Public Health Aspects of Rheumatic Diseases (Liege, Belgium) and the support of the WHO Collaborating Center for Osteoporosis Prevention (Geneva, Switzerland). The following issues were addressed: Is osteoporosis a physiological or a medical condition? What is the evidence for the efficacy of calcium and vitamin D in the management of postmenopausal osteoporosis? What are the risks of self-management by patients in osteoporosis? From their discussions, the panel concluded that: (1) osteoporosis is a disease that requires continuing medical attention to ensure optimal therapeutic benefits; (2) when given in appropriate doses, calcium and vitamin D have been shown to be pharmacologically active (particularly in patients with dietary deficiencies), safe, and effective for the prevention and treatment of osteoporotic fractures; (3) calcium and vitamin D are an essential, but not sufficient, component of an integrated management strategy for the prevention and treatment of osteoporosis in patients with dietary insufficiencies, although maximal benefit in terms of fracture prevention requires the addition of antiresorptive therapy; (4) calcium and vitamin D are a cost-effective medication in the prevention and treatment of osteoporosis; (5) it is apparent that awareness of the efficacy of calcium and vitamin D in osteoporosis is still low and further work needs to be done to increase awareness among physicians, patients, and women at risk; and (6) in order that calcium and vitamin D continues to be manufactured to Good Manufacturing Practice standards and physicians and other health care professionals continue to provide guidance for the optimal use of these agents, they should continue to be classified as medicinal products.

Undertreatment with anti-osteoporotic drugs after hospitalization for fracture

Abstract: This study assessed the proportion of patients treated with anti-osteoporotic drugs during the 1-year period after hospitalization for a fracture, and the influence of a guideline in the period 1998–2000 on the likelihood of receiving treatment for osteoporosis after a fracture. Patients were assessed retrospectively for anti-osteoporotic drug use during a 1-year period following hospitalization for non-traumatic fracture. The PHARMO system, a population-based database (n=865,000) containing drug and hospitalization data of community-dwelling inhabitants of defined areas in the Netherlands, was used. The study population comprised 1654 patients age 50 years and over who were admitted to hospital for a fracture resulting from a fall during the period 1998–2000. The treatment rate of newly treated patients and the change in treatment rate throughout the period 1998–2000 were the outcome measures. The majority of these patients were women (73%), and had femur fractures (51%). In total, 247 out of 1654 patients (15%) were prescribed anti-osteoporotic drugs within 1 year after discharge from the hospital. Of these 247 patients, 86 were newly treated, mainly with bisphosphonates in the year after discharge following the fracture, yielding a new treatment rate of 5%. The likelihood of receiving treatment for osteoporosis following fracture did not change with the calendar year of fracture (OR 0.95; 95% CI: 0.68–1.30). The result of this study shows that despite the introduction of an osteoporosis treatment guideline in 1999 recommending treatment for fracture patients, most of the time, fracture patients are not being treated for osteoporosis. Thus, to a large extent, osteoporosis remains under-treated.

Ibandronate in osteoporosis: preclinical data and rationale for intermittent dosing

Abstract: Ibandronate is a highly potent, nitrogen-containing bisphosphonate. Unlike most other bisphosphonates, it is under clinical development for both oral and intravenous (i.v.) administration. Ibandronate can be used in convenient intermittent regimens that may optimize therapeutic outcome with enhanced compliance by patients. The preclinical pharmacokinetics (PK) and pharmacology of ibandronate have been extensively explored in a large preclinical development program involving various recommended animal models of human osteoporosis. These experimental studies of ibandronate indicate that the preclinical pharmacology and PK profile of ibandronate are broadly similar to those of other nitrogen-containing bisphosphonates. The efficacy of intermittent administration of subcutaneous (s.c.) and i.v. ibandronate has been demonstrated in four animal models (rat, dog, minipig, and monkey). Thus in rats, dogs, and monkeys with estrogen depletion, and in minipigs with glucocorticoid-induced bone loss, ibandronate administered s.c. or i.v. with extended intervals between doses reduces bone turnover, increases bone mineral density, and maintains bone quality in a dose-dependent manner. Furthermore, studies in rats and dogs comparing continuous and intermittent treatment schedules indicate similar efficacy when the same cumulative dose is applied over the duration of the study. These studies with ibandronate illustrate the concept that the total cumulative dose of bisphosphonate administered determines the response, independent of whether the dose is given daily or less frequently in a given time period. The efficacy of intermittent regimens has also been verified in models of secondary osteoporosis due to secondary hyperparathyroidism or immobilization (both in rats), or due to glucocorticoids in minipigs. Important factors for determining efficacy and the magnitude of response are the doses given, the length of the interval between doses, and the underlying bone turnover rate. The mechanisms underlying the remarkable efficacy of intermittent bisphosphonate dosing are not fully understood and further research is needed. Importantly, ibandronate is the only bisphosphonate so far proven to reduce the risk of vertebral fractures significantly with a between-dose interval >2 months, in a prospective clinical trial. Collectively, the preclinical studies on ibandronate have provided a sound basis for the design of the convenient regimens currently being examined in clinical trials.

Calcaneal ultrasound predicts early postmenopausal fractures as well as axial BMD. A prospective study of 422 women

Abstract: Low calcaneal ultrasound measurement (quantitative ultrasound, QUS) has been shown to predict fractures in elderly women. However, only a few studies have examined its ability to predict perimenopausal and early postmenopausal fractures. We conducted a prospective population-based cohort study to assess the capability of QUS as compared to axial BMD measurement to predict early postmenopausal fractures at that age. Four hundred and twenty-two women (mean age 59.6, range 53.7–65.3) from the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) were randomly chosen to undergo a calcaneal ultrasound measurement. In all, 9.4% of these women were premenopausal at the time of measurement. Thirty-two follow-up fractures were reported during the mean follow-up of 2.6 years (SD 0.7). These were validated with patient record perusal. Broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (SI) were significantly lower among women with than without fracture (P-values 0.028, 0.001 and 0.001, respectively). Mean T-score adapted from SI was −1.5 (95% CI −1.7 to −1.2) for fracture group and −1.0 (95% CI −1.1 to −0.9) for the non-fracture group. All QUS measurements predicted fractures even after adjusting for age, weight, height, previous fracture history, femoral neck BMD and use of hormone replacement therapy according to Cox regression. The adjusted hazard ratios (HR, 95% confidence interval) of a follow-up fracture for a 1 SD decrease were 1.80 (1.27–2.56), 1.72 (1.21–2.45) and 1.43 (1.01–2.03) for SOS, SI and BUA, respectively. Similarly, the adjusted HR for a 1 SD decrease of spinal BMD was 1.27 (0.85–1.94) and for that of femoral neck BMD 1.14 (0.78–1.70). In receiver operator analyses, the area under the curve (AUC) was greatest for QUS measurements: SOS (AUC=0.68), stiffness (AUC=0.67), BUA (AUC=0.62) and least for lumbar BMD (AUC=0.56), while and femoral neck BMD (AUC=0.59). The difference between AUCs was statistically significant between SI and lumbar BMD (P=0.02, Duncan’s P=0.07). We conclude that low calcaneal QUS predicts early postmenopausal fractures as well as or even better than axial BMD.

Efficacy of alphacalcidol and calcitriol in primary and corticosteroid-induced osteoporosis: a meta-analysis of their effects on bone mineral density and fracture rate.

Abstract: Vitamin D metabolites alphacalcidol and calcitriol (D-hormones) have been investigated for two decades, but few and conflicting results are available from high-quality randomized controlled trials. Our objectives were to provide an evidence-based update quantitatively summarizing their efficacy on bone mineral density (BMD) and fracture rate. We performed a systematic research of any randomized controlled trial containing relevant data, peer review, data extraction and quality scoring blinded for authors and data sources, and comprehensive meta-analyses of the relevant data. Inclusion criteria were: randomized controlled study, calcitriol or alphacalcidol, BMD or fractures in healthy/osteopenic/osteoporotic patients exposed or not to corticosteroids (CS). Analyses were performed in a conservative fashion using professional dedicated softwares and stratified by outcome, target patients, study quality, and control-group type. Results were expressed as effect size (ES) for bone loss or relative risk (RR) for fracture while allocated to D-hormones vs control. Publication bias and robustness were investigated. Of the trials that were retrieved and subsequently reviewed, 17 papers fitted the inclusion criteria and were assessed. Quality scores ranged from 20 to 100%, the mean (standard deviation) being 72 (22)%. Calcitriol and alphacalcidol were found to have the same efficacy on all outcomes at p>0.13. We globally assessed D-hormones effects in preventing bone loss in patients not exposed to CS, and found positive effect: ES=0.39 (p<0.001). For lumbar spine, this particular effect was 0.43 (p<0.001). D-hormones significantly reduced the overall fracture rates: RR=0.52 (0.46; 0.59) and both vertebral and non-vertebral fractures: RR=0.53 (0.47; 0.60) and RR=0.34 (0.16; 0.71), respectively. No statistical difference in response was observed between results from studies on healthy and osteoporotic patients or depending on the fact that controls were allowed to calcium supplementation. Treatment with D-hormones was evaluated for maintaining spinal bone mass in five trials of patients with CS-induced osteoporosis, and provided ES=0.43 at p<0.001. Only two studies specifically addressed the effects of calcitriol on spinal fracture rate. None of them provided significant results, and the global RR did not reach the significance level as well: RR=0.33 (0.07; 1.51). Our data demonstrated efficacy for DH on bone loss and fracture prevention in patients not exposed to CS and on bone loss in patients exposed to CS, in the light of the most reliable scientific evidence. Their efficacy in reducing the number of fractures in patients exposed to CS remains to be determined.

Periprosthetic bone remodelling of two types of uncemented femoral implant with proximal hydroxyapatite coating: a 3-year follow-up study addressing the influence of prosthesis design and preoperative bone density on periprosthetic bone loss.

Abstract: Periprosthetic bone loss is a major cause of concern in patients undergoing total hip arthroplasty (THA). Further studies are required to identify the factors determining the pattern of bone remodelling following THA and obtain improvements in the design and durability of prostheses. In this study, we monitored periprosthetic bone loss around two different types of hydroxyapatite coated femoral implant over a 3-year period to evaluate their design and investigate the relationship with the preoperative bone mineral density (BMD) at the spine, hip and forearm. Sixty patients (35 F, 25 M, mean age 63 years, range 46–75 years) undergoing THA were randomised to either the Anatomic Benoist Girard (ABG) or Mallory-Head (MH) femoral stem. Preoperative dual-energy X-ray absorptiometry (DXA) scans were acquired of the posteroanterior (PA) and lateral lumbar spine, the contralateral hip and the non-dominant forearm. Postoperative DXA scans were performed to measure periprosthetic BMD at 10 days (treated as baseline), 6 weeks, and 3, 6, 12, 24 and 36 months after THA using a standard Gruen zone analysis. Results were expressed as the percentage change from baseline and the data examined for the differences in bone loss between the different Gruen zones, between the ABG and MH stems, and the relationship with preoperative BMD. A total of 50 patients (24 ABG, 26 MH) completed the study. Three months after THA there was a statistically significant BMD decrease in every Gruen zone that varied between 5.6% and 13.8% for the ABG prosthesis and between 3.8% and 8.7% for the MH prosthesis. Subsequently, in most zones BMD reached a plateau or showed a small recovery. However, BMD continued to fall in Gruen zones 1 and 7 in ABG patients and Gruen zone 1 in MH patients. Bone loss was less in every Gruen zone in MH patients compared with ABG with the largest difference (10%, P=0.018) in Gruen zone 7. Highly significant relationships were found between periprosthetic bone loss and preoperative BMD measured at the PA spine (P<0.001), total hip (P=0.004) and total distal radius (P<0.001). This study showed differences between two different designs of hydroxyapatite-coated implant that confirmed that prosthesis design influences periprosthetic bone loss. The study also showed that patients’ bone density measured at the spine, hip or forearm at the time of operation was a major factor influencing bone loss around the femoral stem.

Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in community dwelling postmenopausal Hungarian women

Abstract: Hypovitaminosis D can result in low bone mass. The prevalence of hypovitaminosis D has public health implications, especially where data are lacking. Since diet and sunlight are the two souces of vitamin D, the results obtained in one geographical region may not be universally applicable. The aim of this study is to characterize the prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in community dwelling postmenopausal Hungarian women. We determined serum levels of 25-hydroxyvitamin D (25-OH-D), PTH, osteocalcin (OC), degradation products of C-terminal telopeptides of type-I collagen (CTx), dietary calcium intake and BMD at L2–L4 lumbar spine (LS) and femur neck (FN) in 319 randomly selected ambulatory postmenopausal women. The prevalence of hypovitaminosis D (serum 25-OH-D≤50 nmol/l) was 56.7%. On comparing patients with normal and low 25-OH-D, a significant difference was found in age (61.6±8.5 years versus 67.3±9.9 years; P<0.001), PTH (3.9±1.9 pmol/l versus 4.3±2.7 pmol/l; P<0.05), FN BMD (0.802±0.123 g/cm2 versus 0.744±0.125 g/cm2; P<0.001) and dietary calcium intake (714.4±199.4 g/day versus 607.9±233 g/day; P<0.001). Osteoporotic patients had a significantly lower 25-OH-D (37.6±19.8 nmol/l versus 56.4±24 nmol/l; P<0.001) and dietary calcium intake (519.2±244.5 mg/day versus 718.2±164.3 mg/day; P<0.001). After controlling for all other variables, 25-OH-D was found to be significantly associated with age, the average hours of sunshine in the 3 months prior to 25-OH-D level determination and dietary calcium intake (r2=0.190; P<0.001). For FN BMD, significant independent predictors were age, body mass index, 25-OH-D and dietary calcium intake (r2=0.435; P<0.001). The prevalence of hypovitaminosis D during spring, summer, autumn and winter was 71%, 46.3%, 49.4% and 56.7%, respectively. There was significant seasonal variation in 25-OH-D, PTH, OC, calcium intake and FN BMD. There is a high prevalence of hypovitaminosis D in healthy postmenopausal Hungarian women, and FN BMD is associated with serum 25-OH-D and dietary calcium intake.