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Steven Boonen

Publications and source records attributed to Steven Boonen.

36 records · Page 2Linked to original sources

Femoral neck trabecular microstructure in ovariectomized ewes treated with calcitonin: MRI microscopic evaluation.

UNLABELLED: Ovariectomy induces deterioration of the trabecular structure in the femoral neck of ewes, as depicted by MR microscopic imaging. This structural deterioration is prevented by salmon calcitonin treatment. INTRODUCTION: This study evaluated the trabecular (Tb) microarchitecture of an ovariectomy (OVX)-induced osteoporotic model in ewes and determined the effects of salmon calcitonin (sCT), an osteoclast inhibitor, on the Tb structure. This is the first report of OVX-induced changes in the Tb structure in the femoral neck in the ewes and effect of sCT on the microarchitecture. MATERIALS AND METHODS: Ewes (5-8 years old, n = 28) were equally allocated into sham (Sham), OVX injected with vehicle, or OVX injected with sCT at 50 or 100 IU, three injections per week. They were killed 6 months after OVX. The femoral neck was examined with an MR imager at 9.4 T in axial, coronal, and sagittal planes. An internal calibration procedure as a means of standardizing image analysis was used to adjust the segmentation threshold. Data from all three planes were averaged. RESULTS AND CONCLUSIONS: Compared with Sham, OVX induced significant changes (p < 0.0125) in the MRI-derived femoral neck Tb structure: Tb bone volume fraction (BV/TV), -18%; Tb number, -20%; Tb separation, +23%; number of free ends, +28%; number of nodes, -39%; number of Tb branches, -23%; mean length of Tb branches, -19%. Compared with OVX, treatment of sCT at 100 IU significantly improved all the Tb structural parameters to the Sham level (p < 0.0001 approximately p = 0.0281), whereas 50 IU significantly increased the Tb number and the mean length of the Tb branches. BV/TV explained 74% of the variation of compressive stress of the trabecular cylinder cores of the femoral neck. Combining all structural parameters in a multivariate regression analysis significantly improved the explanation to 84%, and adding BMD further improved the predictive ability of the model to 92%. We conclude that OVX induces deterioration of the MRI-derived Tb microstructure in the femoral neck of ewes. sCT treatment prevents OVX-induced changes. The femoral neck microarchitecture significantly correlates with its biomechanical properties. Combining microstructural parameters with BMD further improves the prediction of bone biomechanical properties. The effects of sCT on OVX ewes may help explain reduced fracture risk in postmenopausal osteoporotic women treated with sCT.

Animals↗

Evidence from data searches and life-table analyses for gender-related differences in absolute risk of hip fracture after Colles' or spine fracture: Colles' fracture as an early and sensitive marker of skeletal fragility in white men.

UNLABELLED: Based on data searches and life-table analyses, we determined the long-term (remaining lifetime) and short-term (10- and 5-year) absolute risks of hip fracture after sustaining a Colles' or spine fracture and searched for potential gender-related differences. In aging men, Colles' fractures carry a higher absolute risk for hip fracture than spinal fractures in contrast to women. These findings support the concept that forearm fracture is an early and sensitive marker of male skeletal fragility. INTRODUCTION: Colles' fracture occurrence has been largely ignored in public health approaches to identify target populations at risk for hip fracture. The aim of this study was to estimate the long-term and short-term absolute risks of hip fracture after sustaining a Colles' or spine fracture and to search for potential gender-related differences in the relationship between fracture history and future fracture risk. MATERIALS AND METHODS: To determine the long-term (remaining lifetime) and short-term (10- and 5-year) absolute risks of hip fracture, we applied life-table methods using U.S. age- and sex-specific hip fracture incidence rates, U.S. age-specific mortality rates for white women and men, pooled hazard ratios for mortality after Colles' and spine fracture, and pooled relative risks for hip fracture after Colles' and spine fracture, estimated from cohort studies by standard meta-analytic methods. RESULTS: Our results indicate that the estimated remaining lifetime risks are dependent on age in both genders. In women, remaining lifetime risks increase until the age of 80 years, when they start to decline because of the competing probabilities of fracture and death. The same pattern is found in men until the age of 85 years, the increment in lifetime risk being even more pronounced. As expected, the risk of sustaining a hip fracture was found to be higher in postmenopausal women with a previous spine fracture compared with those with a history of Colles' fracture. In men, on the other hand, the prospective association between fracture history and subsequent hip fracture risk seemed to be strongest for Colles' fracture. At the age of 50, for example, the remaining lifetime risk was 13% in women with a previous Colles' fracture compared with 15% in the context of a previous spine fracture and 9% among women of the general population. In men at the age of 50 years, the corresponding risk estimates were 8%, 6%, and 3%, respectively. Similar trends were observed when calculating 5- and 10-year risks. CONCLUSIONS: In aging men, Colles' fractures carry a higher absolute risk for hip fracture than spinal fractures in contrast to women. These findings support the concept that forearm fracture is an early and sensitive marker of male skeletal fragility. The gender-related differences reported in this analysis should be taken into account when designing screening and treatment strategies for prevention of hip fracture in men.

Age Factors↗

Identifying postmenopausal women with osteoporosis by calcaneal ultrasound, metacarpal digital X-ray radiogrammetry and phalangeal radiographic absorptiometry: a comparative study.

Identifying women with osteoporosis remains a clinical challenge, as it may not be feasible or cost-effective to recommend dual-energy X-ray absorptiometry (DXA) for all postmenopausal women. In this regard, quantitative ultrasound (QUS) has emerged as an attractive screening tool because of the (relatively) low cost and because QUS and DXA-assessed BMD appear to be equally predictive of future (hip) fracture risk. The objective of this study was to compare the ability of calcaneal QUS to identify osteoporosis with two alternative potential screening methods: digital X-ray radiogrammetry (DXR) and radiographic absorptiometry (RA). We enrolled a total of 221 postmenopausal community-dwelling Caucasian women aged 50-75 years. Bone mineral density (BMD) was measured at the lumbar spine and the total hip regions using DXA. Calcaneal ultrasound attenuation and velocity were assessed using QUS and metacarpal and phalangeal bone density were estimated by the use of DXR and RA, respectively. Receiver operating characteristic (ROC) curves were constructed by calculating the specificity and sensitivity of QUS, DXR, and RA at different cut-point values in discriminating osteoporosis, as defined by a T-score below -2.5 at the spine or hip using DXA, and the areas under the curves (AUCs) were computed. The sensitivity for identifying women with osteoporosis was 67.6% [95% confidence interval (CI), 50.2-82.0%] using QUS and was 76.9% (95% CI, 60.7-88.8%) and 82.9% (95% CI, 67.9-92.8%), respectively, using DXR and RA. The negative predictive value (NPV, the proportion of patients with a negative test who have no osteoporosis) was 90% for QUS, compared with an NPV of 94% for both DXR and RA. These data suggest that metacarpal DXR and phalangeal RA may be as effective as calcaneal QUS for targeting DXA testing in high-risk postmenopausal women.

Absorptiometry, Photon↗

Role of the androgen receptor in skeletal homeostasis: the androgen-resistant testicular feminized male mouse model.

UNLABELLED: The role of androgen receptor-mediated androgen action on bone was investigated in testicular feminized male (Tfm) mice. Cortical bone was found to be unresponsive to testosterone (T) in orchidectomized Tfm mice, whereas cortical thickness as well as trabecular BMD and structure were fully maintained by T in the corresponding Tabby control mice. These data show an essential role for androgen receptor-mediated androgen action in periosteal bone formation. INTRODUCTION: Androgens can affect the male skeleton both directly-through activation of the androgen receptor (AR)-and indirectly-through stimulation of estrogen receptors after aromatization. We assessed the importance of AR-mediated androgen action on bone in a mouse model of androgen resistance. MATERIALS AND METHODS: Eight-week-old androgen-resistant testicular feminized male (Tfm) and Tabby control mice were orchidectomized (ORX) and treated for 4 weeks with a slow-release testosterone (T) pellet (delivering 167 microg/day) or a placebo pellet. A comprehensive analysis of the skeletal effects of androgen deficiency and replacement was performed using histomorphometry, QCT, and biochemical assessment of bone turnover. RESULTS: As expected, T increased trabecular BMD, volume, number, and width in ORX Tabby mice. In ORX Tfm mice, however, T had less effect on trabecular BMD and no effect on trabecular bone structure. T action on trabecular bone was associated with opposite changes in bone turnover: trabecular and endocortical bone turnover and serum levels of osteocalcin were all reduced by T in ORX Tabby mice, but not in ORX Tfm mice. T also increased cortical thickness (+16%), area, and density in ORX Tabby mice, but not in Tfm mice, resulting in greater bone strength in the Tabby control strain. The positive effects of T on cortical bone reflected a stimulatory effect on periosteal bone formation (+137%), which was again absent in Tfm mice. CONCLUSIONS: These data show that, in male mice, AR-mediated T action is essential for periosteal bone formation and contributes to trabecular bone maintenance.

Androgen-Insensitivity Syndrome↗

Musculoskeletal rehabilitation in osteoporosis: a review.

Measures of musculoskeletal rehabilitation play an integral part in the management of patients with increased fracture risk because of osteoporosis or extraskeletal risk factors. This article delineates current scientific evidence concerning nonpharmacologic approaches that are used in conjunction with pharmacotherapy for prevention and management of osteoporosis. Fractures caused by osteoporotic fragility may be prevented with multidisciplinary intervention programs, including education, environmental modifications, aids, and implementation of individually tailored exercise programs, which are proved to reduce falls and fall-related injuries. In addition, strengthening of the paraspinal muscles may not only maintain BMD but also reduce the risk of vertebral fractures. Given the strong interaction between osteoporosis and falls, selection of patients for prevention of fracture should be based on bone-related factors and on risk factors for falls. Rehabilitation after vertebral fracture includes proprioceptive dynamic posture training, which decreases kyphotic posturing through recruitment of back extensors and thus reduces pain, improves mobility, and leads to a better quality of life. A newly developed orthosis increases back extensor strength and decreases body sway as a risk factor for falls and fall-related fractures. Hip fractures may be prevented by hip protectors, and exercise programs can improve strength and mobility in patients with hip fracture. So far, there is no conclusive evidence that coordinated multidisciplinary inpatient rehabilitation is more effective than conventional hospital care with no rehabilitation professionals involved for older patients with hip fracture. Further studies are needed to evaluate the effect of combined bone- and fall-directed strategies in patients with osteoporosis and an increased propensity to falls.

Accidental Falls↗

Safety and efficacy of risedronate in reducing fracture risk in osteoporotic women aged 80 and older: implications for the use of antiresorptive agents in the old and oldest old.

OBJECTIVES: To determine the efficacy of risedronate in reducing vertebral fracture risk in women aged 80 and older with osteoporosis. DESIGN: Pooled analysis of data from three randomized, double-blind, controlled, 3-year-fracture-endpoint trials conducted from November 1993 to April 1998: Hip Intervention Program (HIP), Vertebral Efficacy with Risedronate Therapy-Multinational (VERT-MN), and VERT-North America (NA). SETTING: Office-based practices, research centers, and osteoporosis clinics in Europe, North America, and Australia. PARTICIPANTS: Osteoporotic (femoral neck bone mineral density T-score < -2.5 standard deviations or at least one prevalent vertebral fracture) women aged 80 and older. INTERVENTION: Patients received placebo (n=688) or risedronate 5 mg/d (n=704) for up to 3 years. All patients received 1,000 mg/d calcium and, if baseline levels were low, up to 500 IU/d vitamin D. MEASUREMENTS: Cumulative incidence of new vertebral fractures. RESULTS: After 1 year, the risk of new vertebral fractures in the risedronate group was 81% lower than with placebo (95% confidence interval=60-91%; P<.001). The number of women who needed to be treated to prevent one new vertebral fracture after 1 year was 12. This early onset of efficacy was consistent across the clinical programs, and antifracture efficacy was confirmed over 3 years. Risedronate was well tolerated, with a safety profile comparable with that of placebo. CONCLUSION: These findings provide the first evidence that, even in the very old, reducing bone resorption rate remains an effective treatment strategy for osteoporosis. Because each therapeutic agent used for the treatment of osteoporosis may have unique characteristics, the observations made in this study should not be assumed to apply to other bisphosphonates.

Aged↗

Androgens and bone.

Loss of estrogens or androgens increases the rate of bone remodeling by removing restraining effects on osteoblastogenesis and osteoclastogenesis, and also causes a focal imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, androgens, as well as estrogens, maintain cancellous bone mass and integrity, regardless of age or sex. Although androgens, via the androgen receptor (AR), and estrogens, via the estrogen receptors (ERs), can exert these effects, their relative contribution remains uncertain. Recent studies suggest that androgen action on cancellous bone depends on (local) aromatization of androgens into estrogens. However, at least in rodents, androgen action on cancellous bone can be directly mediated via AR activation, even in the absence of ERs. Androgens also increase cortical bone size via stimulation of both longitudinal and radial growth. First, androgens, like estrogens, have a biphasic effect on endochondral bone formation: at the start of puberty, sex steroids stimulate endochondral bone formation, whereas they induce epiphyseal closure at the end of puberty. Androgen action on the growth plate is, however, clearly mediated via aromatization in estrogens and interaction with ERalpha. Androgens increase radial growth, whereas estrogens decrease periosteal bone formation. This effect of androgens may be important because bone strength in males seems to be determined by relatively higher periosteal bone formation and, therefore, greater bone dimensions, relative to muscle mass at older age. Experiments in mice again suggest that both the AR and ERalpha pathways are involved in androgen action on radial bone growth. ERbeta may mediate growth-limiting effects of estrogens in the female but does not seem to be involved in the regulation of bone size in males. In conclusion, androgens may protect men against osteoporosis via maintenance of cancellous bone mass and expansion of cortical bone. Such androgen action on bone is mediated by the AR and ERalpha.

Androgens↗

Estrogens are essential for male pubertal periosteal bone expansion.

The skeletal response to estrogen therapy was studied in a 17-yr-old boy with congenital aromatase deficiency. As expected, estrogen therapy (1 mg estradiol valeriate/d from age 17 until 20 yr) normalized total and free testosterone and reduced the rate of bone remodeling. Dual-energy x-ray absorptiometry-assessed areal bone mineral density (BMD) of the lumbar spine and femoral neck increased significantly (by 23% and 14%, respectively), but peripheral quantitative computed tomography at the ultradistal radius revealed no gain of either trabecular or cortical volumetric BMD. The increase in areal BMD was thus driven by an increase in bone size. Indeed, longitudinal bone growth (height, +8.5%) and especially cross-sectional area of the radius (+46%) and cortical thickness (+12%), as measured by peripheral quantitative computed tomography, increased markedly during estrogen treatment. These findings demonstrate that androgens alone are insufficient, whereas estrogens are essential for the process of pubertal periosteal bone expansion typically associated with the male bone phenotype.

Adolescent↗

[Falls among community-dwelling elderly: a pilot study of prevalence, circumstances and consequences in Flanders].

This pilot study was designed to examine prevalence, circumstances and consequences of falls among 131 community-dwelling elderly (mean age = 76.7 y.; SD = 5.4; response = 29.8%). Based on a retrospective analysis, 39.7% of our study population had experienced one (65.4%) or more (34.6%) falls in the preceding year. Falls appeared to occur predominantly while getting up from the bed, chair or bath (18%), cycling (14%), walking on an uneven surface (14%) and during household work (14%). Fall-related injuries were reported in 67.3% of the fallers, fractures in 17.4%. Additionally, a majority of fallers (63.5%) experienced a mild to serious form of anxiety, 48.1% consulted a general practitioner after the fall and 34.6% was hospitalised. In line with data reported in the literature, falls are a common problem in Flanders and are associated with a negative impact on the physical and psychosocial well being of the elderly population. We conclude that there is an urgent need to develop and implement preventive measures as well as multidisciplinary strategies to identify, assess and target high-risk persons for falling.

Accidental Falls↗

Effect of 6-month whole body vibration training on hip density, muscle strength, and postural control in postmenopausal women: a randomized controlled pilot study.

UNLABELLED: High-frequency mechanical strain seems to stimulate bone strength in animals. In this randomized controlled trial, hip BMD was measured in postmenopausal women after a 24-week whole body vibration (WBV) training program. Vibration training significantly increased BMD of the hip. These findings suggest that WBV training might be useful in the prevention of osteoporosis. INTRODUCTION: High-frequency mechanical strain has been shown to stimulate bone strength in different animal models. However, the effects of vibration exercise on the human skeleton have rarely been studied. Particularly in postmenopausal women-who are most at risk of developing osteoporosis-randomized controlled data on the safety and efficacy of vibration loading are lacking. The aim of this randomized controlled trial was to assess the musculoskeletal effects of high-frequency loading by means of whole body vibration (WBV) in postmenopausal women. MATERIALS AND METHODS: Seventy volunteers (age, 58-74 years) were randomly assigned to a whole body vibration training group (WBV, n = 25), a resistance training group (RES, n = 22), or a control group (CON, n = 23). The WBV group and the RES group trained three times weekly for 24 weeks. The WBV group performed static and dynamic knee-extensor exercises on a vibration platform (35-40 Hz, 2.28-5.09g), which mechanically loaded the bone and evoked reflexive muscle contractions. The RES group trained knee extensors by dynamic leg press and leg extension exercises, increasing from low (20 RM) to high (8 RM) resistance. The CON group did not participate in any training. Hip bone density was measured using DXA at baseline and after the 6-month intervention. Isometric and dynamic strength were measured by means of a motor-driven dynamometer. Data were analyzed by means of repeated measures ANOVA. RESULTS: No vibration-related side effects were observed. Vibration training improved isometric and dynamic muscle strength (+15% and + 16%, respectively; p < 0.01) and also significantly increased BMD of the hip (+0.93%, p < 0.05). No changes in hip BMD were observed in women participating in resistance training or age-matched controls (-0.60% and -0.62%, respectively; not significant). Serum markers of bone turnover did not change in any of the groups. CONCLUSION: These findings suggest that WBV training may be a feasible and effective way to modify well-recognized risk factors for falls and fractures in older women and support the need for further human studies.

Aged↗

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

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.

Aged↗

Costs of care after hospital discharge among women with a femoral neck fracture.

A prospective study was done among women who are postmenopausal and who had a displaced femoral neck fracture. The objective was to identify potential predictors of medical care costs during the 1-year after hospital discharge, and to examine the impact of the type of surgical procedure. The design was a 1-year prospective cohort study reflecting day-to-day clinical practice. At four hospitals, 84 women 50 years or older with a displaced femoral neck fracture were enrolled on a consecutive basis. Direct costs of medical care were documented during the 1-year after hospital discharge. Multivariate analyses were done to explore potential predictors of costs. Three fracture groups were defined by the time of surgical repair. Patients in the total hip arthroplasty group were significantly younger than those in the hemiarthroplasty and the internal fixation groups (mean age, 71 years, 81 years, and 80 years, respectively). The mean direct costs of medical care during the 1-year followup after hospital discharge were not significantly different after total hip arthroplasty, hemiarthroplasty, or internal fixation because of large cost variations among patients. A multivariate model identified increasing age and living in an institution at the time of the injury as the two significant determinants of increased medical costs during the 1-year followup after hospital discharge. Direct costs of medical care during the 1-year after hospital discharge do not seem to be associated with the type of surgical procedure. Increasing age and living in an institution at the time of the injury are strong predictors of increased costs.

Aftercare↗

Falls and fractures in postmenopausal women: a review.

Older people are a major risk group for falls. 35-40% of over-65s living at home fall at least once a year, and between a third and a half of these fall twice or more. The figure rises to 50% for the over-80s. Falls contribute to the occurrence of fractures. Of all the fractures linked to osteoporosis and falls, hip fractures are the most important in terms of early death, functional dependence, and costs of care. Many identifiable risk factors have been shown to contribute to hip fracture risk, including low bone density, previous fractures, clinical risk factors for falls, and low body weight. Interaction has been found between falls and osteoporosis in the occurrence of fractures. Prospective studies are needed to evaluate whether a combined bone- and fall-directed therapy can further decrease the risk for fractures in patients with low bone density and an increased fall risk.

Accidental Falls↗

Colles fracture, spine fracture, and subsequent risk of hip fracture in men and women. A meta-analysis.

BACKGROUND: In postmenopausal women, a history of any fracture is an important risk factor for a future hip fracture. Whether similar findings apply to aging men remains to be established. We conducted a systematic review and meta-analysis of the literature to compare men and women with respect to the relative risk of hip fracture after a wrist or spine fracture. METHODS: Studies published in full from January 1982 through September 2002 in English, French, or German were identified from the PubMed database and from reference lists of retrieved articles. We included cohort studies that reported fractures associated with minimal trauma of the wrist or spine as a risk factor for a subsequent hip fracture among (white) women and men who were fifty years old or older. Data were extracted by two independent reviewers and were checked for accuracy in a second review. Differences in assessments were resolved by consensus of the two reviewers. RESULTS: Nine cohort studies were included in this meta-analysis: five studies were conducted in the United States and four, in Europe. After homogeneity of association was demonstrated across all studies, a fixed-effects meta-analysis was used to calculate pooled relative risks with 95% confidence intervals. Among postmenopausal women, the relative risks for a future fracture of the hip after a fracture of the wrist or spine were 1.53 (95% confidence interval, 1.34 to 1.74; p < 0.001) and 2.20 (95% confidence interval, 1.92 to 2.51; p < 0.001), respectively. In older men, these relative risks were 3.26 (95% confidence interval, 2.08 to 5.11; p < 0.001) and 3.54 (95% confidence interval, 2.01 to 6.23; p < 0.001), respectively. Fractures of the distal part of the radius increased the relative risk of hip fracture significantly more in men than in women (p = 0.002). The impact of a spine fracture, conversely, did not differ between genders (p = 0.11). Sensitivity analyses with use of random-effects methodology confirmed these findings to be robust. CONCLUSIONS: This meta-analysis suggests that a previous spine fracture has an equally important impact on the risk of a subsequent hip fracture in both genders. The prospective association between a Colles fracture and a subsequent hip fracture, however, is significantly stronger among men than among postmenopausal women. Men with a Colles fracture are at high risk for a future hip fracture and should be evaluated as candidates for preventive measures.

Age Factors↗

The relationship among history of falls, osteoporosis, and fractures in postmenopausal women.

OBJECTIVE: To study the relative contribution of osteoporosis and falls to the occurrence of symptomatic fractures in postmenopausal women. DESIGN: Retrospective survey of current osteoporosis in relation to falls and fractures in the preceding year. SETTING: Patients of general practitioners of the area around a Belgian university. PARTICIPANTS: A total of 2649 consecutive postmenopausal women (mean age, 61y; range, 45-91y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Current bone density measurements (single-photon absorptiometry in the forearm) were analyzed in relation to self-reported incidence of falls and fractures in the preceding year. RESULTS: Osteoporosis was found in 15% of the patients, 19% reported 1 or more falls during the preceding year, and 1.8% had a fracture during the preceding year. The age-adjusted risk for a fracture in the past 12 months for a 1 standard deviation decrease in bone density was 1.9 (95% confidence interval [CI], 1.4-2.5; P<.01). Adjusted risk for age, bone density, and body mass index (BMI) for a fracture in the past 12 months in patients who reported a fall was 6.0 (95% CI, 3.1-11.5; P<.001). Compared with women without osteoporosis and without a fall, women with osteoporosis without a fall had an age- and BMI-adjusted fracture risk of 2.8 (95% CI, 0.6-12.8; P<.10), and women with osteoporosis and a fall had an adjusted-fracture risk of 24.8 (95% CI, 6.9-88.6; P<.0001). CONCLUSIONS: Falls are a major contributing factor to the occurrence of symptomatic fractures in postmenopausal women, independent of and additive to the risk attributable to age and osteoporosis.

Absorptiometry, Photon↗

Osteoporosis and the growth hormone-insulin-like growth factor axis.

Osteoporosis is the result of an imbalance between bone resorption and bone formation. Currently, mainly drugs that inhibit bone resorption are available for the treatment of osteoporosis. A new approach in the treatment of osteoporosis is the use of anabolic agents that increase bone turnover, both bone formation and resorption. Growth hormone (GH) and insulin-like growth factors (IGFs) are essential in the development and growth of the skeleton and for the maintenance of bone mass and density. We will review the evidence of GH and IGF-I in the pathophysiology and treatment of osteoporosis.

Adult↗

Musculoskeletal effects of the recombinant human IGF-I/IGF binding protein-3 complex in osteoporotic patients with proximal femoral fracture: a double-blind, placebo-controlled pilot study.

The administration of recombinant human IGF-I complexed with its predominant binding protein IGF binding protein-3 (rhIGF-I/IGFBP-3) may allow the safe administration of higher doses of IGF-I than can be accomplished with rhIGF-I alone. The aim of this randomized, double-blind, placebo- controlled pilot study was to evaluate the short-term safety and musculoskeletal effects of rhIGF-I/IGFBP-3 in older women (aged 65-90 yr) with recent hip fracture. Within 72 h after the event, 30 patients received continuous administration of either placebo (n = 10), 0.5 mg/kg.d rhIGF-I/IGFBP-3 (n = 9), or 1 mg/kg.d rhIGF-I/IGFBP-3 (n = 11). Treatment was administered by sc infusion through a portable mini-pump for a total of 8 wk after hip fracture surgery, with patient follow-up to 6 months after surgery. Efficacy evaluations included a contralateral hip bone density determination, markers of bone turnover (including serum osteocalcin and urinary excretion of N-telopeptide), grip strength, and tests of functional ability. During the administration of rhIGF-I/IGFBP-3, mean serum levels of IGF-I significantly (P < 0.001) increased from 83 ng/ml to 289 ng/ml (0.5 mg/kg.d) and 393 ng/ml (1 mg/kg.d), respectively. Both doses were well tolerated, and no hypoglycemia or other therapy-induced side effects were observed. After an initial loss of hip bone density after hip fracture surgery, patients treated with 1 mg/kg.d rhIGF-I/IGFBP-3 regained a substantial portion of their femoral bone mass. At 6 months postfracture (4 months after the 2-month infusion), they showed a statistically not significant decrease from baseline in hip bone density (-2.6%, P = 0.53). Placebo-treated patients, on the other hand, failed to regain lost bone: at 6 months postfracture, bone density in the placebo group had declined by 6.1% (P = 0.04). Additionally, in patients treated with 1.0 mg/kg.d rhIGF-I/IGFBP-3, grip strength had increased from baseline by 11.4% by the end of the study (P = 0.04) whereas patients on placebo lost 11.6% from baseline (P = 0.16). This increase in muscle strength in the high-dose group was associated with a positive effect on functional recovery. We conclude that a 2-month infusion of rhIGF-I/IGFBP-3 in patients with recent hip fracture is feasible, safe, and well tolerated. Analyzing the effects on bone mass, muscle strength, and functional ability, we observed beneficial trends. In the context of a small exploratory study, these findings should be interpreted with caution, but they support the need for future trials to further assess the therapeutic potential of rhIGF-I/IGFBP-3 in elderly subjects with osteoporosis.

Aged↗