Elevated Fracture Risk Research Articles

Bisphosphonates in Patients with Glucocorticoids: Time for Implementation

Use of glucocorticoids (GC) may have devastating effects on bone quality1. From earlier histomorphometric data, we know that bone formation is inhibited by direct suppression of osteoblast function during the use of GC, while bone resorption is unchanged or even elevated, at least partly related to decreased intestinal calcium absorption, elevated urinary calcium excretion, and a tendency to secondary hyperparathyroidism2,3. However, exciting new data provide additional insights into the pathogenesis of Glucocorticoid Induced OsteoPorosis (GIOP)2,3: (1) upregulation of the Wnt inhibitor Dickkopf-1, leading to inhibition of bone formation; (2) increased apoptosis of osteoblasts and osteocytes; (3) differentiation of mesenchymal stem cells into the direction of adipocytes, instead of into osteoblasts; (4) elevated lifespan of osteoclasts, due to decreased apoptosis; and (5) upregulation of expression of RANKL in osteoblasts (and downregulation of osteoprotegerin). Nevertheless, it is important to realize that the (negative) direct and indirect effects of GC on bone are counteracted by the immunosuppressive effects of GC on the underlying disease2,3. Another complicating factor is that use of GC and the underlying disease may both be associated with muscular weakness and, subsequently, increased risk of falling. Use of GC is associated with bone loss, particularly in the early phase of treatment, when the dosage of GC is usually high and the underlying disease for which the GC are prescribed is active. In contrast, in the chronic phase, bone loss may be mild in GC-treated patients, related to the use of lower dosages of GC and to low or preferably absent disease activity. In addition, use of GC is also associated with elevated risk of fracture: In a retrospective cohort study with 244,235 GC-treated patients and the same number of age and sex matched controls, the fracture … Address correspondence to Prof. Lems. E-mail: wf.lems{at}vumc.nl

Population screening for osteoporosis risk: a randomised control trial of medication use and fracture risk

Randomised control trial of osteoporosis screening in 4,800 women aged 45-54 years was carried out. Screened group observed an increase of 7.9% in hormone replacement therapy (HRT) use (p < 0.001), 15% in other osteoporosis treatments (p < 0.001) and a 25.9% reduction in fracture risk compared with control. Screening for osteoporosis significantly increases treatment use and reduces fracture incidence. Population screening programmes can identify menopausal women with low bone mineral density (BMD) and elevated risk of future fracture but require to be proven effective by a randomised control trial. A total of 4,800 women, 45-54 years, were randomised in equal numbers to screening or no screening (control) groups. Following screening, those in the lowest quartile of BMD were advised to consider HRT. Nine years later, the effect of screening on the uptake of treatment and the incidence of fractures were assessed by postal questionnaire. Categorical differences were assessed using chi(2) test. Cox regression was used to assess hazard ratio (HR). Of the screened and the control groups, 52.4% vs 44.5%, respectively, reported taking HRT (p < 0.001). In addition, 36.6% of the screened vs 21.6% of the control groups reported the use of vitamin D, calcium, alendronate, etidronate or raloxifene (p < 0.001). In a per protocol analysis of verified incident fractures, a 25.9% reduction in risk of fractures (of any site) in the screened group was observed (HR = 0.741, 95% CI = 0.551-0.998 adjusted age, weight and height). Screening for osteoporosis as assessed by low bone density significantly increases the use of HRT and other treatments for osteoporosis and reduces fracture incidence.

Combination Of Exercise And Soy Protein Improves Bone Measures And Vascular Calcification In Uremic Mice

Cardiovascular disease (CVD) is the leading cause of death for individuals with chronic kidney disease (CKD), and calcium deposits in the vasculature may partially explain the increase in risk compared to age-and sex-matched controls. Individuals with CKD are also at increased risk for CKD-mineral bone disorder, leading to significantly elevated fracture risk. These conditions may be related to the abnormal mineral metabolism commonly seen in this population, and current pharmacological interventions have been unsuccessful in treating these conditions simultaneously. Soy protein containing phytoestrogens and endurance exercise training have shown potential for improving these disease conditions. PURPOSE: To determine the efficacy of endurance exercise training and soy protein, alone and in combination, on bone and vascular measures in a mouse model of uremia. METHODS: At 8 weeks of age, 60 female Apolipoprotein E-/- mice underwent a two-step surgical procedure to induce uremia. At 12 weeks, they were randomized to one of four treatment groups, and remained on the treatment for 4 months: sedentary/control diet (n=16), sedentary/soy protein diet (n=18), exercise/control diet (n=14), and exercise/soy protein diet (n=12). The control diet contained 20% casein compared to the 20% soy protein, and the exercise consisted of treadmill running 5 days a week for 45 minutes at 18m/min. RESULTS: Both exercise alone and soy protein diet plus exercise compared to sedentary controls produced a modest 7% decrease in vascular calcium score in the proximal aorta (p=0.03) as measured by Alizarin Red staining. Soy plus exercise significantly improved several bone measures including a 52% increase in bone volume fraction (BV/TV p<0.01), a 107% increase in trabecular connective density (p<0.001), a 47% increase in trabecular number (p<0.001), and a 60% decrease in trabecular separation as measured by microCT. Neither exercise nor soy protein alone improved any bone measures. CONCLUSION: Endurance exercise training together with a soy protein diet produced significant improvements in the bone and vasculature suggesting that a combination of dietary and lifestyle changes may be beneficial for treating both vascular calcification and bone disorders in CKD. Supported by the Illinois Soy Board.

Use of anti-depressants and the risk of fracture of the hip or femur

SummaryAnti-depressants are used largely, but have serious side effects. We show that both selective serotonin re-uptake inhibitors (SSRIs) and tricyclic anti-depressants (TCAs) increase the risk of hip/femur fracture and that this risk is time related and depends on the degree of serotonin transporter inhibition. This should be considered when prescribing anti-depressants to patients.IntroductionAnti-depressants are known to have serious side effects. We examined the association between the use of anti-depressants and the risk of hip/femur fractures with a special focus on the relation with the degree of 5-hydroxytryptamine transporter (5-HTT) inhibition and the duration of use.MethodsA case–control study was conducted within the Dutch PHARMO-RLS database. Cases (n = 6,763) were adult patients with a first hip/femur fracture during the study period. For each case, four controls (n = 26341) were matched by age, gender and geographic region.ResultsThe risk of hip/femur fracture increased with current use of SSRIs (adjusted odds ratio (ORadj) 2.35 [95% confidence interval (CI) 1.94–2.84]) and TCAs (ORadj 1.76 [95% CI 1.45–2.15]). The risk of hip/femur fracture declined rapidly after discontinuation of use. The risk of hip/femur fracture increased as the degree of 5-HTT inhibition of all anti-depressants increased from ORadj 1.64 [95% CI 1.14–2.35] for drugs with low 5-HTT inhibition to ORadj 2.31 [95% CI 1.94–2.76] for those with high 5-HTT inhibiting properties.ConclusionCurrent use of both SSRIs and TCAs increase hip/femur fracture risk. Further studies are needed to elucidate the mechanistic pathways and the relation with the underlying pathophysiology. Until then, the elevated fracture risk should be considered when prescribing anti-depressants.

Vertebral fracture assessment using standard bone densitometry equipment predicts incident fractures in women

Vertebral fractures are the most common fracture among the elderly, have a detrimental effect on patients' quality of life, and increase the risk of future fractures. Yet, two-thirds of vertebral fractures remain undiagnosed; therefore, improved detection methods are needed. In this Practice Point commentary, we discuss the study by McCloskey et al., in which low radiation dose imaging with a bone densitometer was used for vertebral fracture assessment (VFA) in a prospective cohort of elderly women. Participants were enrolled in a randomized, double-blind, placebo-controlled trial of the oral bisphosphonate clodronate. Prevalent vertebral fractures detected by VFA were associated with an elevated risk of subsequent osteoporotic fractures, including hip fractures. This finding remained significant after adjustment for age, weight and treatment effect, and in a few instances even after adjustment for femoral BMD. Here, we highlight the importance of identifying vertebral fractures, and the potentially substantial role of VFA in the clinical evaluation and management of patients suspected to have osteoporosis.

Using Radon transform of standard radiographs of the hip to differentiate between post-menopausal women with and without fracture of the proximal femur

Texture features based on the Radon transform were extracted from clinical radiographs of the hip in post-menopausal women. The novel algorithm allowed us to identify patients with fracture of the proximal femur and may provide an alternative to measuring bone mineral density in predicting the fracture-risk in osteoporosis, especially where densitometry is regionally unavailable. The aim of this study is to introduce an algorithm for differentiation between patients with and without fracture of the hip using parameters based on the Radon transform (RT) and applied to standard radiographs of the proximal femur and to compare the results with bone mineral density (BMD). The study comprised 50 post-menopausal women (78.6 +/- 11.5 years of age), including 25 patients with hip fracture and 25 age-matched controls. We obtained lumbar and femoral BMD and standard femoral radiographs. In the radiographs we analysed trabecular patterns of the hip in a region-of-interest of 57 x 29 mm using the RT. From the histogram-representation of the RT, we extracted several characteristic parameters. By ROC and discriminant-analysis, we assessed the statistical power of both methods. For correct differentiation between fracture and non-fracture cases by femoral BMD, area-under-the-curve (AUC) was 0.78; AUC for the RT-based parameters ranged from 0.73 to 0.8. By combination of densitometric and textural information in a multivariate model the fracture status of 84% of subjects was predicted correctly, identification of fracture cases rose to 88%. Identification of fracture patients by RT applied to femoral radiographs was feasible and seemed to have a discriminative potential comparable to that of standard densitometry. In the future, the new method may provide an alternative to DXA or in conjunction with conventional densitometry may enhance the detection of patients with elevated risk of hip fracture.

Serum 25-hydroxyvitamin D and bone mineral density among Hispanic men.

There are few data on the skeletal health of Hispanic men. We observed differences in vitamin D deficiency and low BMD between Hispanic ethnic subgroups that persisted with adjustment for risk factors. Our data indicate a substantial burden of low BMD and vitamin D deficiency among Hispanic men. Disparities within ethnic groups are generally ignored, but in evolving populations they may have implications for public health. We examined ethnic variation in serum 25-hydroxyvitamin D [25(OH)D] and bone mineral density (BMD) among Hispanic American men. Three hundred and fifty-eight Hispanic males 30 to 79 years of age were studied. Logistic regression models assessed variation in odds of vitamin D deficiency (<20 ng/mL) and low BMD (T-score<-1) by ethnicity, with and without adjustment for risk factors (age, smoking, occupation, physical activity, body mass index, and sunlight exposure). Vitamin D deficiency was most common among Puerto Rican (26%), compared with Dominican (21%), Central American (11%), and South American (9%) men. Percentages with low BMD were: South American (44%), Puerto Rican (34%), Dominican (29%), and Central American (23%). Adjustment for age and risk factors failed to account for Hispanic subgroup differences in vitamin D deficiency and low BMD. Population estimates indicate a substantial burden of low BMD and vitamin D deficiency among Hispanic men. Our findings underscore the importance of examining the skeletal health of Hispanic subgroups, and suggest that a considerable number of Hispanic men may be at elevated risk of fracture and vitamin D deficiency.

Doublet stimulation protocol to minimize musculoskeletal stress during paralyzed quadriceps muscle testing

With long-term electrical stimulation training, paralyzed muscle can serve as an effective load delivery agent for the skeletal system. Muscle adaptations to training, however, will almost certainly outstrip bone adaptations, exposing participants in training protocols to an elevated risk for fracture. Assessing the physiological properties of the chronically paralyzed quadriceps may transmit unacceptably high shear forces to the osteoporotic distal femur. We devised a two-pulse doublet strategy to measure quadriceps physiological properties while minimizing the peak muscle force. The purposes of the study were 1) to determine the repeatability of the doublet stimulation protocol, and 2) to compare this protocol among individuals with and without spinal cord injury (SCI). Eight individuals with SCI and four individuals without SCI underwent testing. The doublet force-frequency relationship shifted to the left after SCI, likely reflecting enhancements in the twitch-to-tetanus ratio known to exist in paralyzed muscle. Posttetanic potentiation occurred to a greater degree in subjects with SCI (20%) than in non-SCI subjects (7%). Potentiation of contractile rate occurred in both subject groups (14% and 23% for SCI and non-SCI, respectively). Normalized contractile speed (rate of force rise, rate of force fall) reflected well-known adaptations of paralyzed muscle toward a fast fatigable muscle. The doublet stimulation strategy provided repeatable and sensitive measurements of muscle force and speed properties that revealed meaningful differences between subjects with and without SCI. Doublet stimulation may offer a unique way to test muscle physiological parameters of the quadriceps in subjects with uncertain musculoskeletal integrity.

Age trends in proximal femur geometry in men: variation by race and ethnicity

Data on bone architecture in diverse male populations are limited. We examined proximal femur geometry in 1,190 black, Hispanic, and white men. Cross-sectional analyses indicate greatest bone strength among black men, and greater age-related differences in bone strength among Hispanic men than other subjects at the narrow neck and intertrochanter regions of the proximal femur. Although race/ethnic differences in bone mass are well-documented, less is known about differences in bone architecture. We examined proximal femur geometry in a diverse, randomly-sampled population of 1,190 community-dwelling men (age 30-79 y). Dual X-ray absorptiometry scans were obtained for 355 black, 394 Hispanic, and 441 white subjects. Measures were obtained for the narrow neck (NN), intertrochanter (IT) and shaft regions of the proximal femur via hip structural analysis. Analyses considered bone mineral density (BMD, g/cm2), outer diameter (cm), cross-sectional area (CSA, cm2), section modulus (Z, cm3), and buckling ratio (BR). Results were adjusted for height, weight and physical activity level. Black subjects exhibited greater age-specific BMD, CSA and Z, than their white counterparts. For instance, at age 50 y, NN BMD was approximately 11% higher among black men (p < 0.001). Hispanic men exhibited sharper age-related differences in NN and IT BMD than did others. IT BMD, for instance, decreased by 2.4% with 10 y age among Hispanic subjects, but had virtually no age trend in others (p < 0.001). These results imply greater bone strength among black American men than among their white counterparts, and may indicate elevated fracture risk among older Hispanic American subpopulations.

Besonderheiten der steroidinduzierten Osteoporose

Glucocorticoid-induced osteoporosis (GIOP) is characterized by disturbed bone remodelling with consequent reduced bone mass and abnormally low quality of the bone tissue, resulting in an elevated risk of fracture. Glucocorticoids (GC) inhibit processes of bone formation and accelerate bone degradation, all of which must be taken into account especially in the case of long-term treatment with GC. Appropriate diagnostic procedures must be implemented early in the treatment and throughout the course, as must any preventive (improvement of general condition, calcium, vitamin D) and curative treatment required. When indications are carefully observed and the dosage is constantly checked and adjusted as needed, however, GC are not only helpful and beneficial in the treatment of the basic illnesses they are prescribed for, but on balance can even have a positive effect on bone in phases of high inflammatory activity.

Dietary fat intake and the risk of osteoporotic fractures in the elderly

To explore the association between fat intake, serum lipids and the risk of osteoporotic fractures in the elderly. A hospital-based case-control study. The study was conducted at a tertiary centre and referral hospital for the province of Jaén (Spain). Cases (n=167) were patients aged 65 years or more with a low-energy fracture selected from the population attended at the hospital. Controls (patients without antecedents of any fracture) were 1:1 matched to cases by sex and age (n=167). Diet was assessed by a semiquantitative food frequency questionnaire. Serum total cholesterol and high-density lipoprotein (HDL) cholesterol were also measured. Participants in the two upper quartiles of polyunsaturated fat (PUFA) intake showed an increased risk of fracture, with statistically significant differences with respect to the first quartile in the adjusted model (odds ratio (OR)=3.59; 95% confidence interval (CI)=1.06-12.1 and OR=5.88; 95% CI=1.38-25.02); P=0.01 for the trend test). A higher ratio of monounsaturated fat (MUFA) to PUFA was associated with a reduced risk of fracture (OR=0.20; 95% CI=0.07-0.60 for the fourth quartile; P=0.002 for the trend test). The intake of omega-6 fatty acids was associated with an elevated risk of fracture (OR=3.41; 95% CI=1.05-11.15 for the fourth quartile; P=0.01 for the trend test). HDL-cholesterol levels were inversely associated with the risk of fracture (test for trend P=0.03 across quartiles). PUFA intake was associated with an increased risk of osteoporotic fractures in the elderly, whereas a high ratio of MUFA:PUFA was associated with decreased risk.

Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study

The available data on bone fractures in hemodialysis (HD) patients are limited to results of a few studies of subgroups of patients in the United States. This study describes the prevalence of hip fractures and the incidence and risk factors associated with hip and other fractures in representative groups of HD facilities (n=320) and patients (n=12 782) from the 12 countries in the second phase of the Dialysis Outcomes and Practice Patterns Study (2002-2004). Among prevalent patients, 2.6% had a prior hip fracture. The incidence of fractures was 8.9 per 1000 patient years for new hip fractures and 25.6 per 1000 for any new fracture. Older age (relative risk (RR)(HIP)=1.91, RR(ANY)=1.33, P<0.0001), female sex (RR(HIP)=1.41, P=0.02; RR(ANY)=1.59, P<0.0001), prior kidney transplant (RR(HIP)=2.35, P=0.04; RR(ANY)=1.76, P=0.007), and low serum albumin (RR(HIP)=1.85, RR(ANY)=1.45, per 1 g/dl lower, P<0.0001) were predictive of new fractures. Elevated risk of new hip fracture was observed for selective serotonin reuptake inhibitors and combination narcotic medications (RR=1.63, RR=1.74, respectively, P<0.05). Several medications were associated with risk of any new fracture: narcotic pain medications (RR=1.67, P=0.02), benzodiazepines (RR=1.31, P=0.03), adrenal cortical steroids (RR=1.40, P<0.05), and combination narcotic medications (RR=1.72, P=0.001). Parathyroid hormone (PTH) levels >900 pg/ml were associated with an elevated risk of any new fracture (RR=1.72, P<0.05) versus PTH 150-300. The results suggest that greater selectivity in prescribing several classes of psychoactive drugs and more efficient treatment of secondary hyperparathyroidism may help reduce the burden of fractures in HD patients.

Prise en charge de l’ostéoporose cortisonique

Corticosteroid-induced osteoporosis is common but too often unrecognized, and its management remains insufficient. Bone loss is variable from one patient to another and thus difficult to predict, but all treated patients must be considered at risk. There are tools to assess absolute fracture risk in this case as there are for menopause-associated osteoporosis, and they may help guide the clinician in decision-making. Recent guidelines help the physician to define indications for bone mineral density testing and for therapeutic management. Bisphosphonates are currently the first-line treatment for patients with fractures or elevated fracture risk during corticosteroid treatment.

Clinical assessment of the long‐term risk of fracture in patients with rheumatoid arthritis

To determine whether patients with rheumatoid arthritis (RA) have an increased risk of fracture, and to estimate their long-term absolute fracture risk. We studied patients with RA ages >or=40 years in the British General Practice Research Database, each matched by age, sex, calendar time, and practice to 3 control patients. Incident fractures, as recorded in the computerized medical records, were ascertained over a median followup of 7.6 years. The fracture rate in RA patients compared with controls was adjusted for smoking, body mass index (BMI), and several clinical risk factors, and Cox proportional hazards models were used to calculate the relative risk (RR) of fracture in RA. A risk score was then developed to provide an estimate of the 5- and 10-year fracture risk among RA patients. There were 30,262 patients with RA, of whom 2,460 experienced a fracture during followup. Compared with controls, patients with RA had an increased risk of fracture, which was most marked at the hip (RR 2.0, 95% confidence interval [95% CI] 1.8-2.3) and spine (RR 2.4, 95% CI 2.0-2.8). Indicators of a substantially elevated risk of fracture (at the hip) included >10 years' duration of RA (RR 3.4, 95% CI 3.0-3.9), low BMI (RR 3.9, 95% CI 3.1-4.9), and use of oral glucocorticoids (RR 3.4, 95% CI 3.0-4.0). Modeling of the long-term risk profiles revealed that, for example, in a woman age 65 years with longstanding RA whose risk factors also included low BMI, a history of fracture, and frequent use of oral glucocorticoids, the 5-year risk of hip fracture was 5.7% (95% CI 5.3-6.1%). Patients with RA are at increased risk of osteoporotic fractures. This increased risk is attributable to a combination of disease activity and use of oral glucocorticoids.

Kidney Function Predicts the Rate of Bone Loss in Older Individuals: The Cardiovascular Health Study

Results of cross-sectional analyses of the association of kidney function with bone mineral density (BMD) have been conflicting. We examined the association of cystatin-C, a new marker of kidney function that is unrelated to lean mass, with initial and follow-up BMD, in an ancillary study of the Cardiovascular Health Study, a population-based cohort of individuals > or = 65 years old. Two years after measurement of cystatin-C and other covariates, the first BMD was measured in Pittsburgh, Pennsylvania and Davis, California, by using dual energy x-ray absorptiometry. Follow-up BMD was measured in Pittsburgh 4 years later. Associations of cystatin-C with initial BMD and the change in BMD (%/y) at the hip were examined with linear regression. Analyses were conducted separately for men and women. In 1519 participants who had cystatin-C and initial BMD assessed, 614 had follow-up BMD. The percent annual change in BMD at the total hip by cystatin-C quartiles was -0.24, -0.13, -0.40, and -0.66%/y (first to fourth quartile) in women and -0.02, -0.30, -0.18, and -0.94%/y in men. After adjusting for potential confounders, cystatin-C was marginally associated with initial BMD in men but not women. Cystatin-C was associated with bone loss in men; after adjustment for weight loss, cystatin-C was not associated with bone loss in women. Kidney dysfunction, as assessed by cystatin-C, is associated with a more rapid loss of BMD at the hip, especially in men. Further studies are needed to confirm these findings and to determine whether this loss leads to an elevated risk of fracture.

Risk of Fracture in Women with Type 2 Diabetes: the Women’s Health Initiative Observational Study

Some but not all studies have shown higher rates of fracture in individuals with type 2 diabetes. The objective of the study was to determine the risk of fracture in postmenopausal women with type 2 diabetes and determine whether risk varies by fracture site, ethnicity, and baseline bone density. Women with clinically diagnosed type 2 diabetes at baseline in the Women's Health Initiative Observational Cohort, a prospective study of postmenopausal women (n = 93,676), were compared with women without diagnosed diabetes and risk of fracture overall and at specific sites determined. All fractures and specific sites separately (hip/pelvis/upper leg; lower leg/ankle/knee; foot; upper arm/shoulder/elbow; lower arm/wrist/hand; spine/tailbone) were measured. Bone mineral density (BMD) in a subset also was measured. The overall risk of fracture after 7 yr of follow-up was higher in women with diabetes at baseline after controlling for multiple risk factors including frequency of falls [adjusted relative risk (RR) 1.20, 95% confidence interval (CI) 1.11-1.30]. In a subsample of women with baseline BMD scores, women with diabetes had greater hip and spine BMD. The elevated fracture risk was found at multiple sites (hip/pelvis/upper leg; foot; spine/tailbone) among black women (RR 1.33, 95% CI 1.00-1.75) and women with increased baseline bone density (RR 1.26, 95% CI 0.96-1.66). Women with type 2 diabetes are at increased risk for fractures. This risk is also seen among black and non-Hispanic white women after adjustment for multiple risk factors including frequent falls and increased BMD (in a subset).

Stability of the Metastatic Spine Pre and Post Vertebroplasty

Vertebrae with lytic metastases have an elevated risk of burst fracture and resultant neurologic compromise. Prophylactic vertebroplasty has the potential to reduce pain and the risk of burst fracture in the metastatic spine. The purpose of this study was to quantify the ability of vertebroplasty to stabilize metastatically involved vertebrae against the risk of burst fracture initiation with a standardized model of vertebral metastases. Metastases were simulated in eight fresh-frozen cadaveric thoracolumbar spinal motion segments by removing a central core of trabecular bone and filling the defect with tumor tissue. Specimens were tested under a physiologic level of axial compression, intact, with a simulated tumor and post-vertebroplasty, and ultimately tested to failure. Axial load induced canal narrowing (CN) was used as a measure of the risk of burst fracture initiation. Following testing, vertebrae were axially sectioned to visualize cement fill. Vertebrae with simulated metastases exhibited significantly higher CN than intact specimens (227%+/-109%; P<0.05). Post vertebroplasty, three vertebrae exhibited reduced CN compared with the simulated tumor configuration, whereas the other five had increased CN. Specimens with reduced CN were found to have cement posterior to the tumor, whereas specimens with an increase in CN had cement anterior and lateral to the tumor only. Percutaneous vertebroplasty is effective in decreasing CN if tumor is surrounded posteriorly with cement. However, injecting cement into the posterior third of the vertebral body is risky due to potential extravasation into the canal. Future work aimed at improving cement fill is necessary for safe and consistent stabilization of the metastatic spine with vertebroplasty.

Incidence and Predictors of Fractures in Children After Solid Organ Transplantation: A 5-Year Prospective, Population-Based Study

In this population-based prospective follow-up study, children undergoing solid organ transplantation had a highly elevated risk for fractures: The incidence of all fractures was 6-fold higher (92 versus 14 fractures/1000 persons/year; p < 0.001) and vertebral fractures was 160-fold higher (57 versus 0.35 fractures/1000 persons/year; p < 0.001) in the study group compared with the control population. Thus, screening of vertebral fractures at regular intervals is recommended, and preventive strategies should be studied. The incidence and predictors of fractures after solid organ transplantation are not well documented in the pediatric age group. A total of 196 children, which is 93% of patients surviving kidney, liver, and heart transplantation in our country, participated in a retrospective chart review at enrollment followed by a 5-year prospective follow-up study between January 1999 and December 2004. Hospital and medical records were reviewed. All children underwent clinical examinations and answered questionnaires concerning fracture history at the beginning and at the end of the prospective follow-up. Radiographs of the thoracic and lumbar spine were obtained. The fracture incidence was compared with data obtained from public health registries. Seventy-five (38%) of the transplant patients suffered from a total of 166 fractures after organ transplantation. The incidence of all fractures was 6-fold higher (92 versus 14 fractures/1000 persons/year; p < 0.001) and vertebral fractures was 160-fold higher (57 versus 0.35 fractures/1000 persons/year; p < 0.001) in the study group compared with the control population. The age- and sex-adjusted hazard ratios (95% CI) were 61.3 (40.7-92.4) for vertebral, 17.9 (8.96-35.8) for symptomatic vertebral, 0.99 (0.65-1.50) for nonvertebral, and 2.90 (2.25-3.73) for all fractures in the patients compared with the control population. In a multivariate analysis, older age (hazard ratio [95% CI]; 2.02 [1.07-3.83]), male sex (2.15 [1.22-3.81]), liver transplantation (1.78 [1.01-3.14]), and fractures before transplantation (2.02 [0.92-4.47]) were the most significant independent risk factors. Children undergoing solid organ transplantation have a highly elevated risk for fractures. Screening of vertebral fractures at regular intervals is recommended, and preventive strategies should be studied.

Diuretic use and bone mineral density in older USA men: the osteoporotic fractures in men (MrOS) study

SIR—It is estimated that 25–40% of adults aged 65 years and over use diuretics [1]. The three major classes of diuretics have different effects on renal calcium balance. Loop diuretics increase renal calcium excretion [2], while thiazide and potassium-sparing diuretics exert a hypocalciuric effect. Thiazides facilitate the reabsorption of calcium in the early segment of the convoluted distal tubule, and potassium-sparing diuretics promote reabsorption of calcium in the late segment of the distal tubule [3–5]. Epidemiological data [6–14] and results from randomised controlled trials [15–17] suggest that thiazide diuretic use is associated with a small increase in bone mineral density (BMD) or a decreased rate of bone loss. However, these associations were observed primarily among women. There are few data regarding the effects of loop diuretics on BMD and findings are not consistent across studies [18, 19]. Although some studies have shown that loop diuretic use may be associated with an increased risk of hip and osteoporotic fractures [20–22], it is uncertain whether this possibly elevated fracture risk was mediated by the effect of loop diuretics on bone or rather on fall-related mechanisms, such as dizziness and orthostasis. To our knowledge, no studies have specifically examined whether potassium-sparing diuretics have an independent effect on BMD. Therefore, we conducted a cross-sectional study among participants in the Osteoporotic Fractures in Men (MrOS) study, an ongoing prospective study of community-dwelling men, to investigate the association between current diuretic use and BMD at multiple skeletal sites. We hypothesised that compared with diuretic non-users, loop diuretic users would have a lower mean BMD, while thiazide and potassium-sparing diuretic users would have a higher mean BMD.

Nontraumatic Fracture Risk With Diabetes Mellitus and Impaired Fasting Glucose in Older White and Black Adults

Diabetes mellitus (DM) and related complications may increase clinical fracture risk in older adults. Our objectives were to determine if type 2 diabetes mellitus or impaired fasting glucose was associated with higher fracture rates in older adults and to evaluate how diabetic individuals with fractures differed from those without fractures. The Health, Aging, and Body Composition Study participants were well-functioning, community-dwelling men and women aged 70 to 79 years (N = 2979; 42% black), of whom 19% had DM and 6% had impaired fasting glucose at baseline. Incident nontraumatic clinical fractures were verified by radiology reports for a mean +/- SD of 4.5 +/- 1.1 years. Cox proportional hazards regression models determined how DM and impaired fasting glucose affected subsequent risk of fracture. Diabetes mellitus was associated with elevated fracture risk (relative risk, 1.64; 95% confidence interval, 1.07-2.51) after adjustment for a hip bone mineral density (BMD) and fracture risk factors. Impaired fasting glucose was not significantly associated with fractures (relative risk, 1.34; 95% confidence interval, 0.67-2.67). Diabetic participants with fractures had lower hip BMD (0.818 g/cm(2) vs 0.967 g/cm(2); P<.001) and lean mass (44.3 kg vs 51.7 kg) and were more likely to have reduced peripheral sensation (35% vs 14%), transient ischemic attack/stroke (20% vs 8%), a lower physical performance battery score (5.0 vs 7.0), and falls (37% vs 21%) compared with diabetic participants without fractures (P<.05). These results indicate that older white and black adults with DM are at higher fracture risk compared with nondiabetic adults with a similar BMD since a higher risk of nontraumatic fractures was found after adjustment for hip BMD. Fracture prevention needs to target specific risk factors found in older adults with DM.