Trabecular bone score (TBS) as a new complementary approach for osteoporosis evaluation in clinical practice.

Trabecular bone score (TBS) is a recently-developed analytical tool that performs novel grey-level texture measurements on lumbar spine dual X-ray absorptiometry (DXA) images, and thereby captures information relating to trabecular microarchitecture. In order for TBS to usefully add to bone mineral density (BMD) and clinical risk factors in osteoporosis risk stratification, it must be independently associated with fracture risk, readily obtainable, and ideally, present a risk which is amenable to osteoporosis treatment. This paper summarizes a review of the scientific literature performed by a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. Low TBS is consistently associated with an increase in both prevalent and incident fractures that is partly independent of both clinical risk factors and areal BMD (aBMD) at the lumbar spine and proximal femur. More recently, TBS has been shown to have predictive value for fracture independent of fracture probabilities using the FRAX® algorithm. Although TBS changes with osteoporosis treatment, the magnitude is less than that of aBMD of the spine, and it is not clear how change in TBS relates to fracture risk reduction. TBS may also have a role in the assessment of fracture risk in some causes of secondary osteoporosis (e.g., diabetes, hyperparathyroidism and glucocorticoid-induced osteoporosis). In conclusion, there is a role for TBS in fracture risk assessment in combination with both aBMD and FRAX.

The role of patient-mode high-resolution peripheral quantitative computed tomography indices in the prediction of failure strength of the elderly women's thoracic vertebral body.

UNLABELLED: The correlations between the failure load of 20 T12 vertebral bodies, their patient-mode high-resolution peripheral quantitative computed tomography (HR-pQCT) indices, and the L1 areal bone mineral density (aBMD) were investigated. For the prediction of the T12 vertebral failure load, the T12 HR-pQCT microarchitectural parameters added significant information to that of L1 aBMD and to that of cortical BMD, but not to that of T12 vertebral BMD and not to that of T12 trabecular BMD. INTRODUCTION: HR-pQCT is a new in vivo imaging technique for assessing the three-dimensional microarchitecture of cortical and trabecular bone at the distal radius and tibia. But little is known about this technique in the direct measurement of vertebral body. METHODS: Twenty female donors with the mean age of 80.1 (7.6) years were included in the study. Dual X-ray absorptiometry of the lumbar spine and femur was performed. The spinal specimens (T11/T12/L1) were dissected, scanned using HR-pQCT scanner, and mechanically tested under 4° wedge compression. The L1 aBMD, T12 patient-mode HR-pQCT indices, and T12 vertebral failure loads were analyzed. RESULTS: For the prediction of vertebral failure load, the inclusion of BV/TV into L1 aBMD was the best model (R (2) = 0.52), Tb.N and Tb.Sp added significant information to the L1 aBMD and to the cortical BMD, but none of the vertebral microarchitectural parameters yielded additional significant information to the trabecular BMD (or BV/TV) and to the vertebral BMD. CONCLUSION: Vertebral microarchitectural parameters obtained from the patient-mode HR-pQCT analysis provide significant information on bone strength complementary to that of aBMD and to that of cortical BMD, but not to that of vertebral BMD and not to that of trabecular BMD.

Association between vitamin D receptor gene polymorphisms, falls, balance and muscle power: results from two independent studies (APOSS and OPUS).

SUMMARY: Fall prevention is a key strategy for reducing osteoporotic fractures. We investigated the association between vitamin D receptor (VDR) polymorphisms and reported falls in postmenopausal women. Bsm1 polymorphisms were associated with falls, balance and muscle power measurements. These results may explain some of the excess fracture risk associated with VDR in some studies. INTRODUCTION: Fall prevention is a key strategy for reducing osteoporotic fractures. It has been suggested that vitamin D supplementation may reduce the incidence of falls by reducing body sway and increasing muscle power. The vitamin D receptor gene is a well-studied candidate gene for osteoporosis. We investigated the association between VDR polymorphisms and reported falls in postmenopausal women. METHODS: Falls data were collected in two separate population cohorts. Five polymorphisms of the VDR gene were analysed (Cdx-2, Fok-1, BsmI, Taq1 and Apa1) in the Aberdeen Prospective Osteoporosis Screening Study (APOSS) cohort. Results found in APOSS were then validated in an independent cohort--the Osteoporosis and Ultrasound (OPUS) study (Bsm1 and Fok1 only), where muscle power and balance were also measured. RESULTS: Carriers of the 'B' allele (Bsm1) showed an increased risk for falls. In APOSS, this was statistically significant for visit 3 multiple falls (p = 0.047) and for recurrent falls (p = 0.043). Similar results were found in OPUS for visit 1 falls (p = 0.025) and visit 1 multiple falls (p = 0.015). Bsm1 polymorphisms were also associated with balance and muscle power measurements. CONCLUSIONS: In conclusion, these results demonstrate an association between the Bsm1 polymorphism and risk of falling that may explain some of the excess fracture risk associated with VDR in some studies.

Glucocorticosteroid-induced osteoporosis in adult primiparous Göttingen miniature pigs: effects on bone mineral and mineral metabolism.

Information on the pathophysiology of glucocorticoid-induced osteoporosis (GIO) is limited, since its clinical picture often reflects a combined effect of glucocorticoids (GC) and the treated systemic disease (i.e., inflammation and immobility). In 50 healthy adult (30-mo-old) primiparous Göttingen minipigs, we studied the short-term (8 mo, n = 30) and long-term (15 mo, n = 10) effect of GC on bone and mineral metabolism longitudinally and cross-sectionally compared with a control group (n = 10). All animals on GC treatment received prednisolone orally at a dose of 1.0 mg x kg body wt(-1) x day(-1) for 8 wk and thereafter at 0.5 mg/kg body wt(-1) x day(-1). In the short term, GC reduced bone mineral density (BMD) at the lumbar spine by -47.5 +/- 5.1 mg/cm(3) from baseline (P < 0.001), which was greater (P < 0.05) than the loss [not significant (NS)] in the control group of -11.8 +/- 12.6 mg/cm(3). Calcium absorption decreased from baseline by -2,488 +/- 688 mg/7 days (P < 0.001) compared with -1,380 +/- 1,297 mg/7 days (NS) in the control group. Plasma bone alkaline phosphatase (BAP) decreased from baseline by -17.8 +/- 2.2 U/l (P < 0.000), which was significantly different (P < 0.05) from the value of the control group of -1.43 +/- 4.8 U/l. In the long term, the loss of BMD became more pronounced and bone mineral content (BMC), trabecular thickness, mechanical stability, calcium absorption, 25-hydroxyvitamin D(3), 1,25-dihydroxyvitamin D(3), and parathyroid hormone tended to be lower compared with the control group. There was a negative association between the cumulative dose of GC and BMD, which was associated with impaired osteoblastogenesis. In conclusion, the main outcomes after GC treatment are comparable to symptoms of GC-induced osteoporosis in human subjects. Thus the adult Göttingen miniature pig appears to be a valuable animal model for GC-induced osteoporosis.

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators.

CONTEXT: Raloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known. OBJECTIVE: To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures. DESIGN: The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial. SETTING AND PARTICIPANTS: A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events. INTERVENTIONS: Participants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol. MAIN OUTCOME MEASURES: Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry. RESULTS: At 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1 % (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001 for all comparisons). Women receiving raloxifene had increased risk of venous thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer. CONCLUSIONS: In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.

Hyperthermic fibrinolysis with rt-PA: in vitro results.

PURPOSE: To investigate the influence of hyperthermia up to 45 degrees C on fibrinolysis with recombinant tissue-type plasminogen activator (rt-PA). METHODS: Standardized fibrin clots were incubated in a water bath for 5 hr with either rt-PA (test group) or 0.9% sodium chloride (control group) and blood plasma at temperatures of 30-45 degrees C. Concentrations of D-dimer and time to complete clot lysis were measured. RESULTS: The activity of fibrinolysis with rt-PA rose with increasing temperature: time to lysis approximately halved from 30 degrees C to 40 degrees C and the concentration of D-dimer tripled. In the control group clot size did not change. CONCLUSIONS: Activity of rt-PA-induced fibrinolysis rises distinctly with higher temperatures. Since even healthy subjects show a physiologic decline in body temperature in the extremities, in patients with occlusive arterial disease decreased activity of fibrinolysis with rt-PA can be expected. Controlled hyperthermia may improve fibrinolysis with rt-PA and should be investigated in vivo.

Assessment of fracture risk by bone density measurements.

Bone densitometry in its various applications has become an established tool for the diagnosis of osteoporosis. Bone density has been shown to be significantly associated with the risk of future fracture in many prospective studies. From long-term prospective studies, it can be concluded that peak bone density and bone loss are important predictors of subsequent fracture, and that fracture can be predicted over a longer period. Bone density predicts fracture even in elderly persons aged 80 years and older. However, in this population some fractures, such as the cervical hip fracture, may be more strongly influenced by other risk factors. The differences between the various densitometric techniques in predicting future osteoporotic fracture of any type is marginal. However, it seems that bone density measurements at the site of fracture do perform better than measurements at other sites. There is no evidence that measuring a second site improves the diagnostic capability of bone densitometry. The association between bone density and future fracture is partly independent of age and other significant predictors of fracture such as falls, cognizance, and mobility. Quantitative ultrasonic measures of bone quality have been shown to have a predictive capability that is comparable to that of bone density. From the perspective that bone densitometry and quantitative ultrasound independently predict fractures, these measures actually seem complementary rather than competitive. Simple geometric measures of the bones such as hip axis length and vertebral depth may be derived from images of bone densitometry scans and are also predictive of hip fracture or vertebral fracture independently of bone density. Using the current knowledge of the association between bone density, quantitative ultrasound, geometric properties, and fractures as well as clinical risk factors, new models for fracture prediction can be developed for future application in clinical practice for the benefit of the individual patient.

[Cost and effectiveness of different strategies in diagnosis of osteoporosis]. / Kosten und Nutzen unterschiedlicher Strategien zur Diagnose von Osteoporose.

Osteoporosis represents one of the most common disorders in Germany. Because of the general aging of the population and due to several secular trends (less exercise, nutritional deficits, higher standard of living) the prevalence of osteoporosis will increase substantially. Therefore, it is important to develop preventive strategies and analyze them according to both medical and economical criteria. During the last couple of years substantial progress has been made both in the area of diagnostic approaches as well as treatment modalities. Thus, from a medical point of view important conditions for a positive assessment of the cost-benefit-ratio of diagnostic approaches in osteoporosis are now fulfilled. Currently, a strategy for selective screening of well-defined high risk groups appears to be most appropriate. These include 1. women with subnormal hormonal status provided that other risk factors are present, 2. patients with low-trauma fractures, 3. patients under prolonged steroid therapy, and 4. patients with secondary osteoporosis due to other causes. International studies have demonstrated that even more far-reaching preventive strategies can be conceived that could be both medically and economically effective. Currently, however, data for a detailed cost-benefit-analysis are lacking or based on outdated diagnostic equipment or treatment agents. New Studies on this topic are critically needed to evaluate preventive strategies, specifically for Germany.

A two-year program of aerobics and weight training enhances bone mineral density of young women.

Previous research suggests that physical activity may have a beneficial effect on bone mineral density (BMD) in women. This relationship was explored in a 2-year, randomized, intervention trial investigating the efficacy of exercise and calcium supplementation on increasing peak bone mass in young women. One hundred and twenty-seven subjects (ages of 20-35 years) were randomly assigned either to an exercise program that contained both aerobics and weight training components or to a stretching program. Calcium supplementation (up to 1500 mg/day including dietary intake) or placebo was given in a double-blinded design to all subjects. Spinal trabecular BMD was determined using quantitative computed tomography (QCT). Spinal integral, femoral neck, and trochanteric BMD were measured by dual X-ray absorptiometry (DXA) and calcaneal BMD by single photon absorptiometry (SPA). Fitness variables included maximal aerobic capacity (VO2max), and isokinetic muscle performance of the trunk and thigh. Measurements were made at baseline, 1 year, and 2 years. Sixty-three subjects (32 exercise, 31 stretching) completed the study, and all the measured bone parameters indicated a positive influence of the exercise intervention. There were significant positive differences in BMD between the exercise and stretching groups for spinal trabecular (2.5%), femoral neck (2.4%), femoral trochanteric (2.3%), and calcaneal (6.4%) measurements. The exercise group demonstrated a significant gain in BMD for spinal integral (1.3 +/- 2.8%, p < 0.02), femoral trochanteric (2.6 +/- 6.1%, p < 0.05), and calcaneal (5.6 +/- 5.1, p < 0.01) measurements. In contrast to exercise, the calcium intervention had no positive effect on any of the bone parameters. In regard to fitness parameters, the exercise group completed the study with significant gains in VO2max and isokinetic (peak torque) values for the knee flexion and extension and trunk extension. This study indicates that over a 2-year period, a combined regimen of aerobics and weight training has beneficial effects on BMD and fitness parameters in young women. However, the addition of daily calcium supplementation does not add significant benefit to the intervention.