Cost-effective intervention thresholds against osteoporotic fractures based on FRAX? in Switzerland

Summary

FRAX-based cost-effective intervention thresholds in the Swiss setting were determined. Assuming a willingness to pay at 2× Gross Domestic Product per capita, an intervention aimed at reducing fracture risk in women and men with a 10-year probability for a major osteoporotic fracture at or above 15% is cost-effective.

Introduction

The fracture risk assessment algorithm FRAX? has been recently calibrated for Switzerland. The aim of the present analysis was to determine FRAX-based fracture probabilities at which intervention becomes cost-effective.

Methods

A previously developed and validated state transition Markov cohort model was populated with Swiss epidemiological and cost input parameters. Cost-effective FRAX-based intervention thresholds (cost-effectiveness approach) and the cost-effectiveness of intervention with alendronate (original molecule) in subjects with a FRAX-based fracture risk equivalent to that of a woman with a prior fragility fracture and no other risk factor (translational approach) were calculated based on the Swiss FRAX model and assuming a willingness to pay of 2 times Gross Domestic Product per capita for one Quality-adjusted Life-Year.

Results

In Swiss women and men aged 50?years and older, drug intervention aimed at decreasing fracture risk was cost-effective with a 10-year probability for a major osteoporotic fracture at or above 13.8% (range 10.8% to 15.0%) and 15.1% (range 9.9% to 19.9%), respectively. Age-dependent variations around these mean values were modest. Using the translational approach, treatment was cost-effective or cost-saving after the age 60?years in women and 55 in men who had previously sustained a fragility fracture. Using the latter approach leads to considerable underuse of the current potential for cost-effective interventions against fractures.

Conclusions

Using a FRAX-based intervention threshold of 15% for both women and men should permit cost-effective access to therapy to patients at high fracture probability based on clinical risk factors and thereby contribute to further reduce the growing burden of osteoporotic fractures in Switzerland.     

Reliability of real-time ultrasound measurement of transversus abdominis thickness in healthy trained subjects

Purpose

To investigate intra- and inter-rater reliability of the ultrasound measurement of transversus abdominis (TrA) thickness and thickness change (difference between thickness at rest and during contraction) in asymptomatic, trained subjects. To define the number of repeated measurements that provide acceptable level of reliability. To investigate variability of the measurements over time of 5 days and the reliability of duplicate analysis of images.

Methods

A single-group repeated-measures design was used to assess reliability. Healthy volunteers (n = 10) were subjected to 1-week training in voluntary activation of TrA. Real-time ultrasound imaging and subsequent measurement of the TrA thickness at rest and during voluntary contraction were repeated on Monday, Wednesday and Friday of the next week.

Results

Using a single repeated measurement, intraclass correlation coefficients (ICCs) for TrA thickness were: 0.86–0.95 (intra-rater), 0.86–0.92 (inter-rater); and for TrA thickness change: 0.34–0.56 (intra-rater), 0.47–0.61 (inter-rater). Using the mean of three repeated measurements respective values were: 0.97, 0.96–0.98; and 0.81–0.84, 0.80–0.90. No significant differences were found between mean values of TrA thickness as well as thickness change obtained on three consecutive measurement days. Duplicate analysis of the images was highly reliable with ICCs of 0.89–0.99.

Conclusions

Two repeated measurements for TrA thickness and at least three measurements for TrA thickness change are needed to achieve acceptable levels of intra- and inter-rater reliability. In healthy trained volunteers TrA thickness and thickness change are relatively stable parameters over a 5-day period. Duplicate analysis of the same images by two blinded observers is reliable.     

Modic type I change may predict rapid progressive, deforming disc degeneration: a prospective 1-year follow-up study

Introduction

This prospective magnetic resonance imaging (MRI) study in chronic low-back pain (CLBP) patients evaluated the natural course of degenerative lumbar spine changes in relation to Modic 1 type changes (M1) within 1 year.

Materials and methods

From 3,811 consecutive CLBP patients referred to lumbar spine MRI 54 patients with a large M1 were selected using strict exclusion criteria to exclude specific back disorders. Follow-up MRI was obtained within 11–18 months.

Results

At baseline M1 was associated with an adjacent endplate lesion in 96% of the cases. In follow-up, an unstable M1 was associated both with an increase of endplate lesions, decrease of disc height and change in disc signal intensity, most found at L4/5 or L5/S1. In disc spaces without M1, progression of degenerative changes was rare.

Conclusion

Endplate deformation, decreasing disc height and change of disc signal intensity appear essential features of accelerated degenerative process associated with M1.     

Retroperitoneoscopic drainage of complicated psoas abscesses in patients with tuberculous lumbar spondylitis

Purpose  

Nowadays, endoscopic techniques are widely used in surgical procedures. Retroperitoneoscopy has been an extremely valuable tool for a wide variety of urologic disorders, whereas, it has limited use in orthopedic procedures.     

A morphometric cadaver study of the anterior lumbar epidural space

Introduction

Free disc fragments end often up in the concavity of the anterior epidural space. This space consists of two compartments. The discrepancy between the impressive magnetic resonance imaging findings, clinical symptoms in patients and the problem of treatment options led us to the anatomical determination of anterior epidural space volumes.

Materials and methods

For the first time, the left and right anterior epidural volume between the peridural membrane and the posterior concavity of the lumbar vertebral bodies L3–S1 were determined for each segment. A CT scan and a polyester resin injection were used for the in vitro measurements.

Results

The volumes determined in human cadavers using this method ranged from 0.23 ccm for L3 to 0.34 ccm for L5. The CT concavity volume determination showed this increase in volume from cranial to caudal, as well.

Conclusion

This volume is large enough to hold average-sized slipped discs without causing neurological deficits. A better understanding of the anterior epidural space may allow a better distinction of patient treatment options.     

Increased physical activity is associated with enhanced development of peak bone mass in men: a five-year longitudinal study

Data supporting physical activity guidelines to optimize bone development in men is sparse. Peak bone mass is believed to be important for the risk of osteoporosis later in life. The objective of this study was to determine if an increased amount of physical activity over a 5‐year period was associated with increased bone mineral content (BMC), areal (aBMD) and volumetric (vBMD) bone mineral density, and a favorable development of cortical bone size in young adult men. The original 1068 young men, initially enrolled in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study, were invited to participate in the longitudinal study, and a total of 833 men (78%), 24.1 ± 0.6 years of age, were included in the 5‐year follow‐up. A standardized self‐administered questionnaire was used to collect information about patterns of physical activity at both the baseline and 5‐year follow‐up visits. BMC and aBMD were measured using dual energy X‐ray absorptiometry, whereas vBMD and bone geometry were measured by peripheral quantitative computed tomography. Increased physical activity between the baseline and follow‐up visits was associated with a favorable development in BMC of the total body, and aBMD of the lumbar spine and total hip (p < 0.001), as well as with development of a larger cortex (cortical cross sectional area), and a denser trabecular bone of the tibia (p < 0.001). In conclusion, increased physical activity was related to an advantageous development of aBMD, trabecular vBMD and cortical bone size, indicating that exercise is important in optimizing peak bone mass in young men. © 2012 American Society for Bone and Mineral Research.     

Risk factors for prediction of inadequate response to antiresorptives

Some patients sustain fractures while on antiresorptives. Whether this represents an inadequate response (IR) to treatment or a chance event has not been elucidated. We performed a study to identify which patients are more likely to fracture while on treatment. This is a multicentric, cross‐sectional study of postmenopausal women on antiresorptives for osteoporosis in 12 Spanish hospitals, classified as adequate responders (ARs) if on treatment with antiresorptives for 5 years with no incident fractures or inadequate responders (IRs) if an incident fracture occurred between 1 and 5 years on treatment. Poor compliance, secondary osteoporosis, and previous anti‐osteoporosis treatment other than the assessed were exclusion criteria. Clinical, demographic, analytical, dual‐energy X‐ray absorptiometry (DXA) variables, and proximal femur structure analysis (ImaTx?) and structural/fractal analyses of distal radius were performed. A total of 179 women (76 IRs; mean (SD): age 68.2 (9.0) years; 103 ARs, age 68.5 (7.9) years) were included. History of prior fracture (p = 0.005), two or more falls in the previous year (p = 0.032), low lumbar spine bone mineral density (BMD) (p = 0.02), 25 hydroxyvitamin D (p = 0.017), and hip ImaTx fracture load index (p = 0.004) were associated with IR. In the logistic regression models a fracture before treatment (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.47–8.82; p = 0.005) and levels of 25 hydroxyvitamin D below 20 ng/mL (OR, 3.89; 95% CI, 1.55–9.77; p = 0.004) significantly increased risk for IR, while increased ImaTx fracture load (OR, 0.96; 95% CI, 0.93–0.99; p = 0.006; per every 100 units) was protective, although the latter became not significant when all three variables were fitted into the model. Therefore, we can infer that severity of the disease, with microarchitectural and structure deterioration, as shown by previous fracture and hip analysis, and low levels of 25 hydroxy vitamin D carry higher risk of inadequate response to antiresorptives. More potent regimes should be developed and adequate supplementation implemented to solve this problem. © 2012 American Society for Bone and Mineral Research.     

Impaired bone health and asymptomatic vertebral compressions in fracture-prone children: a case-control study

Frequent fractures in children may be a sign of impaired bone health, but it remains unestablished when and how fracture‐prone children should be assessed. This prospective study elucidated skeletal characteristics and predisposing factors in children with recurrent fractures. Findings were used to establish guidelines for screening. During a 12‐month period we recorded fracture history for all children (n = 1412) treated for an acute fracture at a large university hospital. All apparently healthy children over 4 years of age, who had sustained: (1) at least one vertebral fracture; (2) two long‐bone fractures before age 10 years; or (3) three long‐bone fractures before age 16 years, were recruited. They underwent dual‐energy X‐ray absorptiometry (DXA), laboratory tests, and spinal radiography. Information regarding family history and lifestyle factors were collected. Findings were compared with healthy controls. Sixty‐six fracture‐prone children (44 males, mean age 10.7 years; 5% of all children with fractures) were identified. Altogether, they had sustained 183 long‐bone fractures (median 3, range 0–7); 11 children had sustained vertebral fracture(s). Patients had significantly lower bone mineral density (BMD) at lumbar spine (p < 0.001), hip (p = 0.007), and whole body (p < 0.001) than the controls; only 5 children (8%) had a BMD Z‐score < ?2.0. Asymptomatic vertebral compressions were prevalent, especially in those under 10 years of age. Hypercalciuria (11%) and hyperphosphaturia (22%) were significantly more prevalent than in controls. Serum concentration of 25‐hydroxyvitamin D (S‐25OHD) was below 50 nmol/L in 55%; low levels were associated with low BMD and vertebral compressions. The fracture‐prone children had lower calcium intake, less physical activity, and more often had siblings with fractures than the controls. The findings suggest that a thorough pediatric evaluation, including DXA and spinal radiography, is often indicated already after a second significant low‐energy fracture in children, in order to detect potentially preventable adverse lifestyle factors and nutritional deficits and to identify those with compromised overall bone health. © 2012 American Society for Bone and Mineral Research.     

Regulation of bone mass and osteoclast function depend on the F-actin modulator SWAP-70

Bone remodeling involves tightly regulated bone‐resorbing osteoclasts and bone‐forming osteoblasts. Determining osteoclast function is central to understanding bone diseases such as osteoporosis and osteopetrosis. Here, we report a novel function of the F‐actin binding and regulatory protein SWAP‐70 in osteoclast biology. F‐actin ring formation, cell morphology, and bone resorption are impaired in Swap‐70^?/? osteoclasts, whereas the expression of osteoclast differentiation markers induced in vitro by macrophage colony‐stimulating factor (M‐CSF) and receptor activator of NF‐κB ligand (RANKL) remains unaffected. Swap‐70^?/? mice develop osteopetrosis with increased bone mass, abnormally dense bone, and impaired osteoclast function. Ectopic expression of SWAP‐70 in Swap‐70^?/? osteoclasts in vitro rescues their deficiencies in bone resorption and F‐actin ring formation. Rescue requires a functional pleckstrin homology (PH) domain, known to support membrane localization of SWAP‐70, and the F‐actin binding domain. Transplantation of SWAP‐70–proficient bone marrow into Swap‐70^?/? mice restores osteoclast resorption capacity in vivo. The identification of the role of SWAP‐70 in promoting osteoclast function through modulating membrane‐proximal F‐actin rearrangements reveals a new pathway to control osteoclasts and bone homeostasis. © 2012 American Society for Bone and Mineral Research.