Back pain during different sequential treatment regimens of teriparatide: results from EUROFORS.

OBJECTIVE: To investigate changes in back pain in postmenopausal women with severe osteoporosis who received teriparatide for 24 months or switched at 12 months to raloxifene or no active treatment. STUDY DESIGN AND METHODS: This prospective, controlled, randomised, open-label, 2-year study enrolled 868 postmenopausal women with osteoporosis and a recent fragility fracture. After 12 months of teriparatide (20 microg/day), 507 patients were randomised to further teriparatide (n = 305), raloxifene 60 mg/day (n = 100), or no active treatment (n = 102) for another 12 months (substudy 1); in substudy 2, 199 patients continued teriparatide. All received calcium and vitamin D supplementation. Back pain was self-assessed by patients using a visual analogue scale (0-100 mm). Changes in back pain were analysed using a mixed model for repeated measures. RESULTS: During year 1, back pain decreased from a mean (SD) of 48.9 mm (24.0) at baseline by 11.5 mm (p < 0.001) in the total study population. In substudy 1, mean change in back pain from month 12 (randomisation) to 24 months was -2.2, -4.4 and +0.7 mm in the teriparatide (p = 0.076), raloxifene (p = 0.041), and no active treatment groups (p = 0.751). There were no between-group differences from randomization to 18 or 24 months. In a sensitivity analysis excluding patients with low baseline back pain (VAS < 30 mm), mean change from randomisation to endpoint was significant for teriparatide (-3.9 mm, p = 0.006) and raloxifene (-6.3 mm, p = 0.018) groups. Subgroup analyses of 503 patients who received teriparatide for up to 2 years showed that patients with a recent vertebral fracture had a greater decrease in back pain than those without (p < 0.05). Those with and without mild back pain (>or=30 mm), and those with and without severe back pain (>or=60 mm) at baseline all had a statistically significant reduction in back pain after 24 months (p < 0.05). CONCLUSIONS: Teriparatide treatment is associated with significant reductions in back pain regardless of the presence of recent vertebral fracture. These results need to be considered with caution due to the open-label design of the study.

Quantitative computed tomographic assessment of the effects of 24 months of teriparatide treatment on 3D femoral neck bone distribution, geometry, and bone strength: results from the EUROFORS study.

We studied the changes in bone distribution, geometry, and bone strength based on 3D quantitative computed tomography (QCT) of the femoral neck (FN) in subjects receiving teriparatide (TPTD). Fifty-two postmenopausal women with severe osteoporosis were analyzed. Patients were divided into three subgroups based on their prior treatment with osteoporosis drugs: treatment-naive (Tx-naive; n = 8), pretreated (pre-Tx; n = 12), and pretreated showing an inadequate response to treatment (inad. pre-Tx; n = 32). QCT scans were performed at baseline and after 6, 12, and 24 months of treatment and were analyzed with Mindways QCT-PRO BIT software. Minimum and maximum section modulus, buckling ratio (BR), and cross-sectional area (CSA) were calculated as measurements of bending strength, risk of buckling, and bone apposition, respectively. After 24 months of TPTD treatment, areal and volumetric FN BMD increased significantly by 4.0% and 3.0%, respectively, compared with baseline. Decreases in cortical volumetric BMD occurred in locations not adversely affecting minimum bending strength indicators. Cortical CSA increased by 4.3%, whereas total CSA remained unchanged over the study duration, indicating that endosteal but no periosteal growth was observed. Strength parameters for buckling did not change at 6 and 12 months but improved significantly at 24 months. Measures of bending strength showed a trend toward improvement. Changes tended to be larger in individuals at higher risk of buckling failure. Prior antiresorptive treatment may delay response to TPTD, but based on the small magnitude of the mostly insignificant changes at 6 months, this does not appear to lead to an interim phase of reduced bone strength. In summary, FN QCT provides a tool for detailed longitudinal investigation of bone strength indices in vivo for different loading modes, yields insight into underlying structural changes, and provides relevant mechanostructural information beyond dual-energy X-ray absorptiometry. Continuous TPTD treatment for 24 months improves FN bone strength parameters.

Improvements in vertebral body strength under teriparatide treatment assessed in vivo by finite element analysis: results from the EUROFORS study.

Monitoring of osteoporosis therapy based solely on DXA is insufficient to assess antifracture efficacy. Estimating bone strength as a variable closely linked to fracture risk is therefore of importance. Finite element (FE) analysis-based strength measures were used to monitor a teriparatide therapy and the associated effects on whole bone and local fracture risk. In 44 postmenopausal women with established osteoporosis participating in the EUROFORS study, FE models based on high-resolution CT (HRCT) of T(12) were evaluated after 0, 6, 12, and 24 mo of teriparatide treatment (20 microg/d). FE-based strength and stiffness calculations for three different load cases (compression, bending, and combined compression and bending) were compared with volumetric BMD (vBMD) and apparent bone volume fraction (app. BV/TV), as well as DXA-based areal BMD of the lumbar spine. Local damage of the bone tissue was also modeled. Highly significant improvements in all analyzed variables as early as 6 mo after starting teriparatide were found. After 24 mo, bone strength in compression was increased by 28.1 +/- 4.7% (SE), in bending by 28.3 +/- 4.9%, whereas app. BV/TV was increased by 54.7 +/- 8.8%, vBMD by 19.1 +/- 4.0%, and areal BMD of L(1)-L(4) by 10.2 +/- 1.2%. When comparing standardized increases, FE changes were significantly larger than those of densitometry and not significantly different from app. BV/TV. The size of regions at high risk for local failure was significantly reduced under teriparatide treatment. Treatment with teriparatide leads to bone strength increases for different loading conditions of close to 30%. FE is a suitable tool for monitoring bone anabolic treatment in groups or individual patients and offers additional information about local failure modes. FE variables showed a higher standardized response to changes than BMD measurements, but further studies are needed to show that the higher response represents a more accurate estimate of treatment-induced fracture risk reduction.

Monitoring teriparatide-associated changes in vertebral microstructure by high-resolution CT in vivo: results from the EUROFORS study.

UNLABELLED: We introduce a method for microstructural analysis of vertebral trabecular bone in vivo based on HRCT. When applied to monitor teriparatide treatment, changes in structural variables exceeded and were partially independent of changes in volumetric BMD. INTRODUCTION: Monitoring of osteoporosis therapy based solely on bone densitometry is insufficient to assess anti-fracture efficacy. Assessing bone microstructure in vivo is therefore of importance. We studied whether it is possible to monitor effects of teriparatide on vertebral trabecular microstructure independent of BMD by high-resolution CT (HRCT). MATERIALS AND METHODS: In a subset of 65 postmenopausal women with established osteoporosis who participated in the EUROFORS study, HRCT scans of T(12), quantitative CT of L(1)-L(3), and DXA of L(1)-L(4) were performed after 0, 6, and 12 mo of teriparatide treatment (20 microg/d). We compared BMD and 3D microstructural variables in three groups of women, based on prior antiresorptive treatment: treatment-naïve; pretreated; and pretreated women showing inadequate response to treatment. RESULTS: We found statistically highly significant increases in most microstructural variables and BMD 6 mo after starting teriparatide. After 12 mo, apparent bone volume fraction (app. BV/TV) increased by 30.6 +/- 4.4% (SE), and apparent trabecular number (app. Tb.N.) increased by 19.0 +/- 3.2% compared with 6.4 +/- 0.7% for areal and 19.3 +/- 2.6% for volumetric BMD. The structural changes were partially independent of BMD as shown by a significantly larger standardized increase and a standardized long-term precision at least as good as DXA. Patients who had shown inadequate response to prior osteoporosis treatment did show improvements in BMD and structural measures comparable to treatment-naïve patients. CONCLUSIONS: HRCT is a feasible method for longitudinal microstructural analysis of human vertebrae in vivo, offers information beyond BMD, and is sufficiently precise to show profound effects of teriparatide after 12 mo.

Lifestyle and 30-day complications to surgery for colorectal cancer.

This study aimed to identify lifestyle factors with impact on 30-day mortality and complications after surgery for a first time colorectal adenocarcinoma. All patients in Denmark within a 20 month period were registered in a nationwide database; 57% were included in the analysis. Logistic regression was used, adjusted for age, sex and disease- or treatment related factors. BMI=30 kg/m2 increased the risk of complications in general (CIG), impaired wound healing (IWH), deep wound infection and mortality. Smoking increased the risk of CIG, IWH and mortality. Alcohol increased the risk of IWH and anastomotic leakage. Self perceived physical fitness at or below average increased the risk of CIG, thrombosis, and mortality. The population attributable risk was 23% for complications and 64% for mortality. The results suggest that lifestyle factors are important for the course of the 30-day postoperative period. Lifestyle factors should be considered in future prediction models for outcome after colorectal cancer surgery.

[Outpatient treatment. What is the evidence?]. / Ambulant behandling. Hvad er der evidens for?

In relation to the development of quality standards for the national quality development study, DGMA, a search was made through the literature on outpatient care. The literature was scanty, but some evidence was found on the following: Continuity of care is a patient demand, and several studies show more effective and less expensive treatment when this is ensured. Two studies show impaired quality of treatment, but quality is not defined either precisely or uniformly. Waiting times dissatisfy patients and perhaps diminish the result of treatment and information. Failure to turn up for appointments affects up to 29 per cent of consultations. Non-attendances could be cut down if patient factors and continuity of care are taken into account. Some outpatient consultations could take place in the general practitioner's surgery, if hospital doctors knew more about their capabilities.