Spine radiographs to improve the identification of women at high risk for fractures

Summary

In women older than 60 years with clinical risk factors for osteoporosis but without osteoporosis based on bone mineral density (T-score?≥??2.5), a systematic survey with X-rays of the spine identified previously unknown vertebral deformities in 21% of women.

Introduction

This study determines the prevalence of vertebral deformities in elderly women with clinical risk factors for osteoporosis but with BMD values above the threshold for osteoporosis (T-score?≥??2.5).

Methods

Bisphosphonate naïve women older than 60 years attending 35 general practices in the Netherlands with ≥2 clinical risk factors for osteoporosis were invited for BMD measurement (DXA). In women with T-score?≥??2.5 at both spine and the hips, lateral radiographs of the thoracic and lumbar spine were performed.

Results

Of 631 women with a DXA measurement, 187 (30%) had osteoporosis (T-score?T-score?≥??2.5 at both spine and hip, 387 had additional spine radiographs, of whom 80 (21%) had at least one vertebral deformity.

Conclusion

In elderly women with clinical risk factors for osteoporosis but BMD T-score?≥??2.5, addition of spine radiographs identified vertebral deformities in 21% (95% CI: 17–25). Since these women are at risk of future fractures, antiosteoporotic treatment should be considered.     

Vertebral fractures in women aged 50 years and older with clinical risk factors for fractures in primary care

Background

The identification of vertebral fractures (VFs) is important for decisions on fracture prevention. Vertebral fracture assessment (VFA) was shown to be a patient-friendly and valid method for detecting undiagnosed VFs in (Dutch) women. However, this has only been investigated in women seeking care at secondary or tertiary institutions.

Objective

To investigate the prevalence of previously undiagnosed VFs in women in Dutch primary care using VFA.

Study design

A total of 566 Dutch women aged 50 years and older (mean age, 69 years; SD = 8.4) with clinical risk factors (CRFs) for fractures volunteered for dual-energy X-ray absorptiometry (DXA) measurement and VFA. VFs were defined semi-quantitatively using Genant's method.

Results

One CRF was present in each of 130 women, 274 had two, and 162 women had more than two CRFs. In 120 (21%) of the women, previously unknown osteoporosis (T-score ≤ −2.5 SD) was diagnosed, and in 174 (31%), a previously undiagnosed moderate or severe VF was found. No osteoporosis was found in 130 (75%) of the women with a VF. Based on the outcome of DXA, 21% of the women were eligible for treatment, while the combination of DXA and VFA resulted in a total of 250 (44%) women requiring treatment.

Conclusions

The percentage of previously unknown VFs diagnosed by VFA in women aged 50 years and older with one or more CRFs for fractures in primary care is high. When only using BMD measurements, only half the women eligible for treatment would actually receive this. We recommend performing VFA in all women aged 50 years and older who are referred for DXA based on Dutch case finding criteria.     

Development of draft validation criteria for a soluble biomarker to be regarded as a valid biomarker reflecting structural damage endpoints in rheumatoid arthritis and spondyloarthritis clinical trials

OBJECTIVE: Recent work has shown that several soluble biomarkers, detectable in peripheral blood, synovial fluid, and/or urine, reflect remodeling of joint tissues and may therefore constitute outcome measures that reflect joint damage. Consequently, it is now desirable to begin the process of developing criteria for validation of a soluble biomarker as an outcome measure reflecting structural damage progression in trials of disease-modifying therapies for rheumatoid arthritis (RA) and spondyloarthritis (SpA). Our objective was to develop validation criteria for a soluble biomarker to be regarded as a valid biomarker reflecting radiological endpoints in RA and SpA clinical trials. METHODS: A special interest group was established comprising investigators with expertise in soluble biomarker assay development as well as in outcomes research. This project was initiated by means of a Delphi consensus exercise. A list of draft criteria was first generated following a review of a US National Institutes of Health (NIH) 2000 white paper (available at: http://www.niams.nih.gov/ne/oi/ oabiomarwhipap.htm) that focused on biomarkers in OA, and these were organized under subject headings relevant to the OMERACT filter: truth, discrimination, and feasibility. Additional criteria were solicited from the working group. This was followed by 3 rounds of voting. RESULTS: A list of 31 criteria was generated prior to voting. The first 2 rounds of voting resulted in cumulative agreement that 19 criteria be retained and 4 discarded, while discrepancies were recorded for 8 criteria. In the third round of voting, cumulative agreement was achieved to retain 5 of the 8 discrepant criteria, so that the final list included 24 criteria. CONCLUSION: A draft set of criteria for validation of a soluble biomarker to be regarded as reflecting radiological damage endpoints in clinical trials has been proposed on the basis of consensus.     

Testing of the preliminary OMERACT validation criteria for a biomarker to be regarded as reflecting structural damage endpoints in rheumatoid arthritis clinical trials: the example of C-reactive protein

OBJECTIVE: A list of 14 criteria for guiding the validation of a soluble biomarker as reflecting structural damage endpoints in rheumatoid arthritis (RA) clinical trials was drafted by an international working group after a Delphi consensus exercise. C-reactive protein (CRP), a soluble biomarker extensively studied in RA, was then used to test these criteria. Our objectives were: (1) To assess the strength of evidence in support of CRP as a soluble biomarker reflecting structural damage in RA according to the draft validation criteria. (2) To assess the strength of recommendation for inclusion of individual criteria in the draft set. METHODS: A systematic literature review was conducted to elicit evidence in support of each specific criterion composing the 14-criteria draft set. A summary of the key literature findings per criterion was presented to both the working group and to participants in a special interest soluble biomarker group at OMERACT 8. Participants at OMERACT 8 were asked to rate the strength of evidence and the strength of the recommendation in support of each individual criterion on a 0-10 numerical rating scale. Working group members not present at OMERACT voted by a Web-based survey. RESULTS: Minimal data were extracted from the literature pertaining to those criteria listed under the category of truth. Ratings for strength of evidence were moderate to low (< 7) for CRP as a biomarker reflecting structural damage in RA; this was true for all criteria except those listed under the category of feasibility and 2 listed under the category of discrimination pertaining to assay reproducibility and evidence regarding sources of variability. Ratings for strength of recommendation for inclusion of each of the 14 criteria in the draft set were high (> 7) except for those criteria listed under the category of truth. CONCLUSION: The draft criteria serve as a useful template in the evaluation of the strength of evidence in support of a particular soluble biomarker as reflecting structural damage in RA.     

Review and evaluation of the Dutch guidelines for osteoporosis

RATIONALE: At the request of a Dutch governmental organization, a multidisciplinary group of osteoporosis experts in the Netherlands published in 2002 a guideline on case finding, diagnosis, prevention and treatment of osteoporosis. These guidelines were evaluated for their validity and applicability. METHODS: Analysis by 5 external osteoporosis experts using the 'Appraisal of Guidelines for Research & Evaluation' ('AGREE') instrument. RESULTS: The score for the 6 domains of AGREE was 88% for the scope and purpose domain, 76% for stakeholder involvement, 81% for rigour of development, 84% for clarity and presentation, 77% for applicability and 73% for editorial independence. For single components of the domains of AGREE, highest scores were found for systematic methods used to search for evidence (100%), inclusion of individuals from all the relevant professional groups (95%) and ease of identifying key recommendations (95%). Lowest scores to single components of the several domains were given for piloting among target users (44%). All experts recommended the guidelines for use in practice. CONCLUSIONS: The AGREE instrument scored high for development, clarity and presentation but low for piloting among target users and implementation. Based on the guideline, algorithms from case finding to treatment were constructed that could be tested for piloting among target users and for implementation of the guideline.     

A simple clinical score for estimating the long-term risk of fracture in post-menopausal women

BACKGROUND: Simple tools are needed to identify patients at high risk of fracture. AIM: To develop a simple clinical tool for assessing 5-year risk of fracture. DESIGN: Cohort study. METHODS: The study population consisted of all women aged 50+ included in the THIN Research Database (containing computerized medical records of UK general practices). Using Cox proportional hazards models, a risk score was initially estimated from age, body mass index, and clinical risk factors. The 5-year risk of fracture (survival function) was estimated for each score. RESULTS: The study population included 366 104 women aged > or = 50 years (mean follow-up 5.8 years). Of these, 6453 suffered a hip fracture. Several characteristics independently contributed to the fracture risk score (age, body mass index, fracture and fall history, previous diagnoses and use of medication). The 5-year risks for hip fracture for patients with total scores of 10, 30 and 50 were 0.3% (95%CI 0.3-0.4%), 2.2% (95%CI 2.1-2.2%), and 13.1% (95%CI 12.5-13.7%), respectively. A woman aged 65 years with low BMI and a history of both fracture and falling would have a hip fracture risk score of 37, with a corresponding 5-year risk for a hip fracture of 4.1% (4.0-4.2%). The risk score was validated and tested in another population (from GPRD), with a good concurrence between predicted and observed risks of fracture. DISCUSSION: This risk score predicts the long-term risk of fracture, and could be used for targeting patients for further investigation, such as bone densitometry.     

Evaluation of the efficacy and safety of oral tiludronate in paget's disease of bone

Objective. To assess the optimal dosage of oral tiludronate in Paget's disease of bone. Methods. We studied 149 patients with Paget's disease, in a double-blind, randomized, placebo-controlled trial. Patients were randomly assigned to 1 of 5 therapeutic groups: a daily dose of 100 mg, 200 mg, 400 mg, or 800 mg of oral tiludronate, or a placebo. Treatment was for 3 months, followed by 3 months of placebo-controlled followup. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatinine (OH/Cr) were measured monthly, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self-evaluated from a visual analog scale and a global pain index. Results. Statistical analysis revealed that beginning at a dosage of 200 mg/day, there was a direct dose-dependent effect on the reduction of SAP and OH/Cr levels. Reduction of SAP levels was clinically significant at a dosage of 400 mg (44.9 ± 4.2% reduction at 90 days and 49.2 ± 4.5% at 180 days, mean ± SEM) and at 800 mg (53.4 ± 5% at 90 days and 59.3 ± 4.6% at 180 days). There was a significant reduction in pain in all groups, including the group taking placebo. In only those taking 800 mg/day of tiludronate was there a significant frequency of complete resolution of pain (versus placebo). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance of all 5 regimens was good. Exhaustive biochemical investigations failed to reveal significant toxicity of tiludronate up to the 800-mg daily dose investigated. Conclusion. Because of its significantly better antiresorptive effects and greater analgesic properties (compared with lower dosages), combined with the excellent clinical and biochemical tolerance, the 800-mg daily dose of tiludronate appears to be optimal for the treatment of Paget's disease of bone.