Christian Roux

Effect of risedronate on the risk of hip fracture in elderly women.

BACKGROUNDnRisedronate increases bone mineral density in elderly women, but whether it prevents hip fracture is not known.nnnMETHODSnWe studied 5445 women 70 to 79 years old who had osteoporosis (indicated by a T score for bone mineral density at the femoral neck that was more than 4 SD below the mean peak value in young adults [-4] or lower than -3 plus a nonskeletal risk factor for hip fracture, such as poor gait or a propensity to fall) and 3886 women at least 80 years old who had at least one nonskeletal risk factor for hip fracture or low bone mineral density at the femoral neck (T score, lower than -4 or lower than -3 plus a hip-axis length of 11.1 cm or greater). The women were randomly assigned to receive treatment with oral risedronate (2.5 or 5.0 mg daily) or placebo for three years. The primary end point was the occurrence of hip fracture.nnnRESULTSnOverall, the incidence of hip fracture among all the women assigned to risedronate was 2.8 percent, as compared with 3.9 percent among those assigned to placebo (relative risk, 0.7; 95 percent confidence interval, 0.6 to 0.9; P=0.02). In the group of women with osteoporosis (those 70 to 79 years old), the incidence of hip fracture among those assigned to risedronate was 1.9 percent, as compared with 3.2 percent among those assigned to placebo (relative risk, 0.6; 95 percent confidence interval, 0.4 to 0.9; P=0.009). In the group of women selected primarily on the basis of nonskeletal risk factors (those at least 80 years of age), the incidence of hip fracture was 4.2 percent among those assigned to risedronate and 5.1 percent among those assigned to placebo (P=0.35).nnnCONCLUSIONSnRisedronate significantly reduces the risk of hip fracture among elderly women with confirmed osteoporosis but not among elderly women selected primarily on the basis of risk factors other than low bone mineral density.

Mild prevalent and incident vertebral fractures are risk factors for new fractures

SummaryThis prospective four-year study indicates that post-menopausal osteoporotic women with mild prevalent and incident vertebral fractures have an increased risk of incident fractures.IntroductionMild vertebral fractures are under diagnosed as there is disagreement about their clinical significance. Our aim was to assess the risk of subsequent fractures induced by both prevalent and incident mild vertebral fractures in osteoporotic post-menopausal women.Patients and methodsThree thousand three hundred and fifty-eight patients, aged 74u2009±u20096xa0years, with post-menopausal osteoporosis included in the placebo groups of two clinical trials of strontium ranelate were followed for 4xa0years. A Cox regression model adjusted on age, body mass index and bone mineral density was used to calculate the relative risk (RR) of fracture in subjects with only mild fractures as compared to patients without fracture, and to patients with at least one grade ≥ 2 fracture. These calculations were made for prevalent and then incident fractures.ResultsThe RR of vertebral fracture in 4xa0years was 1.8 (1.3–2.4) pu2009<u20090.001, and 2.7 (2.3–3.3) pu2009<u20090.001 for patients having only mild vertebral fractures and at least one grade ≥ 2 fracture at baseline respectively. The RR of vertebral fracture in the 3rd and 4th years of follow-up was 1.7 (1.1–2.6) pu2009=u20090.01, and 1.9 (1.3–2.6) pu2009<u20090.001 for patients having during the first 2xa0years incident mild fractures only, and for patients having at least one grade ≥ 2 incident fracture respectively. The RR of non-vertebral fracture in 4xa0years was 1.3 (0.9–1.9) pu2009=u20090.15 and 1.7 (1.4–2.1) pu2009<u20090.001 for patients having only mild or at least one grade ≥ 2 vertebral fracture at baseline respectively. For patients aged more than 70xa0years, these RR were 1.45 (0.99–2.11) (pu2009=u20090.06), and 1.72 (1.36–2.18) pu2009<u20090.001 respectively. The RR of non-vertebral fracture in the 3rd and 4th years was 1.68 (1.36–2.09) pu2009<u20090.001 for patients having at least one grade ≥ 2 incident fracture during the 2 first years of follow-up.ConclusionMild vertebral fractures are a risk factor for subsequent vertebral and non-vertebral fracture in postmenopausal women with osteoporosis; 1 out of 4 patients with an incident mild vertebral fracture in 2xa0years will fracture again within the 2 next years.

The severity of vertebral fractures and health-related quality of life in osteoporotic postmenopausal women.

Vertebral fractures are the hallmark of osteoporosis, responsible for increased back pain, impairment of mobility and functional limitations. These factors have an impact on patients’ health-related quality of life (QOL). The aim of this study was to assess QOL, using QUALEFFO, in osteoporotic postmenopausal women, according to the number and the severity of the vertebral fractures. A group of 629 osteoporotic postmenopausal women (60–80xa0years) with symptoms that, according to a rheumatologist, could be related to a vertebral fracture, had spine X-rays with standardized procedures. All the X-rays were assessed in a central facility. The number of fractures was a determinant of a low QOL, as indicated by an increased score in physical function ( P =0.001), social function ( P =0.002) and total score ( P =0.027). Patients with higher grades of vertebral deformities, i.e., more severe fractures, had low QOL in these three domains, too ( P <0.0001, P <0.0001 and P =0.005, respectively). There was no difference in QOL according to the thoracic or lumbar location of the fractures. Both anterior and middle deformities of the vertebral bodies had a negative impact on QOL. In none of the analyses were the pain and mental function domains of QUALEFFO discriminant among the patients. QOL, assessed by an osteoporosis-specific instrument, is decreased in osteoporotic women as a function of both the number and the severity of the vertebral fractures. Treating women with prevalent fractures may avoid a further decrease in their quality of life.

Radiographic methods for evaluating osteoporotic vertebral fractures

UNLABELLEDnReproducible methods for the radiological assessment of osteoporotic vertebral fractures, defined based on accurate criteria, are needed in everyday practice and in therapeutic trials and epidemiological studies.nnnOBJECTIVESnTo describe and to evaluate methods for osteoporotic vertebral fracture assessment based on standard radiographs or dual-energy X-ray absorptiometry (DXA) and to determine the role for each method in clinical practice, therapeutic trials, and epidemiological studies.nnnMETHODSnA review written by a rheumatologist based on his clinical experience and on a literature review was submitted to four experts. Studies in English or French published between 1975 and February 2008 were retrieved from Medline using the keywords vertebral fracture, osteoporosis, vertebral deformity, and vertebral fracture assessment.nnnRESULTSnOne hundred forty-nine articles were selected and read in their full-text version. There was no consensus regarding the definition of osteoporotic vertebral fractures. The following methods were evaluated: visual assessment, Genants semi-quantitative assessment, Jiangs algorithm-based qualitative method, morphometric radiography, and DXA of the spine. In everyday practice, Genants semi-quantitative assessment on standard radiographs may provide useful information on the severity and prognosis of osteoporosis. DXA done for bone mineral density measurement may detect vertebral fractures in asymptomatic patients. Assessment of standard radiographs remains the reference standard for diagnosing vertebral fractures in patients with suggestive symptoms (e.g., pain in the thoracic or lumbar spine, height loss, or thoracic kyphosis). For therapeutic trials and epidemiological studies, Genants semi-quantitative assessment used by a trained and experienced observer is the preferred method, based on its good reproducibility and ability to differentiate fractures from other deformities. However, thousands of radiographs may be needed, making routine interpretation by an expert impractical. A visual semi-quantitative method may be used to separate normal radiographs from radiographs showing possible or obvious fractures, which can then be read by an expert. Alternatively, radiomorphometric indices can be determined on digitized radiographs in combination with a semi-quantitative assessment, with discordant cases being reviewed by an expert. We do not recommend Jiangs method at present, as it is still undergoing validation.

Three-dimensional X-ray absorptiometry (3D-XA): a method for reconstruction of human bones using a dual X-ray absorptiometry device

Three-dimensional accurate evaluation of the geometry of the proximal femur may be helpful for hip fracture risk evaluation. The purpose of this study was to apply and validate a stereo-radiographic 3D reconstruction method of the proximal femur, using contours identification from biplanar DXA images. Twenty-five excised human proximal femurs were investigated using a standard DXA unit. Three-dimensional personalized models were reconstructed using a dedicated non-stereo corresponding contours (NSCC) algorithm. Three-dimensional CT-scan reconstructions obtained on a clinical CT-scan unit were defined as geometric references for the comparison protocol, in order to assess accuracy and reproducibility of the 3D stereo-radiographic reconstructions. The precision of a set of 3D geometric parameters (femoral-neck axis length, mid-neck cross-section area, neck-shaft angle), obtained from stereo-radiographic models was also evaluated. This study shows that the NSCC method may be applied to obtain 3D reconstruction from biplanar DXA acquisitions. Applied to the proximal femur, this method showed good accuracy as compared with high-resolution personalized CT-scan models (mean error = 0.8xa0mm). Moreover, precision study for the set of 3D parameters yielded coefficients of variation lower than 5%. This is the first study providing 3D geometric parameters from standard 2D DXA images using the NSCC method. It has good accuracy and reproducibility in the present study on cadaveric femurs. In vivo prospective studies are needed to evaluate its discriminating potential on hip fracture risk prediction.

Drug Insight: choosing a drug treatment strategy for women with osteoporosis - an evidence-based clinical perspective

Many randomized controlled trials (RCTs) have investigated drug treatment for women at high risk of fracture, with a reduction in fracture risk as their end point. There has also been progress in identifying women at the highest risk of fractures. The most important clinical determinant contributing to the clinical decision of initiating and choosing drug therapy for fracture prevention is a womans fracture risk, which, in RCTs, was determined by menopausal state, age, bone mineral density, fracture history, fall risks and glucocorticoid use. Women with secondary osteoporosis were excluded, except in studies of glucocorticoid use. A second determinant of drug therapy is the evidence for fracture prevention in terms of spectrum (vertebral, nonvertebral and/or hip fractures), size and speed of effect. In the absence of head-to-head RCTs with fracture risk as the end point, however, the efficacy of antifracture drugs cannot be directly compared. Other determinants include the potential extraskeletal benefits and safety concerns of the drug, patient preferences and reimbursement issues.

The expression of CXCR4/CXCL12 determines subsets of patients in systemic lupus erythematosus

Results B cells and CD4 T cells from SLE patients exhibited an over two-fold increase (p 10 compared to those with SLEDAI scores ≤10 (p=0.005), and was 1.36-fold higher in active neuropsychiatric SLE (NPSLE) patients compared to non-NPSLE patients (p=0.11). CXCL12 was significantly up-regulated in lupus nephritis kidneys (n=16), with the extent and level of expression was correlated with histopathological scores.

Bone turnover markers after the menopause: T-score approach

Bone turnover increases at the menopause and is associated with accelerated bone loss. However, it is not known to what extent there is an imbalance between the processes of bone resorption and bone formation, nor whether it is the rate of bone turnover or the bone balance that is most closely associated with the rate of bone loss. We studied 657 healthy women ages 20 to 79 from five European cities (the OPUS Study) and divided them into two premenopausal age groups, 20 to 29 (n=129), 30 to 39years (n=183), and three postmenopausal groups 1 to 10years (n=91), 11 to 20years (n=131) and 21+ years since menopause (n=123). We measured collagen type I C-telopeptide (CTX, a marker of bone resorption) and procollagen I N-propeptide (PINP, a marker of bone formation). We used these two markers to calculate the overall bone turnover and the difference between bone formation and resorption (bone balance) using the results from the women ages 30 to 39years to calculate a standardised score (T-score). We found that the CTX and PINP levels were higher in the women ages 20 to 29 and in the women in the three menopausal groups as compared to women ages 30 to 39years (p<0.001). For example, the CTX and PINP levels were 80 and 33% higher in women 1 to 10years since menopause as compared to women ages 30 to 39years. In this group of postmenopausal women, the bone turnover expressed as a T-score was 0.72 (0.57 to 0.88, 95%CI) and the bone balance was -0.37 (-0.59 to -0.16). There was greater rate of bone loss from the total hip in all the groups of women after the menopause compared to women before the menopause. We conclude that the bone loss after the menopause is associated with both an increase in bone turnover and a negative bone balance and that bone loss was most clearly associated with overall bone turnover.