Jacques Fechtenbaum

Vertebral Fracture Risk Reduction With Strontium Ranelate in Women With Postmenopausal Osteoporosis Is Independent of Baseline Risk Factors

Strontium ranelate (2 g/day) was studied in 5082 postmenopausal women. A reduction in incident vertebral fracture risk by 40% was shown after 3 years. This effect was independent of age, initial BMD, and prevalent vertebral fractures.

Effects of strontium ranelate on spinal osteoarthritis progression

Objective: The aim of this study was to determine whether a 3-year treatment with strontium ranelate could delay the progression of spinal osteoarthritis (OA). Methods: This study was a post-hoc analysis of pooled data from the Spinal Osteoporosis Therapeutic Intervention (SOTI) and TReatment Of Peripheral OSteoporosis (TROPOS) trials performed on 1105 women with osteoporosis and concomitant radiological spinal OA at baseline, and for whom lumbar x-rays were available at baseline and over the 3-year treatment period. The presence and severity of osteophytes, disc space narrowing and sclerosis in the lumbar intervertebral spaces was graded according to a validated method, and an overall OA score was calculated for each intervertebral space. Back pain (measured on a five-point Likert scale only in SOTI) and health-related quality of life (SF-36 questionnaire) were assessed at baseline and after 3 years. Patients who suffered an incident or progressive vertebral fracture during the study were excluded from the analysis. Results: The proportion of patients with worsening overall spinal OA score was reduced by 42% in the strontium ranelate group, compared with placebo (RR, 0.58; 95% CI, 0.42 to 0.79; p = 0.0005). Significantly more patients in the strontium ranelate group experienced an improvement in back pain after 3 years, compared with placebo (p = 0.03), while no significant difference was observed in terms of health-related quality of life between these patient groups. Conclusions: The results of this post-hoc analysis suggest that strontium ranelate could reduce the progression of the radiographic features of spinal OA and back pain in women with osteoporosis and prevalent spinal OA.

Identification of Rheumatoid Arthritis Patients With Vertebral Fractures Using Bone Mineral Density and Trabecular Bone Score

The aim of this study was to test bone mineral density (BMD), trabecular bone score (TBS), and their combination, for detection of rheumatoid arthritis (RA) patients with vertebral fractures (VFs). One hundred eighty-five women aged 56.0 ± 13.5 yr, with RA since 15.5 ± 9.9 yr were studied. Lumbar spine, total hip, and femoral neck BMD were assessed by dual-energy X-ray absorptiometry (DXA). TBS was calculated from anteroposterior image of lumbar spine BMD. VFs from T4 to L4 were evaluated using Vertebral Fracture Assessment software on DXA device. The proportions of patients with VF and T-scores ≤-2.5 were only 24.2%, 21.2%, and 33.3% at lumbar spine, total hip, and femoral neck, respectively. T-scores were significantly lower in patients with VF than in patients without VF, the largest difference being observed at femoral neck (p=0.0001). TBS was significantly lower in patients with VF vs without VF (p=0.0001). The areas under the curves were 0.621, 0.704, 0.703, 0.719, and 0.727 for lumbar spine BMD, TBS, lumbar spine BMD+TBS, total hip BMD, and femoral neck BMD, respectively. The threshold of 1.173 for TBS had the best sensitivity (63%) and specificity (74%). TBS measured at the lumbar spine has a better discrimination value than lumbar spine BMD, and similar to femoral neck BMD, for prediction of presence of VF in patients with RA. In RA subjects with osteopenia, the proportion of patients with VF was higher in the lowest tertile of TBS when compared with the highest tertile. In this population, at low risk according to BMD, TBS could help to detect patients with VF.

Strontium ranelate reduces the risk of vertebral fracture in young postmenopausal women with severe osteoporosis

Objectives: Early osteoporotic fractures have a great impact on disease progression, the first fracture being a major risk factor for further fractures. Strontium ranelate efficacy against vertebral fractures is presently assessed in a subset of women aged 50–65 years. Methods: The Spinal Osteoporosis Therapeutic Intervention (SOTI) was an international, double blind, placebo controlled trial, supporting the efficacy of strontium ranelate 2 g/day in reducing the risk of vertebral fractures in postmenopausal women with osteoporosis and a prevalent vertebral fracture. 353 of these randomly assigned women were included in this analysis. Results: Over 4 years, strontium ranelate significantly reduced the risk of vertebral fracture by 35% (relative risk 0.65; 95% CI 0.42 to 0.99, p<0.05). In the strontium ranelate group, the bone mineral density increased from baseline by 15.8% at lumbar spine and 7.1% at femoral neck. Conclusion: These data demonstrate a significant vertebral antifracture efficacy of strontium ranelate in young postmenopausal women aged 50–65 years with severe osteoporosis and confirm the efficacy of this antiosteoporotic treatment to prevent vertebral fractures, whatever the age of the patient.

Randomized, Double-masked, 2-year Comparison of Tibolone with 17β-Estradiol and Norethindrone Acetate in Preventing Postmenopausal Bone Loss

In this 2-year, randomized study, we compared the efficacy and tolerability of tibolone 2.5 mg (n= 75), tibolone 1.25 mg (n= 76) and estradiol 2 mg plus norethindrone acetate 1 mg (E2/NETA; n= 74) for preventing bone loss in postmenopausal women. Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry, and bone remodeling markers were assessed every 6 months. Side-effects were assessed quarterly. After 24 months, the mean increase (± SD) in lumbar spine BMD from baseline was 3.6%± 2.9%, 1.9%± 3.5% and 6.8%± 4.5% in the tibolone 2.5 mg, tibolone 1.25 mg and E2/NETA groups, respectively. All pairwise differences were significant. The proportion of responders (women with a change from baseline in lumbar spine BMD of ≥−2% after 2 years) was 95.7%, 89.0% and 98.5% with tibolone 2.5 mg, tibolone 1.25 mg and E2/NETA, respectively. Similar results were obtained for femoral BMD, although the difference between tibolone 2.5 mg and E2/NETA was not significant at 24 months. Decreases in bone remodeling markers were similar in the three groups. Vaginal bleeding was more common in the E2/NETA group (33.8%) than with tibolone 2.5 mg (12.0%) or tibolone 1.25 mg (9.2%), as was breast pain (23.0%, 2.7% and 2.6%, respectively). Each treatment effectively prevented bone loss. Overall, tolerability of tibolone was better than with E2/NETA, because of less frequent vaginal bleeding and breast pain. This may promote long-term adherence.

Intermittent cyclic tiludronate in the treatment of osteoporosis.

Abstract: The objective of the study was to determine the efficacy and safety of tiludronate in the treatment of postmenopausal osteoporosis. Two placebo-controlled, randomized, double-masked, multicenter, cyclical, intermittent, dose-ranging studies including 1805 women with low vertebral bone mineral density and prevalent vertebral fractures and 488 women with low bone mineral density and no prevalent fracture were conducted. Patients were randomized to either tiludronate 50 mg/day, tiludronate 200 mg/day or placebo, given orally for the first 7 days of each month. A supplement of 500 mg elemental calcium was provided daily from day 8 to the end of the month. Both studies demonstrated no statistically or clinically relevant trends in the incidence of adverse effects accross the three treatment groups. However, tiludronate administered at these two doses in a cyclic intermittent regimen was not effective in reducing the incidence of vertebral fractures or increasing spinal bone mineral density. Thus, tiludronate, administered at these doses in a cyclic intermittent regimen, cannot be considered an appropriate treatment of postmenopausal osteoporosis, notwithstanding a high safety profile.

Inverse relationship between vertebral fractures and spine osteoarthritis in postmenopausal women with osteoporosis

Background: Although the coexistence of osteoarthritis and osteoporosis is considered as uncommon, it has been suggested that, in postmenopausal women, disc space narrowing increases the risk of vertebral fracture. The aim of this study was to check this hypothesis in postmenopausal women with osteoporosis. Objective: We analysed the relationship between vertebral fractures and spine osteoarthritis in 410 postmenopausal women with osteoporosis: in this population both disc space narrowing and osteophytes are inversely related to vertebral fractures. Patients and methods: This study is based on baseline data collected in a multicentre, prospective and 6-month longitudinal observational study. 410 postmenopausal women (74±5 years) were enrolled who had consulted for back pain, and had osteoporosis (according to WHO definition). Spine x-rays were performed according to standardised procedures. Vertebral fractures were evaluated from T4 to L4 using the Genant’s semiquantitative method; osteoarthritis was evaluated by scoring osteophytes and disc space narrowing at all levels of the thoracic and lumbar spine, and by a qualitative assessment of facet joint arthritis. Results: The prevalence of vertebral fractures was 52.4%. At least one osteophyte, one disc space narrowing and one facet arthritis were present in 90.2, 64.6 and 77.8% of patients respectively. There was an inverse association between vertebral fractures and osteoarthritis: odds ratios adjusted for age and weight (95% CI) were 0.38 (0.17–0.86), p = 0.02 and 0.27 (0.16–0.46), p<10−4 for the presence of at least one osteophyte, and of at least three disc space narrowings respectively. In a cluster analysis, it was possible to identify a subgroup of patients without any disc space narrowing, and another subgroup with all patients having at least one disc space narrowing; the proportion of patients having more than three vertebral fractures was 25.2 and 15.9% in these two clusters respectively. Conclusions: Disc space narrowing and osteophytes are associated with a decreased vertebral fracture prevalence in postmenopausal women with osteoporosis.

Challenges of Cardiovascular Risk Assessment in the Routine Rheumatology Outpatient Setting: An Observational Study of 110 Rheumatoid Arthritis Patients

An annual assessment of cardiovascular (CV) risk factors in rheumatoid arthritis (RA) is recommended, but its practical modalities have not been determined. The objective was to assess the feasibility and usefulness of a standardized CV risk assessment in RA, performed by rheumatologists during outpatient clinics.

Prospective assessment of thoracic kyphosis in postmenopausal women with osteoporosis

We attempt to assess quantitatively thoracic kyphosis and its influence on incident fractures and quality of life over three years in postmenopausal women with osteoporosis and the effect of strontium ranelate on thoracic kyphosis progression. This study was performed on women with postmenopausal osteoporosis from the Spinal Osteoporosis Therapeutic Intervention (SOTI) and Treatment of Peripheral Osteoporosis (TROPOS) studies. Vertebral fractures were assessed on lateral thoracic radiographs performed at baseline and at three years according to standardized procedure. Kyphosis index (KI, %), was defined as the percentage ratio between the maximum depth of thoracic curvature and the height measured from the T4 to the T12 vertebrae. Baseline characteristics of the 3218 patients (1594 strontium ranelate, 1624 placebo) were mean age 73.3 years, spine bone mineral density (BMD) T‐score (L2–4) −3.1, femoral neck T‐score −3.0, and KI 25.4%. In the placebo group, patients with the highest baseline KI experienced significantly more vertebral fractures than those with medium KIs [relative risk (RR) = 1.53; 95% confidence interval (CI) 1.19–1.96, p < .001) or the lowest KIs (RR = 1.70, 95%CI 1.32–2.21, p < .001), even after adjusting for the presence of prevalent fractures, age, body mass index (BMI), and BMD. There was no difference in the risk of nonvertebral fractures according to baseline KI. Three‐year changes in quality‐of‐life physical scores reflected significantly better status for patients in the lowest tertile of KI compared with those in the highest at baseline. Over three years, the KI increased for all patients, indicating worsening of thoracic kyphosis, whatever the presence of prevalent or incident vertebral fractures. This KI progression was lower in the strontium ranelate group than in the placebo group. Thoracic kyphosis is a risk factor for vertebral fractures over three years and influences physical capacity changes in postmenopausal women with osteoporosis. Thoracic kyphosis progression over three years is lower in a subgroup of strontium ranelate–treated patients compared with placebo‐treated patients.

Bone Mineral Measurements in Mice: Comparison of Two Devices

Animal models are widely used to explore the pathogenesis and management of osteoporosis. Mice are increasingly being used in animal models. We have evaluated the precision, accuracy, and ability to monitor changes in bone mineral measurements of mice with the Piximus and Hologic QDR 2000 devices. One hundred and twenty-two C57/BL6 mice were used in this study; 70 of them were put on a low calcium diet and followed prospectively for 14 wk. They were measured using both devices at baseline and at wk 14. Using the Piximus, we measured the whole body, the tibia, and two caudal vertebrae. Using the Hologic, we measured the tibia, which we divided into three equal parts. The remaining mice were used to evaluate the precision and accuracy of the measurement. The accuracy, which was determined only for the Hologic device, revealed a mean difference between the in vivo bone mineral content (BMC) and the ash weight of 0.1 mg. The precision, evaluated from the coefficient of variation (%) and the Smallest Detectable Difference (SDD, in absolute values) was good for both devices, confirming their ability to detect small differences in longitudinal studies: as little as 0.004 g for the BMC of the total tibia on both devices, and 0.003 g/cm2 for whole body bone mineral density (BMD) on the Piximus. The BMC found using the two devices was comparable, whereas the BMD obtained on the Hologic device was nearly double that found using the Piximus. The comparison of the results by Bland and Altmans method showed that the difference between the results was not dependent on the magnitude of the measurement. We concluded that bone density and bone-density changes in mice can be measured precisely in vivo using the Hologic and Piximus devices; the latter being able to measure the whole body BMD with good precision.