The disability associated with hand osteoarthritis is substantial in a cohort of post-menopausal women: the QUALYOR study.

OBJECTIVES: Our primary aims were to assess current prevalence of HOA and the disability associated with this condition, in the group usually most affected, i.e., women older than 55. METHODS: We performed hand radiographs, clinical examination, grip strength measurement, AUSCAN and COCHIN questionnaires in a cohort of postmenopausal women aged at least 55. Radiographic hand OA (RHOA) was defined as at least 2 affected joints among 30, grading 2 or more using the Kellgren Lawrence score but without any HOA symptom. Symptomatic HOA (OA ACR) was defined according to ACR criteria for hand OA. Moderate to severe symptomatic HOA was defined as having OA ACR and AUSCAN total score of >43/100. RESULTS: We enrolled 1,189 participants. The mean age was 71.7 years. Inter-reader reliability of radiographs reading was good (ICC = 0.86) and intra-reader reliability was excellent (ICC = 0.97). Among the 1,189 women, 333 (28.0%) had RHOA, 482 (40.5%) patients fulfilled the ACR criteria for symptomatic HOA and 82 of these (17% of OA ACR population) had moderate to severe symptomatic HOA. The prevalence of symptomatic erosive osteoarthritis was 11.8%. Mean AUSCAN and Cochin scores were higher and grip strength lower in patients with symptomatic HOA compared to patient without HOA. Differences were more noticeable in patients with moderate to severe HOA. CONCLUSIONS: We have assessed disability associated with HOA in greater detail than previously and found that a third of postmenopausal women had RHOA, two fifths had symptomatic HOA and one sixth of symptomatic patients had moderate to severe HOA related disability and a tenth had symptomatic erosive osteoarthritis, representing a substantial burden of disease in our population-based cohort.

The French multicentre elevated bone mass study: prevalence and causes.

The purpose of this multicentric study was to evaluate the prevalence and causes of Elevated Bone Mass (EBM) in patients who underwent DXA scanning over a 10-year period. The prevalence of EBM was 1 in 100. The main causes of EBM were degenerative spine disorders and renal osteodystrophy. INTRODUCTION: Reports of elevated bone mass (EBM) on routine dual energy X-Ray absorptiometry (DXA) scanning are not infrequent. However, epidemiological studies of EBM are few and definition thresholds are variable. The purpose of this French multicentric study was to evaluate the prevalence and causes of EBM in adult patients who underwent DXA scanning over a 10-year period. METHODS: This multicentric, retrospective study was conducted in six French regional bone centres. DXA databases were initially searched for individuals with a bone mineral density (BMD) Z-score ≥ +4 at any site in the lumbar spine or hip from April 1st, 2008 to April 30st, 2018. RESULTS: In all, 72,225 patients with at least one DXA scan were identified. Of these, 909 (322 men and 587 women) had a Z-score ≥ + 4, i.e. a prevalence of 1.26% [1.18-1.34%]. The DXA scan reports and imagery and medical records of the 909 EBM patients were reviewed and 936 causes were found. In 42 patients (4%), no cause could be determined due to unavailability of data. Artefactual causes of EBM were found in 752 patients (80%), in whom the predominant cause was degenerative disease of the spine (613 patients, 65%). Acquired causes of focal EBM-including Paget's disease (n = 7)-were found in 12 patients (1%), and acquired causes of generalized EBM-including renal osteodystrophy (n = 32), haematological disorders (n = 20) and hypoparathyroidism (n = 15)-in 84 patients (9%). Other causes were rare hereditary diseases and unknown EBM in 19 (2%) and 27 (3%) cases respectively. CONCLUSIONS: The prevalence of EBM was approximately 1 in 100. These findings suggest that degenerative disease of the spine is the main cause of EBM, but that acquired or hereditary diseases are also causal factors.

High fracture risk patients with glucocorticoid-induced osteoporosis should get an anabolic treatment first.

Long-term glucocorticoid (GC) therapy induces glucocorticoid-induced osteoporosis (GIOP) and its associated fractures. Most specialty organizations recommend bisphosphonates as first-line therapies based only on bone mineral density efficacy data. Effective treatment of GIOP based on head-to-head trials with fracture endpoint has not yet been established. The pathophysiologic mechanisms of GIOP that lead to the detrimental effects on bone are not yet fully elucidated. Although GCs in an early and transitory period promote osteoclastic activity, in the current paper, we outline why GIOP is in fact a disease of the bone formation and then provide the rationale for the use of bone-forming agents as first-line therapy for patients with high fracture risk in GIOP.

Efficacy of teriparatide compared with risedronate on FRAX®-defined major osteoporotic fractures: results of the VERO clinical trial.

FRAX® calculates the 10-year probability of major osteoporotic fractures (MOF), which are considered to have a greater clinical impact than other fractures. Our results suggest that, in postmenopausal women with severe osteoporosis, those treated with teriparatide had a 60% lower risk of FRAX®-defined MOF compared with those treated with risedronate. INTRODUCTION: The VERO trial was an active-controlled fracture endpoint clinical trial that enrolled postmenopausal women with severe osteoporosis. After 24 months, a 52% reduction in the hazard ratio (HR) of clinical fractures was reported in patients randomized to teriparatide compared with risedronate. We examined fracture results restricted to FRAX®-defined major osteoporotic fractures (MOF), which include clinical vertebral, hip, humerus, and forearm fractures. METHODS: In total, 1360 postmenopausal women (mean age 72.1 years) were randomized to receive subcutaneous daily teriparatide (20 µg) or oral weekly risedronate (35 mg). Patient cumulative incidence of ≥ 1 FRAX®-defined MOF and of all clinical fractures were estimated by Kaplan-Meier analyses, and the comparison between treatments was based on the stratified log-rank test. Additionally, an extended Cox model was used to estimate HRs at different time points. Incidence fracture rates were estimated at each 6-month interval. RESULTS: After 24 months, 16 (2.6%) patients in the teriparatide group had ≥ 1 low trauma FRAX®-defined MOF compared with 40 patients (6.4%) in the risedronate group (HR 0.40; 95% CI 0.23-0.68; p = 0.001). Clinical vertebral and radius fractures were the most frequent FRAX®-defined MOF sites. The largest difference in incidence rates of both FRAX®-defined MOF and all clinical fractures between treatments occurred during the 6- to 12-month period. There was a statistically significant reduction in fractures between groups as early as 7 months for both categories of clinical fractures analyzed. CONCLUSION: In postmenopausal women with severe osteoporosis, treatment with teriparatide was more efficacious than risedronate, with a 60% lower risk of FRAX®-defined MOF during the 24-month treatment period. Fracture risk was statistically significantly reduced at 7 months of treatment. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT01709110 EudraCT Number: 2012-000123-41.

Subchondral tibial bone texture predicts the incidence of radiographic knee osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVES: To evaluate whether trabecular bone texture (TBT) parameters measured on computed radiographs (CR) could predict the onset of radiographic knee osteoarthritis (OA). MATERIALS AND METHODS: Subjects from the Osteoarthritis Initiative (OAI) with no sign of radiographic OA at baseline were included. Cases that developed either a global radiographic OA defined by the Kellgren-Lawrence (KL) scale, a joint space narrowing (JSN) or tibial osteophytes (TOS) were compared with the controls with no changes after 48 months of follow-up. Baseline bilateral fixed flexion CR were analyzed using a fractal method to characterize the local variations. The prediction was explored using logistic regression models evaluated by the area under the receiver operating characteristic curves (AUC). RESULTS: From the 344 knees, 79 (23%) developed radiographic OA after 48 months, 44 (13%) developed progressive JSN and 59 (17%) developed osteophytes. Neither age, gender and BMI, nor their combination predicted poorer KL (AUC 0.57), JSN or TOS (AUC 0.59) scores. The inclusion of the TBT parameters in the models improved the global prediction results for KL (AUC 0.69), JSN (AUC 0.73) and TOS (AUC 0.71) scores. CONCLUSIONS: Several differences were found between the models predictive of three different outcomes (KL, JSN and TOS), indicating different underlying mechanisms. These results suggest that TBT parameters assessed when radiographic signs are not yet apparent on radiographs may be useful in predicting the onset of radiological tibiofemoral OA as well as identifying at-risk patients for future clinical trials.

Low-trauma fractures without osteoporosis.

In clinical practice, areal bone mineral density (aBMD) is usually measured using dual-energy X-ray absorptiometry (DXA) to assess bone status in patients with or without osteoporotic fracture. As BMD has a Gaussian distribution, it is difficult to define a cutoff for osteoporosis diagnosis. Based on epidemiological considerations, WHO defined a DXA-based osteoporosis diagnosis with a T-score <-2.5. However, the majority of individuals who have low-trauma fractures do not have osteoporosis with DXA (i.e., T-score <-2.5), and some of them have no decreased BMD at all. Some medical conditions (spondyloarthropathies, chronic kidney disease and mineral bone disorder, diabetes, obesity) or drugs (glucocorticoids, aromatase inhibitors) are more prone to cause fractures with subnormal BMD. In the situation of fragility fractures with subnormal or normal BMD, clinicians face a difficulty as almost all the pharmacologic treatments have proved their efficacy in patients with low BMD. However, some data are available in post hoc analyses in patients with T score >-2. Overall, in patients with a previous fragility fracture (especially vertebra or hip), treatments appear to be effective. Thus, the authors recommend treating some patients with a major fragility fracture even if areal BMD T score is above -2.5.

Subchondral tibial bone texture analysis predicts knee osteoarthritis progression: data from the Osteoarthritis Initiative: Tibial bone texture & knee OA progression.

OBJECTIVES: To examine whether trabecular bone texture (TBT) parameters assessed on computed radiographs could predict knee osteoarthritis (OA) progression. METHODS: This study was performed using data from the Osteoarthritis Initiative (OAI). 1647 knees in 1124 patients had bilateral fixed flexion radiographs acquired 48 months apart. Images were semi-automatically segmented to extract a patchwork of regions of interest (ROI). A fractal texture analysis was performed using different methods. OA progression was defined as an increase in the joint space narrowing (JSN) over 48 months. The predictive ability of TBT was evaluated using logistic regression and receiver operating characteristic (ROC) curve. An optimization method for features selection was used to reduce the size of models and assess the impact of each ROI. RESULTS: Fractal dimensions (FD's) were predictive of the JSN progression for each method tested with an area under the ROC curve (AUC) up to 0.71. Baseline JSN grade was not correlated with TBT parameters (R < 0.21) but had the same predictive capacity (AUC 0.71). The most predictive model included the clinical covariates (age, gender, body mass index (BMI)), JSN and TBT parameters (AUC 0.77). From a statistical point of view we found higher differences in TBT parameters computed in medial ROI between progressors and non-progressors. However, the integration of TBT results from the whole patchwork including the lateral ROIs in the model provided the best predictive model. CONCLUSIONS: Our findings indicate that TBT parameters assessed in different locations in the joint provided a good predictive ability to detect knee OA progression.

Implications of the calf musculature and Achilles tendon architectures for understanding the site of injury.

UNLABELLED: Clinically the sites of Achilles Tendon (AT) overuse conditions can be divided into the tendon mid-portion and osteotendinous attachment. PURPOSE: We propose an anatomical analysis of the triceps surae musculotendon unit that could provide a possible anatomic explanation for these 2 sites of injury. METHOD: Twelve cadavers (age 74±7 years) were studied. In both legs, calf muscles (lateral gastrocnemius (LG), medial gastrocnemius (MG) and soleus) were dissected and their volumes measured. Fine saw cuts were made in the sagittal plane, either side of the midline of the calcaneus. Each strip contained the distal part of the tendon and its insertion, together with the superior tuberosity of the calcaneus. Trabecular architecture was analyzed from X-rays taken with Faxitron radiography. Histological sections of the enthesis and the thickness of the uncalcified fibrocartilage and the subchondral plate were evaluated. A finite element model of tendon coupled to a rupture index was developed to investigate the AT response to mechanical load. RESULTS: Muscle volume was highest for the soleus, followed by the MG, and LG. Within the AT, the soleus fibers occupy the antero-medial parts, the MG fibers form the posterior lateral layer, yet the LG head fibers retain the antero-lateral part. The quantity of bone and the apparent trabecular thickness at the enthesis were greatest in the central part of the enthesis. Thickness of calcified fibrocartilage tissue was significantly greater in the central part than medially (P=0.04) and laterally (P=0.03). Uncalcified fibrocartilage was significantly thicker medially than laterally (P=0.02). Finally, finite element analysis showed that AT mechanical stress increased with muscle load and converged at 4.6-7.9cm of the enthesis. CONCLUSION: Our data suggest that the triceps surae musculotendon unit is composed of anatomically distinct parts that undergo non-uniform mechanical loading. There are two sites where potentially tendon mechanical stress increases, the medial/central portions of the enthesis and the tendon midportion.

Fracture discrimination by combined bone mineral density (BMD) and microarchitectural texture analysis.

The use of bone mineral density (BMD) for fracture discrimination may be improved by considering bone microarchitecture. Texture parameters such as trabecular bone score (TBS) or mean Hurst parameter (H) could help to find women who are at high risk of fracture in the non-osteoporotic group. The purpose of this study was to combine BMD and microarchitectural texture parameters (spine TBS and calcaneus H) for the detection of osteoporotic fractures. Two hundred and fifty five women had a lumbar spine (LS), total hip (TH), and femoral neck (FN) DXA. Additionally, texture analyses were performed with TBS on spine DXA and with H on calcaneus radiographs. Seventy-nine women had prevalent fragility fractures. The association with fracture was evaluated by multivariate logistic regressions. The diagnostic value of each parameter alone and together was evaluated by odds ratios (OR). The area under curve (AUC) of the receiver operating characteristics (ROC) were assessed in models including BMD, H, and TBS. Women were also classified above and under the lowest tertile of H or TBS according to their BMD status. Women with prevalent fracture were older and had lower TBS, H, LS-BMD, and TH-BMD than women without fracture. Age-adjusted ORs were 1.66, 1.70, and 1.93 for LS, FN, and TH-BMD, respectively. Both TBS and H remained significantly associated with fracture after adjustment for age and TH-BMD: OR 2.07 [1.43; 3.05] and 1.47 [1.04; 2.11], respectively. The addition of texture parameters in the multivariate models didn't show a significant improvement of the ROC-AUC. However, women with normal or osteopenic BMD in the lowest range of TBS or H had significantly more fractures than women above the TBS or the H threshold. We have shown the potential interest of texture parameters such as TBS and H in addition to BMD to discriminate patients with or without osteoporotic fractures. However, their clinical added values should be evaluated relative to other risk factors.

Effects of anti-sclerostin antibody and running on bone remodeling and strength.

Sclerostin antibody (Scl-Ab) represents a promising therapeutic approach to treat patients with osteoporosis. PURPOSE: The aim of this study was to investigate the effects of Scl-Ab, running and a combination of both on bone formation. METHODS: Sixty female Wistar rats, aged 8 months were randomly assigned to five groups (subcutaneous injections performed twice a week): (1) (Sham): sedentary rats + saline, (2) (OVX): ovariectomized rats + saline, (3) (OVX + E): OVX rats + saline + treadmill training (5 times/week, 1 h/day), (4) (OVX + E + S): OVX rats + treadmill training + 5 mg/kg Scl-Ab and (5) (OVX + S): OVX rats + 5 mg/kg Scl-Ab. After 14 weeks, body composition, whole body and femoral BMDs were determined by DXA and serum was collected for analysis of osteocalcin and NTX. Bone microarchitecture was analyzed using µCT and bone strength was assessed at the femur mid-shaft in 3-point bending. RESULTS: Running exercise decreased fat mass as well as the bone resorption marker NTX relative to the non-exercised control groups, effects that were associated with a prevention of the deleterious effects of OVX on whole body and femoral BMDs. Scl-Ab increased the bone formation marker osteocalcin, which resulted in robust increases in BMD and femoral metaphyseal bone volume to levels greater than in the Sham group. OVX + S + E group did not further impact on bone mass relative to the OVX + S group. At the cortical femur diaphysis, Scl-Ab prevented the decreases in bone strength after OVX, while exercise did not affect cortical strength. CONCLUSION: We suggest that while running on a treadmill can prevent some bone loss through a modest antiresorptive effect, it did not contribute to the robust bone-forming effects of Scl-Ab when combined in an estrogen ablation model.

Mesenchymal stem-cell potential in cartilage repair: an update.

Articular cartilage damage and subsequent degeneration are a frequent occurrence in synovial joints. Treatment of these lesions is a challenge because this tissue is incapable of quality repair and/or regeneration to its native state. Non-operative treatments endeavour to control symptoms and include anti-inflammatory medications, viscosupplementation, bracing, orthotics and activity modification. Classical surgical techniques for articular cartilage lesions are frequently insufficient in restoring normal anatomy and function and in many cases, it has not been possible to achieve the desired results. Consequently, researchers and clinicians are focusing on alternative methods for cartilage preservation and repair. Recently, cell-based therapy has become a key focus of tissue engineering research to achieve functional replacement of articular cartilage. The present manuscript is a brief review of stem cells and their potential in the treatment of early OA (i.e. articular cartilage pathology) and recent progress in the field.

Effect of interval-training exercise on subchondral bone in a chemically-induced osteoarthritis model.

OBJECTIVES: The role of subchondral bone in osteoarthritis (OA) development is well admitted. Cross-talk between subchondral bone and cartilage may be disrupted in OA, leading to altered subchondral bone remodeling. Osteocytes are involved in bone remodeling control and could play a key role in OA progression. Our purpose of this study was to evaluate the preventive effect of interval-training exercise on subchondral bone and osteocyte in monosodium iodoacetate (MIA) model of experimental OA. METHODS: At baseline, 48 male Wistar rats (8 weeks old) were separated into two groups: interval-training exercise or no exercise for 10 weeks. After this training period, each group was divided into two subgroups: MIA-injected knee (1 mg/100 µl saline) and saline-injected knee. Four weeks later, rats were sacrificed and carefully dissected. Evaluated parameters were: cartilage degeneration by OA scoring, bone mineral density (BMD) by Dual energy X-ray Absorptiometry (DXA), trabecular subchondral bone microarchitecture by micro-computed tomography (µCT), cortical subchondral bone lacunar osteocyte occupancy (by Toluidine Blue staining) and cleaved caspase-3 positive apoptosis (by epifluorescence). RESULTS: Our results showed deleterious effects of MIA on cartilage. OA induced a decrease in proximal tibia (PT) BMD which was prevented by exercise. Exercise induced increase in full osteocyte lacunae surface and osteocyte occupancy (+60%) of cortical subchondral bone independently of OA. Osteocyte apoptosis (<1%) in cortical subchondral bone was not different whatever the group at sacrifice. CONCLUSION: Our results suggest that preliminary interval-training improved BMD and osteocytes lacunar occupancy in subchondral bone. Our interval-training did not prevent MIA-induced cartilage degeneration.

Tibial subchondral bone mineral density: sources of variability and reproducibility.

OBJECTIVES: It has been shown that subchondral bone mineral density (sBMD) measurement may be a relevant parameter of osteoarthritis (OA) progression. However, factors implicating the reproducibility and contributing to the variability of the measurement have not been fully described. Thus, the aim of this study was to explore the reproducibility of sBMD by Dual energy X-ray Absorptiometry (DXA) and to further examine its sources of variability. METHODS: In this study, short-term, intra and inter-observer reproducibility of sBMD was examined on knee images obtained on DXA scans. The influence of software (lumbar spine and forearm modes), knee positioning (flexion or extension), site and size of regions of interest (ROI) and use of rice, on both lateral and medial tibial sBMD, were assessed. Root mean square coefficient of variation (RMS CV) and least significant changes (LSC) were calculated. RESULTS: The short-term precision of sBMD ranged between 2.24% and 5.12% for RMS CV and between 0.053 and 0.135 g/cm(2) for LSC. Good intra-observer precision was found for knee flexion conditions whatever the software used (RMS CV ranging from 0.43 to 1.41%). The reproducibility was dependant from the ROI size (the ROI including joint space exhibiting better precision results than ROI including solely the subchondral plate). For a constant size of the ROI, the precision results were site-dependant. Inter-observer RMS CV results ranged from 0.59 to 5.01% according to ROI and software used. For the specific task of monitoring medial sBMD in the ROI including solely subchondral plate, forearm flexion condition produced the highest intra-observer and short-term precision (respectively RMS CV: 0.45% and 2.77%; LSC: 0.013 and 0.080 g/cm(2)). CONCLUSION: Taking account into the excellent precision of the sBMD measurements expressed as RMS CV with the protocol proposed in the present study, clinical application of these measurements might be envisaged.

The role of muscle strength & activation patterns in patellofemoral pain.

BACKGROUND: To investigate the extent to which quadriceps muscle activation and strength are responsible for patellofemoral pain. METHODS: A pain on-off switch system synchronized with a force transducer and surface electromyography was utilized on 32 volunteer patellofemoral pain patients during maximal isometric and squat exercises. FINDINGS: There were 26 patients out of the 32 tested who complained of pain during the squat or isometric test, of these 20 subjects presented a significant advantage for the vastus lateralis compared to the vastus medialis obliquis activation and 12 patients had decreased quadriceps strength of the symptomatic compared to the non symptomatic leg. All patients who demonstrated weak vastus medialis obliquis activation during the isometric exercise possessed the same symptoms during the squat. On the other hand, 9 patients who showed diminished vastus medialis obliquis activation during the squat displayed equal activation between the vastus medialis obliquis and the vastus lateralis during the isometric task. With regard to the timing for the onset of muscle activation, there were only 4 patients who had a difference (P=0.03) between the symptomatic (0.042 s) and non-symptomatic legs (0.011 s). INTERPRETATION: Causes for patellofemoral pain vary and are not necessarily a result of quadriceps strength deficit or vastus medialis obliquis activation weakness. Patellofemoral pain patients who possess lower vastus medialis obliquis activation compared to the vastus lateralis do not necessarily have quadriceps weakness while patients presenting with quadriceps strength deficits do not always have an imbalance between vastus medialis obliquis and vastus lateralis activation.

Assessment of bone mineral density and radiographic texture analysis at the tibial subchondral bone.

Microstructural changes of subchondral bone constitute one of the figures characterising osteoarthritis on a structural level. Subchondral bone mineral density may reflect the complex relationship between bone and cartilage submitted to movement and loading. In this review, the authors discussed the interest of tibial subchondral bone mineral density assessment in the perspective of its diagnostic, etiopathogenic and prognostic value in osteoarthritis. In addition, the sources of variability linked to the measurement of tibial subchondral bone mineral density are precised. Trabecular bone structure characterisation by radiographic texture analyses may also represent a new promising tool to evaluate the microarchitectural changes that occur with initiation and progression of osteoarthritis. In this paper, the authors also highlighted the interest of different radiographic texture analyses and their clinical relevance in the field of osteoarthritis.

[Alopecia areata during anti-TNF alpha therapy: Nine cases]. / Pelade au cours d'un traitement par anti-TNF alpha : neuf cas.

BACKGROUND: In recent years, a growing number of biological agents have been introduced for the treatment of various diseases, and their principal adverse events are known. We present nine cases of alopecia areata (AA) developed in patients treated with TNF-α blocking agents. PATIENTS AND METHODS: Nine cases are described: five men and four women of mean age 39.2 years (range: 29-54 years). Two patients had a past history of alopecia areata. The anti-TNF given was adalimumab (Humira(®)) in eight cases and etanercept (Enbrel(®)) in one case. The time lapse to development of AA following introduction of the anti-TNF alpha agent was between six weeks and eight months (mean: 4.2 months). There were five cases of patchy AA and four of AA universalis. Anti-TNF alpha treatment was stopped in all patients. Complete regrowth was seen in five patients. Two patients showed no improvement. In two patients, partial hair regrowth (<50%) was seen after systemic corticosteroid therapy and methotrexate. DISCUSSION: Our nine cases of alopecia areata developed in patients treated with TNF-α blockers constitute the largest series reported to our knowledge. 17 cases of AA during anti-TNF-alpha therapy have previously been described in the literature. AA may be a side effect of anti-TNF-alpha drugs. In our patients, no conclusive triggers could be associated with the development of AA, except a context of stress in four patients. Complete regrowth in three patients after discontinuation of the anti-TNF-alpha (without other therapy) is an additional argument in favour of the implication of biotherapies. However, a random coincidence of AA with anti-TNF-alpha cannot be completely ruled out. The role of anti-TNF-alpha therapy in the pathogenesis of AA is poorly understood. Activation of self-reactive T cells by anti-TNF-alpha could lead to the development of AA.

Exercise and zoledronic acid on lipid profile and bone remodeling in ovariectomized rats: a paradoxical negative association?

Exercise (EXE) and amino-bisphosphonates (BP) are both considered as useful strategies in the prevention of post-menopausal bone loss. Exercise reduces lipid levels, and BP may induce increase in high-density lipoprotein cholesterol (HDL-C). We hypothesized that combined effects of BP and exercise would produce a better improvement of lipid profile. We studied the specific and combined effects of zoledronic acid (Z) and EXE on lipid profile and bone remodeling in mature ovariectomized (OVX) rats. Six-month old female rats were randomly assigned to either a sham-ovx group (n = 12) or one of four OVX groups (n = 12): vehicle-treated sedentary (OVX); OVX + EXE (OVX-E, running on a treadmill for 12 weeks); OVX + Z (20 microg/kg, i.v.), (OVX-Z); OVX + Z+EXE (OVX-ZE). Total cholesterol (TC), HDL-C and bone remodeling markers were measured at baseline and at the end of the study. We demonstrated that both Z and EXE prevented the increase in bone resorption resulting from OVX, and individually improved the atherosclerotic risk index. Therapy with Z resulted in significant increase (39.00 +/- 0.03 vs. 53.6 +/- 0.01 mg/dl; +37.4%, P < 0.05) in serum concentration of HDL-C and a non significant decrease in TC (135.30 +/- 0.03 vs. 144.80 +/- 0.05 mg/dl; -5.8%) in the OVX-Z group compared to the OVX group. Post-menopausal women have elevated risk of CVD and bone resorption, hence, these data ultimately demonstrate (except for the elevated ratio in the combined group) that exercise and zoledronic acid are useful in minimizing the impact of these two processes in women and the combination of the two may be clinically relevant.

Does exercise modify the effects of zoledronic acid on bone mass, microarchitecture, biomechanics, and turnover in ovariectomized rats?

Regular activity has effects on bone size, shape, and density, resulting in an increase in mechanical strength. The mechanism of action that underlies this improvement in bone strength is mainly linked to an increase in bone formation. Zoledronic acid (Z), in contrast, may prevent bone strength changes in ovariectomized (OVX) rodents by its potent antiresorptive effects. Based on these assumptions we hypothesized that combined effects of exercise (E) and Z may produce higher benefits on bone changes resulting from estrogen deficiency than either intervention alone. At 6 months of age, 60 female Wistar rats were OVX or sham operated (SH) and divided into five groups: SH, OVX, OVX-E, OVX-Z, and OVX-ZE. OVX rats were treated with a single IV injection of Z (20 microg/kg) or vehicle and submitted or not to treadmill exercise (15 m/min, 60 min/day, 5 days/week) for 12 weeks. Whole-body BMD and bone turnover markers were analyzed longitudinally. At sacrifice, femurs were removed. BMD by DXA, three-point bending test, and microCT were performed to study biomechanical and trabecular structure parameters, respectively. After 12 weeks, bone volume fraction decreased in OVX rats, whereas bone turnover rate, trabecular spacing, and structure model index increased compared with those in the SH group (P < 0.05). Zoledronic acid prevented the ovariectomy-induced trabecular bone loss and its subsequent trabecular microarchitectural deterioration. Treadmill exercise running was shown to preserve the bone strength and to induce bone turnover changes in favor of bone formation. However, the combined effects of zoledronic acid and running exercise applied simultaneously did not produce any synergetic or additive effects.

Laws' masks descriptors applied to bone texture analysis: an innovative and discriminant tool in osteoporosis.

OBJECTIVE: The objective of this study was to explore Laws' masks analysis to describe structural variations of trabecular bone due to osteoporosis on high-resolution digital radiographs and to check its dependence on the spatial resolution. Laws' masks are well established as one of the best methods for texture analysis in image processing and are used in various applications, but not in bone tissue characterisation. This method is based on masks that aim to filter the images. From each mask, five classical statistical parameters can be calculated. MATERIALS AND METHODS: The study was performed on 182 healthy postmenopausal women with no fractures and 114 age-matched women with fractures [26 hip fractures (HFs), 29 vertebrae fractures (VFs), 29 wrist fractures (WFs) and 30 other fractures (OFs)]. For all subjects radiographs were obtained of the calcaneus with a new high-resolution X-ray device with direct digitisation (BMA, D3A, France). The lumbar spine, femoral neck, and total hip bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry. RESULTS: In terms of reproducibility, the best results were obtained with the TRE5E5 mask, especially for three parameters: "mean", "standard deviation" and "entropy" with, respectively, in vivo mid-term root mean square average coefficient of variation (RMSCV)%= 1.79, 4.24 and 2.05. The "mean" and "entropy" parameters had a better reproducibility but "standard deviation" showed a better discriminant power. Thus, for univariate analysis, the difference between subjects with fractures and controls was significant (P<10(-3)) and significant for each fracture group independently (P<10(-4) for HF, P=0.025 for VF and P< 10(-3) for OF). After multivariate analysis with adjustment for age and total hip BMD, the difference concerning the "standard deviation" parameter remained statistically significant between the control group and the HF and VF groups (P<5 x 10(-5), and P=0.04, respectively). No significant correlation between these Laws' masks parameters and BMD was obtained. In addition, this study showed the dependence of Laws' masks parameters on image resolution, which confirms the necessity to perform Laws' textural measurement on high-resolution images. CONCLUSION: The reproducibility and discriminant power of the Laws' masks analysis has been demonstrated on bone images; thus, this method constitutes a promising routine technique for the determination of osteoporosis fracture risk from radiographs.