Vertebral Scheuermann's disease in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

UNLABELLED: In 27 centres across Europe, the prevalence of deforming spinal Scheuermann's disease in age-stratified population-based samples of over 10,000 men and women aged 50+ averaged 8% in each sex, but was highly variable between centres. Low DXA BMD was un-associated with Scheuermann's, helping the differential diagnosis from osteoporosis. INTRODUCTION: This study aims to assess the prevalence of Scheuermann's disease of the spine across Europe in men and women over 50 years of age, to quantitate its association with bone mineral density (BMD) and to assess its role as a confounder for the radiographic diagnosis of osteoporotic fracture. METHODS: In 27 centres participating in the population-based European Vertebral Osteoporosis Study (EVOS), standardised lateral radiographs of the lumbar and of the thoracic spine from T4 to L4 were assessed in all those of adequate quality. The presence of Scheuermann's disease, a confounder for prevalent fracture in later life, was defined by the presence of at least one Schmorl's node or irregular endplate together with kyphosis (sagittal Cobb angle >40° between T4 and T12) or a wedged-shaped vertebral body. Alternatively, the (rare) Edgren-Vaino sign was taken as diagnostic. The 6-point-per-vertebral-body (13 vertebrae) method was used to assess osteoporotic vertebral shape and fracture caseness. DXA BMD of the L2-L4 and femoral neck regions was measured in subsets. We also assessed the presence of Scheuermann's by alternative published algorithms when these used the radiographic signs we assessed. RESULTS: Vertebral radiographic images from 4486 men and 5655 women passed all quality checks. Prevalence of Scheuermann's varied considerably between centres, and based on random effect modelling, the overall European prevalence using our method was 8% with no significant difference between sexes. The highest prevalences were seen in Germany, Sweden, the UK and France and low prevalences were seen in Hungary, Poland and Slovakia. Centre-level prevalences in men and women were highly correlated. Scheuermann's was not associated with BMD of the spine or hip. CONCLUSIONS: Since most of the variation in population impact of Scheuermann's was unaccounted for by the radiological and anthropometric data, the search for new genetic and environmental determinants of this disease is encouraged.

Effectiveness of risedronate and alendronate on nonvertebral fractures: an observational study through 2 years of therapy.

UNLABELLED: This observational study showed that after 2 years, both risedronate and alendronate lowered the risk of hip and nonvertebral fractures compared with patients filling in a single bisphosphonate prescription. INTRODUCTION: Post hoc analyses of the placebo-controlled trials suggested earlier effects for risedronate (6-12 months) than for alendronate (18-24 months). The present study extends our 1-year observational data that confirmed an earlier fracture reduction with risedronate and evaluated the absolute and relative effectiveness of alendronate and risedronate in clinical practice over 2 years. METHODS: We observed three cohorts of women aged 65 years and older who initiated once-a-week dosing of bisphosphonate therapy; (1) patients adherent to alendronate (n = 21,615), (2) patients adherent to risedronate (n = 12,215), or (3) patients filling only a single bisphosphonate prescription (n = 5,390) as a referent population. Proportional hazard modeling compared the incidence of hip and nonvertebral fractures among the cohorts over 2 years after the initial prescription. RESULTS: In this cohort, we previously showed at 12 months a significant reduction of hip and nonvertebral fractures with risedronate but not with alendronate. At the end of 2 years, the cumulative incidence of hip fractures in the referent cohort was 1.9 %, and incidence of nonvertebral fractures was 6.3 %. Relative to the referent, 6 months after initiating therapy and continuing through 2 years, both risedronate and alendronate cohorts had approximately a 45 % lower incidence of hip fractures and a 30 % lower incidence of nonvertebral fractures. CONCLUSION: These observations suggest that both risedronate and alendronate are effective at reducing the risk of hip and nonvertebral fracture after 2 years of treatment and support the post hoc analyses of placebo-controlled trials indicating an earlier effect of risedronate.

Effect of oral monthly ibandronate on bone microarchitecture in women with osteopenia-a randomized placebo-controlled trial.

UNLABELLED: We have examined the effect of oral monthly ibandronate on distal radius and tibia microarchitecture with high-resolution peripheral quantitative tomography compared with placebo, in women with osteopenia, and found that ibandronate did not significantly affect trabecular bone but improved cortical density and thickness at the tibia. METHODS: We have examined the effect of ibandronate on bone microarchitecture with peripheral high-resolution quantitative computed tomography (HR-pQCT) in a randomized placebo-controlled trial among 148 women with osteopenia. Patients received either oral 150 mg monthly ibandronate or placebo over 24 months. Bone microarchitecture was assessed at baseline, 6, 12, and 24 months, using HR-pQCT at the distal radius and tibia; areal bone mineral density (aBMD) was measured with DXA at the spine, hip, and radius. RESULTS: At 12 months, there was no significant difference in trabecular bone volume at the radius (the primary end point) between women on ibandronate (10.8 ± 2.5%) and placebo (10.5 ± 2.9%), p = 0.25. There was no significant difference in other radius trabecular and cortical microarchitecture parameters at 12 and 24 months. In contrast, at the tibia, cortical vBMD in the ibandronate group was significantly greater than in the placebo group at 6, 12, and 24 months, with better cortical thickness at 6, 12, and 24 months. With ibandronate, aBMD was significantly increased at the hip and spine at 12 and 24 months but at the radius was significantly superior to placebo only at 24 months. Most of the adverse events related to ibandronate were expected with bisphosphonate use, and none of them were serious. CONCLUSION: We conclude that 12 months of treatment with ibandronate in women with osteopenia did not affect trabecular bone microarchitecture, but improved cortical vBMD at the tibia at 12 and 24 months, and preserved cortical thickness at the tibia.

FRAX® probabilities and risk of major osteoporotic fracture in France.

UNLABELLED: The incidence of hip fracture, death and the estimated incidence of major osteoporotic fracture in France were used to determine the lifetime and 10-year probability of fracture and incorporated into a probability model (FRAX®) calibrated to the French population. INTRODUCTION: Fracture probabilities in the French population have not been determined. Our aim was to determine the incidence of hip fracture in France and the estimated 10-year probabilities of hip and major osteoporotic fractures. METHODS: The study population included adults over 50 years living in France in 2004. Incident hip fracture cases were identified from the French PMSI database. Incidence of the other major osteoporotic fractures was imputed from the relationship between hip fracture incidence and other major fracture in Sweden. These data were used to calculate population-based fracture probabilities according to age and BMD using cutoff values for femoral neck T-scores from the NHANES III data in Caucasian women. The probability model (FRAX®) calibrated to the French population was used to compute individual fracture probabilities according to specific clinical risk factors. RESULTS: We identified 15,434 men and 51,469 women with an incident hip fracture. The remaining lifetime probability of hip fracture at 50 years was approximately 10 and 30% respectively. With a femoral neck T-score of -2 SD, one in two women and one in five men would sustain a major osteoporotic fracture in their lifetime. The 10-year probability of other major osteoporotic fractures increased with declining T-score and increasing age. Low body mass index and other clinical risk factors had an independent effect on fracture probability whether or not BMD was included in the FRAX® model. CONCLUSION: This analysis provides detailed estimation on the risk of fracture in the French population and may help to define therapeutic guidelines.

Association of bone microarchitecture with parathyroid hormone concentration and calcium intake in men: the STRAMBO study.

UNLABELLED: OBJECTVIE: In the elderly, vitamin D deficit, low calcium intake, and impaired bone microarchitecture are associated with higher risk of hip fracture. We assessed the association of bone microarchitecture with calcium intake and serum concentrations of 25-hydroxycholecalciferol (25OHD) and parathyroid hormone (PTH) in men. DESIGN: Cross-sectional analysis was performed in 1064 men aged 20-87 years not taking vitamin D or calcium supplements. METHODS: Daily calcium intake was assessed using a food frequency questionnaire. Bone microarchitecture was assessed at distal radius and tibia by high-resolution peripheral quantitative computed tomography. We measured serum and urinary levels of biochemical bone turnover markers (BTMs). Statistical models were adjusted for age, weight, height, and glomerular filtration rate. RESULTS: In 500 men aged <65 years, lower 25OHD levels and low calcium intake were associated with lower trabecular volumetric bone mineral density (Dtrab) at the distal tibia, due to lower trabecular number (Tb.N). Low calcium intake was associated with lower cortical thickness (Ct.Th). Higher PTH level was associated with higher BTM levels. In 563 men aged ≥65 years, the highest PTH quartile was associated with lower Ct.Th (tibia), lower Dtrab (both sites), and lower Tb.N (radius) compared with the lowest quartile. Low calcium intake was associated with lower Tb.N and more heterogenous trabecular distribution. BTM positively correlated with the PTH concentration. CONCLUSION: In older men, elevated PTH concentration is associated with high bone turnover, poor trabecular microarchitecture (radius and tibia), and, at the distal tibia, lower Ct.Th. Low calcium intake is associated with lower Tb.N and more heterogenous trabecular distribution.

Risk factors for peripheral fractures vary by age in older men--the prospective MINOS study.

UNLABELLED: Identification of older men at high risk of peripheral fracture can be improved by assessing prevalent fractures (men aged ≤ 65), history of falls (men aged >65), bone width, and aortic calcifications. INTRODUCTION: Low bone mineral density (BMD) identifies 20% of men who sustain osteoporotic fracture. We studied (1) if the assessment of bone width, aortic calcifications, prevalent falls and fractures improves identification of men at high risk of fracture and (2) if the predictive value of these parameters varies with age. METHODS: Among 781 men aged 50 and over, 61 men sustained 66 low-trauma peripheral fractures during 10 years. History of falls and prevalent fractures was assessed by questionnaire. BMD and bone with were measured by dual X-ray absorptiometry. Abdominal aortic calcifications were assessed on the lateral radiographs of the lumbar spine. RESULTS: Low BMD, low bone width, extended aortic calcifications, prevalent fractures (mainly multiple fractures) and frequent falls were all associated independently with higher risk of fracture. In men aged ≤ 65, prevalent fractures are associated with a significant increase in the risk of fracture (two- to threefold for one and four- to fivefold for multiple prevalent fractures). In men aged >65, history of falls is associated with a higher risk of fracture, e.g. frequent falls are associated with a sixfold increase in the risk of fracture. CONCLUSIONS: Men aged ≤ 65 with multiple prevalent fractures and frequent fallers aged >65 are at particularly high risk of peripheral fracture regardless of BMD.

Is nitric oxide a mediator of the effects of low-intensity electrical stimulation on bone in ovariectomized rats?

Low-intensity electrical stimulation (LIES) may counteract the effects of ovariectomy (OVX) on nitric oxide synthase (NOS) expression, osteocyte viability, bone structure, and microarchitecture in rats (Lirani-Galvão et al., Calcif Tissue Int 84:502-509, 2009). The aim of the present study was to investigate if these effects of LIES could be mediated by NO. We analyzed the effects of NO blockage (by L-NAME) in the response to LIES on osteocyte viability, bone structure, and microarchitecture in OVX rats. Sixty rats (200-220 g) were divided into six groups: sham, sham-L-NAME (6 mg/kg/day), OVX, OVX-L-NAME, OVX-LIES, and OVX-LIES-L-NAME. After 12 weeks, rats were killed and tibiae collected for histomorphometric analysis and immunohistochemical detection of endothelial NOS (eNOS), inducible NOS (iNOS), and osteocyte apoptosis (caspase-3 and TUNEL). In the presence of L-NAME, LIES did not counteract the OVX-induced effects on bone volume and trabecular number (as on OVX-LIES). L-NAME blocked the stimulatory effects of LIES on iNOS and eNOS expression of OVX rats. Both L-NAME and LIES decreased osteocyte apoptosis. Our results showed that in OVX rats L-NAME partially blocks the effects of LIES on bone structure, turnover, and expression of iNOS and eNOS, suggesting that NO may be a mediator of some positive effects of LIES on bone.

Effect of once-yearly zoledronic acid on the spine and hip as measured by quantitative computed tomography: results of the HORIZON Pivotal Fracture Trial.

UNLABELLED: Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength. INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p < 0.01) and QCT (5.7%, p < 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p < 0.0001), total hip (10.8%, p < 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p < 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.

Association between collagen cross-links and trabecular microarchitecture properties of human vertebral bone.

UNLABELLED: It has been suggested that age-related deterioration in trabecular microarchitecture and changes in collagen cross-link concentrations may contribute to skeletal fragility. To further explore this hypothesis, we determined the relationships among trabecular bone volume fraction (BV/TV), microarchitecture, collagen cross-link content, and bone turnover in human vertebral trabecular bone. Trabecular bone specimens from L2 vertebrae were collected from 51 recently deceased donors (54-95 years of age; 20 men and 30 women). Trabecular bone volume and microarchitecture was assessed by microCT and bone formation, reflected by osteoid surface (OS/BS, %), was measured by 2D histomorphometry. Pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) and collagen content in the cancellous bone were analysed by high-performance liquid chromatography. Associations between variables were investigated by Pearson correlations and multiple regression models, which were constructed with BV/TV and collagen cross-links as explanatory variables and microarchitecture parameters as the dependent variables. RESULTS: Microarchitecture parameters were modestly to strongly correlated with BV/TV (r(2)=0.10-0.71). The amount of mature enzymatic PYD and DPD cross-links were not associated with the microarchitecture, either before or after adjustment for BV/TV. However, there was a positive correlation between PEN content and trabecular number (r=0.45, p=0.001) and connectivity density (r=0.40, p=0.004), and a negative correlation between PEN content and trabecular separation (r=-0.29, p=0.04). In the multiple regression models including BV/TV, age and PEN content was still significantly associated with several of the microarchitecture variables. In summary, this study suggests a link between trabecular microarchitecture and the collagen cross-link profile. As PEN reflects non-enzymatic glycation of collagen and generally increases with bone age, the association between PEN and trabecular architecture suggests that the preserved trabeculae may contain mainly old bone and have undergone little remodeling. Thus, vertebral fragility may not only be due to alterations in bone architecture but also to modification of collagen cross-link patterns thereby influencing bone's mechanical behavior.

In osteoporotic women treated with strontium ranelate, strontium is located in bone formed during treatment with a maintained degree of mineralization.

UNLABELLED: In postmenopausal osteoporotic women and up to 3 years of treatment with strontium ranelate, strontium was present only in recently deposited bone tissue resulting from formation activity during the period of treatment. Strontium was shown to be dose-dependently deposited into this newly formed bone with preservation of the mineralization. INTRODUCTION: Interactions between strontium (Sr) and bone mineral and its effects on mineralization were investigated in women treated with strontium ranelate. METHODS: Bone biopsies from osteoporotic women were obtained over 5-year strontium ranelate treatment from phases II and III studies. Bone samples obtained over 3-year treatment were investigated by X-ray microanalysis for bone Sr uptake and focal distribution, and by quantitative microradiography for degree of mineralization. On some samples, Sr distribution (X-ray cartography) was analyzed on whole sample surfaces and the percentage of bone surface containing Sr was calculated. Bone Sr content was chemically measured on whole samples. RESULTS: In treated women, Sr was exclusively present in bone formed during treatment; Sr deposition depended on the dose with higher focal content in new bone structural units than in old ones constantly devoid of Sr, even after 3-year treatment. A plateau in global bone Sr content was reached after 3 years of treatment. Cartography illustrated the extent of surfaces containing Sr, and formation activity during strontium ranelate treatment was higher in cancellous than in cortical bone. Mineralization was maintained during treatment. CONCLUSION: The quality of bone mineral was preserved after treatment with strontium ranelate, supporting the safety of this agent at the bone tissue level.

[New bone imaging techniques in children with chronic kidney disease]. / Nouvelles techniques d'imagerie osseuse: application chez l'enfant atteint de maladie rénale chronique.

Bone damage in the spectrum of chronic kidney disease - mineral and bone disorders (CKD-MBD) represents a daily challenge for pediatric nephrologists. A real measurement of bone mineral density (BMD) by Dual X-ray absorptiometry (DXA) is currently performed to evaluate bone mass in children. However this technique has some limitations. In 2000, the National Institute of Health (NIH) has defined new "quality" criteria for the diagnosis of osteoporosis in addition to a decreased bone mass. Bone strength actually integrates 2 issues: bone density and bone quality (i.e., micro architectural organization, bone turnover, mineralization and micro fractures). These "quality" criteria cannot be evaluated by DXA. Histomorphometry remains the gold standard to evaluate bone but it is rarely performed in clinical practice. New bone imaging techniques have thus been developed, leading to an improvement in bone assessment. They are particularly challenging in children, whose bones continually grow in size, shape and mass.

Low-intensity electrical stimulation counteracts the effects of ovariectomy on bone tissue of rats: effects on bone microarchitecture, viability of osteocytes, and nitric oxide expression.

Low Intensity Electrical Stimulation (LIES) has been used for bone repair, but little is known about its effects on bone after menopause. Osteocytes probably play a role in mediating this physical stimulus and they could act as transducers through the release of biochemical signals, such as nitric oxide (NO). The aim of the present study was to investigate the effects of LIES on bone structure and remodeling, NOS expression and osteocyte viability in ovariectomized (OVX) rats. Thirty rats (200-220 g) were divided into 3 groups: SHAM, OVX, and OVX subjected to LIES (OVX + LIES) for 12 weeks. Following the protocol, rats were sacrificed and tibias were collected for histomorphometric analysis and immunohistochemical detection of endothelial NO synthase (eNOS), inducible NOS (iNOS), and osteocyte apoptosis (caspase-3 and TUNEL). OVX rats showed significant (p < 0.05 vs. SHAM) decreased bone volume (10% vs. 25%) and trabecular number (1.7 vs. 3.9), and increased eroded surfaces (4.7% vs. 3.2%) and mineralization surfaces (15.9% vs. 7.7%). In contrast, after LIES, all these parameters were significantly different from OVX but not different from SHAM. eNOS and iNOS were similarly expressed in subperiosteal regions of tibiae cortices of SHAM, not expressed in OVX, and similarly expressed in OVX + LIES when compared to SHAM. In OVX, the percentage of apoptotic osteocytes (24%) was significantly increased when compared to SHAM (11%) and OVX + LIES (8%). Our results suggest that LIES counteracts some effects of OVX on bone tissue preserving bone structure and microarchitecture, iNOS and eNOS expression, and osteocyte viability.

Risedronate dosing before breakfast compared with dosing later in the day in women with postmenopausal osteoporosis.

UNLABELLED: Two studies in postmenopausal women with osteoporosis provide information about the efficacy and safety of dosing oral risedronate 5 mg daily at a time other than before breakfast (i.e., 2 h before and 2 h after any food and drink other than plain water). A significant increase in lumbar spine BMD was observed for both treatment regimens in the two studies. However, smaller increases in lumbar spine BMD were observed with flexible dosing versus before-breakfast dosing. Geographic region, compliance, and consistency of dosing time appear to affect the amount of increase in BMD observed with flexible dosing. INTRODUCTION: Two studies in postmenopausal women with osteoporosis provide additional information about the efficacy and safety of dosing oral risedronate 5 mg daily at a time other than before breakfast (i.e., 2 h before and 2 h after any food and drink other than plain water). METHODS: One study, flexible dosing, was a 6-month North American study in 730 patients randomized to before-breakfast dosing or flexible dosing later in the day. A second study, IMPACT, was a large (N = 2382), 1-year multinational study in patients that chose their dosing regimen (before breakfast or later in the day). These studies were used to examine the bone mineral density (BMD) response with different dosing regimens. RESULTS: A significant increase in lumbar spine BMD was observed for both treatment regimens in the two studies. However, in both studies, the flexible dosing group had a smaller increase from baseline compared to the before-breakfast regimen (ratio of flexible dosing to before breakfast: flexible dosing study, 0.52; IMPACT study, 0.75). In addition, a relationship between geographic region and BMD response was observed with flexible dosing in both studies. Patients in the flexible dosing group who had greater dosing compliance (based on the number of times the bottle was opened) and consistency of dosing time (bottle opened within a 1.5-h window) had a greater increase in lumbar spine BMD. CONCLUSION: Results of these two studies demonstrate that overall flexible dosing of risedronate leads to smaller BMD gains compared to before-breakfast dosing. This result may be due to poorer adherence to the flexible dosing instructions that may be more pronounced in patients in certain geographic regions. If patients cannot abide by before-breakfast dosing and flexible dosing is an approved option, one can expect suboptimal BMD results with flexible dosing.

Bone microdamage: a clinical perspective.

INTRODUCTION: Microdamage accumulation due to fatigue loading may lead to fracture. In addition, several studies using animal models have suggested in recent years that bisphosphonates might increase microdamage accumulation. METHODS: We have reviewed the literature after a PubMed search, to examine the techniques to look for microcracks, the relationship between microdamage and bone strength, and the influence of anti-osteoporosis agents. RESULTS: Currently, the search for microcracks relies on bulk staining of bone samples, which are then examined on optic microscopy and fluorescence or confocal microscopy. The accumulation of microdamage is associated with fatigue loading and is likely to trigger targeted bone remodeling, especially in cortical bone. Several studies examining beagle dogs receiving bisphosphonates have shown a dose-dependent accumulation of microdamage in bone, with conflicting results regarding the consequences on bone mechanical properties. In living humans, obtaining data is limited to the iliac crest bone. The potential association between long-term bisphosphonate use and microcrack accumulation at the iliac crest bone has not been established unequivocally. CONCLUSIONS: Bone microdamage is critical in the understanding of bone quality. Assessment of microdamage is technically difficult, especially in humans. The clinical impact of microdamage potentially induced by bone drugs has not been established in humans.

Geographical variations in hip fracture risk for women: strong effects hidden in standardised ratios.

UNLABELLED: There was 75% variation in the trend in hip fracture incidence with age in women aged 50 to 85 in France. In southwest France, the women are at higher risk of hip fracture at younger ages. This finding should be taken into account when examining risk factors. INTRODUCTION: Few studies have analysed the geographical variations in the relationship between age and hip fracture incidence. Our goal was to assess these variations among women under 85 within the same country. METHODS: The study population included women aged 50 to 85 who were living in France in 2004. Hip fracture cases were identified in the French Diagnosis Related Groups (DRG)-like database using the diagnosis code for closed hip fractures and procedural codes for treatment. The Moran index and a spatial model using latitude and longitude were used to assess the geographical heterogeneities of cumulative incidence risk (CIR) and age effect. RESULTS: A total of 29,218 hip fracture cases were identified. A south-to-north CIR gradient ranging from 7 to 16% was observed. The variation in the number of years until double hip fracture incidence was 75% (i.e. 1.49 to 2.57 years). In the south, and more markedly in southwest France, the women are at higher risk of hip fracture at a younger age. CONCLUSION: The risk of fracture may be different between women of the same age. This may be hidden in a comparison of standardised ratios. This finding should be considered when examining risk factors and implementing public health interventions.

Effects of infliximab therapy on biological markers of synovium activity and cartilage breakdown in patients with rheumatoid arthritis.

BACKGROUND: Defining the remission criteria of rheumatoid arthritis (RA) remains a critical issue. Markers of synovium activity, urinary glucosyl-galactosyl-pyridinoline (Glc-Gal-PYD) and of cartilage destruction, urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II) have been shown to reflect disease activity and joint damage progression in RA. METHODS: The prospective study cohort comprised 66 RA patients treated with infliximab and methotrexate and 76 healthy controls. Measurements of urinary Glc-Gal-PYD and CTX-II were performed at baseline and at 1 year of infliximab therapy. RESULTS: At baseline, urinary Glc-Gal-PYD and CTX-II levels were increased in patients with RA and correlated with modified Sharp scores and progression of joint damage. Patients with more progressive joint destruction had higher Glc-Gly-PYD and CTX-II baseline levels. CONCLUSION: These markers reflected bone erosion evolution and might be useful for treatment monitoring and evaluation of RA. Markers remained high even in clinical responders after infliximab, suggesting persistence of synovitis.

Ibandronate for the prevention of nonvertebral fractures: a pooled analysis of individual patient data.

UNLABELLED: This analysis was conducted to assess the effect of high versus lower doses of ibandronate on nonvertebral fractures. The results were adjusted for clinical fracture, age, and bone density. The treatment effect was dose-dependent. Higher doses of ibandronate significantly reduced the risk of nonvertebral fractures more effectively compared with lower doses. INTRODUCTION: The objective of this study was to assess the efficacy of different doses of ibandronate on nonvertebral fractures in a pooled analysis. METHODS: Eight randomized trials of ibandronate were reviewed for inclusion. Alternative definitions of high versus low doses based on annual cumulative exposure (ACE) were explored. A time-to-event analysis was conducted using Kaplan-Meier methodology. Hazard ratios (HR) were derived using Cox regression and adjusted for covariates. RESULTS: Combining higher ACE doses of > or = 10.8 mg (150 mg once monthly, 3 mg i.v. quarterly, and 2 mg i.v. every 2 months) versus ACE doses of 5.5 mg, from two trials, resulted in an HR 0.62 (95% CI 0.396-0.974, p = 0.038). There was a dose-response trend with increasing ACE doses (7.2-12 mg) versus ACE of 5.5 mg. CONCLUSIONS: A dose-response effect on nonvertebral fractures was observed when comparing high with low ACE doses. A significant reduction in nonvertebral fractures was noted when pooling data from trials using ACE doses of > or = 10.8 mg versus ACE < or = 7.2 mg; and with ACE > or = 10.8 mg versus ACE of 5.5 mg (38% reduction). Higher ibandronate dose levels (150 mg monthly or 3 mg i.v. quarterly) significantly reduced nonvertebral fracture risk in postmenopausal women.

Simple and sensitive method for quantification of fluorescent enzymatic mature and senescent crosslinks of collagen in bone hydrolysate using single-column high performance liquid chromatography.

A rapid high performance liquid chromatographic method was developed including an internal standard for the measurement of mature and senescent crosslinks concentration in non-demineralized bone hydrolysates. To avoid the demineralization which is a tedious step, we developed a method based on the use of a solid-phase extraction procedure to clean-up the samples. It resulted in sensitive and accurate measurements: the detection limits as low as 0.2 pmol for the pyridimium crosslinks and 0.02 pmol for the pentosidine. The inter- and intra-assay coefficients of variation were as low as 5% and 2%, respectively, for all crosslinks.

Cortical and trabecular bone distribution in the femoral neck in osteoporosis and osteoarthritis.

The increased hip fragility in osteoporosis has been attributed mainly to a thinning of the cortex. In contrast, hip arthritis (OA) is not associated with increased risk of hip fracture. The purpose of this study was to assess cortical and trabecular bone structures and their possible regional variability in the femoral neck taken from patients who sustained an osteoporotic hip fracture (OP) compared with patients with OA. We compared the distribution of bone in the ultradistal femoral neck in 21 postmenopausal women with OA (mean age: 66+/-7.8 years) and 20 postmenopausal women with an osteoporotic hip fracture (OP) (mean age: 79.5+/-1.9 years). Controlateral hip osteoporosis or osteopenia was confirmed in OP by DEXA (T-score: -2.5+/-0.8 in OP; -0.9+/-1.3 in OA). Histomorphometric parameters of bone structure, architecture and connectivity were measured on sections from the ultradistal part of the femoral neck, divided in 4 quadrants. When compared to OA, cortical thickness was significantly decreased in OP (p<0.0005) but was the highest in the inferior part in both groups. Cortical porosity was higher in OA (13.48+/-1.02 and 8.4+/-1.07% in OA and OP respectively). Compared to OA, the trabecular bone volume was decreased by 50% in OP (p<0.0001) with a diminution of the trabecular number (p<0.01) and thickness (p<0.0001). In parallel, OP group was characterized by a poor connectivity evaluated by the decreased number of nodes (p<0.0001), higher trabecular bone pattern factor (p<0.0001) and greater marrow star volume (p<0.0001). The connectivity was the lowest in the inferior quadrant in OP but not in OA. Our data suggest that in addition to the cortical thinning, the loss of the trabecular bone mass and connectivity plays a role in the skeletal fragility associated with hip fracture. Furthermore, the spatial distribution of the trabeculae differs between OP and OA whereas cortical thinning is homogenous.