Philippe Collet

Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts.

BACKGROUND Microgravity has been thought to induce osteoporosis because of reduced weight-bearing. However, up to now, few data have been available about its precise nature and timecourse. METHODS We measured bone mineral density (BMD) at the distal radius and tibia in 15 cosmonauts of the Russian MIR space station who sojourned in space either 1 (n=two), 2 (two), or 6 months (11). After recovery periods of similar duration to the space missions, BMD was measured for the 2-month and 6-month crews. FINDINGS Neither cancellous nor cortical bone of the radius was significantly changed at any of the timepoints. On the contrary, in the weight-bearing tibial site, cancellous BMD loss was already present after the first month and deteriorated with mission duration. In tibial cortices, bone loss was noted after a 2-month flight. In the 6-month group, cortical bone loss was less pronounced than that for cancellous bone. In some individuals, tibial deterioration was great. Actual BMD did not depend on preceding cumulative periods spent in space. During recovery, tibial bone loss persisted, suggesting that the time needed to recover is longer than the mission duration. INTERPRETATION In space, despite physical training, bone loss is an adaptive process that can become pathological after recovery on Earth. Striking interindividual variations in bone responses seem to suggest a need for adequate crew preselection. Targeted treatment or prevention strategies would be useful, not only for space purposes, but also for the increasing number of osteoporotic patients on Earth.

Space-related bone mineral redistribution and lack of bone mass recovery after reambulation in young rats

This study reports the effects of a 14-day spaceflight followed by a 14-day reambulation period on bones of 56-day-old male rats compared with synchronous (S) and vivarium (V) control animals. Femur, tibia, and humerus bone mineral densities (BMD); bone calcium and phosphorus concentrations ([Ca2+] and [P]), measured by X-ray microanalysis (XRM), on tibia, vertebra, and calvaria; and histomorphometric data on proximal primary and secondary spongiosae (I and II SP, respectively) of the tibia and humerus were measured. After the flight in flown rats (compared with S), BMD was lower in the distal femur and remained similar to S in humerus and tibia, [Ca2+] and [P] were lower in tibia II SP and higher in calvaria, tibia I SP width and II SP bone volume were lower, resorption was markedly higher in tibia II SP, and no difference in formation parameters was observed. After reambulation, BMD was lower in long bones of both flight and S groups compared with V. Bone loss appeared in humeral II SP and worsened in tibial II SP in flown rats. Tibial formation parameters were higher in flown rats compared with V and S, indicating the onset of an active recovery. Tibial XRM [Ca2+] and [P] in flown rats remained below control levels.This study reports the effects of a 14-day spaceflight followed by a 14-day reambulation period on bones of 56-day-old male rats compared with synchronous (S) and vivarium (V) control animals. Femur, tibia, and humerus bone mineral densities (BMD); bone calcium and phosphorus concentrations ([Ca2+] and [P]), measured by X-ray microanalysis (XRM), on tibia, vertebra, and calvaria; and histomorphometric data on proximal primary and secondary spongiosae (I and II SP, respectively) of the tibia and humerus were measured. After the flight in flown rats (compared with S), BMD was lower in the distal femur and remained similar to S in humerus and tibia, [Ca2+] and [P] were lower in tibia II SP and higher in calvaria, tibia I SP width and II SP bone volume were lower, resorption was markedly higher in tibia II SP, and no difference in formation parameters was observed. After reambulation, BMD was lower in long bones of both flight and S groups compared with V. Bone loss appeared in humeral II SP and worsened in tibial II SP in flown rats. Tibial formation parameters were higher in flown rats compared with V and S, indicating the onset of an active recovery. Tibial XRM [Ca2+] and [P] in flown rats remained below control levels.

Safety of rituximab in rheumatoid arthritis patients with a history of severe or recurrent bacterial infection: Observational study of 30 cases in everyday practice

OBJECTIVES To report our experience with rituximab therapy in patients with rheumatoid arthritis (RA) and a history of severe or recurrent bacterial infections. PATIENTS AND METHODS Retrospective observational study in five rheumatology departments experienced in the use of biotherapies. Patients were included if they had RA and a history of severe or recurrent bacterial infection (requiring admission and/or intravenous antimicrobial therapy) that contraindicated the introduction or continuation of TNFalpha antagonist therapy. RESULTS Of 161 RA patients given rituximab in the five study centers, 30 met the inclusion criteria, 23 females and seven males with a mean age of 58.4+/-11.8 years and a mean disease duration of 11.4+/-13.9 years. Among them, 22 had rheumatoid factors and 21 had received TNFalpha antagonist therapy (one agent in 15 patients, two in five patients and three in one patient). Prior infections were as follows: septicemia, n=2; lower respiratory tract infection or lung abscess, n=12; prosthesis infection, n=3; septic arthritis, n=3; endocarditis, n=1; pyelonephritis, n=2; osteitis, n=4; and various skin infections (erysipelas, cellulitis or skin abscess), n=6. Of these 33 infections, 21 occurred during TNFalpha antagonist therapy. During rituximab therapy, all patients received concomitant glucocorticoid therapy (mean dosage, 12+/-7.9 mg/day). The number of rituximab cycles was one in 13 patients, two in seven patients and three or more in 10 patients. Mean time from the single or last serious infection and the first rituximab infusion was 20.1+/-18.7 months. Mean follow-up since the first rituximab infusion was 19.3+/-7.4 months. During follow-up, six (20%) patients experienced one infection each. Immunoglobulin levels after rituximab therapy were within the normal range. CONCLUSION Rituximab therapy was well tolerated in 24 (80%) of 30 patients with RA and a history of severe or recurrent bacterial infection. In everyday practice, rituximab therapy seems safe with regard to the recurrence of infectious episodes. However, longer follow-ups are needed.

Lower bone cellular activities in male and female mature C3H/HeJ mice are associated with higher bone mass and different pyridinium crosslink profiles compared to C57BL/6J mice

The female inbred strains of C3H/HeJ (C3H) and C57BL/6J mice (B6), having high and low femoral peak bone mass, respectively, were proposed as models for studying the genetic regulation of bone mass. Here, we compared the known bone phenotype, in 4.5-month-old C3H versus B6 mice, in both genders. Femoral bone mineral content, trabecular bone mass, and thickness at the distal metaphysis were higher in C3H mice. In the long bones, deoxypyridinoline content was lower and pyridinoline/deoxypyridinoline ratios were greater in C3H. Intrafibrillar collagen packing is different not only within strains but also within sexes. Bone resorption activity, evaluated by urinary pyridinium crosslinks and active resorption surfaces in the femoral metaphysis, was lower in C3H. Bone formation activity, evaluated by serum osteocalcin and alkaline phosphatase (ALP) levels, as well as histomorphometric indices of bone formation in the femoral metaphysis and the cortical tibia, was lower in C3H. Conversely, the ALP- and Von Kossa-positive colony-forming units were more numerous in bone marrow cell cultures originating from male C3H. In both strains, resorption and formation activities were lower in males than in females. In C3H, males had lower bone mass than females whereas the opposite was seen in B6. In conclusion, we found that the lower cellular activities in C3H were associated with high cancellous bone mass and pyridinium crosslink levels, which might account for the more mineralized bone in C3H mice compared to that in B6 mice.

High prevalence of dementia in women with osteoporosis

INTRODUCTION Alzheimers disease or other Dementias (ADD) and postmenopausal osteoporosis are two major public health problems with a huge impact on mortality. Here, we examined the prevalence of ADD in postmenopausal women with osteoporosis, monitored within a dedicated fracture liaison service. METHODS We conducted a cross-sectional observational study in a population of 2041 women, visiting the university hospital of Saint-Etienne for a peripheral fragility fracture. We assessed the prevalence of ADD among these patients and compared to French population. We also compared the characteristics of women with ADD and without ADD. RESULTS ADD prevalence was on average 13.5% in the population of interest with a mean age of 85years. As women with ADD were older than women without ADD, the prevalence of the disease significantly increased with age as 0%, 1.8%, 13% and 29.7% in<55, 55-74, 75-79 and 85-89years old groups, respectively. Proximal femoral fracture was the most frequent fracture (77%) followed by wrist fracture (13%), and then proximal humerus fracture (10%). ADD prevalence observed in our study was 3 to 4 times the ADD prevalence in France. Despite the overall increase of the ADD prevalence with age, it was still 2.2 and 1.9 times that of the French female population in the 80-84 and 85-89 age groups respectively. CONCLUSION ADD prevalence was higher in postmenopausal women with severe osteoporosis, especially those with femoral fractures. Thus, our results incite to a more efficient care of this population with a high risk of fracture and mortality.

Cementoplasty in the Treatment of Avascular Necrosis of the Hip

Objective. This retrospective study evaluated the role of percutaneous cementoplasty in the treatment of avascular necrosis (AVN) of the hip in order to postpone or avoid total hip replacement. Methods. The study population comprised 40 patients (47 hips) with mean age of 46 ± 4.7 years and mean body mass index of 26.7 ± 4.6 kg/m2. AVN was classified according to the Ficat-Arlet classification as one stage I, 30 stage II, and 16 stage III. The minimum followup was 9 months. Results. It was found that 74.5% of hips were secondarily operated for total hip replacement a mean of 19.9 ± 15 months (median 14 mo) after cementoplasty. As well, 94% of patients with stage 3AVN and 68% with stage 2AVN underwent surgery. Twelve hips were not operated, with a mean followup of 39 ± 19.2 months. Pain decreased by more than 80% after cementoplasty in two-thirds of patients, but the mean pain-free interval was only 8.1 ± 6.6 months (median 5 mo). Nineteen of the 29 working patients were able to transiently return to work. The outcome was more unfavorable with radiological stage III AVN, joint effusion, and/or a double-line sign around the lesions on magnetic resonance images. Conclusion. Despite early relief of pain, the results of the cementoplasty technique were disappointing, with need for arthroplasty surgery in most cases within 2 years. Alternative percutaneous techniques using different filler materials with osteoinductive properties should be evaluated in further studies.

Evaluation of bone quality with trabecular bone score in active spondyloarthritis

OBJECTIVE Many patients with spondyloarthritis (SpA) are at risk of fracture due to bone fragility, whereas their bone mineral density (BMD) is not significantly diminished. Other tools, such as trabecular bone score (TBS), evaluating other characteristics of bone tissue are therefore necessary in order to evaluate bone changes in these patients. Therefore we evaluated TBS as a bone quality marker, in a cohort of patients with SpA and investigated which clinical and biological factors were correlated with TBS values. METHODS Patients fulfilling ASAS criteria of SpA with a BMD assessment and visiting our department for initiation or switch of a biologic treatment were selected. The clinical and biological data were collected at the time of BMD measurement. RESULTS Ninety-five patients were included in the study, with a mean age of 40.2 and a mean disease duration of 8.2 years. Lumbar BMD T-score was <-1 and <-2.5 in 17% and 3% of patients, respectively. On average, TBS value was 1.34±0.12. Lumbar BMD was positively correlated with TBS (r=0.61), while disease duration, disease activity score and serum PTH levels were negatively correlated with TBS (r=-0.24, r=-0.33, and r=-0.27, respectively). These correlations persisted in a multivariate analysis. Furthermore, more than half of the patients with a BMD level above -2.5 T-score had a low TBS value. CONCLUSION Our results show that TBS provides information additional to BMD on the bone status of patients with SpA. They suggest that TBS may help in identifying those patients at risk of fracture.

3D ultrasound compared to magnetic resonance imaging and 2D ultrasound in assessing rheumatoid arthritis activity: A 6-month pilot study.

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 31 decembre 2014

A seven-year longitudinal study of bone mineral density in elderly with unrecognised obstructive sleep apnoea: the PROOF cohort study

Background Osteoporosis (OP) and obstructive sleep apnea (OSA) are two common serious disorders in the elderly associated. Although clinical studies suggest an association between these two diseases, their co-existence in elderly is controversial. Objectives This study explores the longitudinal changes on bone mineral density (BMD) in a large sample of older subjects with and without OSA. Methods 406 subjects, initially aged 68.8±1 y, were examined at baseline and after 7 y. At baseline they had anthropometric data, home polygraphy, assessment of daily energy expenditure, and dual-energy X-ray absorptiometry (DXA). At follow-up, clinical and DXA data were also collected. Results A significant decrease in prevalence of OP and osteopenia was present both at lumbar and femoral sites. Considering the changes in BMD and T-score according to severity of OSA, there was a significant decrease in cases with OP. After adjustment for gender, anthropometric and metabolic variables, univariate and multivariate regression analyses showed a significant association between changes of BMD and gender without contribution of metabolic and sleep related respiratory factors. Conclusions In older healthy subjects, a reduced prevalence of OP was found in a 7-y follow-up independently of the presence or not of OSA. The impact of chronic intermittent hypoxia on bone mineral loss appears quite limited in such an elderly population.