Volleyball and Basketball Enhanced Bone Mass in Prepubescent Boys.

The aim of this study was to examine the effect of volleyball and basketball practice on bone acquisition and to determine which of these 2 high-impact sports is more osteogenic in prepubertal period. We investigated 170 boys (aged 10-12 yr, Tanner stage I): 50 volleyball players (VB), 50 basketball players (BB), and 70 controls. Bone mineral content (BMC, g) and bone area (BA, cm(2)) were measured by dual-energy X-ray absorptiometry at different sites. We found that, both VB and BB have a higher BMC at whole body and most weight-bearing and nonweight-bearing sites than controls, except the BMC in head which was lower in VB and BB than controls. Moreover, only VB exhibited greater BMC in right and left ultra-distal radius than controls. No significant differences were observed between the 3 groups in lumbar spine, femoral neck, and left third D radius BMC. Athletes also exhibited a higher BA in whole body, limbs, lumbar spine, and femoral region than controls. In addition, they have a similar BA in head and left third D radius with controls. The VB exhibited a greater BA in most radius region than controls and a greater femoral neck BA than BB. A significant positive correlation was reported between total lean mass and both BMC and BA in whole body, lumbar spine, total hip, and right whole radius among VB and BB. In summary, we suggest that volleyball and basketball have an osteogenic effect BMC and BA in loaded sites in prepubescent boys. The increased bone mass induced by both volleyball and basketball training in the stressed sites was associated to a decreased skull BMC. Moreover, volleyball practice produces a more sensitive mechanical stress in loaded bones than basketball. This effect seems translated by femoral neck expansion.

Soccer increases bone mass in prepubescent boys during growth: a 3-yr longitudinal study.

The aim of this study was to examine the effect of 3-yr soccer practice on bone acquisition in prepubescent boys. We investigated 65 boys (aged 10-13 yr, Tanner stage I) at baseline, among which only 40 boys (Tanner stages II and III) have continued the 3-yr follow-up: 23 soccer players (F) completed 2-5 h of training plus 1 competition game per week and 17 controls (C). Bone mineral density (BMD, g/cm(2)) and bone mineral content (BMC, g) were measured by dual-energy X-ray absorptiometry at different sites. At baseline, BMD was higher in soccer players than in controls in the whole body and legs. In contrast, there was nonsignificant difference BMD in head, femoral neck, arms, and BMC in all measured sites between groups. At 3-yr follow-up, soccer players were found to have higher BMD and BMC at all sites than controls, except for head BMD and BMC and arms BMC in which the difference was nonsignificant between groups. During the 3-yr follow-up, the soccer players were found to gain significantly more in lumbar spine (31.2% ± 2.9% vs 23.9% ± 2.1%; p < 0.05), femoral neck (24.1% ± 1.8% vs 11.4% ± 1.9%; p < 0.001), whole body (16.5% ± 1.4% vs 11.8% ± 1.5%; p < 0.05), and nondominant arm BMD (18.2% ± 1.4% vs 13.6% ± 1.7%; p < 0.05) as well as lumbar spine (62.5% ± 20.1% vs 39.5% ± 20.1%; p < 0.001), femoral neck, (37.7% ± 14.2% vs 28.9% ± 12.8%; p < 0.05) and nondominant arm BMC (68.6% ± 22.9% vs 50.1% ± 22.4%; p < 0.05) than controls. In contrast, soccer players have less %BMD and %BMC changes in the head than controls. A nonsignificant difference was found in legs, dominant arm, head %BMD and %BMC changes, and whole-body %BMC changes between groups. In summary, we suggest that soccer has an osteogenic effect BMD and BMC in loaded sites in pubertal soccer players. The increased bone mass induced by soccer training in the stressed sites was associated to a decreased skull bone mass after 3 yr of follow-up.

Young male soccer players exhibit additional bone mineral acquisition during the peripubertal period: 1-year longitudinal study.

The aim of this study was to determine whether soccer could have different bone benefits in prepubescent and pubescent boys. We investigated 76 boys aged 10 to 13 years during a 1-year study. All boys were prepubescent at the beginning of the study (T0); pubescent status was determined by a complete 24-h urine hormonal assay of FSH-LH, with LH ≤ 0.31 IU/24 h and FSH ≤ 2.19 IU/24 h corresponding to prepubescent Tanner stage I and with 0.31 < LH < 0.95 IU/24 h and 1.57 < FSH < 3.77 IU/24 h corresponding to pubescent Tanner stage II. At the end of the study (T1), 35 boys remained prepubescent (22 soccer players (F1) and 13 controls (C1)), and 41 boys had entered puberty (26 soccer players (F2) and 15 controls (C2)). Soccer players completed 2 to 5 h of training plus one competition game per week during the school year, and controls only had physical education at school. Bone mineral content (BMC) was measured at T0 and T1 by DPX in the lumbar spine, total hip, and whole body (WB) for a comparison between soccer players and controls. At T0, no BMC difference was found between F1 and C1, but BMC was higher in F2 than C2 in WB and weight-bearing sites. At T1, BMC was higher in WB and weight-bearing sites in both F1 and F2 compared to their respective controls. Between T0 and T1, soccer induced a BMC gain at weight-bearing sites in both F1 and F2 compared to C1 and C2, respectively. The soccer-related bone gain was greater in WB and weight-bearing (the lumbar spine, total hip, and supporting leg) and non-weight-bearing bones (dominant arm and nondominant arm) in boys who became pubescent than in boys who remained prepubescent. In conclusion, 1-year study in young male soccer players demonstrates that the process of bone accretion at the very early phase of puberty is more intensely stimulated by the combination of physical exercise and sexual impregnation than by one of these factors alone.

Trabecular and cortical bone density and architecture in women after 60 days of bed rest using high-resolution pQCT: WISE 2005.

Prolonged bed rest is used to simulate the effects of spaceflight and causes disuse-related loss of bone. While bone density changes during bed rest have been described, there are no data on changes in bone microstructure. Twenty-four healthy women aged 25 to 40 years participated in 60 days of strict 6-degree head-down tilt bed rest (WISE 2005). Subjects were assigned to either a control group (CON, n = 8), which performed no countermeasures; an exercise group (EXE, n = 8), which undertook a combination of resistive and endurance training; or a nutrition group (NUT, n = 8), which received a high-protein diet. Density and structural parameters of the distal tibia and radius were measured at baseline, during, and up to 1 year after bed rest by high-resolution peripheral quantitative computed tomography (HR-pQCT). Bed rest was associated with reductions in all distal tibial density parameters (p < 0.001), whereas only distal radius trabecular density decreased. Trabecular separation increased at both the distal tibia and distal radius (p < 0.001), but these effects were first significant after bed rest. Reduction in trabecular number was similar in magnitude at the distal radius (p = 0.021) and distal tibia (p < 0.001). Cortical thickness decreased at the distal tibia only (p < 0.001). There were no significant effects on bone structure or density of the countermeasures (p ≥ 0.057). As measured with HR-pQCT, it is concluded that deterioration in bone microstructure and density occur in women during and after prolonged bed rest. The exercise and nutrition countermeasures were ineffective in preventing these changes.

WISE-2005: bed-rest induced changes in bone mineral density in women during 60 days simulated microgravity.

To better understand the effects of prolonged bed-rest in women, 24 healthy women aged 25 to 40 years participated in 60-days of strict 6° head-down tilt bed-rest (WISE-2005). Subjects were assigned to either a control group (CON, n=8) which performed no countermeasure, an exercise group (EXE, n=8) undertaking a combination of resistive and endurance training or a nutrition group (NUT, n=8), which received a high protein diet. Using peripheral quantitative computed tomography (pQCT) and dual X-ray absorptiometry (DXA), bone mineral density (BMD) changes at various sites, body-composition and lower-leg and forearm muscle cross-sectional area were measured up to 1-year after bed-rest. Bone loss was greatest at the distal tibia and proximal femur, though losses in trabecular density at the distal radius were also seen. Some of these bone losses remained statistically significant one-year after bed-rest. There was no statistically significant impediment of bone loss by either countermeasure in comparison to the control-group. The exercise countermeasure did, however, reduce muscle cross-sectional area and lean mass loss in the lower-limb and also resulted in a greater loss of fat mass whereas the nutrition countermeasure had no impact on these parameters. The findings suggest that regional differences in bone loss occur in women during prolonged bed-rest with incomplete recovery of this loss one-year after bed-rest. The countermeasures as implemented were not optimal in preventing bone loss during bed-rest and further development is required.

Pathophysiology of bone loss in disuse osteoporosis.

Osteoporosis, or rather the localised bone loss observed in patients with spinal cord injury, as well as during any type of immobilisation involves various processes and structures including the direct response of the musculoskeletal system to unloading, the central and peripheral nervous systems and their effects on bone cells and on the vascular system, the bone remodelling unit in its marrow compartment and a number of local factors controlling cell-cell cross-talk as well as calciotropic hormones. The authors present a detailed review of these different mechanisms which are all involved regardless of the type of immobilisation: pathological, environmental, or experimental. These factors are interconnected and put bone at the centre of the regulation of body homeostasis. A better knowledge of these mechanisms should promote the development of preventive therapies for the often neglected osteoporotic fractures that occur in patients with spinal cord injury.

Chronic eosinophilic pneumonia (Carrington's disease) and rheumatoid arthritis.

We describe the case of a 60-year-old woman with chronic eosinophilic pneumonia (Carrington's disease) who developed symmetric rheumatoid factor-negative polyarthritis suggestive of rheumatoid arthritis. Although these two diseases are well documented as separate entities, 10 cases in the literature suggest possible links. However, the course in our patient raised the possibility of Churg-Strauss syndrome, a condition that may overlap with chronic eosinophilic pneumonia.

Bone mineral density of young boy soccer players at different pubertal stages: relationships with hormonal concentration.

OBJECTIVES: To examine the effects of soccer in relation with the hormonal concentration, on the bone mass of young Tunisian players at different pubertal stages. METHODS: Two groups of 152 young boys (age: 13.3+/-0.9 years) participated in this study: (1) 91 soccer players, and (2) 61 non-athletic boys used as control subjects. The bone mineral density (BMD) and the bone mineral content (BMC) were measured by dual-energy X-ray absorptiometry (DXA). Pubertal stages were assessed, and serum concentrations of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), growth hormone (GH) and the total testosterone were measured. RESULTS: The BMD and BMC for whole body, lumbar spine, femoral neck, pelvis and lower limbs were higher in soccer players than in controls (p<0.001). In early puberty, the soccer players also exhibited significantly greater BMD and BMC in the whole body and in weight-bearing bones compared with the controls (p<0.001). However, there was no intersubject variability due to puberty in either BMD or BMC. The pubescent soccer players had significantly higher hormonal concentrations of IGF-1 and IGFBP-3 than their counterpart controls (p<0.05). Moreover, the whole body BMD was significantly (p<0.001) correlated with GH, IGF-1 and IGFBP-3 but not with the testosterone concentrations. CONCLUSION: The soccer participation of boys is generally associated with the improvement of their bone mass which is mainly marked at early and late puberty. The relationships between somatotropic axis hormones and BMD of the players may be linked to the parallel development of these two parameters during puberty.

High-resolution pQCT analysis at the distal radius and tibia discriminates patients with recent wrist and femoral neck fractures.

We depict a fragility bone state in two primitive osteoporosis populations using 3D high-resolution peripheral in vivo QCT (HR-pQCT). Postmenopausal women (C, controls, n = 54; WF, wrist, n = 50; HF, hip, n = 62 recent fractured patients) were analyzed for lumbar and hip DXA areal BMD (aBMD), cancellous and cortical volumetric BMD (vBMD), and microstructural and geometric parameters on tibia and radius by HR-pQCT. Principal component analysis (PCA) allowed extracting factors that best represent bone variables. Comparison between groups was made by analysis of covariance (ANCOVA). Two factors (>80% of the entire variability) are extracted by PCA: at the radius, the first is a combination of trabecular parameters and the second of cortical parameters. At the tibia, we found the reverse. Femoral neck aBMD is decreased in WF (8.6%) and in HF (18%) groups (no lumbar difference). WF showed a approximately 20% reduction in radius trabecular vBMD and number. Radius cortical vBMD and thickness decrease by 6% and 14%, respectively. At the tibia, only the cortical compartment is affected, with approximately 20% reduction in bone area, thickness, and section modulus and 6% reduction in vBMD. HF showed same radius trabecular alterations than WF, but radius cortical parameters are more severely affected than WF with reduced bone area (25%), thickness (28.5%), and vBMD (11%). At the tibia, trabecular vBMD and number decrease by 26% and 17.5%, respectively. Tibia cortical bone area, thickness, and section modulus showed a >30% decrease, whereas vBMD reduction reached 13%. Geometry parameters at the tibia displayed the greatest differences between healthy and fractured patients and between wrist and hip fractures.

Long-term soccer practice increases bone mineral content gain in prepubescent boys.

INTRODUCTION: Soccer is a highly osteogenic sport in pubescent adolescents and adults, particularly in weight-bearing bones. However, little is known about its effects in children despite the fact that soccer practice usually starts before puberty. The aim of this study was to verify whether soccer was able to increase bone mineral content (BMC) of weight-bearing bones by modifying bone remodelling in relation to the level of training in prepubescent boys compared to controls. METHODS: At baseline we investigated 39 prepubescent soccer players (11.7+/-0.8 years) divided into two groups according to the duration of training (2 and 4h/week) and 13 controls (10.7+/-0.6 years). BMC and bone resorption marker (CTX) were measured, respectively, by dual-energy X-ray absorptiometry (DEXA) and ELISA. Then, measurements were performed twice during a 10-month survey: only 27 boys remaining prepubescent were analysed. RESULTS: At baseline, no BMC difference was found in weight-bearing sites between soccer players and controls. Nevertheless, soccer players BMC gain significantly increased in total hip (+10.7%, P<0.05), lumbar spine (+10.5%, P<0.05) and legs, the increase being more marked in the longest duration training group (4h/weeks), particularly after a summer resting period. Meanwhile, resorption activity decreased. At the same time, cranial BMC was decreased in soccer players (-4.6%, P<0.001). CONCLUSION: BMC is not significantly enhanced in soccer prepubescent boys in comparison with controls. Nevertheless, the annual gain is greater in soccer players than in controls, especially after a rest period.

Retroperitoneal fibrosis: a rare vascular and immune entity disclosed by chronic lombalgia.

Retroperitoneal fibrosis is a rare inflammatory and fibrotic process in the retroperitoneal peri-aortic tissues, associated with ureters and other abdominal organs' entrapment. Here we report an original observation of a 55-year-old patient presenting with chronic lombalgia disclosing idiopathic retroperitoneal fibrosis. After one-year follow-up, treatment with corticosteroids led to a complete clinical, biological, and radiological response. Pathogenesis and therapeutic options in idiopathic retroperitoneal fibrosis are discussed.

A 1-year case-control study in patients with rheumatoid arthritis indicates prevention of loss of bone mineral density in both responders and nonresponders to infliximab.

The goal of the present study was to record changes in bone mineral density (BMD) and markers of bone turnover in patients with rheumatoid arthritis (RA) who were treated with methotrexate combined (or not combined) with infliximab. Included were 90 patients with RA who required anti-TNF-alpha therapy with infliximab because of persistent active disease despite treatment with methotrexate. The historical control group included 99 patients with RA who were treated with methotrexate at a time when anti-TNF-alpha treatment was not yet available. Lumbar and femoral neck BMD was measured using dual energy X-ray absorptiometry at baseline and 1 year later. Osteocalcin, C-terminal cross-linked telopeptide of type I collagen, parathyroid hormone and 25-hydroxycholecalciferol were measured in plasma at baseline and 1 year later. At 1 year BMD had decreased in the control group at spine (P < 0.01) and femoral neck (P < 0.001). In contrast, BMD at spine and femoral neck did not change after 1 year of infliximab treatment. At the same time point, no change in bone remodelling markers was observed. No association was observed between clinical response and changes in BMD, indicating that even those who did not respond clinically did not lose bone over a 1-year period. These data confirm the BMD decrease observed in RA patients treated with methotrexate alone. This bone loss was prevented by infliximab therapy. Importantly, this beneficial effect was also observed in apparent nonresponders.

Cancellous bone structure of iliac crest biopsies following 370 days of head-down bed rest.

INTRODUCTION: Static bone histomorphometry was applied to existing iliac bone sections originating from a 370-d 5 degrees head-down bed rest experiment. This bed rest experiment is the longest ever to have been conducted. We hypothesized that bed rest would decrease cancellous bone volume fraction and that this effect would be reversed by countermeasures. METHODS: Eight healthy male subjects underwent 370 d of 5 degrees head-down bed rest. Three subjects were treated with bisphosphonate (Xidifon, potassium salt of ethane-1-hydroxy-1-disphosphonate, EHDP) combined with an exercise regimen (1-2 h x d(-1)) for the entire study period. Five subjects underwent 120 d of bed rest without countermeasures followed by 250 d of bed rest with the exercise regimen. Transiliac bone biopsies were obtained either at baseline and day 366, or at baseline, day 116, and day 366 at alternating sides of the ileum. Static histomorphometry was performed using a computerized method. RESULTS: The 120 d of head-down bed rest without countermeasures resulted in decreased bone volume fraction BV/TV (-6.3%, p = 0.046) and trabecular number (Tb.N; -10.2%, p = 0.080) and increased trabecular separation (Tb.Sp; 14.7%, p = 0.020), whereas the 250 d of subsequent head-down bed rest with exercise treatment prevented further significant deterioration of the histomorphometric measures. DISCUSSION: The 120 d of 5 degrees head-down bed rest without countermeasures induced significant deterioration of iliac crest cancellous bone histomorphometric properties. On average, the countermeasures consisting of either bisphosphonate and exercise, or exercise alone were able to either prevent or stop immobilization-induced changes of the iliac cancellous bone structure.

Androgens and bone metabolism.

The gradual reductions in bone mass and skeletal calcium density seen throughout adulthood occur in parallel with changes in the production of bioactive sex hormones in both men and women. The long-held belief that osteoporosis is dependent on androgens in men and estrogens in women has been challenged by recent reports of osteoporosis in young men with normal testosterone levels but extremely low estrogen levels. A review of the literature indicates that estrogens have a far greater influence on bone mass than do androgens. This may suggest new approaches to the treatment of male osteoporosis. Furthermore, osteoporosis induced by prostate cancer treatment should receive greater medical attention.

Leptin modulates both resorption and formation while preventing disuse-induced bone loss in tail-suspended female rats.

In vitro studies have demonstrated leptin-positive effects on the osteoblast lineage and negative effects on osteoclastogenesis. Therefore, we tested the hypothesis that leptin may prevent tail-suspension-induced bone loss characterized by an uncoupling pattern of bone remodeling, through both mechanisms. Female rats were randomly tail-suspended or not and treated either with ip administration of leptin or vehicle for 3, 7, and 14 d. As measured by dual energy x-ray absorptiometry, tail-suspension induced a progressive decrease in tibia-metaphysis bone mineral density, which was prevented by leptin. Histomorphometry showed that this was related to the prevention of the transient increase in osteoclast number observed with suspension at d 7. These effects could be mediated by the receptor activator of nuclear factor kappaB-ligand (RANKL)/osteoprotegerin (OPG) pathway since we observed using direct RT-PCR, a suspension-induced increase in RANKL gene expression in proximal tibia at d 3, which was counterbalanced by leptin administration with a similar 3-fold increase in OPG expression and a RANKL to OPG ratio close to nonsuspended conditions. In addition, leptin prevented the decrease in bone formation rate induced by tail-suspension at d 14. The latter could be related to the role of leptin in mediating the reciprocal differentiation between adipocytes and osteoblasts, because leptin concurrently blunted the disuse-induced increase in bone marrow adipogenesis. In summary, these data suggest that peripheral administration of leptin could prevent disuse-induced bone loss through, first, a major inhibitory effect on bone resorption and, second, a delayed effect preventing the decrease in bone formation.

Interactions between estrogen and mechanical strain effects on U2OS human osteosarcoma cells are not influenced by estrogen receptor type.

Estrogens (E) and mechanical strain (MS) exert direct effects on osteoblast activity, with good evidence of interactions between their respective effects. Osteoblasts express both forms of estrogen receptors (ER) ERalpha and ERbeta, and previous studies have suggested a specific role for each receptor. Therefore, our working hypothesis was that the interactions between E and MS on osteoblast activity vary depending on which ER is preferentially activated. Using human osteosarcoma cells U2OS stably transfected either with ERalpha or ERbeta, we evaluated the effects of cyclical cell loading on a F-3000 Flexercell Strain Unit (1.5% elongation, 10 min/day) in presence of estradiol (E2) 10(-8) M or not. The original U2OS cell line, which does not express ER, was characterized by low alkaline phosphatase (AP) activity. In both U2OS-ERalpha and U2OS-ERbeta cell lines, MS induced similar increases in AP activity and gene expression as measured by real-time quantitative RT-PCR, and a decrease in type I collagen gene expression. MS and E2 had a synergistic effect on AP activity as compared to each stimulus alone. No change in proliferation rate was observed. Neither proliferation nor differentiation of the original U2OS cell line was altered by strain or E2. In summary, our data showing differences in response to MS between the U2OS with no ER expression and the U2OS-ERalpha or -ERbeta cell lines provide additional evidence that ER plays a critical role in mechanotransduction. However, we were not able to demonstrate that interactions between E and MS were dependent on ER type in U2OS osteosarcoma cells.

Increase of both angiogenesis and bone mass in response to exercise depends on VEGF.

UNLABELLED: Physiological angiogenesis during bone remodeling is undefined. Treadmill-running rats displayed bone marrow angiogenesis concomitant with bone formation increase and resorption decrease and upregulation of VEGF and its R1 receptor mRNA in proximal tibia. VEGF blockade over 5 weeks of training fully prevented the exercise-induced bone mass gain. INTRODUCTION: We investigated the role of vascular endothelial growth factor (VEGF) and angiogenesis in the osteogenic response to exercise. MATERIALS AND METHODS: Nine-week-old male Wistar rats were treadmill-trained at 60% Vo(2max) for various periods. Bone and vascular histomorphometry was performed after 2- and 5-week experiments. On-line RT PCR for VEGF and its receptors R1 and R2 was done after a 10-day experiment. In the 5-week experiment, running rats received either a VEGF inhibitory antibody or a placebo. RESULTS: After 2 weeks, tibial BMD did not change; however, vessel number in the proximal metaphysis increased by 20% in running versus sedentary rats. In running rats, vessel number correlated positively (r = 0.88) with bone formation rate and negatively (r = -0.85) with active resorption surfaces. After 10 days of training, upregulation of VEGF and VEGF receptor R1 mRNA was detected in periosteum and metaphyseal bone. VEGF blockade in 5-week trained rats fully prevented the exercise-induced increase in metaphyseal BMD (9%) and cancellous bone volume (BV/TV; 25%), as well as the increased vessel number (25%). In 5-week placebo-treated running rats, bone formation rate returned to initial values, whereas osteoclastic surfaces continued to decline compared with both sedentary and anti-VEGF-treated running rats. CONCLUSION: VEGF signaling-mediated bone angiogenesis is tightly related to exercise-induced bone cellular uncoupling and is indispensable for bone gain induced by exercise.

Focal contact clustering in osteoblastic cells under mechanical stresses: microgravity and cyclic deformation.

We quantitatively compared vinculin-related adhesion parameters in osteoblastic cells submitted to two opposing mechanical stresses: low deformation and frequency strain regimens (stretch conditions) and microgravity exposure (relaxed conditions). In both ROS 17/2.8 cells and rat primary osteoblastic cells, 1% cyclic deformations at 0.05 Hz for 10 min per day for seven days stimulated cell growth compared to static culture conditions, while relaxed ROS cells proliferated in a similar way to static cultures (BC). We studied the short-term (up to 24 h) adaptation of focal contact reorganization under these two conditions. Cyclic deformation induced a biphasic response comprising the formation of new focal contacts followed by clustering of these focal contacts in both ROS cells and primary osteoblasts. Microgravity exposure induced a reduction in focal contact number and clustering in ROS cells. To evaluate whether the proliferation (stretch) or survival (relaxed) status of ROS cells influences focal contact organization, we inhibited the ERK proliferative-dependent pathway. Inhibition of proliferation by PD98059 was partially reversed, but not fully restored by stretch. Stretch-induced clustering of vinculin-positive contacts also persisted in the presence of PD98059, whereas the increase in focal contact number was abolished. In conclusion, we show that focal contacts are mechanoeffectors, and we suggest that their morphologic organization might serve as a discriminant functional parameter between survival and proliferation status in ROS 17/2.8 osteoblastic cells.

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.

Noninvasive in vivo monitoring of bone architecture alterations in hindlimb-unloaded female rats using novel three-dimensional microcomputed tomography.

UNLABELLED: We tested a novel microcomputed tomograph designed to longitudinally and noninvasively monitor bone alterations in hindlimb-unloaded female rats at a resolution of 26 microm over a period of 3 weeks. This prototype has a potential to detect three-dimensional trabecular microarchitectural changes induced by growth and unloading. INTRODUCTION: Until now, data concerning structural changes of cancellous bone have only been available after necropsy of animals. In this study, we tested a novel microcomputed tomography (microCT) technique designed to monitor such changes repeatedly at a resolution of 26 microm with an acquisition time of about 10 minutes to map the entire proximal tibial metaphysis. MATERIALS AND METHODS: Four-month-old female Wistar rats were randomized to seven groups of 10 animals to be either tail-suspended or to act as controls. MicroCT and DXA measurements were performed at 0, 7, 14, and 23 days in suspended and control rats. One group was killed at each of these time points, and bone samples were processed for histomorphometry and ex vivo microCT. RESULTS: We verified that a good correlation was obtained between two-dimensional bone parameters evaluated in longitudinal tibial sections either by histomorphometry or microCT and microCT parameters obtained from either in vivo or ex vivo tibias. The longitudinal survey allowed earlier detection of both growth and unloading-related bone changes than the transverse survey. In controls, aging induced denser bones, reorganization of the trabecular network toward a more oriented plate-like structure, and an isotropic pattern. Unloading first inhibited cortical and cancellous bone growth and then induced bone loss characterized by fewer trabeculae, reduced connectivity density, and enhanced structure model index (SMI), revealing a lighter cancellous structure with development of rod-like characteristics. CONCLUSION: We show for the first time that this microCT prototype has a great potential to accurately, repeatedly, reliably, and rapidly investigate alterations of three-dimensional trabecular microarchitecture.