Mineral loss in cortical and trabecular bone during high-dose prednisone treatment

To evaluate the effect of prednisone and triple treatment (sodium fluoride, calcium, and vitamin D) on trabecular and cortical bone serial bone mineral content (BMC) measurements were made at a metaphyseal (BMCD) and diaphyseal (BMCP) site on the forearm on 31 consecutive and previously bone-healthy patients scheduled for at least 24 weeks high-dose prednisone treatment. The patients were randomized into two further treatment groups: group I (n = 16) received prednisone plus triple treatment and group II (n = 15) received only prednisone. The two groups were similar with regard to age, sex, prednisone dose, and initial BMC. During 24 weeks treatment, BMCD (partially representing trabecular bone) and BMCP (mainly representing cortical bone) fell significantly and similarly, demonstrating that there is no preventive effect on bone mineral loss on the triple regimen. The BMC fall after 12 weeks was significantly more pronounced for metaphyseal (partially trabecular) than for diaphyseal (cortical) bone, whereas the values did not differ significantly after 24 weeks; this indicates a greater sensitivity to the hormone treatment of trabecular bone. In the entire group, the fall in BMC correlated positively with individual prednisone dose, significant at the diaphyseal site (r = 0.39, P less than 0.05), but not at the metaphyseal site (r = 0.31, P = 0.08). It is concluded that corticosteroid-induced osteopenia is a diffuse bone disease which affects trabecular as well as cortical bone, suggesting that BMC measured on the forearm reflects changes in bone mineral at other locations.     

Differential effects of glucocorticoids on cortical appendicular and cortical vertebral bone mineral content

Summary The susceptibility to glucocorticoid-induced bone loss may vary in different parts of the skeleton. We studied 62 patients with rheumatoid arthritis, 26 of whom were on low-dose glucocorticoid treatment. Bone mineral content (BMC) in the forearm was measured by single photon absorptiometry at a cortical, diaphyseal, and at a mixed cortical and trabecular, metaphyseal site. Lumbar BMC was measured by dual energy computed tomography in a trabecular and a cortical region of interest. The presence of vertebral deformities was evaluated on lateral spine radiographs. After correction for possibly confounding variables, prednisone therapy significantly influenced BMC at both the trabecular (-22.0%, 95% confidence interval-36.0% to-8.1%) and cortical (-24.8%, 95% confidence interval-39.3% to-10.3%) lumbar site. A significant effect was also seen at the metaphyseal (-15.7%, 95% confidence interval-27.1% to-4.2%), but not the diaphyseal (-3.9%, 95% confidence interval-14.1% to 6.4%) site in the forearm. Correlations between peripheral and vertebral BMC were moderate at best. The diaphyseal to metaphyseal BMC ratio did not identify patients with vertebral osteoporosis. It is concluded that the anterior cortical rim of the vertebral body is more susceptible to the effects of glucocorticoids than the cortical bone in the forearm, and that measurements of trabecular and anterior cortical vertebral BMC are essential in the management of patients with possible glucocorticoid-associated osteoporosis.     

PIXImus Bone Densitometer and Associated Technical Measurement Issues of Skeletal Growth in the Young Rat

The PIXImus dual-energy X-ray absorptiometer (DXA) is designed to measure body composition, bone mineral content (BMC), area (BA), and density (BMD) in mice and rats. The aims of this study were to longitudinally measure BMC, BA, and BMD in growing rats and to identify potential technical problems associated with the PIXImus. Total femur and lumbar DXA measurements, body weight, and length of initially 3-week-old rats (n = 10) were taken at weeks 5, 9, and 14. BMC and BMD of femoral metaphyseal and diaphyseal regions rich in trabecular and cortical bone, respectively, were obtained. Results showed significant increases in body weight, total femur BMC and BMD, lumbar area, length, BMC, and BMD at each time point. There was a significant positive correlation between body weight and total femur BMD (r = 0.97, P < 0.001) as well as lumbar BMD (r = 0.99, P < 0.001). BMD values for the femoral metaphyseal region and the lumbar spine were also positively correlated (r = 0.96, P < 0.01). Several technical issues (e.g., positioning of animals), difficulties (e.g., in analysis of images), and limitations (e.g., inability to detect underdeveloped calcified bone in growing animals and bone edge detection) of the software pertinent to the PIXImus were evident. In conclusion, despite limitations in the software, the PIXImus is a valuable tool for studying skeletal development of growing rats.     

Vertebral cortical bone mass measurement by a new quantitative computer tomography method: Correlations with vertebral trabecular bone measurements

Summary Previous studies comparing axial and appendicular skeleton have shown that trabecular bone loss is greater than cortical bone loss. However, whether the same difference exists between the trabecular and the cortical compartments of the vertebral body remains to be determined. In this study, we used quantitative computer tomography (QCT) to simultaneously measure the cortical rim of the vertebral body as well as trabecular bone. In 99 Caucasian women (mean age 53.8±13.0 years, range 26–79 years) we found a significant correlation between cortical mineral content (BMC_c) and both single (SE) and dual energy (DE) trabecular mineral content (BMC_T) (r=0.62,P<0.0001 for both regressions). The cross-sectional rates of bone loss per year were 1.32%, 1.16%, and 0.59% for SE-BMC_T, DE-BMC_T, and BMC_C, respectively. BMC_C decreased at a rate that was 45–51% that of SE-BMC_T and DE-BMC_T, respectively. Our results indicate that (1) QCT may provide a useful means to selectively measure cortical density in vertebral bodies; (2) the decrease of cortical density over time in the spine appears to have been underestimated previously by extrapolation from appendicular bone measurements; (3) because measurements of the entire vertebral body (exclusive of the posterior elements) may provide information that is more representative of spine changes with age, a measurement that includes both areas might be more useful than one measuring only the trabecular region.     

Bone mineral content of the femoral neck and shaft: Relation between cortical and trabecular bone

Summary Bone mineral content (BMC) of the femoral neck and shaft was determined with dual photon absorptiometry, using¹⁵³Gd. Comparison of BMC with the amount of hydroxyapatite (HA) ofin vitro specimen showed correlation coefficients of 0.992 and 0.996 for the femoral neck and shaft respectively. In the femoral neck the amount of cortical bone in a bone section varies from 16% ash weight in the proximal part of 71% in the distal part. Corresponding to the site of BMC measurements, the cortical bone constitutes 57% in the femoral neck and 95% in the femoral shaft. The precision error of measurements of BMCin vivo, expressed as the coefficient of variation for repeated determinations, was 1.4% for the femoral neck and 1.3% for the femoral shaft. In the femoral neck it is possible to distinguish between structures consisting mainly of cortical bone and structures containing mostly trabecular bone. While the cortical bone value decreases only slowly with age in normal women, corresponding to BMC of the femoral shaft, the trabecular bone value decreases rapidly even compared with BMC of the femoral neck. Despite the significant correlation between the values for cortical and trabecular bone a distinction seems essential from a clinical point of view.     

Accuracy and precision of peripheral quantitative computed tomography measurements at the tibial metaphysis.

The ability of 29 peripheral quantitative computed tomography (pQCT) software analysis modes at defining cortical from trabecular bone at three tibial metaphyseal regions was evaluated using five cadaveric tibiae. The accuracy of pQCT was determined by comparing the bone mineral content (BMC) with the ash weight. The precision of the pQCT scanner was calculated using repeated measurements. All the analysis modes had a good accuracy when measuring total bone area and a poor accuracy when measuring cortical bone area at the proximal 5% and distal 4% regions. For trabecular bone measured at all three regions and cortical bone area measured at the proximal 10% region, the Stratec peel mode 5 was the most accurate analysis mode. Highly significant correlations (r = 0.71-0.98) and a moderate accuracy error (coefficient of variation [CV] = 5-22%) was found between ash weight and BMC when using this mode. The precision of bone mineral density (BMD) measurements was good (total, CV = 2-5%; trabecular, CV = 2-5%; cortical, CV = 4-6%). pQCT is a moderately accurate, precise method of measuring trabecular and total BMD at the tibial metaphysis. The authors recommend caution when interpreting results for cortical BMD, as cortical area measurements at the metaphyseal region are less accurate and less precise.     

Comparison of Three Bone Densitometry Methods in Osteoporotic Women

Three techniques of bone mass measurement were evaluated in the diagnosis of postmenopausal osteoporosis; the overlap in the measurements and the capacity for discriminating was determined among 51 postmenopausal normal (mean age 66.6 ± 8.4 years) and 42 postmenopausal osteoporotic women (mean age 68.5 ± 7.5 years). All bone mass was evaluated by total body bone mineral content (BMC_TB), density (BMD_TB), ultrasound bone velocity (UBV) in proximal phalanxes 2–5 of the nondominant hand (UBV = mean value of all ultrasound measurements), and peripheral quantitative computed tomography of the nondominant forearm (pQCT). BMC_TB was found to be significantly better (P < 0.0001) for diagnosing postmenopausal osteoporosis than the other methods; both cortical and trabecular pQCT measurements were more discriminating than the corresponding UBV measurements (P < 0.001). T-score values in normals, subjects versus osteoporotic ones were BMC_TB−1.15 ± 0.79 versus −3.17 ± 0.74; BMD_TB−1.01 ± 0.97 versus −3.28 ± 0.81; UBV −1.51 ± 1.02 versus −2.34 ± 1.21; trabecular-pQCT −0.40 ± 0.72 versus −1.57 ± 0.37; cortical-pQCT −1.00 ± 0.87 versus −2.67 ± 0.53; and total-pQCT −0.65 ± 1.01 versus −2.34 ± 0.27, respectively. The overlap in values between the postmenopausal normal and postmenopausal osteoporotic groups was 50% with UBV, 6% with BMC_TB, 9% with BMD_TB, 25% with cortical pQCT, and 42% with trabecular pQCT. BMC_TB, BMD_TB, UBV, and pQCT correlated well with each other as measurements of bone mass, but BMC_TB was more discriminating than the other measurements in the diagnosis of osteoporosis. Received: 7 June 1995 / Accepted: 21 May 1997     

Multislice computed tomography of the distal radius metaphysis: relationship of cortical bone structure with gender, age, osteoporotic status, and mechanical competence.

We explore the relationship of region-specific densitometric and geometry-based (cortical) parameters at the distal radial metaphysis with gender, age, and osteoporotic status, using multislice computed tomography (CT). We specifically test the hypothesis that these parameters can improve the prediction of mechanical strength of the distal radius vs bone mass (bone mineral content [BMC]). The BMC was determined in 56 forearm specimens with peripheral dual-energy X-ray absorptiometry (DXA). Trabecular and cortical density and geometric properties of the metaphyseal cortex were determined using multislice CT and proprietary image analysis software. Specimens were tested to failure in a fall simulation, maintaining the integrity of the elbow joint and hand. Women displayed significantly lower failure strength (-34%), BMC (-35%), trabecular density (-26%), and cortical area (-12%) than men. The reduction of trabecular density with age and osteoporotic status was stronger than that of cortical density or thickness. DXA explained approx 50% (r2) of the variability in bone failure loads. This proportion was slightly increased (55%) when adding geometry-based parameters. The study suggests that high-resolution tomographic measurements with current clinical imaging methodology can marginally improve the prediction of mechanical failure strength. Further efforts are required to improve spatial resolution for determining metaphyseal cortical properties clinically.     

Bone mineral and stiffness loss at the distal femur and proximal tibia in acute spinal cord injury

Summary

Computed tomography and finite element modeling were used to assess bone mineral and stiffness loss at the knee following acute spinal cord injury (SCI). Marked bone mineral loss was observed from a combination of trabecular and endocortical resorption. Reductions in stiffness were 2-fold greater than reductions in integral bone mineral.

Introduction

SCI is associated with a rapid loss of bone mineral and an increased rate of fragility fracture. The large majority of these fractures occur around regions of the knee. Our purpose was to quantify changes to bone mineral, geometry, strength indices, and stiffness at the distal femur and proximal tibia in acute SCI.

Methods

Quantitative computed tomography (QCT) and patient-specific finite element analysis were performed on 13 subjects with acute SCI at serial time points separated by a mean of 3.5 months (range 2.6–4.8 months). Changes in bone mineral content (BMC) and volumetric bone mineral density (vBMD) were quantified for integral, trabecular, and cortical bone at epiphyseal, metaphyseal, and diaphyseal regions of the distal femur and proximal tibia. Changes in bone volumes, cross-sectional areas, strength indices and stiffness were also determined.

Results

Bone mineral loss was similar in magnitude at the distal femur and proximal tibia. Reductions were most pronounced at epiphyseal regions, ranging from 3.0 % to 3.6 % per month for integral BMC (p?<?0.001) and from 2.8 % to 3.4 % per month (p?<?0.001) for integral vBMC. Trabecular BMC decreased by 3.1–4.4 %/month (p?<?0.001) and trabecular vBMD by 2.7–4.7 %/month (p?<?0.001). A 3.8–5.4 %/month reduction was observed for cortical BMC (p?<?0.001); the reduction in cortical vBMD was noticeably lower (0.6–0.8 %/month; p?≤?0.01). The cortical bone loss occurred primarily through endosteal resorption, and reductions in strength indices and stiffness were some 2-fold greater than reductions in integral bone mineral.

Conclusions

These findings highlight the need for therapeutic interventions targeting both trabecular and endocortical bone mineral preservation in acute SCI.     

Bone mineral content in women: Trends of change

Altogether 426 women had their forearm bone mineral content (BMC) measured with single photon absorptiometry (SPA): one group in the early 1970s, another about 18 years later. Both groups represented purportedly healthy subjects. A third group of 328 women, measured at the same time as the second group, was from the same population but chosen by random selection (the population-based group). In the two sets of non-population-based women there was a small percentage reduction in the cortical forearm bone mass in the recent measurement as compared with the earlier measurement. This was significant only in women below 70 years of age. The forearm BMC, both cortical and trabecular, was less in all age groups of women randomly selected from the same population as the healthy control sample. This difference emphasizes the importance of selecting normative data from a population-based sample.     

Dynamic Effects of the Third Generation Bisphosphonate of Risedronate on Rat Osteoporotic Fractures for Clinical Usage Guidance

ObjectiveTo better understand the risks of bisphosphonates in order to develop guidance for appropriate clinical usage, to compared femoral fracture healing at different time points and to explore the effects of Residronate on fracture healing.MethodsOsteoporosis model was achieved by ovariectomy surgery, followed by surgical incision of left femoral shaft 4 weeks after ovariectomy surgery. Three days after fracture surgery, risedronateor saline was fed by intragastric administration. X ray examination was used to check the callus formation, Bone Mineral Density (BMD), Bone Mineral Content (BMC), biomechanical, imaging and micromorphological of bone tissue as well as the trabecular bone parameters were all examined. The femoral pathology tissue of each rat was used to analyze trabecular bone parameters, including trabecular bone volume/tissue volume (Tb. BV/TV), bone surface to tissue volume ratio (BS/TV), trabecular bone mineral density (Tb. BMD), trabecular bone number (Tb. N), trabecular bone thickness (Tb. Th) and small bone Trabecular bone space (Tb. Sp).Results Via X‐ray and pathologically, risedronate treatment promoted the callus forming at the fracture site during the following 6 weeks after osteoporotic fracture by X‐ray (P < 0.01), increased the local bone mineral density (P < 0.01), and accelerated the fracture healing during the first 3 weeks (P <0.01), but delayed facture healing in the later 3 weeks (P < 0.01). Risedronate increased the bone continuity of fracture at 7th week, but this phenomenon was not found at the 10th week (P < 0.01). Delayed fracture healing occurred locally at the fracture site. At 7th week, Risedronate may promote cartilage cells proliferating at fracture site, increase the dense of bone trabeculae and the connection of bone trabeculae, thicken the bone cortex showing better fracture healing than OPF‐Saline groups (P < 0.01). However, these parameter did not continue during the 7th and 10th weeks. Comparing the first and the later 3 weeks, the rats in group Osteoporotic Fracture‐Risedronate (OPF‐RD) accelerated the local fracture healing in the first 3 weeks but not in the last 3 weeks, which is consistent for the BMD and BMC among each group (P < 0.05). Through evaluation of bone mineral density and bone mineral content, risedronate dramatically increased the BMD at the fracture site and resulted in reduction of BMC by risedronate at the fracture site (P < 0.05) among each group still exist, indicating dramatic (P < 0.05). Through load testing, Risedronate increased the structural strength and mechanical indexes of the new callus (P < 0.01).ConclusionRisedronate can improve the structural strength and mechanical index of newborn callus. Longer than 7 weeks usage of third generation bisphosphonate of risedronate does not contribute to osteoporotic fracture.     

Cortical and trabecular bone contribute strength to the osteopenic distal radius

Fractures of the distal radius are common, especially in postmenopausal women, and their prevalence increases with age. Knowledge of the factors that increase the risk of fracture in this metaphyseal region would have predictive and therapeutic implications. Of particular interest in this study were (a) the relative contributions of cortical and trabecular bone to the strength of the distal radius and (b) the best radiographic features to use as strength indicators. In 21 forearms from fresh cadavera (median age at the time of death, 75 years), single photon absorptiometry and quantitative computed tomography were used to determine bone mineral content (BMC), density (BMC/W), and cross-sectional properties of the radius at distal and midshaft sites. Mechanical testing of the forearms then was used to determine the ultimate force and energy to cause the type of fracture that might be caused by a fall on the outstretched hand. Twelve of the 17 tested specimens sustained a fracture of the distal radius, and five sustained a fracture of the scaphoid. In the group of fractures of the distal radius, we found the cross-sectional area and moment of inertia of the cortical shell at the metaphyseal site to be better correlates of strength than the trabecular area and trabecular moment. In contrast, strength correlated much better with trabecular density than with cortical density. Overall, the best correlates of strength were the BMC and BMC/W at either the distal or proximal site. On balance, these results suggest that the thin cortical shell contributes substantially more to the mechanical strength of the distal radius than has been commonly appreciated.     

Lower trabecular volumetric BMD at metaphyseal regions of weight‐bearing bones is associated with prior fracture in young girls

Understanding the etiology of skeletal fragility during growth is critical for the development of treatments and prevention strategies aimed at reducing the burden of childhood fractures. Thus we evaluated the relationship between prior fracture and bone parameters in young girls. Data from 465 girls aged 8 to 13 years from the Jump‐In: Building Better Bones study were analyzed. Bone parameters were assessed at metaphyseal and diaphyseal sites of the nondominant femur and tibia using peripheral quantitative computed tomography (pQCT). Dual‐energy X‐ray absorptiometry (DXA) was used to assess femur, tibia, lumbar spine, and total body less head bone mineral content. Binary logistic regression was used to evaluate the relationship between prior fracture and bone parameters, controlling for maturity, body mass, leg length, ethnicity, and physical activity. Associations between prior fracture and all DXA and pQCT bone parameters at diaphyseal sites were nonsignificant. In contrast, lower trabecular volumetric BMD (vBMD) at distal metaphyseal sites of the femur and tibia was significantly associated with prior fracture. After adjustment for covariates, every SD decrease in trabecular vBMD at metaphyseal sites of the distal femur and tibia was associated with 1.4 (1.1–1.9) and 1.3 (1.0–1.7) times higher fracture prevalence, respectively. Prior fracture was not associated with metaphyseal bone size (ie, periosteal circumference). In conclusion, fractures in girls are associated with lower trabecular vBMD, but not bone size, at metaphyseal sites of the femur and tibia. Lower trabecular vBMD at metaphyseal sites of long bones may be an early marker of skeletal fragility in girls. © 2011 American Society for Bone and Mineral Research.     

Bone mass in female cynomolgus macaques: A cross-sectional and longitudinal study by age

A cross-sectional study by age was designed to evaluate and describe the bone mineral content (BMC, g) and density (BMD, g/cm²) in a population of female cynomolgus macaques (Macaca fascicularis). Dual-energy X-ray absorptiometry was used to measure, in segments L2-L4 of the lumbar spine, the BMC (BMC_s), BMD (BMD_s), length, and total-body BMC (BMC_TB) in 171 female monkeys ranging in age between 3.7 and 22.0 years. The animals were divided into three age groups: (1) young (<6.5 years, n=51); (2) adult (>6.5 years and <10.5 years, n=63); and (3) mature (>10.5 years, n=57). Young animals had a significantly lower (P<0.05) body weight and shorter trunk length than adult or mature animals. Young animals also had significantly less (P<0.05) BMC_S, BMD_S, and BMC_TB than adult or mature animals, and had significantly shorter (P<0.05) lumbar spine vertebral segments than the other two groups. Longitudinally, 63 animals had repeated lumbar spine scans to examine changes over time. Young animals showed a positive and significant change (P<0.05) in BMC_S and BMD_S through time, whereas these parameters did not change in adult animals, and mature animals had a trend towards bone loss through time. Densitometric results suggested that peak bone mass in the lumbar spine was achieved by 9 years of age. Radiographic and dental criteria were developed to identify animals that had reached peak bone mass, and the combined radiographic and dental scoring system reliably identified animals 9 years and older. Female cynomolgus macaques 9 years old or older are recommended for investigations of bone remodeling and associated conditions, such as osteoporosis.     

Genetic variations that regulate bone morphology in the male mouse skeleton do not define its susceptibility to mechanical unloading

Genetics can substantially influence bone morphology and may define the skeleton's response to mechanical unloading. Recent data indicated that disuse produces different site-specific responses in the skeleton of genetically distinct adult female C3H/HeJ (C3H) and BALB/cByJ (BALB) mice; while disuse BALB mice had significantly less bone than age-matched controls in the distal and diaphyseal femur, the removal of weight bearing had a much smaller influence in C3H. Using adult male mice from these two inbred strains, the hypothesis was tested that interactions between genetic variations and anatomic location define bone morphology and its susceptibility to unloading. Four-month-old male BALB and C3H mice were either subjected to 21 days of hindlimb unloading or served as controls. Multiple cortical and trabecular regions within the distal and diaphyseal femur were analyzed by micro-computed tomography. C3H controls had significantly greater diaphyseal and metaphyseal cortical bone area (45% and 32%) and greater metaphyseal trabecular bone volume fraction (67%) than BALB controls, but epiphyseal trabecular bone volume fraction was similar between the two strains. Despite these substantial, site-specific differences in bone morphology, disuse induced similar changes in bone morphology in these two strains. Compared to controls, disuse BALB and C3H had significantly less metaphyseal (17% and 19%) and epiphyseal (10% and 13%) trabecular bone, while diaphyseal and metaphyseal cortical bone geometry was unaffected. These data indicate that the genetic variations that caused spatially nonuniform differences in trabecular and cortical bone morphology between the two strains had little influence on the susceptibility of a specific site to unloading. Cross-gender comparisons with previous data from female BALB and C3H mice further suggest strong interactions by which gender, genotype, and anatomical location define the response of the skeleton to the removal of weight bearing.     

Differential turnover of cortical and trabecular bone in transgenic mice overexpressing cathepsin K

Cathepsin K is a major osteoclastic protease. We have recently shown that overexpression of mouse cathepsin K gene in transgenic UTU17 mouse model results in high turnover osteopenia of metaphyseal trabecular bone at the age of 7 months. The present report extends these studies to a systematic analysis of cortical bone in growing and adult mice overexpressing cathepsin K. Mice homozygous for the transgene locus (UTU17+/+) and their control littermates were studied at the age of 1, 3, 7, and 12 months. Bone properties were analyzed using peripheral quantitative computed tomography (pQCT), histomorphometry, histochemistry, radiography, and biomechanical testing. In addition, the levels of biochemical markers of bone turnover were measured in the sera. Unexpectedly, cortical thickness and cortical bone mineral density were increased in the diaphyseal region of growing and adult UTU17+/+ mice. This was associated with an increased number of vascular canals leading to increased cortical porosity in UTU17+/+ mice without changes in the ultimate bending force or stiffness of the bone. In UTU17+/+ mice, osteopenia of metaphyseal trabecular bone was observed already at the age of 1 month. In sera of 1-month-old UTU17+/+ mice, the activity of tartrate-resistant acid phosphatase 5b was decreased and the levels of osteocalcin increased. Our results support the role of cathepsin K as a major proteinase in osteoclastic bone resorption. Excessive production of cathepsin K induced osteopenia of metaphyseal trabecular bone and increased the porosity of diaphyseal cortical bone. The increased cortical thickness and bone mineral density observed in diaphyses of UTU17+/+ mice demonstrate the different nature and reactivity of trabecular and cortical bone in mice. These results suggest that the biomechanical properties of cortical bone are preserved through adaptation as outlined in Wolff's law.     

Short-term and long-term site-specific effects of tennis playing on trabecular and cortical bone at the distal radius

Mechanical loading during growth magnifies the normal increase in bone diameter occurring in long bone shafts, but the response to loading in long bone ends remains unclear. The aim of the study was to investigate the effects of tennis playing during growth at the distal radius, comparing the bone response at trabecular and cortical skeletal sites. The influence of training duration was examined by studying bone response in short-term (children) and long-term (young adults) perspectives. Bone area, bone mineral content (BMC), and bone mineral density (BMD) of the radius were measured by DXA in 28 young (11.6 ± 1.4 years old) and 47 adult tennis players (22.3 ± 2.7 years old), and 70 age-matched controls (12 children, 58 adults) at three sites: the ultradistal region (trabecular), the mid-distal region, and the third-distal region (cortical). At the ultradistal radius, young and adult tennis players displayed similar side-to-side differences, the asymmetry in BMC reaching 16.3% and 13.8%, respectively (P < 0.0001). At the mid- and third-distal radius, the asymmetry was much greater in adults than in children (P < 0.0001) for all the bone parameters (mid-distal radius, +6.6% versus +15.6%; third-distal radius, +6.9% versus +13.3%, for BMC). Epiphyseal bone enduring longitudinal growth showed a great capacity to respond to mechanical loading in children. Prolonging tennis playing into adulthood was associated with further increase in bone mineralization at diaphyseal skeletal sites. These findings illustrate the benefits of practicing impact-loading sports during growth and maintaining physical activity into adulthood to enhance bone mass accrual and prevent fractures later in life.     

Bone geometry and density in the skeleton of pre-pubertal gymnasts and school children

We have studied the differences between the peripheral and axial skeleton of pre-pubertal gymnasts and controls. We hypothesised that compared to controls, gymnasts would have larger and stronger radius and tibia diaphyses with greater bone mineral content and larger cross-sectional muscle area. At the distal metaphyseal sites of the radius and tibia, gymnasts would have greater bone cross-sectional area and total and trabecular volumetric bone mineral density (vBMD). Differences between the lumbar spine, total body and body composition in gymnasts versus controls were also studied. Peripheral quantitative computed tomography (pQCT) was used to measure bone geometry, density and muscle of the peripheral skeleton; dual energy X-ray absorptiometry (DXA) for total body and axial measurements.

Eighty-six pre-pubertal children, 44 gymnasts (mean age 9.0 years, range 5.4–11.9 years) and 42 controls (mean age 8.8 years, range 5.6–11.9 years) were studied. Eighty-four children were Caucasian, one child was mixed race, one Chinese. Data were adjusted for age, sex and height. Differences in the effect size between sexes were also tested.

At the 50% radius diaphysis gymnasts had larger bones (9.2%, p = 0.0054) with greater cortical area (8.2%, p = 0.022) and stress strain index (surrogate measure of bone strength) than controls (13.6%, p = 0.015). The effect size was different between males and females for cortical thickness (p = 0.03). At the 65% tibia diaphysis, gymnasts had greater cortical area (5.3%, p = 0.057) and thickness (6.2%, p = 0.068) than controls; consequently, bone strength was 5.4% higher (p = 0.14). There were no significant differences in cortical volumetric bone mineral density (vBMD) at the radius or tibia diaphysis between the groups. There was a difference in effect size for tibia muscle cross-sectional area between the sexes (p = 0.035). At the distal radius and tibia total and trabecular vBMD was greater (Total: radius 17%, p < 0.0001, tibia: 5.7%, p = 0.0053; trabecular: radius 21%, p < 0.0001, tibia 4.5%, p = 0.11). Bone size was not different in gymnasts compared to controls

Lumbar spine BMC (12.3%, p = 0.0007), areal bone mineral density (aBMD) (9.1%, p = 0.0006) and bone mineral apparent density (BMAD) (7.6%, p = 0.0047) were greater in gymnasts but vertebral size was not significantly different. Likewise, total body BMD (3.5%, p = 0.0057) and BMC (4.78%, p = 0.085) were greater in gymnasts but there were no differences in skeletal size.

These data suggest site-specific differences in how the pre-pubertal skeleton develops in response to the repetitive loading it experiences when participating in regular gymnastics. At diaphyseal sites these differences are predominantly in the bone and muscle geometry and not density. Conversely, at trabecular sites, the differences are increased density rather than geometry.

In conclusion, the present study has demonstrated skeletal differences between gymnasts and controls. These differences appear to be site and sex specific.     

ONO-5334, a cathepsin K inhibitor,improves bone strength by preferentially increasing cortical bone mass in ovariectomized rats

This study compared the effects of ONO-5334, a cathepsin K inhibitor, with those of alendronate on bone mass and strength in ovariectomized rats. Ovariectomy resulted in significant elevation in urinary deoxypyridinoline and plasma C-terminal cross-linking telopeptide of type I collagen (CTX) 8 weeks after surgery. Peripheral quantitative computed tomography analysis showed that total, trabecular, and cortical bone mineral content (BMC) decreased in the proximal tibia, which was paralleled with a significant decline in bone strength. Treatment with ONO-5334 (0.12, 0.6, 3 or 15 mg/kg) once daily for 8 weeks dose-dependently restored the decrease in total BMC and bone mineral density (BMD) in the proximal tibia and suppressed urinary deoxypyridinoline and plasma CTX levels. Alendronate (1 mg/kg, once daily) also fully restored these bone mass parameters. Separate analysis of trabecular and cortical bones, however, showed that ONO-5334 only partially restored trabecular BMD and BMC at 15 mg/kg, whereas alendronate fully restored these parameters. On the other hand, ONO-5334 increased both cortical BMD and BMC with an effect more potent than that of alendronate. Bone geometric analysis indicated that ONO-5334 at 15 mg/kg decreased endosteal circumference without affecting periosteal circumference, resulting in marked increase in cortical thickness. Interestingly, the effects of ONO-5334 on bone strength parameters were more prominent than those of alendronate, although the two test compounds had a similar effect on total BMC. Taken together, our results indicate that ONO-5334 has pharmacological characteristics different from those of alendronate and may offer a unique therapy for patients with osteoporosis.     

Odanacatib Treatment Affects Trabecular and Cortical Bone in the Femur of Postmenopausal Women: Results of a Two‐Year Placebo‐Controlled Trial

Odanacatib, a selective cathepsin K inhibitor, increases areal bone mineral density (aBMD) at the spine and hip of postmenopausal women. To gain additional insight into the effects on trabecular and cortical bone, we analyzed quantitative computed tomography (QCT) data of postmenopausal women treated with odanacatib using Medical Image Analysis Framework (MIAF; Institute of Medical Physics, University of Erlangen, Erlangen, Germany). This international, randomized, double‐blind, placebo‐controlled, 2‐year, phase 3 trial enrolled 214 postmenopausal women (mean age 64 years) with low aBMD. Subjects were randomized to odanacatib 50 mg weekly (ODN) or placebo (PBO); all participants received calcium and vitamin D. Hip QCT scans at 24 months were available for 158 women (ODN: n = 78 women; PBO: n = 80 women). There were consistent and significant differential treatment effects (ODN‐PBO) for total hip integral (5.4%), trabecular volumetric BMD (vBMD) (12.2%), and cortical vBMD (2.5%) at 24 months. There was no significant differential treatment effect on integral bone volume. Results for bone mineral content (BMC) closely matched those for vBMD for integral and trabecular compartments. However, with small but mostly significant differential increases in cortical volume (1.0% to 1.3%) and thickness (1.4% to 1.9%), the percentage cortical BMC increases were numerically larger than those of vBMD. With a total hip BMC differential treatment effect (ODN‐PBO) of nearly 1000 mg, the proportions of BMC attributed to cortical gain were 45%, 44%, 52%, and 40% for the total, neck, trochanter, and intertrochanter subregions, respectively. In postmenopausal women treated for 2 years, odanacatib improved integral, trabecular, and cortical vBMD and BMC at all femur regions relative to placebo when assessed by MIAF. Cortical volume and thickness increased significantly in all regions except the femoral neck. The increase in cortical volume and BMC paralleled the increase in cortical vBMD, demonstrating a consistent effect of ODN on cortical bone. Approximately one‐half of the absolute BMC gain occurred in cortical bone. © 2014 American Society for Bone and Mineral Research.