Trabecular Bone Sites Research Articles

The relationship between chemerin, bone metabolism, the RANKL/RANK/OPG system, and bone mineral density in girls with anorexia nervosa

Based on recent studies in humans, chemerin has been classified as an adipokine that might be associated with osteoporosis and BMD. Bone loss is common in adolescents with anorexia nervosa (AN). Moreover, dysfunction in the production of chemerin has also been shown. Therefore, we carried out a comparative analysis between chemerin, bone metabolism, the RANKL/RANK/OPG system, and BMD in girls with AN. Plasma chemerin, OC, CTx, OPG, and sRANKL were determined by ELISA in 75 girls with AN aged 12.6-17.8 years. BMD was assessed by DXA and expressed as Z-score according to the lumbar spine (s) and total body (TB) sites. According to the s-BMD- and TB-BMD Z-score, girls with AN were divided into two subgroups with parallel analyses used: normal (Z-score > -2.0) and low (Z-score ≤ -2.0) s-BMD, and normal (Z-score > -2.0) and low (Z-score ≤ -2.0) TB-BMD. Mean OC and the OPG/sRANKL ratio were markedly lower in the low s-BMD subgroup compared to the normal s-BMD subgroup. The s-Z-score values (both low and normal) correlated significantly and positively with the OPG/sRANKL ratio. Only in the low s-BMD subgroup did chemerin correlate significantly and positively with all nutritional indices and the OPG/sRANKL ratio. In the low TB-BMD subgroup the mean OC and the OPG/sRANKL ratio were lower than in the normal TB-BMD subgroup. The TB-Z-score values (both normal and low) correlated significantly and positively with all nutritional indices and the OPG/sRANKL ratio. The low TB-Z-score values correlated significantly and positively also with chemerin. In the low TB-BMD subgroup chemerin correlated significantly and positively with weight and BMI (expressed as absolute values), Cole index, the duration of the disease, and OPG/sRANKL ratio while its correlation with age was negative. Undernutrition and associated deficit of adipose tissue may result in inadequate chemerin production and skeletal disorders in girls with AN. Chemerin acts as a coordinator of the dynamic balance between bone metabolism and the OPG/RANK/RANKL system and, in turn, may contribute to the loss of bone mass in girls with AN. The cortical bone site seems to be more severely responsive to chemerin actions than the trabecular bone site.

Peak vertical jump power predicts radial bone strength better than hand grip strength in healthy individuals.

Osteoporosis is considered a pediatric disease with geriatric consequences. However, measuring bone strength in children is complex and creates a practical problem for health professionals, teachers and parents. A non-invasive measure of muscle fitness that correlates to bone strength may provide a means to monitor bone strength throughout the lifespan. Therefore, the purpose of this study was to investigate the relationship between common muscle function tests (relative grip strength (RGS), peak vertical jump power (PP)) and bone strength in the radial diaphysis and epiphysis of a healthy population. Healthy participants (n=147 (81 female)) performed a bilateral grip strength test using a hand dynamometer, and a maximal vertical jump test. Peak vertical jump power was calculated from maximal jump height using the Sayer’s equation. Moment of inertia (MoI), cortical area (CoA), cortical bone mineral density (cBMD), and polar strength-strain index (SSIp) were measured using peripheral Quantitative Computed Tomography (pQCT) to determine bone strength parameters at the 66% radial site (predominantly cortical bone). At the 4% site (trabecular bone site), bone mineral content (vBMC.tb), bone mineral density (vBMD.tb), total area (ToA.tb) and bone strength index (BSIc) were measured. Hierarchical multiple regression analyses determined the relationship of each muscle function test for each bone envelope (cortical and trabecular). For the cortical bone measurements: RGS, and PP were both significantly correlated with CoA, MoI, and SSIp. Peak vertical jump power predicted bone strength parameters to a greater extent compared to RGS. For the trabecular bone envelope, RGS was not a predictor of bone strength however peak power was a significant predictor of bone strength parameters. Peak vertical jump power was a significant predictor of bone strength at both trabecular and cortical radial sites. Interestingly PP, a lower limb measurement explained the most variance in the bone strength of the upper limb.

Changes to bone mineral density, the trabecular bone score and hip structural analysis following parathyroidectomy: a case report

BackgroundReduction in bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) occurs in secondary hyperparathyroidism associated with chronic kidney disease. BMD generally increases following parathyroidectomy, however longitudinal changes to other DXA-derived parameters, the trabecular bone score (TBS) and hip structural analysis (HSA), have not been described. Postoperative calcium requirements and positive calcium balance raise concerns for an increased risk of vascular calcification. This case illustrates the dramatic increase in BMD that can follow parathyroidectomy in a patient on dialysis, and for the first time demonstrates improvements to HSA parameters and to the TBS.Case presentationA 30-year old woman on haemodialysis underwent subtotal parathyroidectomy for secondary hyperparathyroidism. She developed a post-operative ‘hungry bone syndrome’ requiring substantial calcium and calcitriol supplementation. Six months post-parathyroidectomy, BMD increased by 42% at the lumbar spine, 30% at the femoral neck and 25% at the total proximal femur, with increases sustained over the following 18 months. The TBS increased by 8%. HSA showed a 63% increase in femoral neck cortical thickness and 38% reduction in the buckling ratio, consistent with increased femoral neck stability. The abdominal aortic vascular calcification score (0–24) increased from zero 8-years pre-parathyroidectomy to 2/24 at 18-months post-parathyroidectomy.ConclusionBMD losses incurred by secondary hyperparathyroidism recover rapidly after parathyroidectomy, particularly at sites of trabecular bone. Bone architectural parameters, measured as the TBS and by HSA, also improve. Greater BMD gains may be associated with higher post-operative calcium requirements. While bone is the major reservoir for post-parathyroidectomy calcium supplementation, positive calcium balance may contribute to vascular calcification risk.

P196 Predictors of fracture in patients with primary hyperparathyroidism

Abstract Background Primary hyperparathyroidism (PHPT) is a recognised risk factor for fractures as the persistently elevated parathyroid hormone levels are associated with lower bone mineral density (BMD). In early osteoporosis (<65 years), there is mainly trabecular bone loss while with increasing age, the largest loss of absolute bone mass occurs in cortical sites. Our aim was to compare cortical versus trabecular bone sites to determine which sites better predict fracture in PHPT patients referred for dual-energy X-ray absorptiometry (DEXA) scan in an observational cohort. Methods 508 patients with PHPT referred for DEXA scan at Royal Lancaster Infirmary (UK) between 2006-2016 were included in a retrospective data analysis. Data collected included femoral and lumbar BMD, age, gender, height, weight, BMI, rheumatoid arthritis, smoking, alcohol, family history of fractures, secondary osteoporosis and long-term steroid use and was used to look at predictors of fractures using BMD at different sites. Simple statistics using independent t-tests and chi-squared tests were initially used and subsequently, logistic models were fitted unadjusted and adjusted confounding variables. Results 97 males (19%) and 411 females (81%) were included, with 111 patients sustaining at least one fracture (21.9%). Mean age was 65 years (SD 0.55). Advanced age, female gender and a reduced BMD were all statistically significant factors associated with an increased risk of fractures. Smoking and long-term steroid use were also shown to increase risk of fracture however these were non-statistically significant. Adjusting for age and gender, a reduced L4 BMD was the strongest statistically significant predictor of fracture (OR 0.139, 95% CI: 0.112-0.782). Multivariate analysis revealed that a reduced L3 BMD was the strongest statistically significant predictor of fracture (OR 0.170, 95% CI: 0.071-0.72). Conclusion Overall, our study suggests that a reduced BMD at trabecular sites is a stronger predictor of fracture compared to cortical sites [Table 1]. Older age and female gender significantly increased the risk of fracture in PHPT patients. To the best of our knowledge, this is the first study looking at specific bone sites as independent predictors of fracture in PHPT patients. This analysis should be repeated using a larger cohort to validate our results. Disclosures D. Mariannis None. M. Bukhari None.

Alendronate disturbs femoral growth due to changes during immunolocalization of transforming growth factor-β1 and bone morphogenetic protein-2 in epiphyseal plate.

BACKGROUNDThe epiphyseal growth plate is an important anatomical segment localized on the ends of a long bone. Despite the abovementioned atractive reasons for alendronate’s use, few data on the effect of alendronate during epiphyseal growth exist.AIMVerify the effect of alendronate on the growth epiphyseal plate, and compare its effect with the size of the femur during the double-staining of the immunolocalization of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP2) in endochondral ossifing in specimens that have received alendronate.METHODSForty newborn rats were randomly divided into two groups: a control group (were given applications of 1 mg/kg physiologic saline) and a group that received Alendronate (a dose of 2.5 mg/kg). These groups were then divided into two subgroups for euthanasia in two and 12 d of life. After euthanasia, the femurs were removed, and the femoral bones were measured linearly between the apex of the greater trochanter until the lower intercondylar midlle face to verify the probable bone growth between 3 and 12 d in control and alednroanto treated rats. Posteriorly, the surgical pieces were also sent to the histopathology laboratory to produce histological slides. The obtained slides were stained with hematoxylin and eosin to measure each of the cartilage zones in endochondral development. and other slides were immunohistochemically tested for anti- TGF-β1 and BMP-2 antibodies to investigate the immunolocalization of these proteins in the epiphyseal plaque area.RESULTSOn the third day, some diferences between the control group and specimens treated with alendronate were verified. Macroscopiccaly, we found similarities in size between the femoral bones when we compared the control group with the specimens that received alendronate. On the 12th day, the bone size of the mice receiving the drug was significantly smaller than those of the control group. These results coincide with changes in the TGF-β1 and BMP-2 expression. In the specimens that received alendronate, the TGF-β1 was expressed in some sites of trabecular bone that was neoformed, peripherally to the bone marrow area. The BMP-2 was also positive in proliferative chondrocytes and hypertrofic chondrocytes. On the 12th day, all layers of chondrocytes exhibited positivity for BMP-2 in the specimens that received alendronate. In the interface between the trabecular bone and cartilage, an area of disorganized bone deposition was evident. Neoformed bone also appeared to be different at 12 d. In the control group, BMP-2 was positive in an intense area of bone trabeculae, whereas the alendronate-treated group showed TGF-β1 positive trabeculae and a greater bone area.CONCLUSIONAlendronate alters the immunolocalization of TGF-β1 and BMP-2 simultaneously, a condition that changes the usual histological aspects of the cartilage zone and impairs epiphysis growth and femur growth.

An innovative self‐tapping underprepared implant‐ in vivo histologic and histomorphometric analysis

Background The bone site preparation plays a key role in osseointegration development because it allows to obtain an implant bone bed adequately adapted to the implant geometry thus ensuring sufficient primary implant stability without excessive bone compression. Surgical trauma and bone temperature raise during standard drilling procedures are other crucial factors. Recent studies showed improved healing and biomechanics by preserving the bone bulk using osseodensification drills. Aim/Hypothesis The working hypotheses of the present study is that a specifically designed self-tapping implant may be placeed in an extremely underprepared low-density trabecular bone site may achieve the same histologic and biomechanical results as a standard implant placed with adequate preparation. Material and Methods Two female sheep, 4–5 years old, were included in the study. After dissection of the soft tissues, iliac crests were exposed and five osteotomic sites were prepared in each (left and right) side. In the right side of each animal (test group) implant bone sites were prepared using only the pilot drill 1.8 mm in diameter. Ten Expander® 3.8 × 10 mm implants (NoDrill®, Milano, Italy) were inserted. In the left side of each animal (control group) implant bone sites were prepared using the following burs sequence- pilot drill 1.8 mm in diameter, twist drill 2.8 mm in diameter and the final drill 3.2 mm in diameter. Ten 3.8 × 10 mm Dynamix® implants (Cortex, Shlomi, Israel) were used. After 2 months of healing, biomechanical (micromotion under later forces (VAM), reverse torque (RT) and ISQ) and histomorphometrical data (BIC% and BV%) of test and control group were calculated and statistically compared by the T-test. Results No implant failure was recorded. The host bone density (basal %Bone Volume) measured 26.17% ± 2.35%. Implants in the test group showed a bone-to-implant contact percentage (%BIC) of 70.91% ± 7.95%, while control group implants showed a BIC value of 49.33% ± 10.73%. The peri-implant Bone Volume measured 41.83% ± 6.30% in test group and 29.61% ± 5.05% in control group. These parameters were statistically different between the two groups. The biomechanical analysis of secondary implant stability revealed a VAM value of 82.6 ± 23.27 μm in test group and 60.5 ± 16.58 μm in control group. The reverse torque (RT) was 98.2 ± 16.81 N cm in test group and 98.8 ± 24.40 N cm in control one. The condensation phenomenon characterized by a higher bone volume percentage around implant than in the neighboring areas, caused by implant threads geometry, was evident at low magnification. The preservation of the peri-implant bone bulk during drilling procedures resulted in high new bone apposition. Conclusion and Clinical Implications Results from the present study show that it is possible to insert a self-tapping implant using a single drill protocol in low density bone achieving a histologic and biomechanical integration comparable to the standard implants placed using standard drilling sequence. This innovative fixture geometry (coupled with minimum bone removal) was able to achieve higher osseointegration value than control group and to cause a bone corticalization around implant threads.

Site specific measurements of bone formation using [18F] sodium fluoride PET/CT.

Dynamic positron emission tomography (PET) imaging with fluorine-18 labelled sodium fluoride ([18F]NaF) allows the quantitative assessment of regional bone formation by measuring the plasma clearance of fluoride to bone at any site in the skeleton. Today, hybrid PET and computed tomography (CT) dual-modality systems (PET/CT) are widely available, and [18F]NaF PET/CT offers a convenient non-invasive method of studying bone formation at the important osteoporotic fracture sites at the hip and spine, as well as sites of pure cortical or trabecular bone. The technique complements conventional measurements of bone turnover using biochemical markers or bone biopsy as a tool to investigate new therapies for osteoporosis, and has a potential role as an early biomarker of treatment efficacy in clinical trials. This article reviews methods of acquiring and analyzing dynamic [18F]NaF PET/CT scan data, and outlines a simplified approach combining venous blood sampling with a series of short (3- to 5-minute) static PET/CT scans acquired at different bed positions to estimate [18F]NaF plasma clearance at multiple sites in the skeleton with just a single injection of tracer.

A multi-method assessment of bone maintenance and loss in an Imperial Roman population: Implications for future studies of age-related bone loss in the past.

One of the hallmarks of contemporary osteoporosis and bone loss is dramatically higher prevalence of loss and fragility in females post-menopause. In contrast, bioarchaeological studies of bone loss have found a greater diversity of age- and sex-related patterns of bone loss in past populations. We argue that the differing findings may relate to the fact that most studies use only a single methodology to quantify bone loss and do not account for the heterogeneity and complexity of bone maintenance across the skeleton and over the life course. We test the hypothesis that bone mass and maintenance in trabecular bone sites versus cortical bone sites will show differing patterns of age-related bone loss, with cortical bone sites showing sex difference in bone loss that are similar to contemporary Western populations, and trabecular bone loss at earlier ages. We investigated this hypothesis in the Imperial Roman population of Velia using three methods: radiogrammetry of the second metacarpal (N = 71), bone histology of ribs (N = 70), and computerized tomography of trabecular bone architecture (N = 47). All three methods were used to explore sex and age differences in patterns of bone loss. The suite of methods utilized reveal differences in the timing of bone loss with age, but all methods found no statistically significant differences in age-related bone loss. We argue that a multi-method approach reduces the influence of confounding factors by building a reconstruction of bone turnover over the life cycle that a limited single-method project cannot provide. The implications of using multiple methods beyond studies of bone loss are also discussed.

Bone Matrix Composition Following PTH Treatment is Not Dependent on Sclerostin Status.

Sclerostin and parathyroid hormones are strong negative and positive regulators of bone formation, respectively. The anabolic response induced by intermittent (iPTH) treatment is sclerostin status-dependent. However, the interaction between sclerostin and iPTH at the matrix level is unknown. The goal of the current study was to determine if iPTH treatment affects matrix composition and, if so, whether these effects are dependent on sclerostin status. Humeral trabecular and cortical bone sites from 16 week old male wild-type (WT) and sclerostin knockout (KO) mice, which had been treated with vehicle or iPTH from age 10-16 weeks, were examined by micro-computed tomography (µCT) to measure bone volume, backscatter scanning electron microscopy (bSEM) to assess global mineralization, and Fourier transform infrared microspectroscopy (FTIRM) to examine matrix composition (mineral-to-matrix ratio, crystallinity, collagen cross-link ratio, and carbonate substitution). The FTIRM measurements were restricted to the tissue formed during the 6-week treatment period. iPTH treatment led to increased trabecular bone volume (p < 0.001) and this effect was much greater in KO mice than WT mice (interaction effect, p < 0.001). iPTH treatment led to reduced trabecular crystallinity (p = 0.047), increased cortical bone area (p < 0.001), decreased cortical bone crystallinity (p = 0.002) and increased cortical bone collagen cross-linking (p = 0.028) to similar degrees in both WT and KO mice. Compared to WT mice, sclerostin KO mice had higher trabecular and cortical bone mass (p < 0.001) and lower mineral-to-matrix ratio in the trabecular (p = 0.010) and cortical (p = 0.016) compartments. Thus, iPTH-induced changes in bone mass are dependent upon sclerostin status in the trabecular compartment, but not in the cortical compartment. In contrast, iPTH-induced changes in matrix composition are sclerostin-independent in both trabecular and cortical compartments.

Implant design and its effects on osseointegration over time within cortical and trabecular bone

Healing chambers present at the interface between implant and bone have become a target for improving osseointegration. The objective of the present study was to compare osseointegration of several implant healing chamber configurations at early time points and regions of interest within bone using an in vivo animal femur model. Six implants, each with a different healing chamber configuration, were surgically implanted into each femur of six skeletally mature beagle dogs (n = 12 implants per dog, total n = 72). The implants were harvested at 3 and 5 weeks post-implantation, non-decalcified processed to slides, and underwent histomorphometry with measurement of bone-to-implant contact (BIC) and bone area fraction occupied (BAFO) within healing chambers at both cortical and trabecular bone sites. Microscopy demonstrated predominantly woven bone at 3 weeks and initial replacement of woven bone by lamellar bone by 5 weeks. BIC and BAFO were both significantly increased by 5 weeks (p < 0.001), and significantly higher in cortical than trabecular bone (p < 0.001). The trapezoidal healing chamber design demonstrated a higher BIC than other configurations. Overall, a strong temporal and region-specific dependence of implant osseointegration in femurs was noted. Moreover, the findings suggest that a trapezoidal healing chamber configuration may facilitate the best osseointegration. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1091-1097, 2016.

Finite Element Simulation: The Effects of Loading Modes at Different Anatomical Sites of Trabecular Bone on Morphological Indices

The relationship between morphological parameter and different type of loading orientation on elastic behavior and yielding of trabecular may provide insight towards osteoporotic bone losses during normal activities. This paper attempts to predict the elastic and failure behavior of different loading modes (tensile and compression) on anatomic sites and morphological indices through finite element (FE) simulation. Specimens extracted from bovine femoral trabecular bone were imaged using micro computed tomography (μCT). Morphological studies were done followed by FE analysis. Results demonstrated differences between yield behaviors on anatomic sites were reflected onto the morphological indices and the type of loading modes. The yield initiated earlier in rod-like than plate-like trabecular in both loading condition but showed different failure behavior in rod-like trabecular with small differences in maximum stress between tensile and compressive. However, in many cases, trabecular models tend to have oblique fracture pattern in all anatomic sites. Through these findings, improved prediction of elastic properties and yield behavior by computational means provide insight in the development of bone substitute material depending on the anatomic site as well as in osteoporotic bone pathological treatment to monitor losses in trabecular struts.

Trabecular bone deterioration at the greater trochanter of mice with unilateral obstructive nephropathy

Our previous study showed the early molecular responses of bone in response to obstructive nephropathy in a unilateral ureteral obstruction (UUO) mouse model. Here, we addressed the changes in trabecular bone properties at greater trochanter, the proximal and the distal metaphysis of femur in UUO mice. The male mice were subjected to UUO (n=10) or sham operation (n=10). All mice were killed on day 7 after the surgical operation. The micro-computed tomography (micro-CT) analysis for different femoral trabecular bone sites demonstrated pathological alterations of trabecular bone mass and micro-networks at greater trochanter as shown by decreases in bone mineral density/bone volume (P<0.05) and trabecular number (P<0.05) and increases in trabecular separation (P<0.01) and bone surface/bone volume (P<0.05) in UUO mice. The present study demonstrates that UUO-induced unilateral obstructive nephropathy has markedly detrimental effects on the trabecular trochanter of the femur.

A comparison of bone density and bone morphology between patients presenting with hip fractures, spinal fractures or a combination of the two

BackgroundCurrently it is uncertain how to define osteoporosis and who to treat after a hip fracture. There is little to support the universal treatment of all such patients but how to select those most in need of treatment is not clear. In this study we have compared cortical and trabecular bone status between patients with spinal fractures and those with hip fracture with or without spinal fracture with the aim to begin to identify, by a simple clinical method (spine x-ray), a group of hip fracture patients likely to be more responsive to treatment with current antiresorptive agents.MethodsComparison of convenience samples of three groups of 50 patients, one with spinal fractures, one with a hip fracture, and one with both. Measurements consist of bone mineral density at the lumbar spine, at the four standard hip sites, number, distribution and severity of spinal fractures by the method of Genant, cortical bone thickness at the infero-medial femoral neck site, femoral neck and axis length and femoral neck width.ResultsPatients with spinal fractures alone have the most deficient bones at both trabecular and cortical sites: those with hip fracture and no spinal fractures the best at trabecular bone and most cortical bone sites: and those with both hip and spinal fractures intermediate in most measurements. Hip axis length and neck width did not differ between groups.ConclusionThe presence of the spinal fracture indicates poor trabecular bone status in hip fracture patients. Hip fracture patients without spinal fractures have a bone mass similar to the reference range for their age and gender. Poor trabecular bone in hip fracture patients may point to a category of patient more likely to benefit from therapy and may be indicated by the presence of spinal fractures.

Organic nitrates for osteoporosis: an update

The number of osteoporotic fractures is increasing worldwide as populations age. An inexpensive and widely available treatment is necessary to alleviate this increase in fractures. Current treatments decrease fractures at trabecular bone sites (spine) but have limited effects at cortical sites (hip, legs, forearm and upper arm)-the most common sites of osteoporotic fracture. Treatments are also limited by costs, side effects and lack of availability. Nitric oxide (NO) is a novel agent that has the potential to influence cortical bone, is inexpensive, widely available and has limited side effects. In this review, we will evaluate the in vitro and in vivo data that support the concept that NO is important in bone cell function, review the observational, case control and randomized trial data on organic nitrates and the effects of these agents on bone turnover, geometry and strength.

Can Early Onset of Disease Be One of the Risk Factors for Low Bone Mineral Density in Patients with Inflammatory Bowel Disease?

Can Early Onset of Disease Be One of the Risk Factors for Low Bone Mineral Density in Patients with Inflammatory Bowel Disease?

Effect of sclerostin-neutralising antibody on periarticular and systemic bone in a murine model of rheumatoid arthritis: a microCT study

IntroductionPatients with chronic inflammatory diseases have increased bone loss and bone fragility and are at increased risk of fracture. Although anti-resorptive drugs are effective in blocking inflammation-induced bone loss, they are less effective at rebuilding bone. We have previously shown that treatment with sclerostin antibody (Scl-AbI) builds bone and can prevent or restore bone loss in a murine model of inflammatory bowel disease. In this study, we tested the effect of Scl-AbI in a murine model of rheumatoid arthritis (the collagen-induced arthritis model, CIA). We hypothesised that sclerostin blockade can protect and restore bone both locally and systemically without affecting progression of inflammation.MethodsCIA was induced in male DBA/1 mice, which were treated with either PBS or Scl-AbI (10 mg/kg, weekly) prophylactically for 55 days or therapeutically for 21 days (starting 14 days post onset of arthritis). Systemic inflammation was assessed by measuring the serum concentration of anti-CII IgG1, IgG2a and IgG2b by ELISA. Changes in bone mass and structure, either at sites remote from the joints or at periarticular sites, were measured using DEXA and microCT. Bone focal erosion was assessed in microCT scans of ankle and knee joints.ResultsCirculating anti-CII immunoglobulins were significantly elevated in mice with CIA and there were no significant differences in the levels of anti-CII immunoglobulins in mice treated with PBS or Scl-ABI. Prophylactic Scl-AbI treatment prevented the decrease in whole body bone mineral density (BMD) and in the bone volume fraction at axial (vertebral body) and appendicular (tibial proximal metaphysis trabecular and mid-diaphysis cortical bone) sites seen in PBS-treated CIA mice, but did not prevent the formation of focal bone erosions on the periarticular bone in the knee and ankle joints. In the therapeutic study, Scl-AbI restored BMD and bone volume fraction at all assessed sites but was unable to repair focal erosions.ConclusionsSclerostin blockade prevented or reversed the decrease in axial and appendicular bone mass in the murine model of rheumatoid arthritis, but did not affect systemic inflammation and was unable to prevent or repair local focal erosion.

Nitric Oxide Donors for the Treatment of Osteoporosis

The number of osteoporotic fractures is increasing worldwide as populations age. An inexpensive and widely available treatment is necessary to alleviate this increase in fractures. Current treatments decrease fractures at trabecular bone sites (spine) but have limited effects at cortical sites (hip, legs, forearm, and upper arm)-the most common sites of osteoporotic fracture. Treatments are also limited by costs, side effects, and lack of availability. Nitric oxide is a novel agent that has the potential to influence cortical bone, is inexpensive, is widely available, and has limited side effects. In this review we evaluate the in vitro and in vivo data which support the concept that nitric oxide is important in bone cell function, review the observational and case-control studies reporting on subjects taking organic nitrates that act as nitric oxide donors, and review the effects of nitrates on bone mineral density measurements and fracture risk.

Comparisons of trabecular and cortical bone in late adolescent black and white females

Few childhood studies have investigated racial differences in volumetric bone mineral density (vBMD), bone geometry, and bone strength indices measured by three-dimensional bone imaging. The purpose of this study was to compare trabecular and cortical bone parameters at the radius and tibia between late adolescent white and black females using peripheral quantitative computed tomography (QCT). White (n=25) and black females (n=25), 18-19years of age, were pair-matched for age, height, and fat-free soft tissue mass. Peripheral QCT scans were obtained at the 4% (trabecular bone), 20% (cortical bone), and 66% [muscle cross-sectional area (CSA)] sites from the distal metaphyses. Bone strength was determined from vBMD and bone geometry to calculate bone strength index (BSI; trabecular site) and polar strength-strain index (SSI; cortical site). Radial SSI was not different between groups; however, blacks had greater radial BSI (P=0.02) than whites. After adjustment for the longer forearm in blacks, the greater radial BSI in blacks no longer remained. At the tibia, blacks versus whites had greater bone strength at the trabecular and cortical bone sites (BSI, P=0.03; SSI, P=0.04, respectively). When controlling for differences in tibial length and muscle CSA, the higher estimates of bone strength persisted in blacks versus whites (BSI, P=0.01; SSI, P=0.02). Our data suggest that when differences in body size are considered, late adolescent black versus white females have a stronger bone profile, due to greater bone geometry and vBMD, at the trabecular and cortical regions of the tibia but not at the radius.

Reduced physical activity corresponds with greater bone loss at the trabecular than the cortical bone sites in men

Previous research has been inconclusive as to whether high peak bone mineral density (BMD, g/cm 2) resulting from previous physical activity is retained with reduced activity later in life. The aim of this 12-year longitudinal study was to investigate the association between BMD loss and reduced physical activity (h/wk) at trabecular and cortical bone sites in men. Three groups with a mean age of 17 years at baseline were investigated: i) 51 athletes who discontinued their active careers during the follow-up period (former athletes), ii) 16 athletes who were active throughout the follow-up period (active athletes), and iii) 25 controls. BMD loss at the hip, spine, and pelvis (mainly trabecular bone) was compared to BMD loss at femur, humerus, and legs (mainly cortical bone) during a 12-year follow-up period. Across the total follow-up period in the total cohort, reduced physical activity was more strongly associated with changes at trabecular BMD sites, i.e. hip, spine, and pelvis ( B = 0.008–0.005 g/cm 2 per weekly hour physical activity (h), p < 0.001), than at cortical bone sites, i.e. humerus, legs ( B = 0.002–0.003 g/cm 2/h, p < 0.05), and femur ( p > 0.05). At the final follow-up, former athletes showed higher BMD than controls only at the cortical bone sites of the humerus, legs, and femur (difference 0.05–0.10 g/cm 2, p < 0.05). In conclusion, this study indicates that predominantly trabecular bone is lost with reduced physical activity levels in young men. Benefits were still evident at the more cortical sites eight years after the discontinuation of an active sports career.

Prolonged Treatments With Antiresorptive Agents and PTH Have Different Effects on Bone Strength and the Degree of Mineralization in Old Estrogen-Deficient Osteoporotic Rats

Current approved medical treatments for osteoporosis reduce fracture risk to a greater degree than predicted from change in BMD in women with postmenopausal osteoporosis. We hypothesize that bone active agents improve bone strength in osteoporotic bone by altering different material properties of the bone. Eighteen-month-old female Fischer rats were ovariectomized (OVX) or sham-operated and left untreated for 60 days to induce osteopenia before they were treated with single doses of either risedronate (500 μg/kg, IV), zoledronic acid (100 μg/kg, IV), raloxifene (2 mg/kg, PO, three times per week), hPTH(1-34) (25 μg/kg, SC, three times per week), or vehicle (NS; 1 ml/kg, three times per week). Groups of animals were killed after days 60 and 180 of treatment, and either the proximal tibial metaphysis or lumbar vertebral body were studied. Bone volume and architecture were assessed by μCT and histomorphometry. Measurements of bone quality included the degree of bone mineralization (DBM), localized elastic modulus, bone turnover by histomorphometry, compression testing of the LVB, and three-point bending testing of the femur. The trabecular bone volume, DBM, elastic modulus, and compressive bone strength were all significantly lower at day 60 post-OVX (pretreatment, day 0 study) than at baseline. After 60 days of all of the bone active treatments, bone mass and material measurements agent were restored. However, after 180 days of treatment, the OVX + PTH group further increased BV/TV (+30% from day 60, p < 0.05 within group and between groups). In addition, after 180 days of treatment, there was more highly mineralized cortical and trabecular bone and increased cortical bone size and whole bone strength in OVX + PTH compared with other OVX + antiresorptives. Treatment of estrogen-deficient aged rats with either antiresorptive agents or PTH rapidly improved many aspects of bone quality including microarchitecture, bone mineralization, turnover, and bone strength. However, prolonged treatment for 180 days with PTH resulted in additional gains in bone quality and bone strength, suggesting that the maximal gains in bone strength in cortical and trabecular bone sites may require a longer treatment period with PTH.