Prunes preserve cortical density and estimated strength of the tibia in a 12-month randomized controlled trial in postmenopausal women: The Prune Study.

Non-pharmacological therapies, such as whole-food interventions, are gaining interest as potential approaches to prevent and/or treat low bone mineral density (BMD) in postmenopausal women. Previously, prune consumption preserved two-dimensional BMD at the total hip. Here we demonstrate that prune consumption preserved three-dimensional BMD and estimated strength at the tibia. PURPOSE: Dietary consumption of prunes has favorable impacts on areal bone mineral density (aBMD); however, more research is necessary to understand the influence on volumetric BMD (vBMD), bone geometry, and estimated bone strength. METHODS: This investigation was a single center, parallel arm 12-month randomized controlled trial (RCT; NCT02822378) to evaluate the effects of 50 g and 100 g of prunes vs. a Control group on vBMD, bone geometry, and estimated strength of the radius and tibia via peripheral quantitative computed tomography (pQCT) in postmenopausal women. Women (age 62.1 ± 5.0yrs) were randomized into Control (n = 78), 50 g Prune (n = 79), or 100 g Prune (n = 78) groups. General linear mixed effects (LME) modeling was used to assess changes over time and percent change from baseline was compared between groups. RESULTS: The most notable effects were observed at the 14% diaphyseal tibia in the Pooled (50 g + 100 g) Prune group, in which group × time interactions were observed for cortical vBMD (p = 0.012) and estimated bone strength (SSI; p = 0.024); all of which decreased in the Control vs. no change in the Pooled Prune group from baseline to 12 months/post. CONCLUSION: Prune consumption for 12 months preserved cortical bone structure and estimated bone strength at the weight-bearing tibia in postmenopausal women.

A new hip fracture risk index derived from FEA-computed proximal femur fracture loads and energies-to-failure.

Hip fracture risk assessment is an important but challenging task. Quantitative CT-based patient-specific finite element (FE) analysis (FEA) incorporates bone geometry and bone density in the proximal femur. We developed a global FEA-computed fracture risk index to increase the prediction accuracy of hip fracture incidence. PURPOSE: Quantitative CT-based patient-specific finite element (FE) analysis (FEA) incorporates bone geometry and bone density in the proximal femur to compute the force (fracture load) and energy necessary to break the proximal femur in a particular loading condition. The fracture loads and energies-to-failure are individually associated with incident hip fracture, and provide different structural information about the proximal femur. METHODS: We used principal component analysis (PCA) to develop a global FEA-computed fracture risk index that incorporates the FEA-computed yield and ultimate failure loads and energies-to-failure in four loading conditions of 110 hip fracture subjects and 235 age- and sex-matched control subjects from the AGES-Reykjavik study. Using a logistic regression model, we compared the prediction performance for hip fracture based on the stratified resampling. RESULTS: We referred the first principal component (PC1) of the FE parameters as the global FEA-computed fracture risk index, which was the significant predictor of hip fracture (p-value < 0.001). The area under the receiver operating characteristic curve (AUC) using PC1 (0.776) was higher than that using all FE parameters combined (0.737) in the males (p-value < 0.001). CONCLUSIONS: The global FEA-computed fracture risk index increased hip fracture risk prediction accuracy in males.

The relationship between bone strain index, bone mass, microarchitecture and mechanical behavior in human vertebrae: an ex vivo study.

The aim of this study was to determine whether the Bone Strain Index (BSI), a recent DXA-based bone index, is related to bone mechanical behavior, microarchitecture and finally, to determine whether BSI improves the prediction of bone strength and the predictive role of BMD in clinical practice. PURPOSE: Bone Strain Index (BSI) is a new DXA-based bone index that represents the finite element analysis of the bone deformation under load. The current study aimed to assess whether the BSI is associated with 3D microarchitecture and the mechanical behavior of human lumbar vertebrae. METHODS: Lumbar vertebrae (L3) were harvested fresh from 31 human donors. The anteroposterior BMC (g) and aBMD (g/cm2) of the vertebral body were measured using DXA, and then the BSI was automatically derived. The trabecular bone volume (Tb.BV/TV), trabecular thickness (Tb.Th), degree of anisotropy (DA), and structure model index (SMI) were measured using µCT with a 35-µm isotropic voxel size. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies under displacement control to assess failure load and stiffness. RESULTS: The BSI was significantly correlated with failure load and stiffness (r = -0.60 and -0.59; p < 0.0001), aBMD and BMC (r = -0.93 and -0.86; p < 0.0001); Tb.BV/TV and SMI (r = -0.58 and 0.51; p = 0.001 and 0.004 respectively). After adjustment for aBMD, the association between BSI and stiffness, BSI and SMI remained significant (r = -0.51; p = 0.004 and r = -0.39; p = 0.03 respectively, partial correlations) and the relation between BSI and failure load was close to significance (r = -0.35; p = 0.06). CONCLUSION: The BSI was significantly correlated with the microarchitecture and mechanical behavior of L3 vertebrae, and these associations remained statistically significant regardless of aBMD.

Vertebral Fracture Risk Thresholds from Phantom-Less Quantitative Computed Tomography-Based Finite Element Modeling Correlate to Phantom-Based Outcomes.

INTRODUCTION: Osteoporosis indicates weakened bones and heightened fracture susceptibility due to diminished bone quality. Dual-energy x-ray absorptiometry is unable to assess bone strength. Volumetric bone mineral density (vBMD) from quantitative computed tomography (QCT) has been used to establish guidelines as equivalent measurements for osteoporosis. QCT-based finite element analysis (FEA) has been implemented using calibration phantoms to establish bone strength thresholds based on the established vBMD. The primary aim was to validate vertebral failure load thresholds using a phantom-less approach with previously established thresholds, advancing a phantom-free approach for fracture risk prediction. METHODOLOGY: A controlled cohort of 108 subjects (68 females) was used to validate sex-specific vertebral fracture load thresholds for normal, osteopenic, and osteoporotic subjects, obtained using a QCT/FEA-based phantom-less calibration approach and two material equations. RESULTS: There were strong prediction correlations between the phantom-less and phantom-based methods (R2: 0.95 and 0.97 for males, and R2: 0.96 and 0.98 for females) based on the two equations. Bland Altman plots and paired t-tests showed no significant differences between methods. Predictions for bone strengths and thresholds using the phantom-less method matched those obtained using the phantom calibration and those previously established, with ≤4500 N (fragile) and ≥6000 N (normal) bone strength in females, and ≤6500 N (fragile) and ≥8500 N (normal) bone strength in males. CONCLUSION: Phantom-less QCT-based FEA can allow for prospective and retrospective studies evaluating incidental vertebral fracture risk along the spine and their association with spine curvature and/or fracture etiology. The findings of this study further supported the application of phantom-less QCT-based FEA modeling to predict vertebral strength, aiding in identifying individuals prone to fractures. This reinforces the rationale for adopting this method as a comprehensive approach in predicting and managing fracture risk.

Mechanical Stress Via Muscle Contractile Exercise Suppresses Atrophic Alterations of Bone-microstructure in Immobilized Rat Femurs.

OBJECTIVES: This study aimed to determine whether mechanical stress via muscle contractile exercise with belt electrode-skeletal muscle electrical stimulation (B-SES) device effectively prevents immobilization-induced bone atrophy. METHODS: Wistar rats were randomly divided into the control (CON) group, immobilization (IM) group (immobilized treatment only), HES and LES groups (immobilized treatment and high or low-intensity electrical muscular stimulation through B-SES device). Bilateral femurs were used for X-ray micro-CT and biomechanical tests. RESULTS: The maximum load value was significantly lower in the IM and HES groups than in the CON group and significantly higher in the LES group than in the IM group. The maximum crushing load was significantly lower in the IM, HES, and LES groups than in the CON group, and significantly higher in the HES and LES groups than that in the IM group. In micro-CT, the mechanical stress by B-SES device did not affect degenerative microstructural changes in the cortical bone, but prevented those changes in the cancellous bone. CONCLUSIONS: Applying mechanical stress via B-SES device suppressed the loss of cancellous bone density and degenerative microstructural changes caused by immobilization, which in turn suppressed the reduction of bone strength. From these findings, muscle contractile exercise may be effective in preventing immobilization-induced bone atrophy.

Exercise training and bone mineral density in postmenopausal women: an updated systematic review and meta-analysis of intervention studies with emphasis on potential moderators.

The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the corresponding implication of bone and menopausal status or supervision in postmenopausal women. A comprehensive search of eight electronic databases according to the PRISMA statement up to August 9, 2022, included controlled exercise trials ≥ 6 months. BMD changes (standardized mean differences: SMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) were considered as outcomes. Study group comparisons were conducted for osteopenia/osteoporosis versus normal BMD, early versus late postmenopausal women, and predominantly supervised versus predominantly non-supervised study arms. We applied an inverse heterogeneity (IVhet) model. In summary, 80 studies involving 94 training and 80 control groups with a pooled number of 5581 participants were eligible. The IVhet model determined SMDs of 0.29 (95% CI: 0.16-0.42), 0.27 (95% CI: 0.16-0.39), and 0.41 (95% CI: 0.30-0.52) for LS, FN, and THBMD, respectively. Heterogeneity between the trial results varied from low (I2 = 20%, TH BMD) to substantial (I2 = 68%, LS-BMD). Evidence for publication bias/small study effects was negligibly low (FN-, TH-BMD) to high (LSBMD). We observed no significant differences (p > .09) for exercise effects on LS-, FN-, or TH-BMD-LS between studies/study arms with or without osteopenia/osteoporosis, early versus late postmenopausal women, or predominantly supervised versus non-supervised exercise programs. Using robust statistical methods, the present work provides further evidence for a positive effect of exercise on BMD in postmenopausal women. Differences in bone status (osteopenia/osteoporosis versus normal bone), menopausal status (early versus late postmenopausal), and supervision (yes versus no) did not significantly affect the exercise effects on BMD at LS or proximal femur.

Zoledronic acid after spinal cord injury mitigates losses in proximal femoral strength independent of ambulation ability.

Rapid bone loss can occur after spinal cord injury (SCI) and a standard of care to prevent or treat this phenomenon is an active area of research. Using advanced analysis techniques, this study demonstrates that zoledronic acid, a possible treatment, prevented loss of bone strength at the hip following SCI. INTRODUCTION: Bone loss below the level of neurological lesion is a well-known complication of spinal cord injury (SCI), and effective preventive treatment for this phenomenon is an active area of research. Zoledronic acid has demonstrated efficacy to attenuate bone loss at the hip after SCI, but previous studies relied on measurements from dual-energy X-ray absorptiometry. The purpose of this investigation was to more thoroughly characterize changes to bone mineral and strength at the proximal femur in individuals receiving zoledronic acid in the acute SCI stage; we also examined the influence of ambulatory ability on bone outcomes. METHODS: Participants randomized to either zoledronic acid (n = 29) or placebo (n = 30) received computed tomography (CT) scans and ambulatory assessments at baseline and 6 and 12 months following drug infusion. CT-based finite element (FE) modeling was used to predict changes in proximal femoral strength associated with treatment. RESULTS: After 12 months, FE-predicted bone strength was reduced by a mean (SD) of 9.6 (17.9)% in the zoledronic acid group versus 24.6 (24.5)% in the placebo group (p = 0.007). These differences in strength were explained by reductions in CT measurements of both trabecular (p < 0.001) and cortical (p ≤ 0.021) bone at the femoral neck and trochanteric region. Ambulation ability influenced select trabecular and cortical parameters, but we were unable to detect an impact on FE-predicted bone strength. CONCLUSION: These findings demonstrate that treatment with zoledronic acid in acute SCI attenuates losses in proximal femoral strength, which may reduce the risk of hip fractures across patients with varying degrees of ambulatory abilities.

SHP-1 Protein Tyrosine Phosphatase Affects Early Postnatal Bone Development in Mice.

The Src homology region 2 domain-containing phosphatase-1 (SHP-1) is an intracellular tyrosine phosphatase that plays a negative regulatory role in immune cell signaling. Absent or diminished SHP-1 catalytic activity results in reduced bone mass with enhanced bone resorption. Here, we sought to investigate if Shp1 overexpression leads to increased bone mass and improved mechanical properties. Male and female wildtype (WT) and SHP1-transgenic (Tg) mice at 28, 56, and 84 days of age were compared. We applied microcomputed tomography to assess femoral cortical bone geometry and trabecular architecture and 3-point mechanical bending to assess mid-diaphyseal structural and estimated material properties. Serum OPG, RANKL, P1NP, and CTX-1 concentrations were measured by enzyme-linked immunoassay. The majority of transgene effects were restricted to the 28-day-old mice. Trabecular bone volume per total volume, trabecular number, and connectivity density were greater in 28-day-old female SHP1-Tg mice when compared to WTs. SHP1-Tg female mice showed increased total and medullary areas, with no difference in cortical area and thickness. Cortical tissue mineral density was strongly genotype-dependent. Failure load, yield load, ultimate stress, and yield stress were all lower in 28-day-old SHP1-Tg females. In 28-day-old SHP1-Tg females, circulating levels of OPG and P1NP were higher and RANKL levels were lower than WT controls. Our study demonstrates a role for SHP-1 in early postnatal bone development; SHP-1 overexpression negatively impacted whole bone strength and material properties in females.

Evaluation of Volumetric Bone Mineral Density, Bone Microarchitecture, and Bone Strength in Patients with Achondroplasia Caused by FGFR3 c.1138G > A Mutation.

Achondroplasia (ACH) is a skeletal disorder caused by fibroblast growth factor receptor 3 (FGFR3) variants. Volumetric bone mineral density (vBMD), bone microarchitecture, and strength have not been evaluated in these patients previously. This study aims to evaluate vBMD, bone microarchitecture, and strength in ACH patients. Seventeen patients underwent clinical and biochemical evaluations, and genetic testing. High-resolution peripheral quantitative computed tomography was performed in 10 ACH patients and 21 age- and sex-matched healthy subjects. All individuals had the hotspot mutation of c.1138G > A in FGFR3. Linear growth retardation, disproportionate short stature, and genu varum are the most common manifestations. The mean height was 108.82 ± 24.08 cm (Z score: - 5.72 ± 0.96). Total vBMD in the ACH and the control groups was 427.08 ± 49.29 mg HA/cm3 versus 300.35 ± 69.92 mg HA/cm3 (p < 0.001) at the radius and 336.90 ± 79.33 mg HA/cm3 versus 292.20 ± 62.35 mg HA/cm3 (p = 0.098) at the tibia; both at the radius and tibia, vBMD of trabecular bones was significantly lower in the ACH group than in the control group, but vBMD of cortical bones was slightly higher in the ACH group. Trabecular separation and cortical thickness in the ACH group were significantly higher than those in the control group, but trabecular number was significantly decreased in the ACH group. Stiffness and failure load were only better at the radius in the ACH group. ACH patients have higher total and cortical vBMD, lower trabecular vBMD, worse trabecular bone microarchitecture, thicker cortical bone thickness, and better estimated bone strength.

Bone Microarchitecture and Strength Changes During Teriparatide and Zoledronic Acid Treatment in a Patient with Pregnancy and Lactation-Associated Osteoporosis with Multiple Vertebral Fractures.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis, of which the pathogenesis and best treatment options are unclear. In this report, we describe the case of a 34-year old woman diagnosed with severe osteoporosis and multiple vertebral fractures after her first pregnancy, who was subsequently treated with teriparatide (TPTD) and zoledronic acid (ZA). We describe the clinical features, imaging examination, and genetic analysis. Substantial improvements were observed in areal and volumetric bone mineral density (BMD), microarchitecture, and strength between 7 and 40 months postpartum as assessed by dual-energy X-ray absorptiometry at the total hip and spine and by high-resolution peripheral quantitative CT at the distal radius and tibiae. At the hip, spine, and distal radius, these improvements were mainly enabled by treatment with TPTD and ZA, while at the distal tibiae, physiological recovery and postpartum physiotherapy due to leg pain after stumbling may have played a major role. Additionally, the findings show that, despite the improvements, BMD, microarchitecture, and strength remained severely impaired in comparison with healthy age- and gender-matched controls at 40 months postpartum. Genetic analysis showed no monogenic cause for osteoporosis, and it is suggested that PLO in this woman could have a polygenic origin with possible susceptibility based on familiar occurrence of osteoporosis.

Bone-specific physical activity questionnaire-derived skeletal loading score predicts bone geometry, density, and strength indices: a cross-sectional study.

INTRODUCTION: The bone-specific physical activity questionnaire (BPAQ) provides a bone-relevant index of physical activity participation according to the mechanical loads experienced across the life span. MATERIALS AND METHODS: We aimed to examine relationships between historical bone-relevant physical activity and pQCT-derived parameters of bone strength. We recruited 532 healthy volunteers (277 males, 255 females) across a broad age range (4-97 years). Peripheral quantitative computed tomography (XCT-3000, Stratec, Germany) was used to examine volumetric bone density, area, and strength indices of the non-dominant tibia and radius. Exercise loading history from birth was determined using the past BPAQ (pBPAQ) score. Pearson correlation analysis was used to examine relationships between pBPAQ scores and pQCT parameters. RESULTS: Independent of sex, pBPAQ scores were associated with total density at the 38% and 66% tibial sites and the 66% radial site (r = 0.145-0.261, p ˂ 0.05), total area at the 38% tibial site and 4% and 66% radial sites (r = 0.129-0.156, p ˂ 0.05), and strength indices at all measured sites (r = 0.123-0.234, p < 0.05). CONCLUSION: We conclude that, independent of sex, historical bone-relevant physical activity is associated with pQCT-derived indices of bone strength, indicating that pBPAQ captures the characteristics of bone loading history that are likely to be relevant adaptive stimuli. A larger sample is required to examine the influence of age on this relationship.

The Utility of Preclinical Models in Understanding the Bone Health of Transgender Individuals Undergoing Gender-Affirming Hormone Therapy.

PURPOSE OF REVIEW: To summarise the evidence regarding the effects of gender-affirming hormone therapy (GAHT) on bone health in transgender people, to identify key knowledge gaps and how these gaps can be addressed using preclinical rodent models. RECENT FINDINGS: Sex hormones play a critical role in bone physiology, yet there is a paucity of research regarding the effects of GAHT on bone microstructure and fracture risk in transgender individuals. The controlled clinical studies required to yield fracture data are unethical to conduct making clinically translatable preclinical research of the utmost importance. Novel genetic and surgical preclinical models have yielded significant mechanistic insight into the roles of sex steroids on skeletal integrity. Preclinical models of GAHT have the potential inform clinical approaches to preserve skeletal integrity and prevent fractures in transgender people undergoing GAHT. This review highlights the key considerations required to ensure the information gained from preclinical models of GAHT are informative.

Bone Quality in Competitive Athletes: A Systematic Review.

The study objective was to assess bone quality measured by high resolution peripheral quantitative computed tomography (HR-pQCT) in competitive athletes. Medline, EMBASE and Sport Discus were searched through May 2022. Prior to submission, a follow-up database search was performed (January 2023). Studies of competitive athletes using HR-pQCT to assess bone quality were included. Athletes were aged between 14 and 45 years. Data extraction included study design and location (country), skeletal imaging modality and site, bone variables and any additional musculoskeletal-related outcome. Information identifying sports and athletes were also extracted. This review included 14 manuscripts and a total of 928 individuals (male: n=75; female: n=853). Athletes comprised 78% (n=722) of the included individuals and 93% of athletes were female. Assessment scores indicate the studies were good to fair quality. The athletes included in this review can be categorized into three groups: 1) healthy athletes, 2) athletes with compromised menstrual function (e.g., amenorrhoea), and 3) athletes with compromised bone health (e.g., bone stress injuries). When assessing bone quality using HR-pQCT, healthy competitive athletes had denser, stronger and larger bones with better microarchitecture, compared with controls. However, the same cannot be said for athletes with amenorrhoea or bone stress injuries.

The role of microscopic properties on cortical bone strength of femoral neck.

BACKGROUND: Femoral neck fractures are serious consequence of osteoporosis (OP), numbers of people are working on the micro-mechanisms of femoral neck fractures. This study aims to investigate the role and weight of microscopic properties on femoral neck maximum load (Lmax), funding the indicator which effects Lmax most. METHODS: A total of 115 patients were recruited from January 2018 to December 2020. Femoral neck samples were collected during the total hip replacement surgery. Femoral neck Lmax, micro-structure, micro-mechanical properties, micro-chemical composition were all measured and analyzed. Multiple linear regression analyses were performed to identify significant factors that affected the femoral neck Lmax. RESULTS: The Lmax, cortical bone mineral density (cBMD), cortical bone thickness (Ct. Th), elastic modulus, hardness and collagen cross-linking ratio were all significantly decreased, whereas other parameters were significantly increased during the progression of OP (P < 0.05). In micro-mechanical properties, elastic modulus has the strongest correlation with Lmax (P < 0.05). The cBMD has the strongest association with Lmax in micro-structure (P < 0.05). In micro-chemical composition, crystal size has the strongest correlation with Lmax (P < 0.05). Multiple linear regression analysis showed that elastic modulus was most strongly related to Lmax (ß = 0.920, P = 0.000). CONCLUSIONS: Compared with other parameters, elastic modulus has the greatest influence on Lmax. Evaluation of microscopic parameters on femoral neck cortical bone can clarify the effects of microscopic properties on Lmax, providing a theoretical basis for the femoral neck OP and fragility fractures.

Transcriptome profile reveals novel candidate genes associated with bone strength in end-of-lay hens.

Bone weakness causes many problems such as osteoporosis, bone fractures, and economic loss, especially at the late stage of lay, in laying hen production. However, the genetic factors and molecular mechanism affecting the bone strength is still largely unknown. To elucidate the molecular mechanism and genetic factors affecting bone strength, a total of six cDNA libraries were constructed and used to compare genetic differences between tibia with higher（Group HBS）and lower（Group LBS）breaking strength in Hyline grey layers. A comparison between Groups HBS and LBS revealed nine differentially expressed genes, of which five were upregulated and four were downregulated in the LBS relative to the HBS in tibia. Our results showed novel candidate genes concerned with bone strength in the late laying period. These include transcription factor paired box protein Pax-5 (Pax5), tissue inhibitor of Metallopoteinase-4 (TIMP4), Kelch-like protein 14 (KLHL14), predicted MAGUK p55 subfamily member 7 isoform X4 (MPP7) and Osteoclast-associated Ig-like receptor (OSCAR). Our data provide a vital resource for discovering important candidate genes associated with bone strength and will help further study the molecular mechanisms for bone remodeling.

Bone adaptation and osteoporosis prevention in hibernating mammals.

Hibernating bears and rodents have evolved mechanisms to prevent disuse osteoporosis during the prolonged physical inactivity that occurs during hibernation. Serum markers and histological indices of bone remodeling in bears indicate reduced bone turnover during hibernation, which is consistent with organismal energy conservation. Calcium homeostasis is maintained by balanced bone resorption and formation since hibernating bears do not eat, drink, urinate, or defecate. Reduced and balanced bone remodeling protect bear bone structure and strength during hibernation, unlike the disuse osteoporosis that occurs in humans and other animals during prolonged physical inactivity. Conversely, some hibernating rodents show varying degrees of bone loss such as osteocytic osteolysis, trabecular loss, and cortical thinning. However, no negative effects of hibernation on bone strength in rodents have been found. More than 5000 genes in bear bone tissue are differentially expressed during hibernation, highlighting the complexity of hibernation induced changes in bone. A complete picture of the mechanisms that regulate bone metabolism in hibernators still alludes us, but existing data suggest a role for endocrine and paracrine factors such as cocaine- and amphetamine-regulated transcript (CART) and endocannabinoid ligands like 2-arachidonoyl glycerol (2-AG) in decreasing bone remodeling during hibernation. Hibernating bears and rodents evolved the capacity to preserve bone strength during long periods of physical inactivity, which contributes to their survival and propagation by allowing physically activity (foraging, escaping predators, and mating) without risk of bone fracture following hibernation. Understanding the biological mechanisms regulating bone metabolism in hibernators may inform novel treatment strategies for osteoporosis in humans.

Maintenance of increased bone mass after PTH withdrawal by sequential medicarpin treatment via augmentation of cAMP-PKA pathway.

Osteoporosis is a metabolic bone disorder associated with impaired bone microarchitecture leading to fragility fractures. Long-term usage of parathyroid hormone (PTH) enhances bone resorption and leads to osteosarcoma in rats which limits its exposure to maximum 2 years in human. Notably, the anabolic effects of PTH do not endure in the absence of sustained administration. Studies in our lab identified osteogenic and antiresorptive activity in medicarpin, a phytoestrogen belonging to the pterocarpan class. Considering dual-acting property of medicarpin and limitations of PTH therapy, we envisaged that medicarpin sequential treatment after PTH withdrawal could serve as promising therapeutic approach for osteoporosis treatment. As PTH exerts its bone anabolic effect by increasing osteoblast survival, our study aims to determine whether medicarpin amplifies this effect of PTH. Our results show that PTH withdrawal led to reduced bone mineral density and bone parameters, while sequential treatment of medicarpin after PTH withdrawal significantly enhanced these parameters. Remarkably, these effects were more pronounced than 8-week PTH treatment. Sequential therapy also significantly increased P1NP levels and decreased CTX levels and TRAP positive cells compared to PTH 8W group where CTX levels were quite high due to bone resorptive action of PTH. Protein expression studies revealed that medicarpin along with PTH betters the antiapoptotic potential compared to PTH alone, through augmentation of cyclic adenosine monophosphate-PKA-CREB pathway. These results proclaim that medicarpin sequential treatment prevented the reduction in bone accrual and strength accompanying PTH withdrawal and also aided in antiapoptotic role of PTH. The study points toward the potential use of medicarpin as a replacement therapeutic option postdiscontinuation of PTH.

Is it important to achieve physical activity recommendations at early stages of life to improve bone health?

Research in bone health during childhood is limited and important to prevent future diseases, particularly, osteoporosis. Bone parameters using DXA and pQCT in 295 Spanish children were evaluated and we found a benefit of meeting the World Health Organization physical activity recommendations in bone composition in childhood. PURPOSE: To investigate the association between physical activity (PA) and bone health in a Spanish paediatric cohort, considering the influence of meeting/not meeting the current World Health Organization (WHO) PA recommendations and to elucidate if there are differences between boys and girls. METHODS: In a cohort of children born in the region of Aragon (Spain) in 2009, followed until the age of 7 years, bone parameters were assessed using dual-energy X-ray absorptiometry (DXA) (whole body scan) and peripheral quantitative computed tomography (pQCT) (tibia scanned at the 8% (distal) and 38% (diaphyseal) of the total tibia length) in 295 7-year-old children (154 boys) in the last evaluation performed between 2016 and 2017. PA was assessed using GT3X Actigraph accelerometers. RESULTS: Boys had significantly higher areal bone mineral density (aBMD), higher total bone mineral content (BMC) at the diaphyseal site and higher trabecular BMC and vBMD, and higher total bone area at the distal site than girls (p<0.01 for all of them). Both boys and girls complying with the WHO PA recommendations had significantly higher trabecular BMC than their inactive counterparts. CONCLUSIONS: Meeting WHO PA recommendations has a beneficial effect in bone composition in childhood both in boys and in girls.

Age-related reference data of bone microarchitecture, volumetric bone density, and bone strength parameters in a population of healthy Brazilian men: an HR-pQCT study.

In a cross-sectional cohort of 340 healthy Brazilian men aged 20 to 92 years, data on density, structure, and strength of the distal radius and tibia were obtained using high-resolution peripheral quantitative computed tomography (HR-pQCT) to develop age- and site-specific reference curves. Age-dependent changes differed between the sites and bone compartments (trabecular and cortical). INTRODUCTION: The aim of this study was to establish age-related reference curves for bone densities, microarchitectural properties, and estimated failure load measured by HR-pQCT (distal radius and tibia) in men. Also, to correlate bone stiffness with the other HR-pQCT parameters, areal bone mineral density (BMD) by DXA and trabecular bone score (TBS). METHODS: Healthy Brazilian men (n = 340) between the ages of 20 and 92 years were recruited. Non-dominant radius and left tibia were scanned using HR-pQCT (Xtreme CT I). Standard and automated segmentation methods were performed, and bone strength estimated by FE analysis. Bone mineral density at lumbar spine, total hip, femoral neck, and TBS were measured using DXA (Hologic, QDR4500). RESULTS: Age-related reference curves were constructed at the distal radius and tibia for volumetric bone density, morphometry, and estimated bone strength parameters. There was a linear relationship with age only for thickness measurements of distal radius (trabecular: R2 0.108, p<0.001; cortical: R2 0.062, p=0.002) and tibia (trabecular: R2 0.109, p<0.001; cortical: R2 0.063, p=0.010), and bone strength at distal radius (R2 0.157, p<0.001). The significant correlations (p <0.05) found by Pearson's correlations (r) between bone stiffness and all other variables measured by HR-pQCT and DXA showed to be stronger at the tibia site than the distal radius. CONCLUSION: The current study expands the HR-pQCT worldwide database and presents an adequate methodology for the construction of reference data in other populations. Moreover, the correlation of bone strength estimated by FEA with other bone microstructural parameters provided by HR-pQCT helps to determine the contribution of each of these variables to fracture risk prediction in men.

Bone material strength index as measured by in vivo impact microindentation is normal in subjects with high-energy trauma fractures.

Bone material properties were assessed using impact microindentation in patients with high-energy trauma fractures. Compared to patients with low-energy trauma fractures, bone material strength index was significantly higher in patients with high-energy trauma fractures, and did not differ between patients with osteopenia and those with osteoporosis within each trauma group. INTRODUCTION: Impact microindentation (IMI) is a technique to assess tissue-level properties of bone at the tibia. Bone material strength index (BMSi), measured by IMI, is decreased in patients with low-energy trauma fractures, independently of areal bone mineral density (aBMD), but there is no information about BMSi in patients with high-energy trauma fractures. In the present study, we evaluated tissue-level properties of bone with IMI in patients with high-energy trauma fractures. METHODS: BMSi was measured 3.0 months (IQR 2.0-5.8) after the fracture in 40 patients with high-energy trauma and 40 age- and gender-matched controls with low-energy trauma fractures using the OsteoProbe® device. RESULTS: Mean age of high- and low-energy trauma patients was 57.7 ± 9.1 and 57.2 ± 7.7 years, respectively (p = 0.78). Fracture types were comparable in high- vs low-energy trauma patients. Lumbar spine (LS)-aBMD, but not femoral neck (FN)-aBMD, was higher in high- than in low-energy trauma patients (LS 0.96 ± 0.13 vs 0.89 ± 0.13 g/cm2, p = 0.02; FN 0.75 ± 0.09 vs 0.72 ± 0.09 g/cm2, p = 0.09). BMSi was significantly higher in high- than in low-energy trauma patients (84.4 ± 5.0 vs 78.0 ± 4.6, p = 0.001), also after adjusting for aBMD (p = 0.003). In addition, BMSi did not differ between patients with osteopenia and those with osteoporosis within each trauma group. CONCLUSION: Our data demonstrate that BMSi and LS-aBMD, but not FN-aBMD, are significantly higher in high-energy trauma patients compared to matched controls with similar fractures from low-energy trauma. Further studies of non-osteoporotic patients with high-energy trauma fracture with measurements of BMSi are warranted to determine whether IMI might help in identifying those with reduced bone strength.