Am I big boned? Bone length scaled reference data for HRpQCT measures of the radial and tibial diaphysis in White adults.

Cross-sectional size of a long bone shaft influences its mechanical properties. We recently used high-resolution peripheral quantitative computed tomography (HRpQCT) to create reference data for size measures of the radial and tibial diaphyses. However, data did not take into account the impact of bone length. Human bone exhibits relatively isometric allometry whereby cross-sectional area increases proportionally with bone length. The consequence is that taller than average individuals will generally have larger z-scores for bone size outcomes when length is not considered. The goal of the current work was to develop a means of determining whether an individual's cross-sectional bone size is suitable for their bone length. HRpQCT scans performed at 30 % of bone length proximal from the distal end of the radius and tibia were acquired from 1034 White females (age = 18.0 to 85.3 y) and 392 White males (age = 18.4 to 83.6 y). Positive relationships were confirmed between bone length and cross-sectional areas and estimated mechanical properties. Scaling factors were calculated and used to scale HRpQCT outcomes to bone length. Centile curves were generated for both raw and bone length scaled HRpQCT data using the LMS approach. Excel-based calculators are provided to facilitate calculation of z-scores for both raw and bone length scaled HRpQCT outcomes. The raw z-scores indicate the magnitude that an individual's HRpQCT outcomes differ relative to expected sex- and age-specific values, with the scaled z-scores also considering bone length. The latter enables it to be determined whether an individual or population of interest has normal sized bones for their length, which may have implications for injury risk. In addition to providing a means of expressing HRpQCT bone size outcomes relative to bone length, the current study also provides centile curves for outcomes previously without reference data, including tissue mineral density and moments of inertia.

Lifelong Fitness in Ambulatory Children and Adolescents with Cerebral Palsy I: Key Ingredients for Bone and Muscle Health.

Physical activity of a sufficient amount and intensity is essential to health and the prevention of a sedentary lifestyle in all children as they transition into adolescence and adulthood. While fostering a fit lifestyle in all children can be challenging, it may be even more so for those with cerebral palsy (CP). Evidence suggests that bone and muscle health can improve with targeted exercise programs for children with CP. Yet, it is not clear how musculoskeletal improvements are sustained into adulthood. In this perspective, we introduce key ingredients and guidelines to promote bone and muscle health in ambulatory children with CP (GMFCS I-III), which could lay the foundation for sustained fitness and musculoskeletal health as they transition from childhood to adolescence and adulthood. First, one must consider crucial characteristics of the skeletal and muscular systems as well as key factors to augment bone and muscle integrity. Second, to build a better foundation, we must consider critical time periods and essential ingredients for programming. Finally, to foster the sustainability of a fit lifestyle, we must encourage commitment and self-initiated action while ensuring the attainment of skill acquisition and function. Thus, the overall objective of this perspective paper is to guide exercise programming and community implementation to truly alter lifelong fitness in persons with CP.

Minced muscle autografting improves bone healing but not muscle function in a porcine composite injury model.

Composite tissue injuries (CTIs) in extremities include segmental bone defects (SBDs) and volumetric muscle loss. The objective of this study was to determine if skeletal muscle autografting with minced muscle grafts (MMGs) could improve healing in an SBD and improve muscle function in a porcine CTI model that includes an SBD and adjacent volumetric muscle loss injury. Adult Yucatan Minipigs were stratified into three groups including specimens with an isolated SBD, an SBD with volumetric muscle loss (CTI), and an SBD with volumetric muscle loss treated with MMG (CTI + MMG). Bone healing was quantified with serial x-rays and postmortem computed tomography scanning. Muscle function was quantified with a custom in vivo force transducer. Muscle tissue content was determined by biochemical analyses and histology. Anterior cortex-modified Radiographic Union Score for Tibia fractures (mRUSTs) decreased from 2.7 to 1.9 (p = 0.003) in CTI versus SBD animals. MMG improved anterior mRUST scores to 2.5 in CTI + MMG specimens (p = 0.030 compared to CTI specimens) and overall mRUST scores increased from 9.4 in CTI specimens to 11.1 in CTI + MMG specimens (p = 0.049). Residual strength deficits at euthanasia were 42% in SBD (p < 0.001), 44% in CTI (p < 0.001), and 48% in CTI + MMG (p < 0.001) compared to preoperative values. There were no differences in strength deficits between the three groups. Biochemical and histologic analyses demonstrated scattered differences between the three groups compared to contralateral muscle. MMG improved bone healing. However, the primary cause of muscle dysfunction and biochemical changes was the presence of an SBD. Clinical significance: Early mitigation of SBDs may be necessary to prevent muscle damage and weakness in patients sustaining composite extremity trauma.

Bone Morphogenetic Protein-2 Rapidly Heals Two Distinct Critical Sized Segmental Diaphyseal Bone Defects in a Porcine Model.

INTRODUCTION: Segmental bone defects (SBDs) are devastating injuries sustained by warfighters and are difficult to heal. Preclinical models that accurately simulate human conditions are necessary to investigate therapies to treat SBDs. We have developed two novel porcine SBD models that take advantage of similarities in bone healing and immunologic response to injury between pigs and humans. The purpose of this study was to investigate the efficacy of Bone Morphogenetic Protein-2 (BMP-2) to heal a critical sized defect (CSD) in two novel porcine SBD models. MATERIALS AND METHODS: Two CSDs were performed in Yucatan Minipigs including a 25.0-mm SBD treated with intramedullary nailing (IMN) and a 40.0-mm SBD treated with dual plating (ORIF). In control animals, the defect was filled with a custom spacer and a bovine collagen sponge impregnated with saline (IMN25 Cont, n = 8; ORIF40 Cont, n = 4). In experimental animals, the SBD was filled with a custom spacer and a bovine collage sponge impregnated with human recombinant BMP-2 (IMN25 BMP, n = 8; ORIF40 BMP, n = 4). Healing was quantified using monthly modified Radiographic Union Score for Tibia Fractures (mRUST) scores, postmortem CT scanning, and torsion testing. RESULTS: BMP-2 restored bone healing in all eight IMN25 BMP specimens and three of four ORIF40 BMP specimens. None of the IMN25 Cont or ORIF40 Cont specimens healed. mRUST scores at the time of sacrifice increased from 9.2 (±2.4) in IMN25 Cont to 15.1 (±1.0) in IMN25 BMP specimens (P < .0001). mRUST scores increased from 8.2 (±1.1) in ORIF40 Cont to 14.3 (±1.0) in ORIF40 BMP specimens (P < .01). CT scans confirmed all BMP-2 specimens had healed and none of the control specimens had healed in both IMN and ORIF groups. BMP-2 restored 114% and 93% of intact torsional stiffness in IMN25 BMP and ORIF40 BMP specimens. CONCLUSIONS: We have developed two porcine CSD models, including fixation with IMN and with dual-plate fixation. Porcine models are particularly relevant for SBD research as the porcine immunologic response to injury closely mimics the human response. BMP-2 restored healing in both CSD models, and the effects were evident within the first month after injury. These findings support the use of both porcine CSD models to investigate new therapies to heal SBDs.

Enhanced Bone Size, Microarchitecture, and Strength in Female Runners with a History of Playing Multidirectional Sports.

PURPOSE: Female runners have high rates of bone stress injuries (BSIs), including stress reactions and fractures. The current study explored multidirectional sports (MDS) played when younger as a potential means of building stronger bones to reduce BSI risk in these athletes. METHODS: Female collegiate-level cross-country runners were recruited into groups: 1) RUN, history of training and/or competing in cross-country, recreational running/jogging, swimming, and/or cycling only, and 2) RUN + MDS, additional history of training and/or competing in soccer or basketball. High-resolution peripheral quantitative computed tomography was used to assess the distal tibia, common BSI sites (diaphysis of the tibia, fibula, and second metatarsal), and high-risk BSI sites (base of the second metatarsal, navicular, and proximal diaphysis of the fifth metatarsal). Scans of the radius were used as control sites. RESULTS: At the distal tibia, RUN + MDS ( n = 18) had enhanced cortical area (+17.1%) and thickness (+15.8%), and greater trabecular bone volume fraction (+14.6%) and thickness (+8.3%) compared with RUN ( n = 14; all P < 0.005). Failure load was 19.5% higher in RUN + MDS ( P < 0.001). The fibula diaphysis in RUN + MDS had an 11.6% greater total area and a 11.1% greater failure load (all P ≤ 0.03). At the second metatarsal diaphysis, total area in RUN + MDS was 10.4% larger with greater cortical area and thickness and 18.6% greater failure load (all P < 0.05). RUN + MDS had greater trabecular thickness at the base of the second metatarsal and navicular and greater cortical area and thickness at the proximal diaphysis of the fifth metatarsal (all P ≤ 0.02). No differences were observed at the tibial diaphysis or radius. CONCLUSIONS: These findings support recommendations that athletes delay specialization in running and play MDS when younger to build a more robust skeleton and potentially prevent BSIs.

Physical Therapist Management of Patients With Suspected or Confirmed Osteoporosis: A Clinical Practice Guideline From the Academy of Geriatric Physical Therapy.

A clinical practice guideline on physical therapist management of patients with suspected or confirmed osteoporosis was developed by a volunteer guideline development group (GDG) that was appointed by the Academy of Geriatric Physical Therapy (APTA Geriatrics). The GDG consisted of an exercise physiologist and 6 physical therapists with clinical and methodological expertise. The guideline was based on a systematic review of existing clinical practice guidelines, followed by application of the ADAPTE methodological process described by Guidelines International Network for adapting guidelines for cultural and professional utility. The recommendations contained in this guideline are derived from the 2021 Scottish Intercollegiate Guideline Network (SIGN) document: Management of Osteoporosis and the Prevention of Fragility Fractures. These guidelines are intended to assist physical therapists practicing in the United States, and implementation in the context of the US health care system is discussed.

Physical Therapist Management of Patients With Suspected or Confirmed Osteoporosis: A Clinical Practice Guideline From the Academy of Geriatric Physical Therapy.

A clinical practice guideline on physical therapist management of patients with suspected or confirmed osteoporosis was developed by a volunteer guideline development group (GDG) that was appointed by the Academy of Geriatric Physical Therapy (APTA Geriatrics). The GDG consisted of an exercise physiologist and 6 physical therapists with clinical and methodological expertise. The guideline was based on a systematic review of existing clinical practice guidelines, followed by application of the ADAPTE methodological process described by Guidelines International Network for adapting guidelines for cultural and professional utility. The recommendations contained in this guideline are derived from the 2021 Scottish Intercollegiate Guideline Network (SIGN) document: Management of Osteoporosis and the Prevention of Fragility Fractures. These guidelines are intended to assist physical therapists practicing in the United States, and implementation in the context of the US health care system is discussed.

Characteristics of Interventions to Improve Bone Health in Children With Cerebral Palsy: A Systematic Review.

PURPOSE: A systematic review evaluated exercise parameters and ages that produced the most improvement in bone among individuals with cerebral palsy (CP) ages 3 to 21 years. METHODS: PubMed, Scopus, Ebscohost, and Web of Science identified potential articles. Covidence was used to identify eligible citations and assess bias. The osteogenic index (OI) was used to evaluate intervention parameters. RESULTS: The database search identified 312 citations. Twelve full-text articles were included. A 1-hour calisthenic exercise program performed 2 to 3 times a week for 8 months targeting each body region had the highest effect size and a substantial OI. Most of the interventions reviewed had low OIs. Activities of longer duration and greater intensity had greater OIs and prepubertal age-enhanced treatment effects. CONCLUSION: Bone interventions for individuals with CP have low OIs, and principles of mechanostat theory should be applied to exercise dosing.

Physical activity induced adaptation can increase proximal femur strength under loading from a fall onto the greater trochanter.

Physical activity enhances proximal femur bone mass, but it remains unclear whether the benefits translate into an enhanced ability to resist fracture related loading. We recently used baseball pitchers as a within-subject controlled model to demonstrate physical activity induced proximal femur adaptation in regions associated with weight bearing and increased strength under single-leg stance loading. However, there was no measurable benefit to resisting common injurious loading (e.g. a fall onto the greater trochanter). A lack of power and a small physical activity effect size may have contributed to the latter null finding. Softball pitchers represent an alternative within-subject controlled model to explore adaptation of the proximal femur to physical activity, exhibiting greater dominant-to-nondominant (D-to-ND) leg differences than baseball pitchers. The current study used quantitative computed tomography, statistical parametric mapping, and subject-specific finite element (FE) modeling to explore adaptation of the proximal femur to physical activity in female softball pitchers (n = 25). Female cross-country runners (n = 15) were included as symmetrically loaded controls, showing very limited D-to-ND leg differences. Softball pitchers had D-to-ND leg differences in proximal femur, femoral neck, and trochanteric volumetric bone mineral density and content, and femoral neck volume. Voxel-based morphometry analyses and cortical bone mapping showed D-to-ND leg differences within a large region connecting the superior femoral head, inferior femoral neck and medial intertrochanteric region, and within the greater trochanter. FE modeling revealed pitchers had 19.4% (95%CI, 15.0 to 23.9%) and 4.9% (95%CI, 1.7 to 8.2%) D-to-ND leg differences in predicted ultimate strength under single-leg stance loading and a fall onto the greater trochanter, respectively. These data affirm the spatial and strength adaptation of the proximal femur to weight bearing directed loading and demonstrate that the changes can also have benefits, albeit smaller, on resisting loads associated with a sideways fall onto the greater trochanter.

Bone Microarchitecture and Strength Adaptation to Physical Activity: A Within-Subject Controlled HRpQCT Study.

PURPOSE: Physical activity benefits bone mass and cortical bone size. The current study assessed the impact of chronic (≥10 yr) physical activity on trabecular microarchitectural properties and microfinite element analyses of estimated bone strength. METHODS: Female collegiate-level tennis players (n = 15; age = 20.3 ± 0.9 yr) were used as a within-subject controlled model of chronic unilateral upper-extremity physical activity. Racquet-to-nonracquet arm differences at the distal radius and radial diaphysis were assessed using high-resolution peripheral quantitative computed tomography. The distal tibia and the tibial diaphysis in both legs were also assessed, and cross-country runners (n = 15; age = 20.8 ± 1.2 yr) included as controls. RESULTS: The distal radius of the racquet arm had 11.8% (95% confidence interval [CI] = 7.9% to 15.7%) greater trabecular bone volume/tissue volume, with trabeculae that were greater in number, thickness, connectivity, and proximity to each other than that in the nonracquet arm (all P < 0.01). Combined with enhanced cortical bone properties, the microarchitectural advantages at the distal radius contributed a 18.7% (95% CI = 13.0% to 24.4%) racquet-to-nonracquet arm difference in predicted load before failure. At the radial diaphysis, predicted load to failure was 9.6% (95% CI = 6.7% to 12.6%) greater in the racquet versus nonracquet arm. There were fewer and smaller side-to-side differences at the distal tibia; however, the tibial diaphysis in the leg opposite the racquet arm was larger with a thicker cortex and had 4.4% (95% CI = 1.7% to 7.1%) greater strength than the contralateral leg. CONCLUSION: Chronically elevated physical activity enhances trabecular microarchitecture and microfinite element estimated strength, furthering observations from short-term longitudinal studies. The data also demonstrate that tennis players exhibit crossed symmetry wherein the leg opposite the racquet arm possesses enhanced tibial properties compared with in the contralateral leg.

Designing Exercise to Improve Bone Health Among Individuals With Cerebral Palsy.

PURPOSE: Individuals with cerebral palsy (CP), ambulatory or not, have less bone strength and density than their peers. Aging individuals with CP are at a higher risk for nontraumatic fractures, progressive deformity, pain, and spinal stenosis. Critical periods for skeletal formation are during prepuberty and adolescence. Applying mechanostat theory to exercise design for individuals with CP may be beneficial. METHODS: Principles of mechanostat theory, particularly the osteogenic index, is applied to guide the design of exercise programs based on varying levels of physical capacity. RESULTS: Recommendations are made for optimizing dosing of a variety of interventions for improving bone health among individuals with CP based on mechanostat theory with specific type, number of repetitions, and frequency. CONCLUSIONS: Researchers and clinicians are called to action to consider the role of exercise throughout the lifespan for all individuals with CP, regardless of level of severity.

Heterogeneous Spatial and Strength Adaptation of the Proximal Femur to Physical Activity: A Within-Subject Controlled Cross-Sectional Study.

Physical activity (PA) enhances proximal femur bone mass, as assessed using projectional imaging techniques. However, these techniques average data over large volumes, obscuring spatially heterogeneous adaptations. The current study used quantitative computed tomography, statistical parameter mapping, and subject-specific finite element (FE) modeling to explore spatial adaptation of the proximal femur to PA. In particular, we were interested in adaptation occurring at the superior femoral neck and improving strength under loading from a fall onto the greater trochanter. High/long jump athletes (n = 16) and baseball pitchers (n = 16) were utilized as within-subject controlled models as they preferentially load their take-off leg and leg contralateral to their throwing arm, respectively. Controls (n = 15) were included but did not show any dominant-to-nondominant (D-to-ND) leg differences. Jumping athletes showed some D-to-ND leg differences but less than pitchers. Pitchers had 5.8% (95% confidence interval [CI] 3.9%-7.6%) D-to-ND leg differences in total hip volumetric bone mineral density (vBMD), with increased vBMD in the cortical compartment of the femoral neck and trochanteric cortical and trabecular compartments. Voxel-based morphometry analyses and cortical bone mapping showed pitchers had D-to-ND leg differences within the regions of the primary compressive trabeculae, inferior femoral neck, and greater trochanter but not the superior femoral neck. FE modeling revealed pitchers had 4.1% (95% CI 1.4%-6.7%) D-to-ND leg differences in ultimate strength under single-leg stance loading but no differences in ultimate strength to a fall onto the greater trochanter. These data indicate the asymmetrical loading associated with baseball pitching induces proximal femur adaptation in regions associated with weight bearing and muscle contractile forces and increases strength under single-leg stance loading. However, there were no benefits evident at the superior femoral neck and no measurable improvement in ultimate strength to common injurious loading during aging (ie, fall onto the greater trochanter), raising questions as to how to better target these variables with PA. © 2019 American Society for Bone and Mineral Research.

Baseball and Softball Pitchers are Distinct Within-Subject Controlled Models for Exploring Proximal Femur Adaptation to Physical Activity.

Within-subject controlled models in individuals who preferentially load one side of the body enable efficient exploration of the skeletal benefits of physical activity. There is no established model of physical activity-induced side-to-side differences (i.e., asymmetry) at the proximal femur. Proximal femur asymmetry was assessed via dual-energy X-ray absorptiometry in male jumping athletes (JMP, n = 16), male baseball pitchers (BB, n = 21), female fast-pitch softball pitchers (SB, n = 22), and controls (CON, n = 42). The jumping leg was the dominant leg in JMP, whereas in BB, SB and CON the dominant leg was contralateral to the dominant/throwing arm. BB and SB had 5.5% (95% CI 3.9-7.0%) and 6.5% (95% CI 4.8-8.2%) dominant-to-nondominant leg differences for total hip areal bone mineral density (aBMD), with the asymmetry being greater than both CON and JMP (p < 0.05). BB and SB also possessed dominant-to-nondominant leg differences in femoral neck and trochanteric aBMD (p < 0.001). SB had 9.7% (95% CI 6.4-13.0%) dominant-to-nondominant leg differences in femoral neck bone mineral content, which was larger than any other group (p ≤ 0.006). At the narrow neck, SB had large (> 8%) dominant-to-nondominant leg differences in cross-sectional area, cross-sectional moment of inertia and section modulus, which were larger than any other group (p ≤ 0.02). Male baseball and female softball pitchers are distinct within-subject controlled models for exploring adaptation of the proximal femur to physical activity. They exhibit adaptation in their dominant/landing leg (i.e., leg contralateral to the throwing arm), but the pattern differs with softball pitchers exhibiting greater femoral neck adaptation.

Adaptation of the proximal humerus to physical activity: A within-subject controlled study in baseball players.

The proximal humerus is a common, yet understudied site for osteoporotic fracture. The current study explored the impact of prolonged physical activity on proximal humerus bone health by comparing bone properties between the throwing and nonthrowing arms within professional baseball players. The proximal humerus in throwing arms had 28.1% (95% CI, 17.8 to 38.3%) greater bone mass compared to nonthrowing arms, as assessed using dual-energy x-ray absorptiometry. At the level of the surgical neck, computed tomography revealed 12.0% (95% CI, 8.2 to 15.8%) greater total cross-sectional area and 31.0% (95% CI, 17.8 to 44.2%) greater cortical thickness within throwing arms, which contributed to 56.8% (95% CI, 44.9 to 68.8%) greater polar moment of inertia (i.e., estimated ability to resist torsional forces) compared to nonthrowing arms. Within the humeral head and greater tubercle regions, throwing arms had 3.1% (95% CI, 1.1 to 5.1%) more trabecular bone, as assessed using high-resolution magnetic resonance imaging. Three-dimensional mapping of voxel- and vertex-wise differences between arms using statistical parametric mapping techniques revealed throwing arms had adaptation within much of the proximal diaphysis, especially the posterolateral cortex. The pattern of proximal diaphysis adaptation approximated the pattern of strain energy distribution within the proximal humerus during a fastball pitch derived from a musculoskeletal and finite element model in a representative player. These data demonstrate the adaptive ability of the proximal humerus to physical activity-related mechanical loads. It remains to be established how they translate to exercise prescription to improve bone health within the proximal humerus; however, they provide unique insight into the relationship between prolonged loading and skeletal adaptation at a clinically relevant osteoporotic site.

The proto-oncogene function of Mdm2 in bone.

Mouse double minute 2 (Mdm2) is a multifaceted oncoprotein that is highly regulated with distinct domains capable of cellular transformation. Loss of Mdm2 is embryonically lethal, making it difficult to study in a mouse model without additional genetic alterations. Global overexpression through increased Mdm2 gene copy number (Mdm2Tg ) results in the development of hematopoietic neoplasms and sarcomas in adult animals. In these mice, we found an increase in osteoblastogenesis, differentiation, and a high bone mass phenotype. Since it was difficult to discern the cell lineage that generated this phenotype, we generated osteoblast-specific Mdm2 overexpressing (Mdm2TgOb ) mice in 2 different strains, C57BL/6 and DBA. These mice did not develop malignancies; however, these animals and the MG63 human osteosarcoma cell line with high levels of Mdm2 showed an increase in bone mineralization. Importantly, overexpression of Mdm2 corrected age-related bone loss in mice, providing a role for the proto-oncogenic activity of Mdm2 in bone health of adult animals.

Defective Hand1 phosphoregulation uncovers essential roles for Hand1 in limb morphogenesis.

The morphogenesis of the vertebrate limbs is a complex process in which cell signaling and transcriptional regulation coordinate diverse structural adaptations in diverse species. In this study, we examine the consequences of altering Hand1 dimer choice regulation within developing vertebrate limbs. Although Hand1 deletion via the limb-specific Prrx1-Cre reveals a non-essential role for Hand1 in mouse limb morphogenesis, altering Hand1 phosphoregulation, and consequently Hand1 dimerization affinities, results in a severe truncation of proximal-anterior limb elements. Molecular analysis reveals a non-cell-autonomous mechanism that causes widespread cell death within the embryonic limb bud. In addition, we observe changes in proximal-anterior gene regulation, including a reduction in the expression of Irx3, Irx5, Gli3 and Alx4, all of which are upregulated in Hand2 limb conditional knockouts. A reduction of Hand2 and Shh gene dosage improves the integrity of anterior limb structures, validating the importance of the Twist-family bHLH dimer pool in limb morphogenesis.

Hemangioma in the Anterior Thigh With Corresponding Periosteal Bone Reaction.

A 24-year-old female runner presented to physical therapy via direct access with an 8-month history of mid-thigh pain. At the onset of her symptoms, radiographs were negative; following physical therapy evaluation, additional imaging was requested. Lateral-view radiographs revealed cortical hypertrophy with no stress fracture. Magnetic resonance imaging revealed an enhancing mass adjacent to the anterolateral surface of the mid shaft of the femur, with associated cortical hypertrophy, consistent with a deep intramuscular hemangioma. J Orthop Sports Phys Ther 2017;47(3):218. doi:10.2519/jospt.2017.6302.

Electroacupuncture Promotes Central Nervous System-Dependent Release of Mesenchymal Stem Cells.

Electroacupuncture (EA) performed in rats and humans using limb acupuncture sites, LI-4 and LI-11, and GV-14 and GV-20 (humans) and Bai-hui (rats) increased functional connectivity between the anterior hypothalamus and the amygdala and mobilized mesenchymal stem cells (MSCs) into the systemic circulation. In human subjects, the source of the MSC was found to be primarily adipose tissue, whereas in rodents the tissue sources were considered more heterogeneous. Pharmacological disinhibition of rat hypothalamus enhanced sympathetic nervous system (SNS) activation and similarly resulted in a release of MSC into the circulation. EA-mediated SNS activation was further supported by browning of white adipose tissue in rats. EA treatment of rats undergoing partial rupture of the Achilles tendon resulted in reduced mechanical hyperalgesia, increased serum interleukin-10 levels and tendon remodeling, effects blocked in propranolol-treated rodents. To distinguish the afferent role of the peripheral nervous system, phosphoinositide-interacting regulator of transient receptor potential channels (Pirt)-GCaMP3 (genetically encoded calcium sensor) mice were treated with EA acupuncture points, ST-36 and LIV-3, and GV-14 and Bai-hui and resulted in a rapid activation of primary sensory neurons. EA activated sensory ganglia and SNS centers to mediate the release of MSC that can enhance tissue repair, increase anti-inflammatory cytokine production and provide pronounced analgesic relief. Stem Cells 2017;35:1303-1315.

Physical Activity for Strengthening Fracture Prone Regions of the Proximal Femur.

PURPOSE OF REVIEW: Physical activity improves proximal femoral bone health; however, it remains unclear whether changes translate into a reduction in fracture risk. To enhance any fracture-protective effects of physical activity, fracture prone regions within the proximal femur need to be targeted. RECENT FINDINGS: The proximal femur is designed to withstand forces in the weight-bearing direction, but less so forces associated with falls in a sideways direction. Sideways falls heighten femoral neck fracture risk by loading the relatively weak superolateral region of femoral neck. Recent studies exploring regional adaptation of the femoral neck to physical activity have identified heterogeneous adaptation, with adaptation principally occurring within inferomedial weight-bearing regions and little to no adaptation occurring in the superolateral femoral neck. There is a need to develop novel physical activities that better target and strengthen the superolateral femoral neck within the proximal femur. Design of these activities may be guided by subject-specific musculoskeletal modeling and finite-element modeling approaches.

Lnk Deficiency Leads to TPO-Mediated Osteoclastogenesis and Increased Bone Mass Phenotype.

The Lnk adapter protein negatively regulates the signaling of thrombopoietin (TPO), the main megakaryocyte (MK) growth factor. Lnk-deficient (-/-) mice have increased TPO signaling and increased MK number. Interestingly, several mouse models exist in which increased MK number leads to a high bone mass phenotype. Here we report the bone phenotype of these mice. MicroCT and static histomorphometric analyses at 20 weeks showed the distal femur of Lnk-/- mice to have significantly higher bone volume fraction and trabecular number compared to wild-type (WT) mice. Notably, despite a significant increase in the number of osteoclasts (OC), and decreased bone formation rate in Lnk-/- mice compared to WT mice, Lnk-/- mice demonstrated a 2.5-fold greater BV/TV suggesting impaired OC function in vivo. Additionally, Lnk-/- mouse femurs exhibited non-significant increases in mid-shaft cross-sectional area, yet increased periosteal BFR compared to WT femurs was observed. Lnk-/- femurs also had non-significant increases in polar moment of inertia and decreased cortical bone area and thickness, resulting in reduced bone stiffness, modulus, and strength compared to WT femurs. Of note, Lnk is expressed by OC lineage cells and when Lnk-/- OC progenitors are cultured in the presence of TPO, significantly more OC are observed than in WT cultures. Lnk is also expressed in osteoblast (OB) cells and in vitro reduced alkaline phosphatase activity was observed in Lnk-/- cultures. These data suggest that both direct effects on OB and OC as well as indirect effects of MK in regulating OB contributes to the observed high bone mass. J. Cell. Biochem. 118: 2231-2240, 2017. © 2017 Wiley Periodicals, Inc.