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ObjectiveBone stress injuries (BSIs) are classified in clinical practice as being at low- or high-risk for complication based on the injury location. However, this dichotomous approach has not been sufficiently validated. The purpose of this systematic review was to examine the prognostic role of injury location on return-to-sport (RTS) and treatment complications after BSI of the lower extremity and pelvis.DesignSystematic review and meta-analysis.Data sourcesPubMed, Web of Science, Cochrane CENTRAL and Google Scholar databases were searched from database inception to December 2021.Eligibility criteria for selecting studiesPeer-reviewed studies that reported site-specific RTS of BSIs in athletes.ResultsSeventy-six studies reporting on 2974 BSIs were included. Sixteen studies compared multiple injury sites, and most of these studies (n=11) described the anatomical site of injury as being prognostic for RTS or the rate of treatment complication. Pooled data revealed the longest time to RTS for BSIs of the tarsal navicular (127 days; 95% CI 102 to 151 days) and femoral neck (107 days; 95% CI 79 to 135 days) and shortest duration of time for BSIs of the posteromedial tibial shaft (44 days, 95% CI 27 to 61 days) and fibula (56 days; 95% CI 13 to 100 days). Overall, more than 90% of athletes successfully returned to sport. Treatment complication rate was highest in BSIs of the femoral neck, tarsal navicular, anterior tibial shaft and fifth metatarsal; and lowest in the fibula, pubic bone and posteromedial tibial shaft.ConclusionThis systematic review supports that the anatomical site of BSIs influences RTS timelines and the risk of complication. BSIs of the femoral neck, anterior tibial shaft and tarsal navicular are associated with increased rates of complications and more challenging RTS.PROSPERO registration numberCRD42021232351.

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.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.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 P0.005). Failure load was 19.5% higher in RUN + MDS ( P0.001). 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 P0.05). 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.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.

IntroductionRunning is one of the most popular recreational activities worldwide, due to its low cost and accessibility. However, little is known about the impact of running on knee joint health in runners with and without a history of knee surgery. The primary aim of this longitudinal cohort study is to compare knee joint structural features on MRI and knee symptoms at baseline and 4-year follow-up in runners with and without a history of knee surgery. Secondary aims are to explore the relationships between training load exposures (volume and/or intensity) and changes in knee joint structure and symptoms over 4 years; explore the relationship between baseline running biomechanics, and changes in knee joint structure and symptoms over 4 years. In addition, we will explore whether additional variables confound, modify or mediate these associations, including sex, baseline lower-limb functional performance, knee muscle strength, psychological and sociodemographic factors.Methods and analysisA convenience sample of at least 200 runners (sex/gender balanced) with (n=100) and without (n=100) a history of knee surgery will be recruited. Primary outcomes will be knee joint health (MRI) and knee symptoms (baseline; 4 years). Exposure variables for secondary outcomes include training load exposure, obtained daily throughout the study from wearable devices and three-dimensional running biomechanics (baseline). Additional variables include lower limb functional performance, knee extensor and flexor muscle strength, biomarkers, psychological and sociodemographic factors (baseline). Knowledge and beliefs about osteoarthritis will be obtained through predefined questions and semi-structured interviews with a subset of participants. Multivariable logistic and linear regression models, adjusting for potential confounding factors, will explore changes in knee joint structural features and symptoms, and the influence of potential modifiers and mediators.Ethics and disseminationApproved by the La Trobe University Ethics Committee (HEC-19524). Findings will be disseminated to stakeholders, peer-review journals and conferences.

Background: Physical activity maintains musculoskeletal and general overall health. Declining physical performance is the most obvious indicator of declining health with aging. Early identification of declining physical performance using biomarkers would be useful in predicting treatment outcomes and identifying potential therapeutics. Method: As γ-aminobutyric acid (GABA), a muscle autocrine factor, can function as muscle relaxant and L-α-aminobutyric acid (L-AABA), is a biomarker for malnutrition, and depression, we sought to determine if they may also be useful for monitoring physical performance during aging. Serum levels were quantified in 120 individuals divided by age, gender, and physical capacity into low (LP), average (AP), and high (HP) performers and correlated with physical parameters and performance. Results: Both GABA and the ratio of GABA/AABA (G/A), but not AABA, were highly positively associated with age (Pearson correlations r=0.35, p=0.0001 for GABA, and r=0.31, p=0.0007 for G/A, n=120). GABA showed negative associations in the whole cohort with physical performance (fast gait speed, 6 minute walking test (6MWT), PROMIS score, and SF36 PFS raw score) and with subtotal and femoral neck bone mineral density (BMD). L-AABA was positively associated with usual gait speed, 6MWT, total SPPB score, and SF36 PFS raw score in total 120 human subjects, also with 6MWT and SF36 PFS raw score in the 60 male subjects, but no associations were observed in the 60 females. As both GABA and L-AABA appear to be indicative of physical performance, but in opposite directions, we examined the G/A ratio. Unlike GABA, the G/A ratio showed a more distinct association with mobility tests such as total SPPB score, usual and fast gait speed, 6MWT, and SF36 PFS raw score in the males, regardless of age and metabolic status. Serum G/A ratio could be potentially linked to physical performance in the male population. Conclusions: All these findings strongly suggest that GABA, L-AABA, and the G/A ratio in human serum may be useful markers to link with age and physical function. Taking these aminobutyric acids into consideration may significantly enhance the goal of identifying universal biomarkers to accurately predict physical performance and the beneficial effects of exercise on aging.

PURPOSE OF REVIEW: In this review, we discuss the mechanism of action of gabapentinoids and the potential consequences of long-term treatment with these drugs on the musculoskeletal system. RECENT FINDINGS: Gabapentinoids, such as gabapentin (GBP) and pregabalin (PGB) were designed as antiepileptic reagents and are now commonly used as first-line treatment for neuropathic pain and increasingly prescribed off-label for other pain disorders such as migraines and back pain. GBP and PGB exert their analgesic actions by selectively binding the α(2)δ(1) auxiliary subunit of voltage-sensitive calcium channels, thereby inhibiting channel function. Numerous tissues express the α(2)δ(1) subunit where GBP and PGB can alter calcium-mediated signaling events. In tissues such as bone, muscle, and cartilage, α(2)δ(1) has important roles in skeletal formation, mechanosensation, and normal tissue function/repair that may be affected by chronic use of gabapentinoids. SUMMARY: Long-term use of gabapentinoids is associated with detrimental musculoskeletal outcomes, including increased fracture risk. Therefore, understanding potential complications is essential for clinicians to guide appropriate treatments.

Vor allem Läufer kennen das Problem: völlig unvermittelt bekommen sie Beschwerden, die so stark sind, dass sie nicht mehr weitermachen können. Im schlimmsten Fall leiden sie an den schmerzhaften Folgen einer Stressfraktur. Wer im Training die richtigen Reize setzt, kann das Risiko für derartige Verletzungen deutlich verringern.

The tibia is a common site for bone stress injuries, which are believed to develop from microdamage accumulation to repetitive sub-yield strains. There is a need to understand how the tibia is loaded in vivo to understand how bone stress injuries develop and design exercises to build a more robust bone. Here, we use subject-specific, muscle-driven, finite element simulations of 11 basketball players to calculate strain and strain rate distributions at the midshaft and distal tibia during six activities: walking, sprinting, lateral cut, jumping after landing, changing direction from forward-to-backward sprinting, and changing direction while side shuffling. Maximum compressive strains were at least double maximum tensile strains during the stance phase of all activities. Sprinting and lateral cut had the highest compressive (-2,862 ± 662 με and -2,697 ± 495 με, respectively) and tensile (973 ± 208 με and 942 ± 223 με, respectively) strains. These activities also had the highest strains rates (peak compressive strain rate = 64,602 ± 19,068 με/s and 37,961 ± 14,210 με/s, respectively). Compressive strains principally occurred in the posterior tibia for all activities; however, tensile strain location varied. Activities involving a change in direction increased tensile loads in the anterior tibia. These observations may guide preventative and management strategies for tibial bone stress injuries. In terms of prevention, the strain distributions suggest individuals should perform activities involving changes in direction during growth to adapt different parts of the tibia and develop a more fatigue resistant bone. In terms of management, the greater strain and strain rates during sprinting than jumping suggests jumping activities may be commenced earlier than full pace running. The greater anterior tensile strains during changes in direction suggest introduction of these types of activities should be delayed during recovery from an anterior tibial bone stress injury, which have a high-risk of healing complications.

Objective Identifying muscle weakness and probable sarcopenia using strength tests requires reference data. This study aimed to provide age- and sex-specific normative data for grip strength and common variations of the Sit-to-Stand (STS) test: time to complete 5 stands (5x-STS) and number of stands completed in 30 seconds (30s-STS). Predictors of test performance were also explored. Methods Dominant hand grip strength was assessed in adults (age = 18–80 years) using a digital dynamometer, and 5x-STS and 30s-STS performance were assessed synchronously during a single 30-second test. Sex-specific centile curves were generated using the lambda-mu-sigma method. Results Data from 2301 participants (female = 1682, male = 619) were included. Peak median grip strength occurred in female participants at 33.9 years of age (27.9 kg) and in male participants at 37.6 years of age (47.2 kg). 5x-STS and 30s-STS performance peaked at the youngest age (18.0 years) in both female participants (8.16 seconds and 17.2 repetitions) and male participants (8.02 seconds and 17.7 repetitions). Test performances were lowest for all tests at the oldest age in the database. Predictors of better test performance included lower age and higher self-reported physical functioning and appendicular skeletal muscle mass, to name a few. White participants had better performance than Black participants on the STS tests. Conclusion The generated centile curves reveal the pattern of change in muscle strength for tests recommended to identify probable sarcopenia. The curves can be used in rehabilitation to assess an individual’s performance relative to sex- and age-specific norms. To aid use of the data, a downloadable Excel-based calculator is provided to compute participant-specific percentiles, z scores, and t scores for each outcome and plot performance on the centile curves. Impact Physical therapists have an important role in identifying and treating individuals with sarcopenia and other causes of muscle weakness. The reference data provided for common clinical muscle strength tests provide therapists an ability to assess an individual’s relative performance. Lay Summary Knowing the normal or expected strength for an individual’s age and sex is essential to identifying muscle weakness. This study provides age- and sex-specific normal values for hand grip strength and sit-to-stand tests in adults aged 18 to 80 years.

Background There is a clinical need to be able to reliably detect meaningful changes (0.1 to 0.2 m/s) in usual gait speed (UGS) considering reduced gait speed is associated with morbidity and mortality. Research question What is the impact of tester on UGS assessment, and the influence of test repetition (trial 1 vs. 2), timing method (manual stopwatch vs. automated timing), and starting condition (stationary vs. dynamic start) on the ability to detect changes in UGS and fast gait speed (FGS)? Methods UGS and FGS was assessed in 725 participants on a 8-m course with infrared timing gates positioned at 0, 2, 4 and 6 m. Testing was performed by one of 13 testers trained by a single researcher. Time to walk 4-m from a stationary start (i.e. from 0-m to 4-m) was measured manually using a stopwatch and automatically via the timing gates at 0-m and 4-m. Time taken to walk 4-m with a dynamic start was measured during the same trial by recording the time to walk between the timing gates at 2-m and 6-m (i.e. after 2-m acceleration). Results Testers differed for UGS measured using manual vs. automated timing (p = 0.02), with five and two testers recording slower and faster UGS using manual timing, respectively. 95% limits of agreement for trial 1 vs. 2, manual vs. automated timing, and dynamic vs. stationary start ranged from ±0.15 m/s to ±0.20 m/s, coinciding with the range for a clinically meaningful change. Limits of agreement for FGS were larger ranging from ±0.26 m/s to ±0.35 m/s. Significance Repeat testing of UGS should performed by the same tester or using an automated timing method to control for tester effects. Test protocol should remain constant both between and within participants as protocol deviations may result in detection of an artificial clinically meaningful change.

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.

Stress fracture is a common injury among athletes and military personnel and is associated with fatigue-initiated damage and impact loading. The recovery of bending strength has been shown to be a function of the rest days allowed after fatigue loading in rodents and the aim of this study was to investigate if similar results would occur under impact conditions. In this study, cyclic axial compression load was applied in vivo on the right forelimbs while left forelimbs served as controls. Two rest groups were used: one day of rest and seven days of rest. Afterwards, all ulnae were scanned using micro-Computed Tomography followed by impact testing. The micro-CT scan confirmed the formation of woven bone on loaded ulnae after seven days rest. The peak impact force was 37.5% higher in the control (mean = 174.96 ± 33.25 N) specimens compared to the loaded bones (mean = 130.34 ± 22.37 N). Fourier-transformed infrared spectroscopy analyses suggested no significant change of chemical composition in the cortical region between the loaded and control ulnae, but woven bone region had lower carbonate and amide I content than contralateral controls (p < 0.05). We find that cyclic fatigue loading had a negative effect on bone's impact response. Bones that experienced fatigue loading became less stiff, weaker, and more prone to fracture when subjected to impact. The formation of woven bone after seven days of rest did not restore the stiffness upon impact and confirm that rest time is crucial to the recovery of fatigue damage.

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.

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 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.

Low-risk bone stress injuries (BSIs) of the tibia and metatarsal diaphyses account for more than half of BSIs in runners. They interrupt training and are managed using noninvasive approaches that are designed to achieve a speedy but safe return to running.What is the optimal load to manage low-risk tibial and metatarsal BSIs and safely return to running?Optimal load can be guided by knowledge of the BSI healing process and is symptom driven. At all stages, the optimal load does not produce symptoms during, after, or the day following loading.A period of initial load reduction, via partial or non-weight bearing, is typically needed to alleviate presenting symptoms. Analgesics or nonsteroidal anti-inflammatory drugs may be used in the short term (sooner than 7 days), but only for resting pain and night pain. Healing supplements (eg, low-intensity pulsed ultrasound and/or recombinant parathyroid hormone therapy) may be attempted to influence tissue healing. Athletes can maintain cardiopulmonary fitness via cross-training, while simultaneously addressing musculoskeletal fitness. A return-to-run program can be initiated once an athlete is pain free during daily activities for 5 consecutive days. Progress is directed by symptom provocation and initially focuses on increasing running volume before speed. Optimal loading should be continued following return to running and may include jump training and/or gait retraining to reduce subsequent BSI risk. The optimal loading approach to managing low-risk tibial and metatarsal BSIs is clinically successful, but requires further scientific validation.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a powerful tool to assess bone health. To determine how an individual's or population of interest's HR-pQCT outcomes compare to expected, reference data are required. This study provides reference data for HR-pQCT measures acquired in a population of White adults.PURPOSE: To provide age- and sex-specific reference data for high-resolution peripheral quantitative computed tomography (HR-pQCT) measures of the distal and diaphyseal radius and tibia acquired using a second-generation scanner and percent-of-length offsets proximal from the end of the bone.METHODS: Data were acquired in White adults (aged 18-80 years) living in the Midwest region of the USA. HR-pQCT scans were performed at the 4% distal radius, 30% diaphyseal radius, 7.3% distal tibia, and 30% diaphyseal tibia. Centile curves were fit to the data using the LMS approach.RESULTS: Scans of 867 females and 317 males were included. The fitted centile curves reveal HR-pQCT differences between ages, sexes, and sites. They also indicate differences when compared to data obtained by others using fixed length offsets. Excel-based calculators based on the current data were developed and are provided to enable computation of subject-specific percentiles, z-scores, and t-scores and to plot an individual's outcomes on the fitted curves. In addition, regression equations are provided to convert estimated failure load acquired with the conventional criteria utilized with first-generation scanners and those specifically developed for second-generation scanners.CONCLUSION: The current study provides unique data and resources. The combination of the reference data and calculators provide clinicians and investigators an ability to assess HR-pQCT outcomes in an individual or population of interest, when using the described scanning and analysis procedure. Ultimately, the expectation is these data will be expanded over time so the wealth of information HR-pQCT provides becomes increasingly interpretable and utilized.

Bone stress injuries (BSIs) occur at inopportune times to invariably interrupt training. All BSIs in runners occur due to an "error" in workload wherein the interaction between the number and magnitude of bone tissue loading cycles exceeds the ability of the tissue to resist the repetitive loads. There is not a single optimal bone workload, rather a range which is influenced by the prevailing scenario. In prepubertal athletes, optimal bone workload consists of low-repetitions of fast, high-magnitude, multidirectional loads introduced a few times per day to induce bone adaptation. Premature sports specialization should be avoided so as to develop a robust skeleton that is structurally optimized to withstand multidirectional loading. In the mature skeleton, optimal workload enables gains in running performance but minimizes bone damage accumulation by sensibly progressing training, particularly training intensity. When indicated (e.g., following repeated BSIs), attempts to reduce bone loading magnitude should be considered, such as increasing running cadence. Determining the optimal bone workload for an individual athlete to prevent and manage BSIs requires consistent monitoring. In the future, it may be possible to clinically determine bone loads at the tissue level to facilitate workload progressions and prescriptions.

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.

PURPOSE: 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. METHODS: 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. RESULTS: BB and SB had 5.5% (95%CI, 3.9 to 7.0%) and 6.5% (95%CI, 4.8 to 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 (p8%) 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). CONCLUSION: 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.

SUMMARY: Eggs contain bioactive compounds thought to benefit pediatric bone. This cross-sectional study shows a positive link between childhood egg intake and radius cortical bone. If randomized trials confirm our findings, incorporating eggs into children’s diets could have a significant impact in preventing childhood fractures and reducing the risk of osteoporosis. INTRODUCTION: This study examined the relationships between egg consumption and cortical bone in children. METHODS: The cross-sectional study design included 294 9–13-year-old black and white males and females. Three-day diet records determined daily egg consumption. Peripheral quantitative computed tomography measured radius and tibia cortical bone. Body composition and biomarkers of bone turnover were assessed using dual-energy X-ray absorptiometry and ELISA, respectively. RESULTS: Egg intake was positively correlated with radius and tibia cortical bone mineral content (Ct.BMC), total bone area, cortical area, cortical thickness, periosteal circumference, and polar strength strain index in unadjusted models (r = 0.144–0.224, all P < 0.050). After adjusting for differences in race, sex, maturation, fat-free soft tissue mass (FFST), and protein intakes, tibia relationships were nullified; however, egg intake remained positively correlated with radius Ct.BMC (r = 0.138, P = 0.031). Egg intake positively correlated with total body bone mineral density, BMC, and bone area in the unadjusted models only (r = 0.119–0.224; all P < 0.050). After adjusting for covariates, egg intake was a positive predictor of radius FFST (β = 0.113, P < 0.050) and FFST was a positive predictor of Ct.BMC (β = 0.556, P < 0.050) in path analyses. There was a direct influence of egg on radius Ct.BMC (β =0.099, P =0.035), even after adjusting for the mediator, FFST (β = 0.137, P = 0.020). Egg intake was positively correlated with osteocalcin in both the unadjusted (P = 0.005) and adjusted (P = 0.049) models. CONCLUSION: If the positive influence of eggs on Ct.BMC observed in this study is confirmed through future randomized controlled trials, whole eggs may represent a viable strategy to promote pediatric bone development and prevent fractures.

Study Design Descriptive study. Background Professional meetings, such as the American Physical Therapy Association's (APTA's) Combined Sections Meeting (CSM), provide forums for sharing information. However, it was reported that only one-quarter of orthopaedic and sports physical therapy abstracts presented at the CSM between 2000 and 2004 went on to full-text publication. This low conversion rate raises a number of concerns regarding the full dissemination of work within the profession. Objectives The purpose of this study was to determine the full-text publication rate of work presented in abstract form at subsequent CSMs and investigate factors influencing the rate. Methods A systematic search was undertaken to locate full-text publications of orthopaedic and sports physical therapy abstracts presented at CSMs between 2005 and 2011. Eligible publications were published within 5 years following abstract presentation. The influences of year of abstract presentation, APTA section, presentation type, institution of origin, study design, and study significance were assessed. Results Over one-third (38.6%) of presented abstracts progressed to full-text publication. Odds of full-text publication increased if the abstract was presented as a platform presentation, originated from a doctorate-granting institution, reported findings of an experimental study, or reported a statistically significant finding. Conclusion The full-text publication rate for orthopaedic and sports physical therapy abstracts presented at recent CSMs has increased by over 50% compared to that reported for the preceding period. The rate is now in the range of that reported in comparable clinical disciplines, demonstrating important progress in the full dissemination of work within the profession. J Orthop Sports Phys Ther, Epub 7 Oct 2017. doi:10.2519/jospt.2018.7581.

IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p

The growing field of regenerative rehabilitation has great potential to improve clinical outcomes for individuals with disabilities. However, the science to elucidate the specific biological underpinnings of regenerative rehabilitation-based approaches is still in its infancy and critical questions regarding clinical translation and implementation still exist. In a recent roundtable discussion from International Consortium for Regenerative Rehabilitation stakeholders, key challenges to progress in the field were identified. The goal of this article is to summarize those discussions and to initiate a broader discussion among clinicians and scientists across the fields of regenerative medicine and rehabilitation science to ultimately progress regenerative rehabilitation from an emerging field to an established interdisciplinary one. Strategies and case studies from consortium institutions-including interdisciplinary research centers, formalized courses, degree programs, international symposia, and collaborative grants-are presented. We propose that these strategic directions have the potential to engage and train clinical practitioners and basic scientists, transform clinical practice, and, ultimately, optimize patient outcomes.

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.

If a tree falls in a forest and no one is around to hear it, does it make a sound? Analogous to this familiar philosophical thought experiment, an editorial needs to be sensed (ie, read) to provoke a reaction—to have impact. To paraphrase the late Wall Street Journal editor Robert Bartley, editorials deliver the science behind ideas, while other journal sections deliver the science behind the experiments and analyses.1 We believe editorials should: (1) stimulate discussion around a specific topic or new study (eg, recent editorials about acute:chronic workload ratios2 3), (2) propose new theories or challenge the existing dogma (eg, whether sports medicine screening adds any value4 5) or (3) deliver a call to action (eg, addressing the myth that obesity is caused by physical inactivity as opposed to a bad diet6). Here, we provide tips for writing an editorial for the British Journal of Sports Medicine (BJSM) and encourage your input on this ‘meta’ discussion. Following the teachings of Sinek,7 editorials need to get straight to the point by starting with why. Why write the editorial? What is the motivation? The opening statement is critical to setting the scene. It may take the form of the principal finding/s from the study/ies being …

PTH is an osteoanabolic for treating osteoporosis but its potency wanes. Disabling the transcription factor nuclear matrix protein 4 (Nmp4) in healthy, ovary-intact mice enhances bone response to PTH and bone morphogenetic protein 2 and protects from unloading-induced osteopenia. These Nmp4−/− mice exhibit expanded bone marrow populations of osteoprogenitors and supporting CD8+ T cells. To determine whether the Nmp4−/− phenotype persists in an osteoporosis model we compared PTH response in ovariectomized (ovx) wild-type (WT) and Nmp4−/− mice. To identify potential Nmp4 target genes, we performed bioinformatic/pathway profiling on Nmp4 chromatin immunoprecipitation sequencing (ChIP-seq) data. Mice (12 w) were ovx or sham operated 4 weeks before the initiation of PTH therapy. Skeletal phenotype analysis included microcomputed tomography, histomorphometry, serum profiles, fluorescence-activated cell sorting and the growth/mineralization of cultured WT and Nmp4−/− bone marrow mesenchymal stem progenitor cells (MSPCs). ChIP-seq data were derived using MC3T3-E1 preosteoblasts, murine embryonic stem cells, and 2 blood cell lines. Ovx Nmp4−/− mice exhibited an improved response to PTH coupled with elevated numbers of osteoprogenitors and CD8+ T cells, but were not protected from ovx-induced bone loss. Cultured Nmp4−/− MSPCs displayed enhanced proliferation and accelerated mineralization. ChIP-seq/gene ontology analyses identified target genes likely under Nmp4 control as enriched for negative regulators of biosynthetic processes. Interrogation of mRNA transcripts in nondifferentiating and osteogenic differentiating WT and Nmp4−/− MSPCs was performed on 90 Nmp4 target genes and differentiation markers. These data suggest that Nmp4 suppresses bone anabolism, in part, by regulating IGF-binding protein expression. Changes in Nmp4 status may lead to improvements in osteoprogenitor response to therapeutic cues.

ContextInsulin resistance is an adverse health outcome that accompanies obesity. Fat mass is negatively associated with the bone mass after adjustment for confounders. Insulin resistance might be an intermediary in this relationship.ObjectiveTo determine whether insulin resistance is an intermediary in the relationship between adiposity and bone mass in adolescents.DesignCross-sectional secondary analysis of baseline data from a previous randomized trial.SettingUniversity research facility.ParticipantsA total of 240 adolescents (68% female), aged 7 to 15 years.Main Outcome MeasuresUsing dual energy x-ray absorptiometry, bone mineral content (BMC), areal bone mineral density, lean mass, and fat mass were measured. Skeletal sites of interest included the total body and lumbar spine (LS). Waist circumference was measured using an anthropometric tape measure. Insulin and glucose were measured in fasting sera, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Path analysis was performed to determine whether the relationship between adiposity and bone was mediated through insulin resistance.ResultsFat mass (r = 0.467; P < 0.001) and waist circumference (r = 0.487; P < 0.001) correlated positively with HOMA-IR. Controlling for race, sex, maturation, lean mass, and height, fat mass, waist circumference, and HOMA-IR were negatively associated with LS BMC and total body areal bone mineral density (P < 0.05 for all). Additionally, path models for fat mass (95% CI, −5.893 to −0.956) and waist circumference (95% CI, −15.473 to −2.124) showed a negative relationship with LS BMC via HOMA-IR.ConclusionsThese results support an intermediary role of insulin resistance in the relationship between adiposity and LS bone mass.

Approximately 10% of all bone fractures do not heal, resulting in patient morbidity and healthcare costs. However, no pharmacological treatments are currently available to promote efficient bone healing. Inhibition of Ca2+ /calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) reverses age-associated loss of trabecular and cortical bone volume and strength in mice. In the current study, we investigated the role of CaMKK2 in bone fracture healing and show that its pharmacological inhibition using STO-609 accelerates early cellular and molecular events associated with endochondral ossification, resulting in a more rapid and efficient healing of the fracture. Within 7 days postfracture, treatment with STO-609 resulted in enhanced Indian hedgehog signaling, paired-related homeobox (PRX1)-positive mesenchymal stem cell (MSC) recruitment, and chondrocyte differentiation and hypertrophy, along with elevated expression of osterix, vascular endothelial growth factor, and type 1 collagen at the fracture callus. Early deposition of primary bone by osteoblasts resulted in STO-609-treated mice possessing significantly higher callus bone volume by 14 days following fracture. Subsequent rapid maturation of the bone matrix bestowed fractured bones in STO-609-treated animals with significantly higher torsional strength and stiffness by 28 days postinjury, indicating accelerated healing of the fracture. Previous studies indicate that fixed and closed femoral fractures in the mice take 35 days to fully heal without treatment. Therefore, our data suggest that STO-609 potentiates a 20% acceleration of the bone healing process. Moreover, inhibiting CaMKK2 also imparted higher mechanical strength and stiffness at the contralateral cortical bone within 4 weeks of treatment. Taken together, the data presented here underscore the therapeutic potential of targeting CaMKK2 to promote efficacious and rapid healing of bone fractures and as a mechanism to strengthen normal bones. © 2018 American Society for Bone and Mineral Research.