Which risk factors determine cartilage thickness and composition change in radiographically normal knees? - Data from the Osteoarthritis Initiative.

Objective: Therapy for osteoarthritis ideally aims at preserving structure before radiographic change occurs. This study tests: a) whether longitudinal deterioration in cartilage thickness and composition (transverse relaxation-time T2) are greater in radiographically normal knees "at risk" of incident osteoarthritis than in those without risk factors; and b) which risk factors may be associated with these deteriorations. Design: 755 knees from the Osteoarthritis Initiative were studied; all were bilaterally Kellgren Lawrence grade [KLG] 0 initially, and had magnetic resonance images available at 12- and 48-month follow-up. 678 knees were "at risk", whereas 77 were not (i.e., non-exposed reference). Cartilage thickness and composition change was determined in 16 femorotibial subregions, with deep and superficial T2 being analyzed in a subset (n â€‹= â€‹59/52). Subregion values were used to compute location-independent change scores. Results: In KLG0 knees "at risk", the femorotibial cartilage thinning score (-634 â€‹± â€‹516 â€‹µm) over 3 years exceeded the thickening score by approximately 20%, and was 27% greater (p â€‹< â€‹0.01; Cohen D -0.27) than the thinning score in "non-exposed" knees (-501 â€‹± â€‹319 â€‹µm). Superficial and deep cartilage T2 change, however, did not differ significantly between both groups (p â€‹≥ â€‹0.38). Age, sex, body mass index, knee trauma/surgery history, family history of joint replacement, presence of Heberden's nodes, repetitive knee bending were not significantly associated with cartilage thinning (r2<1%), with only knee pain reaching statistical significance. Conclusions: Knees "at risk" of incident knee OA displayed greater cartilage thinning scores than those "non-exposed". Except for knee pain, the greater cartilage loss was not significantly associated with demographic or clinical risk factors.

The specialist in regeneration-the Axolotl-a suitable model to study bone healing?

While the axolotl's ability to completely regenerate amputated limbs is well known and studied, the mechanism of axolotl bone fracture healing remains poorly understood. One reason might be the lack of a standardized fracture fixation in axolotl. We present a surgical technique to stabilize the osteotomized axolotl femur with a fixator plate and compare it to a non-stabilized osteotomy and to limb amputation. The healing outcome was evaluated 3 weeks, 3, 6 and 9 months post-surgery by microcomputer tomography, histology and immunohistochemistry. Plate-fixated femurs regained bone integrity more efficiently in comparison to the non-fixated osteotomized bone, where larger callus formed, possibly to compensate for the bone fragment misalignment. The healing of a non-critical osteotomy in axolotl was incomplete after 9 months, while amputated limbs efficiently restored bone length and structure. In axolotl amputated limbs, plate-fixated and non-fixated fractures, we observed accumulation of PCNA+ proliferating cells at 3 weeks post-injury similar to mouse. Additionally, as in mouse, SOX9-expressing cells appeared in the early phase of fracture healing and amputated limb regeneration in axolotl, preceding cartilage formation. This implicates endochondral ossification to be the probable mechanism of bone healing in axolotls. Altogether, the surgery with a standardized fixation technique demonstrated here allows for controlled axolotl bone healing experiments, facilitating their comparison to mammals (mice).

Radiographically normal knees with contralateral joint space narrowing display greater change in cartilage transverse relaxation time than those with normal contralateral knees: a model of early OA? - data from the Osteoarthritis Initiative (OAI).

OBJECTIVE: To develop a model of early osteoarthritis, by examining whether radiographically normal knees with contralateral joint space narrowing (JSN), but without contralateral trauma history, display greater longitudinal cartilage composition change (transverse relaxation time; T2) than subjects with bilaterally normal knees. METHODS: 120 radiographically normal knees (Kellgren Lawrence grade [KLG] 0) from the Osteoarthritis Initiative were studied. 60 case knees displayed definite contralateral radiographic knee osteoarthritis (KLG ≥ 2) whereas 60 reference subjects were bilaterally KLG0, and were matched 1:1 to cases based on age, sex, and BMI. All had multi-echo spin-echo MRI acquired at year (Y) 1 and 4 follow-up, with cartilage T2 being determined in superficial and deep cartilage layers across 16 femorotibial subregions. T2 across all regions was considered the primary analytic focus. RESULTS: Of 60 KLG0 case knees (30 female, age: 65.0 ± 8.8 y, BMI: 27.6 ± 4.4 kg/m2), 21/22/13/4 displayed contralateral JSN 0/1/2/3, respectively. The longitudinal increase in the deep layer cartilage T2 between Y1 and Y4 was significantly greater (P = 0.03; Cohen's D 0.50) in the 39 KLG0 case knees with contralateral JSN (1.2 ms; 95% confidence interval [CI] [0.4, 2.0]) than in matched KLG0 reference knees (0.1 ms; 95% CI [-0.5, 0.7]). No significant differences were identified in superficial T2 change. T2 at Y1 was significantly greater in case than in reference knees, particularly in the superficial layer of the medial compartment. CONCLUSIONS: Radiographically normal knees with contralateral, non-traumatic JSN represent an applicable model of early osteoarthritis, with deep layer cartilage composition (T2) changing more rapidly than in bilaterally normal knees. CLINICALTRIALS. GOV IDENTIFICATION: NCT00080171.

T1 and T2* mapping of the human quadriceps and patellar tendons using ultra-short echo-time (UTE) imaging and bivariate relaxation parameter-based volumetric visualization.

Quantification of magnetic resonance (MR)-based relaxation parameters of tendons and ligaments is challenging due to their very short transverse relaxation times, requiring application of ultra-short echo-time (UTE) imaging sequences. We quantify both T1 and T2* in the quadriceps and patellar tendons of healthy volunteers at a field strength of 3 T and visualize the results based on 3D segmentation by using bivariate histogram analysis. We applied a 3D ultra-short echo-time imaging sequence with either variable repetition times (VTR) or variable flip angles (VFA) for T1 quantification in combination with multi-echo acquisition for extracting T2*. The values of both relaxation parameters were subsequently binned for bivariate histogram analysis and corresponding cluster identification, which were subsequently visualized. Based on manually-drawn regions of interest in the tendons on the relaxation parameter maps, T1 and T2* boundaries were selected in the bivariate histogram to segment the quadriceps and patellar tendons and visualize the relaxation times by 3D volumetric rendering. Segmentation of bone marrow, fat, muscle and tendons was successfully performed based on the bivariate histogram analysis. Based on the segmentation results mean T2* relaxation times, over the entire tendon volumes averaged over all subjects, were 1.8 ms ±â€¯0.1 ms and 1.4 ms ±â€¯0.2 ms for the patellar and quadriceps tendons, respectively. The mean T1 value of the patellar tendon, averaged over all subjects, was 527 ms ±â€¯42 ms and 476 ms ±â€¯40 ms for the VFA and VTR acquisitions, respectively. The quadriceps tendon had higher mean T1 values of 662 ms ±â€¯97 ms (VFA method) and 637 ms ±â€¯40 ms (VTR method) compared to the patellar tendon. 3D volumetric visualization of the relaxation times revealed that T1 values are not constant over the volume of both tendons, but vary locally. This work provided additional data to build upon the scarce literature available on relaxation times in the quadriceps and patellar tendons. We were able to segment both tendons and to visualize the relaxation parameter distributions over the entire tendon volumes.

From macroscopic mechanics to cell-effective stiffness within highly aligned macroporous collagen scaffolds.

In the design of macroporous biomaterial scaffolds, attention is payed predominantly to the readily accessible macroscopic mechanical properties rather than to the mechanical properties experienced by the cells adhering to the material. However, the direct cell mechanical environment has been shown to be of special relevance for biological processes such as proliferation, differentiation and extracellular matrix formation both in vitro and in vivo. In this study we investigated how individual architectural features of highly aligned macroporous collagen scaffolds contribute to its mechanical properties on the macroscopic vs. the microscopic scale. Scaffolds were produced by controlled freezing and freeze-drying, a method frequently used for manufacturing of macroporous biomaterials. The individual architectural features of the biomaterial were carefully characterized to develop a finite element model (FE-model) that finally provided insights in the relation between the biomaterial's mechanical properties on the macro-scale and the properties on the micro-scale, as experienced by adhering cells. FE-models were validated by experimental characterization of the scaffolds, both on the macroscopic and the microscopic level, using mechanical compression testing and atomic force microscopy. As a result, a so-called cell-effective stiffness of these non-trivial scaffold architectures could be predicted for the first time. A linear dependency between the macroscopic scaffold stiffness and the cell-effective stiffness was found, with the latter being consistently higher by a factor of 6.4 ±â€¯0.6. The relevance of the cell-effective stiffness in controlling progenitor cell differentiation was confirmed in vitro. The obtained information about the cell-effective stiffness is of particular relevance for the early stages of tissue regeneration, when the cells first populate and interact with the biomaterial. Beyond the specific biomaterial investigated here, the introduced method is transferable to other complex biomaterial architectures. Design-optimization in 3D macroporous scaffolds that are based on a deeper understanding of the mechanical environment provided to the cells will help to enhance biomaterial-based tissue regeneration approaches.

Author Correction: Tibio-Femoral Contact Force Distribution is Not the Only Factor Governing Pivot Location after Total Knee Arthroplasty.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Tibio-Femoral Contact Force Distribution is Not the Only Factor Governing Pivot Location after Total Knee Arthroplasty.

Total knee arthroplasty aims to mimic the natural knee kinematics by optimizing implant geometry, but it is not clear how loading relates to tibio-femoral anterior-posterior translation or internal-external pivoting. We hypothesised that the point of pivot in the transverse plane is governed by the location of the highest axial force. Tibio-femoral loading was measured using an instrumented tibial component in six total knee arthroplasty patients (aged 65-80y, 5-7y post-op) during 5-6 squat repetitions, while knee kinematics were captured using a mobile video-fluoroscope. In the range of congruent tibio-femoral contact the medial femoral condyle remained approximately static while the lateral condyle translated posteriorly by 4.1 mm (median). Beyond the congruent range, the medial and lateral condyle motions both abruptly changed to anterior sliding by 4.6 mm, and 2.6 mm respectively. On average, both the axial loading and pivot position were more medial near extension, and transferred to the lateral side in flexion. However, no consistent relationship between pivoting and load distribution was found across all patients throughout flexion, with R2 values ranging from 0.00 to 0.65. Tibio-femoral kinematics is not related to the load distribution alone: medial loading of the knee does not necessarily imply a medial pivot location.

Cartilage loss in radiographically normal knees depends on radiographic status of the contralateral knee - data from the Osteoarthritis Initiative.

OBJECTIVE: To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis (OA), but without contralateral trauma history, display greater cartilage thickness loss than knees from subjects with bilaterally radiographically normal knees. METHODS: 828 radiographically normal knees (Kellgren Lawrence grade [KLG] 0) from the Osteoarthritis Initiative [OAI] were studied; 150 case knees displayed definite radiographic knee OA (KLG ≥ 2) contralaterally, and had MRI double echo steady state (DESS) images available at 12 and 48 month follow-up. 678 reference knees displayed KLG0 at the contralateral side. Cartilage thickness change was determined in femorotibial subregions and location-independent cartilage thinning scores were computed. Case and reference knees were compared using ANCOVA. RESULTS: Of the 150 KLG0 case knees, 108 had a contralateral KLG2 knee (50 without, and 58 with joint space narrowing [JSN]), 31 a KLG3 and 11 a KLG4 knee. The cartilage thinning score tended to be greater in case than reference knees; the cartilage thinning score in KLG0 case knees with contralateral radiographic JSN (-858 µm; [95% confidence interval -1016, -701 µm]) was significantly greater (P = 0.0012) than that in bilaterally KLG0 reference knees (-634 µm; [-673, -596 µm]), whereas KLG0 knees with contralateral KLG2 without JSN only showed relatively small thinning scores (-530 µm, [-631, -428 µm]). Region-specific analysis suggested greater rates of cartilage loss in case than in reference knees in the lateral, rather than medial, femorotibial compartment. CONCLUSIONS: Radiographically normal knees with contralateral JSN may serve as a human model of early OA, for testing disease modifying drugs in clinical trials designed to prevent cartilage loss before the onset of radiographic change. CLINICALTRIALS. GOV IDENTIFICATION: NCT00080171.

A biomaterial with a channel-like pore architecture induces endochondral healing of bone defects.

Biomaterials developed to treat bone defects have classically focused on bone healing via direct, intramembranous ossification. In contrast, most bones in our body develop from a cartilage template via a second pathway called endochondral ossification. The unsolved clinical challenge to regenerate large bone defects has brought endochondral ossification into discussion as an alternative approach for bone healing. However, a biomaterial strategy for the regeneration of large bone defects via endochondral ossification is missing. Here we report on a biomaterial with a channel-like pore architecture to control cell recruitment and tissue patterning in the early phase of healing. In consequence of extracellular matrix alignment, CD146+ progenitor cell accumulation and restrained vascularization, a highly organized endochondral ossification process is induced in rats. Our findings demonstrate that a pure biomaterial approach has the potential to recapitulate a developmental bone growth process for bone healing. This might motivate future strategies for biomaterial-based tissue regeneration.

A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge.

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232-243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1.

Rapid detection of periprosthetic joint infection using a combination of 16s rDNA polymerase chain reaction and lateral flow immunoassay: A Pilot Study.

OBJECTIVES: The objective of this study was to develop a test for the rapid (within 25 minutes) intraoperative detection of bacteria from synovial fluid to diagnose periprosthetic joint infection (PJI). METHODS: The 16s rDNA test combines a polymerase chain reaction (PCR) for amplification of 16s rDNA with a lateral flow immunoassay in one fully automated system. The synovial fluid of 77 patients undergoing joint aspiration or primary or revision total hip or knee surgery was prospectively collected. The cohort was divided into a proof-of-principle cohort (n = 17) and a validation cohort (n = 60). Using the proof-of-principle cohort, an optimal cut-off for the discrimination between PJI and non-PJI samples was determined. PJI was defined as detection of the same bacterial species in a minimum of two microbiological samples, positive histology, and presence of a sinus tract or intra-articular pus. RESULTS: The 16s rDNA test proved to be very robust and was able to provide a result in 97% of all samples within 25 minutes. The 16s rDNA test was able to diagnose PJI with a sensitivity of 87.5% and 82%, and a specificity of 100% and 89%, in the proof-of-principle and validation cohorts, respectively. The microbiological culture of synovial fluid achieved a sensitivity of 80% and a specificity of 93% in the validation cohort. CONCLUSION: The 16s rDNA test offers reliable intraoperative detection of all bacterial species within 25 minutes with a sensitivity and specificity comparable with those of conventional microbiological culture of synovial fluid for the detection of PJI. The 16s rDNA test performance is independent of possible blood contamination, culture time and bacterial species.Cite this article: V. Janz, J. Schoon, C. Morgenstern, B. Preininger, S. Reinke, G. Duda, A. Breitbach, C. F. Perka, S. Geissler. Rapid detection of periprosthetic joint infection using a combination of 16s rDNA polymerase chain reaction and lateral flow immunoassay: A Pilot Study. Bone Joint Res 2018;7:12-19. DOI: 10.1302/2046-3758.71.BJR-2017-0103.R2.

Mechanosensation across borders: fibroblasts inside a macroporous scaffold sense and respond to the mechanical environment beyond the scaffold walls.

In tissue defects, cells face distinct mechanical boundary conditions, but how this influences early stages of tissue regeneration remains largely unknown. Biomaterials are used to fill defects but also to provide specific mechanical or geometrical signals. However, they might at the same time shield mechanical information from surrounding tissues that is relevant for tissue functionalisation. This study investigated how fibroblasts in a soft macroporous biomaterial scaffold respond to distinct mechanical environments while they form microtissues. Different boundary stiffnesses counteracting scaffold contraction were provided via a newly developed in vitro setup. Online monitoring over 14 days revealed 3.0 times lower microtissue contraction but 1.6 times higher contraction force for high vs. low stiffness. This difference was significant already after 48 h, a very early stage of microtissue growth. The microtissue's mechanical and geometrical adaptation indicated a collective cellular behaviour and mechanical communication across scaffold pore walls. Surprisingly, the stiffness of the environment influenced cell behaviour even inside macroporous scaffolds where direct cell-cell contacts are hindered. Mechanical communication between cells via traction forces is essential for tissue adaptation to the environment and should not be blocked by rigid biomaterials. Copyright © 2017 John Wiley & Sons, Ltd.

In vivo hip joint loads and pedal forces during ergometer cycling.

The rising prevalence of osteoarthritis and an increase in total hip replacements calls for attention to potential therapeutic activities. Cycling is considered as a low impact exercise for the hip joint and hence recommended. However, there are limited data about hip joint loading to support this claim. The aim of this study was to measure synchronously the in vivo hip joint loads and pedal forces during cycling. The in vivo hip joint loads were measured in 5 patients with instrumented hip implants. Data were collected at several combinations of power and cadence, at two saddle heights. Joint loads and pedal forces showed strong linear correlation with power. So the relationship between the external pedal forces and internal joint forces was shown. While cycling at different cadences the minimum joint loads were acquired at 60RPM. The lower saddle height configuration results in an approximately 15% increase compared to normal saddle height. The results offered new insights into the actual effects of cycling on the hip joint and can serve as useful tools while developing an optimum cycling regimen for individuals with coxarthrosis or following total hip arthroplasty. Due to the relatively low contact forces, cycling at a moderate power level of 90W at a normal saddle height is suitable for patients.

Mediolateral force distribution at the knee joint shifts across activities and is driven by tibiofemoral alignment.

AIMS: Tibiofemoral alignment is important to determine the rate of progression of osteoarthritis and implant survival after total knee arthroplasty (TKA). Normally, surgeons aim for neutral tibiofemoral alignment following TKA, but this has been questioned in recent years. The aim of this study was to evaluate whether varus or valgus alignment indeed leads to increased medial or lateral tibiofemoral forces during static and dynamic weight-bearing activities. PATIENTS AND METHODS: Tibiofemoral contact forces and moments were measured in nine patients with instrumented knee implants. Medial force ratios were analysed during nine daily activities, including activities with single-limb support (e.g. walking) and double-limb support (e.g. knee bend). Hip-knee-ankle angles in the frontal plane were analysed using full-leg coronal radiographs. RESULTS: The medial force ratio strongly correlated with the tibiofemoral alignment in the static condition of one-legged stance (R² = 0.88) and dynamic single-limb loading (R² = 0.59) with varus malalignment leading to increased medial force ratios of up to 88%. In contrast, the correlation between leg alignment and magnitude of medial compartment force was much less pronounced. A lateral shift of force occurred during activities with double-limb support and higher knee flexion angles. CONCLUSION: The medial force ratio depends on both the tibiofemoral alignment and the nature of the activity involved. It cannot be generalised to a single value. Higher medial ratios during single-limb loading are associated with varus malalignment in TKA. The current trend towards a 'constitutional varus' after joint replacement, in terms of overall tibiofemoral alignment, should be considered carefully with respect to the increased medial force ratio. Cite this article: Bone Joint J 2017;99-B:779-87.

Impaired fracture healing with high non-union rates remains irreversible after traumatic brain injury in leptin-deficient mice.

Patients with traumatic brain injury (TBI) and long-bone fractures can show increased callus formation. This effect has already been reproduced in wild-type (wt) mice. However, the mechanisms remain poorly understood. Leptin is significantly increased following TBI, while its role in bone healing remains unclear. The aim of this study was to evaluate fracture healing in leptin-deficient ob/ob mice and to measure any possible impact of TBI on callus formation. 138 female, 12 weeks old, ob/ob mice were divided into four groups: Control, fracture, TBI and combined trauma. Osteotomies were stabilized with an external fixator; TBI was induced with Controlled Cortical Impact Injury. Callus bridging was weekly evaluated with in vivo micro-CT. Biomechanical testing was performed ex vivo. Micro-CT showed high non-union rates after three and four weeks in the fracture and combined trauma group. No differences were observed in callus volume, density and biomechanical properties at any time point. This study shows that bony bridging is impaired in the present leptin-deficient trauma model. Furthermore, the phenomenon of increased callus formation after TBI could not be reproduced in ob/ob mice, as in wt mice. Our findings suggest that the increased callus formation after TBI may be dependent on leptin signaling.

The haematoma and its role in bone healing.

Fracture treatment is an old endeavour intended to promote bone healing and to also enable early loading and regain of function in the injured limb. However, in today's clinical routine the healing potential of the initial fracture haematoma is still not fully recognized. The Arbeitsgemeinschaft für Osteosynthesefragen (AO) formed in Switzerland in 1956 formulated four AO principles of fracture treatment which are still valid today. Fracture treatment strategies have continued to evolve further, as for example the relatively new concept of minimally invasive plate osteosynthesis (MIPO). This MIPO treatment strategy harbours the benefit of an undisturbed original fracture haematoma that supports the healing process. The extent of the supportive effect of this haematoma for the bone healing process has not been considered in clinical practice so far. The rising importance of osteoimmunological aspects in bone healing supports the essential role of the initial haematoma as a source for inflammatory cells that release the cytokine pattern that directs cell recruitment towards the injured tissue. In reviewing the potential benefits of the fracture haematoma, the early development of angiogenic and osteogenic potentials within the haematoma are striking. Removing the haematoma during surgery could negatively influence the fracture healing process. In an ovine open tibial fracture model the haematoma was removed 4 or 7 days after injury and the bone that formed during the first two weeks of healing was significantly reduced in comparison with an undisturbed control. These findings indicate that whenever possible the original haematoma formed upon injury should be conserved during clinical fracture treatment to benefit from the inherent healing potential.

[Steel or titanium for osteosynthesis : A mechanobiological perspective]. / Stahl oder Titan bei der Osteosynthese : Eine mechanobiologische Perspektive.

BACKGROUND: An implant used for stabilizing a fracture creates a mechanical construct, which directly determines the biology of bone healing. The stabilization of fractures places high mechanical demands on implants and therefore steel and titanium are currently almost exclusively used as the materials of choice. OBJECTIVES: The possible range of attainable mechanobiological stimulation for mechanotherapy as a function of plate stiffness depending on the selection of the plate material and the physical and mechanical properties of the material options are discussed. MATERIAL AND METHODS: An overview of the material properties of steel and titanium is given. For dynamically fixed long bone fractures as examples, various finite element models of plate osteosynthesis (steel/titanium) are created and the plate working length (PWL, screw configuration close to fracture) is varied. The interfragmentary movement (IFM) as a measure of mechanobiological stimulation is evaluated. RESULTS: Stimulation in the form of IFM varies across the fracture and also as a function of the osteosynthesis material and the configuration. The influence of the material appears to be notably smaller than the influence of PWL but both lose their influence largely over a bridged fracture situation (contact). With a flexible titanium plate and large PSS, a greater mechanobiological stimulation is produced. CONCLUSION: An essential prerequisite for the secondary fracture healing is an appropriate mechanobiological environment, which can be controlled by the osteosynthesis material and the configuration and is also affected by the type of fracture and load.

Muscle and tendon adaptation in adolescent athletes: A longitudinal study.

There is evidence that a non-uniform adaptation of muscle and tendon in young athletes results in increased tendon stress during mid-adolescence. The present longitudinal study investigated the development of the morphological and mechanical properties of muscle and tendon of volleyball athletes in a time period of 2 years from mid-adolescence to late adolescence. Eighteen elite volleyball athletes participated in magnetic resonance imaging and ultrasound-dynamometry sessions to determine quadriceps femoris muscle strength, vastus lateralis, medialis and intermedius morphology, and patellar tendon mechanical and morphological properties in mid-adolescence (16 ± 1 years) and late adolescence (18 ± 1 years). Muscle strength, anatomical cross-sectional area (CSA), and volume showed significant (P < 0.05) but moderate increases of 13%, 6%, and 6%, respectively. The increase of patellar tendon CSA (P < 0.05) was substantially greater (27%) and went in line with increased stiffness (P < 0.05; 25%) and reduced stress (P < 0.05; 9%). During late adolescence, a pronounced hypertrophy of the patellar tendon led to a mechanical strengthening of the tendon in relation to the functional and morphological development of the muscle. These adaptive processes may compensate the unfavorable relation of muscle strength and tendon loading capacity in mid-adolescence and might have implications on athletic performance and tendon injury risk.

Longitudinal bone, muscle and adipose tissue changes in physically active subjects - sex differences during adolescence and maturity.

OBJECTIVES: To explore changes in bone, muscle and adipose tissue composition in athletes with high physical activity levels at different stages of life. METHODS: Thigh MRIs were acquired at baseline and 2-year follow-up for 20 young (16±1 years) and 20 mature (46±5 years) athletes (10 males, 10 females, respectively). Longitudinal changes in cross-sectional areas (CSAs) of femoral bone, quadriceps muscle, and thigh subcutaneous (SCF) and intermuscular (IMF) adipose tissue were evaluated. RESULTS: Adolescent males displayed significant muscle (+5.0%, 95%CI: 0.8, 9.2) and bone growth (+2.9%, 95%CI: 1.3, 4.5), whereas adolescent females did not (muscle: +0.8%, 95%CI: -2.2, 3.8; bone: +1.9%, 95%CI: -2.1, 5.6). Adolescent and mature females showed significant SCF increases (+11.0%, 95%CI: 0.9, 21.1 and +6.0%, 95%CI: 0.6, 11.4, respectively), whereas adolescent and mature males did not (+7.2%, 95%CI: -8.0, 22.5 and +1.5%, 95%CI: -9.7, 11.8, respectively). Muscle and bone changes were highly correlated in adolescent males (r=0.66), mature males (r=0.75) and mature females (r=0.68) but not in adolescent females (r=-0.11). CONCLUSIONS: The results suggest sex-specific patterns of age-related change in bone, muscle and adipose tissue, and tight coupling of bone and muscle growth. Sex-specific bone-muscle-adipose tissue relationships may have implications for understanding sex differences in fracture risk.