Microfracture technique combined with mesenchymal stem cells inducer represses miR-708-5p to target special at-rich sequence-binding protein 2 to drive cartilage repair and regeneration in rabbit knee osteoarthritis.

Knee osteoarthritis (KOA) is a degenerative joint illness which leads to knee pain and functional limitation. In this study, we combined microfracture surgery with kartogenin (KGN), a small bioactive molecule used to promote the differentiation of mesenchymal stem cells (MSCs), and explored its impact on cartilage repair and possible latent mechanisms of action. The research offers a brand-new idea for the clinical cure of KOA. The microfracture technique in combination with KNG treatment was performed on a rabbit model of KOA. Animal behaviour was evaluated after the intra-articular injection of miR-708-5p and Special AT-rich sequence binding protein 2 (SATB2) lentiviruses. Later, the expression of the tumour necrosis factor α (TNF-α) and interleukin- 1 (IL-1), the pathology of synovial tissue and cartilage tissue, and the positive cartilage type II collagen, MMP-1, MMP-3 and TIMP-1 were detected. Finally, a luciferase assay was conducted to verify the interaction of miR-708-5p and SATB2. Our results showed that miR-708-5p was elevated in the rabbit KOA model; however, the expression of SATB2 was reduced. Meanwhile, the microfracture technology combined with MSCs inducer KGN drove cartilage repair and regeneration in rabbit KOA by repressing the miR-708-5p expression. We also found that miR-708-5p directly targeted the SATB2 mRNA to regulate its expression. Furthermore, our data urged that elevating miR-708-5p or restraining SATB2 may reverse the therapeutic effect of the microfracture technique combined with MSCs inducer on rabbit KOA. Microfracture technique combined with MSCs inducer represses miR-708-5p to target SATB2 to drive cartilage repair and regeneration in rabbit KOA. This indicates that the microfracture technique combined with MSCs inducers is supposed to be an effective latent method for osteoarthritis cure.

The Effect of Injection of Secretome of Umbilical Cord Mesenchymal Stem Cells in Articular Cartilage Repair in Sheep Model.

INTRODUCTION: Articular cartilage is an avascular, aneural, and lymphatic tissue with limited capacity to regenerate. Numerous techniques have been employed to repair or regenerate; however, the success rate varies. In fact, most of them result in the formation of fibrocartilage, not hyaline cartilage. The future of treating cartilage defects lies in providing biological solutions through cartilage regeneration. Mesenchymal stem cells (MSCs) represent a promising therapy for cartilage regeneration. These cells secrete factors that enhance cartilage repair. This study studied the effects of intra-articular injection of human umbilical cord MSC (hUC-MSC) secretome on cartilage damage in a sheep model. METHODS: Standardized rectangular (5x5 mm) full-thickness chondral defects were created in the lateral femoral condyle of 15 adult sheep and debrided down to the subchondral bone plate. Three treatment groups were tested: 4 microfracture perforations using 1.0mm diameter awls (group 1), intra-articular injection of hUC-MSC secretome (group 2), and a combination of microfracture and intra-articular injection of hUC-MSC secretome (group 3). The osteochondral repair was assessed at 6 months using an established macroscopic and histological analyses. RESULTS: Macroscopically, combined therapy application shows significant cartilage repair improvement compared to microfracture alone (p=0.004). Microscopically, the application of combined therapy shows significant improvement of cartilage repair compared to secretome injection alone (p=0.031). CONCLUSION: Microfracture combined with injection of hUCB-MSCs secretome could be an effective alternative for repairing articular cartilage defects in vivo.

Cartilaginous Metabolomics Reveals the Biochemical-Niche Fate Control of Bone Marrow-Derived Stem Cells.

Joint disorders have become a global health issue with the growth of the aging population. Screening small active molecules targeting chondrogenic differentiation of bone marrow-derived stem cells (BMSCs) is of urgency. In this study, microfracture was employed to create a regenerative niche in rabbits (n = 9). Cartilage samples were collected four weeks post-surgery. Microfracture-caused morphological (n = 3) and metabolic (n = 6) changes were detected. Non-targeted metabolomic analysis revealed that there were 96 differentially expressed metabolites (DEMs) enriched in 70 pathways involved in anti-inflammation, lipid metabolism, signaling transduction, etc. Among the metabolites, docosapentaenoic acid 22n-3 (DPA) and ursodeoxycholic acid (UDCA) functionally facilitated cartilage defect healing, i.e., increasing the vitality and adaptation of the BMSCs, chondrogenic differentiation, and chondrocyte functionality. Our findings firstly reveal the differences in metabolomic activities between the normal and regenerated cartilages and provide a list of endogenous biomolecules potentially involved in the biochemical-niche fate control for chondrogenic differentiation of BMSCs. Ultimately, the biomolecules may serve as anti-aging supplements for chondrocyte renewal or as drug candidates for cartilage regenerative medicine.

The combination of microfracture with induction of Wnt / ß- Catenin pathway, leads to enhanced cartilage regeneration.

INTRODUCTION: Microfracture does not lead to complete healing of full-thickness cartilage defects. The aim of this study was to evaluate the effect of modifying Wnt/ß-catenin signaling following microfracture, on the restoration of a full-thickness cartilage defect in a rabbit model. The modification of the canonical Wnt pathway was achieved through per os administration of lithium carbonate, which is an intracellular inhibitor of glycogen synthase kinase 3-ß (Gsk3-ß) and therefore induces Wnt/ß-catenin signaling. MATERIALS AND METHODS: Full-thickness cartilage defects of 4 mm in diameter were created in the patellar groove of the right femurs of 18 male New Zealand white rabbits. The rabbits were divided into three groups of six (n = 6) based on post-surgery treatment differences, as follows: microfracture only (group 1), microfracture plus lithium carbonate 7 mM in the drinking water for 1 week (group 2), microfracture plus lithium carbonate 7 mM in the drinking water for 4 weeks (group 3). All animals were sacrificed 9 weeks after surgery. The outcome was assessed histologically, by using the International Cartilage Repair Society (ICRS) visual histological scale. Immunohistochemistry for type II collagen was also conducted. RESULTS: Statistical analysis of the histological ICRS scores showed that group 3 was significantly superior to group 1 in four out of six ICRS categories, while group 2 was superior to 1 in only two out of six. CONCLUSION: The combination of microfracture and systematic administration of lithium carbonate 7 mM for 4 weeks shows statistically significant superiority in four out of six ICRS categories compared with microfracture only for the treatment of full-thickness cartilage defects in a rabbit experimental model.

Elevated Microdamage Spatially Correlates with Stress in Metastatic Vertebrae.

Metastasis of cancer to the spine impacts bone quality. This study aims to characterize vertebral microdamage secondary to metastatic disease considering the pattern of damage and its relationship to stress and strain under load. Osteolytic and mixed osteolytic/osteoblastic vertebral metastases were produced in athymic rats via HeLa cervical or canine Ace-1 prostate cancer cell inoculation, respectively. After 21 days, excised motion segments (T12-L2) were µCT scanned, stained with BaSO4 and re-imaged. T13-L2 motion segments were loaded in axial compression to induce microdamage, re-stained and re-imaged. L1 (loaded) and T12 (unloaded) vertebrae were fixed, sample blocks cut, polished and BSE imaged. µFE models were generated of all L1 vertebrae with displacement boundary conditions applied based on the loaded µCT images. µCT stereological analysis, BSE analysis and µFE derived von Mises stress and principal strains were quantitatively compared (ANOVA), spatial correlations determined and patterns of microdamage assessed qualitatively. BaSO4 identified microdamage was found to be spatially correlated with regions of high stress in µFEA. Load-induced microdamage was shown to be elevated in the presence of osteolytic and mixed metastatic disease, with diffuse, crossed hatched areas of microdamage present in addition to linear microdamage and microfractures in metastatic tissue, suggesting diminished bone quality.

Stress Fractures: Concepts and Therapeutics.

Context: Stress fractures are repetitive use injuries in which recurrent strains lead to material fatigue and microarchitectural discontinuities. They account for up to 20% of athletic injuries, more often in women and in the setting of track-and-field events. In women, menstrual disturbances, low body mass index, low energy intake, and sometimes low bone mass, may be contributing factors. There are no standard protocols for evaluation or management of stress fractures. Evidence Acquisition: Available literature published in English was retrieved using the following terms: stress fractures; fractures; osteoporosis, athletes, premenopausal women, and athletic triad; through PubMed. Reviews, original reports, and case reports were all included. Evidence Synthesis: Despite lack of consistency among the publications, a phenotype emerges, namely of individuals whose bone mineral density is reduced along with low intake of dietary calcium and low circulating levels of 25-hydroxy vitamin D. Limited experience suggests that calcium and vitamin D supplementation might be helpful. Bisphosphonates or teriparatide may accelerate fracture healing in special circumstances. Conclusions: Most individuals who experience a stress fracture are young and healthy and do not appear to have an underlying metabolic bone disease. On the other hand, the presence of low bone mass and hormonal disturbances in some afflicted individuals might identify a cohort who needs endocrinological attention. Prospective, well-designed studies of stress fractures are needed to elucidate further underlying pathophysiological elements that predispose such individuals. Guidelines for prevention and treatment may follow from such well-controlled studies.

Material heterogeneity in cancellous bone promotes deformation recovery after mechanical failure.

Many natural structures use a foam core and solid outer shell to achieve high strength and stiffness with relatively small amounts of mass. Biological foams, however, must also resist crack growth. The process of crack propagation within the struts of a foam is not well understood and is complicated by the foam microstructure. We demonstrate that in cancellous bone, the foam-like component of whole bones, damage propagation during cyclic loading is dictated not by local tissue stresses but by heterogeneity of material properties associated with increased ductility of strut surfaces. The increase in surface ductility is unexpected because it is the opposite pattern generated by surface treatments to increase fatigue life in man-made materials, which often result in reduced surface ductility. We show that the more ductile surfaces of cancellous bone are a result of reduced accumulation of advanced glycation end products compared with the strut interior. Damage is therefore likely to accumulate in strut centers making cancellous bone more tolerant of stress concentrations at strut surfaces. Hence, the structure is able to recover more deformation after failure and return to a closer approximation of its original shape. Increased recovery of deformation is a passive mechanism seen in biology for setting a broken bone that allows for a better approximation of initial shape during healing processes and is likely the most important mechanical function. Our findings suggest a previously unidentified biomimetic design strategy in which tissue level material heterogeneity in foams can be used to improve deformation recovery after failure.

[Pathogenesis of atypical femoral fracture].

We demonstrated microdamage accumulation in the fracture sites in the patients of subtrochanteric atypical femoral fracture with long term bisphosphonate therapy and of incomplete shaft fracture of lateral femoral bowing without bisphosphonate therapy. Based on these findings, pathogenesis of atypical femoral fracture is revealed stress fracture caused by accumulation of microdamages between distal to the lesser trochanter and proximal to the supracondylar flare in the femur in association with severely suppressed bone turnover and/or abnormal lower limb alignment, that causes stress concentration on the lateral side cortex of the femur.

The cumulative incidence of and risk factors for latent beaking in patients with autoimmune diseases taking long-term glucocorticoids and bisphosphonates.

SUMMARY: The incidence of beaking, which has been reported to precede atypical femoral fracture, was high and increased over 2 years in patients with autoimmune diseases who were taking bisphosphonates and glucocorticoids. Regular femoral X-rays are strongly recommended to screen for beaking, and bisphosphonate drug holidays should be considered. INTRODUCTION: Atypical femoral fractures (AFFs) have been recently recognized as complications associated with bisphosphonate (BP) use. AFFs are considered to be stress fractures; localized periosteal thickening of the lateral cortex is often present at the fracture site; this thickening is termed "beaking." Beaking has been reported to precede AFF. The aims of the present study were to evaluate the incidence of latent beaking in patients with autoimmune diseases taking BPs and glucocorticoids and to identify risk factors for beaking. METHODS: A total of 125 patients with autoimmune diseases who were taking BPs and glucocorticoids was included; 116 patients underwent X-rays and analysis of serum and urine bone metabolic markers annually for 2 years. Mean patient age was 54.5 years; there were 105 (90.5%) females and the mean duration of disease was 13.2 years. Focal lateral cortical thickening in femoral X-rays was defined as beaking. RESULTS: Beaking was detected in 15 femora of 10 patients (8.0%) at the time of recruitment. Over the 2-year observation period, the incidence of beaking increased to 21 femora of 12 patients (10.3%), and a complete AFF at the location of beaking occurred in one patient. Beaking was associated with a longer duration of BP treatment (6.1 ± 1.0 years vs. 5.0 ± 2.9 years, p = 0.01). Age 40-60 years, BP therapy ≥4 years, and diabetes mellitus were significantly associated with beaking. CONCLUSIONS: The incidence of beaking was high, and increased over 2 years, in patients with autoimmune diseases who were taking BPs and glucocorticoids. Regular femoral X-rays are strongly recommended to screen for beaking. Long-term BP/glucocorticoid use was a risk factor for beaking in patients with autoimmune diseases; BP drug holidays should be considered.

Aspectos clínicos de las fracturas por stress / Clinical features of stress fractures

Las fracturas de stress son el resultado de la reiteración de cargas mecánicas en ciclos de intensidad, duración y frecuencia variables que, aplicadas como estímulos únicos, no serían suficientes para provocarlas. En líneas generales, el mecanismo propuesto para la generación de las fracturas de stress por fatiga es un desborde de la capacidad reparatoria de las microfracturas provocadas por las cargas de un exigente entorno mecánico, que corre a cargo de la remodelación ósea. Inicialmente fueron reportadas en el personal militar (en especial reclutas durante el período de instrucción) y luego en deportistas de diversas disciplinas que implican correr y/o saltar. Siendo esta la población primariamente en riesgo, se identificaron numerosos factores adicionales. En esta revisión se expondrán solamente aquellos de naturaleza endocrinometabólica y biomecánica. El síntoma inicial más frecuente de las fracturas por fatiga es el dolor focal, y su frecuencia es alta en los miembros inferiores. Se presenta al final de la actividad física, para luego extenderse a todo su curso y, finalmente, afectar también la deambulación diaria. El examen físico típicamente denota hipersensibilidad o dolor localizado sobre el área del hueso afectado, que a veces puede estar tumefacta. El diagnóstico se basa en las imágenes; la resonancia magnética nuclear es a de mayor sensibilidad y especificidad y la que permite un diagnóstico temprano, lo que es importante para prevenir un potencial progreso de la lesión a una fractura completa, osteosíntesis retardada o no unión, y necrosis ósea. (AU)

Stress fractures are the result of repeated cyclical loading whose intensity, duration and frequency are variable. These loads, applied as single stimuli, would not be enough to produce them. Overall, the proposed mechanism that generates fatigue fractures is an overflow in repair capacity, which is normally run by bone remodeling. They were first reported in military population (especially recruits during the training period) and later in athletes of various disciplines that involve running and / or jumping. This is primarily the population at risk. Other factors have been identified, only endocrine, metabolic and biomechanical will be discussed. The most common initial symptom of fatigue fractures is focal pain and frequency is high in the lower limbs. They appear at the end of physical activity, then spread throughou their course, and ultimately affect the daily ambulation. Physical examination typically shows hypersensitivity or localized pain on the area of the affected bone, which can sometimes be swollen. Diagnosis is based on images. Nuclear magnetic resonance has the highest sensitivity and specificity and allows early diagnosis, what is essential to prevent a potential progression of injury to a complete fracture, delayed healing or nonunion and bone necrosis. (AU)

Potential pathogenic mechanism for stress fractures of the bowed femoral shaft in the elderly: Mechanical analysis by the CT-based finite element method.

INTRODUCTION: Stress fractures of the bowed femoral shaft (SBFs) may be one of the causes of atypical femoral fractures (AFFs). The CT-based finite element method (CT/FEM) can be used to structurally evaluate bone morphology and bone density based on patient DICOM data, thereby quantitatively and macroscopically assessing bone strength. Here, we clarify the pathogenic mechanism of SBFs and demonstrate this new understanding of AFFs through mechanical analysis by CT/FEM. PATIENTS AND METHODS: A prospective clinical study was performed from April 2012 to February 2014. We assembled two study groups, the bowed AFF group (n=4 patients; mean age, 78.0 years) including those with a prior history of AFF associated with bowing deformity and the thigh pain group (n=14 patients; mean age, 78.6 years) comprising outpatients with complaints of thigh pain and tenderness. Stress concentration in the femoral shaft was analysed by CT/FEM, and the visual findings and extracted data were assessed to determine the maximum principal stress (MPS) and tensile stress-strength ratio (TSSR). In addition, we assessed femoral bowing, bone density, and bone metabolic markers. Wilcoxon's rank sum test was used for statistical analysis. RESULTS: All patients in the bowed AFF group showed a marked concentration of diffuse stress on the anterolateral surface. Thirteen patients in the thigh pain group had no significant findings. However, the remaining 1 patient had a finding similar to that observed in the bowed AFF group, with radiographic evidence of bowing deformity and a focally thickened lateral cortex. Patients were reclassified as having SBF (n=5) or non-SBF (n=13). Statistical analysis revealed significant differences in MPS (p=0.0031), TSSR (p=0.0022), and femoral bowing (lateral, p=0.0015; anterior, p=0.0022) between the SBF and non-SBF groups, with no significant differences in bone density or bone metabolic markers. CONCLUSIONS: Significant tensile stress due to bowing deformity can induce AFFs. SBFs should be considered a novel subtype of AFF, and patients with complaints of thigh pain and femoral shaft bowing deformity must be considered at high risk for AFFs. This project (Ref: AOTAP 13-13) was supported by AOTrauma Asia Pacific.

Femoral and tibial stress fractures associated with vitamin D insufficiency.

We describe a case highlighting the need to consider hypovitaminosis-D when investigating background causation and treatment of femoral and tibial stress fractures. The case also suggests that prescribing calcium and vitamin D supplementation may help with fracture healing in soldiers presenting with stress fractures who may have unrecognised hypovitaminosis-D which if left untreated may delay fracture healing.

Nitric oxide-mediated vasodilation increases blood flow during the early stages of stress fracture healing.

Despite the strong connection between angiogenesis and osteogenesis in skeletal repair conditions such as fracture and distraction osteogenesis, little is known about the vascular requirements for bone formation after repetitive mechanical loading. Here, established protocols of damaging (stress fracture) and nondamaging (physiological) forelimb loading in the adult rat were used to stimulate either woven or lamellar bone formation, respectively. Positron emission tomography was used to evaluate blood flow and fluoride kinetics at the site of bone formation. In the group that received damaging mechanical loading leading to woven bone formation (WBF), (15)O water (blood) flow rate was significantly increased on day 0 and remained elevated 14 days after loading, whereas (18)F fluoride uptake peaked 7 days after loading. In the group that received nondamaging mechanical loading leading to lamellar bone formation (LBF), (15)O water and (18)F fluoride flow rates in loaded limbs were not significantly different from nonloaded limbs at any time point. The early increase in blood flow rate after WBF loading was associated with local vasodilation. In addition, Nos2 expression in mast cells was increased in WBF-, but not LBF-, loaded limbs. The nitric oxide (NO) synthase inhibitor N(ω)-nitro-l-arginine methyl ester was used to suppress NO generation, resulting in significant decreases in early blood flow rate and bone formation after WBF loading. These results demonstrate that NO-mediated vasodilation is a key feature of the normal response to stress fracture and precedes woven bone formation. Therefore, patients with impaired vascular function may heal stress fractures more slowly than expected.

Periostin deficiency increases bone damage and impairs injury response to fatigue loading in adult mice.

Bone damage removal and callus formation in response to fatigue loading are essential to prevent fractures. Periostin (Postn) is a matricellular protein that mediates adaptive response of cortical bone to loading. Whether and how periostin influences damage and the injury response to fatigue remains unknown. We investigated the skeletal response of Postn(-/-) and Postn(+/+) mice after fatigue stimulus by axial compression of their tibia. In Postn(+/+) mice, cracks number and surface (CsNb, CsS) increased 1h after fatigue, with a decrease in strength compared to non-fatigued tibia. At 15 days, CsNb had started to decline, while CtTV and CtBV increased in fatigued vs non-fatigued tibia, reflecting a woven bone response that was present in 75% of the fatigued bones. Cortical porosity and remodelling also prominently increased in the fatigued tibia of Postn(+/+) mice. At 30 days, paralleling a continuous removal of cortical damage, strength of the fatigued tibia was similar to the non-fatigue tibia. In Postn(-/-) mice, cracks were detectable even in the absence of fatigue, while the amount of collagen crosslinks and tissue hardness was decreased compared to Postn(+/+). Fatigue significantly increased CsNb and CsS in Postn(-/-), but was not associated with changes in CtTV and CtBV, as only 16% of the fatigued bones formed some woven bone. Cortical porosity and remodelling did not increase either after fatigue in Postn(-/-), and the level of damage remained high even after 30 days. As a result, strength remained compromised in Postn(-/-) mice. Contrary to Postn(+/+), which osteocytic lacunae showed a change in the degree of anisotropy (DA) after fatigue, Postn(-/-) showed no DA change. Hence periostin appears to influence bone materials properties, damage accumulation and repair, including local modeling/remodeling processes in response to fatigue. These observations suggest that the level of periostin expression could influence the propensity to fatigue fractures.

MCP-1 expression is specifically regulated during activation of skeletal repair and remodeling.

Monocyte chemotactic protein-1 (MCP-1) belongs to the CC chemokine superfamily and plays a critical role in the recruitment and activation of leukocytes during acute inflammation. We hypothesize that MCP-1 is also an important chemokine that regulates the recruitment and activation of bone cells required for skeletal repair and remodeling. We used the ulnar stress fracture (SFx) model, which allows investigation of focal remodeling with a known time course and precise anatomical location. SFx were created in the right ulna of female Wistar rats using cyclic end loading. Unloaded animals were used as a control. Rats were killed 4 h and 1, 4, 7, and 14 days after loading (n = 10/group); RNA was extracted and converted to cDNA for quantitative PCR analysis using TaqMan gene expression assays. Four hours after loading, MCP-1 gene expression was increased ~30-fold (P < 0.001), remained elevated at 24 h (~12-fold, P < 0.001), then declined by day 14. Relative to the contralateral limb, expression of the receptors CCR1 and CCR2 increased over the 14 days, being significant by 4 days for CCR1 and 14 days for CCR2 (P < 0.05). Other inflammation-related chemokines (RANTES, MIP1a) were not increased at these early time points. Using in situ hybridization and immunohistochemistry in separate animal groups (n = 5/group, control, days 1, 4, 7), MCP-1 mRNA and protein were localized in periosteal osteoblasts associated with woven bone formation at the fracture exit point but not in osteocytes adjacent to the SFx. These data support an important role for MCP-1 in the early phase of SFx repair and activated remodeling.

Female recruits sustaining stress fractures during military basic training demonstrate differential concentrations of circulating IGF-I system components: a preliminary study.

OBJECTIVE: Stress fracture injuries sustained during military basic combat training (BT) are a significant problem and occur at a higher rate in female recruits than male recruits. Insulin-like growth factor-I (IGF-I) is an easily measured biomarker that is involved in bone formation and positively correlated with bone mineral density, especially in women. This study examined the response of the IGF-I system between female soldiers that sustained a stress fracture (SFX, n=13) during BT and female soldiers who did not (NSFX, n=49). DESIGN: Female soldiers (n=62, 18.8 ± 0.6 yr) from 2 companies of a gender-integrated combat battalion in the Israeli Defense Forces participated in this study. Height, weight and blood draws were taken upon entry to BT (preBT) and after a four-month BT program (postBT). Stress fractures were diagnosed by bone scan. Serum was analyzed for total IGF-I, free IGF-I, IGF binding proteins (IGFBP)1-6, BAP, calcium, CTx, IL1ß, IL6, PINP, PTH, TNFα, TRAP, and 25(OH)D. Statistical differences between SFX and NSFX groups and time points were assessed by RM ANOVA with Fisher post-hoc (p≤0.05). RESULTS: The SFX group was significantly taller and had lower BMI than NSFX (p≤0.05). Serum concentrations of total IGF-I, bioavailable IGF-I, other bone biomarkers, and cytokines were not significantly different between SFX and NSFX preBT. Serum IGFBP-2 and IGFBP-5 were significantly higher in the SFX compared to the NSFX preBT (p≤0.05). In both groups, total IGF-I increased pre to postBT (p≤0.05). Additionally, a significant difference was observed in the bioavailable IGF-I response pre to postBT for both groups. The SFX group demonstrated a significant decrease in bioavailable IGF-I pre to postBT (preBT: 0.58 ± 0.58 ng/mL; postBT 0.39 ± 0.48; p≤0.05) whereas the NSFX group demonstrated a significant increase in bioavailable IGF-I pre to postBT (preBT: 0.53 ± 0.37 ng/mL; postBT: 0.63 ± 0.45; p≤0.05). CONCLUSIONS: Our study demonstrated that serum IGF-I changes during basic training and that women sustaining stress fractures during BT significantly decreased bioavailable IGF-I, whereas their uninjured counter parts increased bioavailable IGF-I. These results suggest that stress fracture susceptibility may be related to differential IGF-I system concentrations and response to physical training.

Quantification of skeletal blood flow and fluoride metabolism in rats using PET in a pre-clinical stress fracture model.

PURPOSE: Blood flow is an important factor in bone production and repair, but its role in osteogenesis induced by mechanical loading is unknown. Here, we present techniques for evaluating blood flow and fluoride metabolism in a pre-clinical stress fracture model of osteogenesis in rats. PROCEDURES: Bone formation was induced by forelimb compression in adult rats. (15)O water and (18)F fluoride PET imaging were used to evaluate blood flow and fluoride kinetics 7 days after loading. (15)O water was modeled using a one-compartment, two-parameter model, while a two-compartment, three-parameter model was used to model (18)F fluoride. Input functions were created from the heart, and a stochastic search algorithm was implemented to provide initial parameter values in conjunction with a Levenberg-Marquardt optimization algorithm. RESULTS: Loaded limbs are shown to have a 26% increase in blood flow rate, 113% increase in fluoride flow rate, 133% increase in fluoride flux, and 13% increase in fluoride incorporation into bone as compared to non-loaded limbs (p < 0.05 for all results). CONCLUSIONS: The results shown here are consistent with previous studies, confirming this technique is suitable for evaluating the vascular response and mineral kinetics of osteogenic mechanical loading.

[Secondary osteoporosis UPDATE. Stress fracture and bone metabolism marker in long distance runners].

Stress fracture is one of the common injuries of over-use syndrome among long-distance runners. This injury is more common among women, often relating to anorexia, menstrual disorder and the lowering of bone density. An early diagnosis is considered to be of importance for a rapid recovery which leads to successful return to sporting performance. The bone metabolism marker, especially the bone absorption marker, often indicates a high density when the stress fracture is occurred. This could lead to early diagnosis and a new prognosis technique.