Estrogen influences on neuromuscular function in postmenopausal women.

Exposure to ovarian sex steroids during different life phases has long-term effects on women's health and wellbeing. Menopause is characterized by rapid decline in ovarian sex steroids already during mid-life, between the ages of 46 and 52. Due to the menopause-related hormonal changes, women in most western countries live more than one-third of their lives in postmenopausal status. The role of ovarian steroids on neuromuscular function in middle-aged and older women has been investigated since the 1980s with increasing volume of research during the last decades. This review considers how different components of the neuromuscular system may be influenced by estrogens and so affects neuromuscular function in postmenopausal women. The main focus is on muscle strength and power, which are closely associated with mobility and functional capacity among older populations. In the end of the review, we summarize recent findings on the underlying biological mechanisms in skeletal muscle that could explain the association between hormone replacement therapy and neuromuscular function among postmenopausal women.

The influence of physical activity during youth on structural and functional properties of the Achilles tendon.

Achilles tendinopathy is a highly prevalent sports injury. Animal studies show a growth response in tendons in response to loading in the immature phase but not after puberty maturation. The aim of this investigation was to examine the structural and material properties in long distance runners who were either physically active (HAY) or inactive (LAY) in young age. Twelve men in HAY group and eight men in LAY group participated. Structural, functional, and biochemical properties of Achilles tendon were estimated from magnetic resonance imaging, ultrasound video recordings, mechanical tests, and tendon biopsies, respectively. There was no difference between the groups with respect to tendon cross-sectional area or tendon free length. There was no difference between the groups with respect to maximal force or mechanical properties. The collagen content, enzymatic and nonenzymatic cross-link density did not differ between the groups, nor did collagen fibril density, diameter, and area. There was a correlation between age and pentosidine/collagen within the groups [(HAY: P < 0.05 and r(2) = 0.47) and (LAY: P < 0.05 and r(2) = 0.52)]. The data suggest that high or low activity during youth did not appreciably influence the mechanical, structural, or biochemical properties of the Achilles tendon in adult long distance runners.

Diffusion of ionic and non-ionic contrast agents in articular cartilage with increased cross-linking--contribution of steric and electrostatic effects.

OBJECTIVE: To investigate the effect of threose-induced collagen cross-linking on diffusion of ionic and non-ionic contrast agents in articular cartilage. DESIGN: Osteochondral plugs (Ø=6mm) were prepared from bovine patellae and divided into two groups according to the contrast agent to be used in contrast enhanced computed tomography (CECT) imaging: (I) anionic ioxaglate and (II) non-ionic iodixanol. The groups I and II contained 7 and 6 sample pairs, respectively. One of the paired samples served as a reference while the other was treated with threose to induce collagen cross-linking. The equilibrium partitioning of the contrast agents was imaged after 24h of immersion. Fixed charge density (FCD), water content, contents of proteoglycans, total collagen, hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP) and pentosidine (Pent) cross-links were determined as a reference. RESULTS: The equilibrium partitioning of ioxaglate (group I) was significantly (p=0.018) lower (-23.4%) in threose-treated than control samples while the equilibrium partitioning of iodixanol (group II) was unaffected by the threose-treatment. FCD in the middle and deep zones of the cartilage (p<0.05) and contents of Pent and LP (p=0.001) increased significantly due to the treatment. However, the proteoglycan concentration was not systematically altered after the treatment. Water content was significantly (-3.5%, p=0.007) lower after the treatment. CONCLUSIONS: Since non-ionic iodixanol showed no changes in partition after cross-linking, in contrast to anionic ioxaglate, we conclude that the cross-linking induced changes in charge distribution have greater effect on diffusion compared to the cross-linking induced changes in steric hindrance.

Resistance training induced increase in muscle fiber size in young and older men.

Muscle strength and mass decline in sedentary individuals with aging. The present study investigated the effects of both age and 21 weeks of progressive hypertrophic resistance training (RT) on skeletal muscle size and strength, and on myostatin and myogenin mRNA expression in 21 previously untrained young men (26.0 ± 4.3 years) and 18 older men (61.2 ± 4.1 years) and age-matched controls. Vastus lateralis muscle biopsies were taken before and after RT. Type I and type II muscle fiber cross-sectional areas increased more in young men than in older men after RT (P < 0.05). Concentric leg extension increased (P < 0.05) more after 10.5 weeks in young men compared to older men, but after 21 weeks no statistical differences existed. The daily energy and protein intake were greater (P < 0.001) in young subjects. Both myostatin and myogenin mRNA expression increased in older when compared with young men after RT (P < 0.05). In conclusion, after RT, muscle fiber size increased less in older compared to young men. This was associated with lower protein and energy intake and increases in myostatin gene expression in older when compared to young men.

Computed tomography detects changes in contrast agent diffusion after collagen cross-linking typical to natural aging of articular cartilage.

OBJECTIVE: The effect of threose-induced collagen cross-linking on the mechanical and diffusive properties of cartilage was investigated in vitro. In particular, we investigated the potential of Contrast Enhanced Computed Tomography (CECT) to detect changes in articular cartilage after increased collagen cross-linking, which is an age-related phenomenon. METHODS: Osteochondral plugs (Ø=6.0 mm, n=28) were prepared from intact bovine patellae (n=7). Two of the four adjacent samples, prepared from each patella, were treated with threose to increase the collagen cross-linking, while the other two specimen served as paired controls. One sample pair was mechanically tested and then mechanically injured using a material testing device. Contrast agent [ioxaglate (Hexabrix™)] diffusion was imaged in the other specimen pair for 25 h using CECT. Water fraction, collagen and proteoglycan content, collagen network architecture and the amount of cross-links [hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP) and pentosidine (Pent)] of the samples were also determined. RESULTS: Cartilage collagen cross-linking, both Pent and LP, were significantly (P<0.001) increased due to threose treatment. CECT could detect the increased cross-links as the contrast agent penetration and the diffusion flux were significantly (P<0.05) lower in the threose treated than in untreated samples. The equilibrium modulus (+164%, P<0.05) and strain dependent dynamic modulus (+47%, P<0.05) were both significantly greater in the threose treated samples than in reference samples, but there was no association between the initial dynamic modulus and the threose treatment. The water fraction, proteoglycan and collagen contents, as well as collagen architecture, were not significantly altered by the threose treatment. CONCLUSIONS: To conclude, the CECT technique was found to be sensitive at detecting changes in cartilage tissue due to increased collagen cross-linking. This is important since increased cross-linking has been proposed to be related to the increased injury susceptibility of tissue.

Strength, [corrected] endurance or combined training elicit diverse skeletal muscle myosin heavy chain isoform proportion but unaltered androgen receptor concentration in older men.

We investigated whether the myosin heavy chain (MyHC) proportion and androgen receptor (AR) concentration in skeletal muscle differ following 21 weeks of strength, endurance and combined training in untrained older men. Strength (S) and endurance (E) groups trained twice per week and combined (S+E) group trained four times per week (two strength and two endurance). Muscle biopsies were obtained before and after the training period from m. vastus lateralis (VL) and AR mRNA and protein concentration and MyHC proportion were determined. 1RM increased during the training period in S, S+E and E but the changes were greater in S and S+E than in E. Statistically significant increases were observed only in S and S+E in maximal isometric force as well as in VL thickness. VO (2max) increased significantly only in E. MyHCIIa proportion increased in S, while MyHCIIa proportion decreased and MyHCI increased (p<0.05) in E. No statistically significant changes were observed in serum testosterone and in AR mRNA or protein concentrations. The present results indicate that 21 weeks of strength, endurance or combined training changed MyHC proportion according to the training method but did not have an effect on AR mRNA or protein expression in skeletal muscle at rest.

Corticosteroid injections, eccentric decline squat training and heavy slow resistance training in patellar tendinopathy.

A randomized-controlled single-blind trial was conducted to investigate the clinical, structural and functional effects of peritendinous corticosteroid injections (CORT), eccentric decline squat training (ECC) and heavy slow resistance training (HSR) in patellar tendinopathy. Thirty-nine male patients were randomized to CORT, ECC or HSR for 12 weeks. We assessed function and symptoms (VISA-p questionnaire), tendon pain during activity (VAS), treatment satisfaction, tendon swelling, tendon vascularization, tendon mechanical properties and collagen crosslink properties. Assessments were made at 0 weeks, 12 weeks and at follow-up (half-year). All groups improved in VISA-p and VAS from 0 to 12 weeks (P<0.05). VISA-p and VAS improvements were maintained at follow-up in ECC and HSR but deteriorated in CORT (P<0.05). In CORT and HSR, tendon swelling decreased (-13+/-9% and -12+/-13%, P<0.05) and so did vascularization (-52+/-49% and -45+/-23%, P<0.01) at 12 weeks. Tendon mechanical properties were similar in healthy and injured tendons and were unaffected by treatment. HSR yielded an elevated collagen network turnover. At the half-year follow-up, treatment satisfaction differed between groups, with HSR being most satisfied. Conclusively, CORT has good short-term but poor long-term clinical effects, in patellar tendinopathy. HSR has good short- and long-term clinical effects accompanied by pathology improvement and increased collagen turnover.

Leisure-time physical activity and high-risk fat: a longitudinal population-based twin study.

BACKGROUND AND OBJECTIVE: Exercise is thought to reduce high-risk body fat, but intervention studies are frequently limited by short follow-ups and observational studies by genetic selection. Therefore, we studied the effects of a physically inactive vs active lifestyle on high-risk (visceral, liver and intramuscular) fat in twin pairs discordant for leisure-time physical activity habits for over 30 years. DESIGN: A longitudinal population-based twin study. SUBJECTS: Sixteen middle-aged (50-74 years) same-sex twin pairs (seven monozygotic (MZ), nine dizygotic (DZ)) with long-term discordance for physical activity habits were comprehensively identified from the Finnish Twin Cohort (TWINACTIVE study). Discordance was initially defined in 1975 and the same co-twin remained significantly more active during the 32-year-long follow-up. MAIN OUTCOME MEASURES: Magnetic resonance imaging-assessed visceral, liver and intramuscular fat. RESULTS: In within-pair analyses carried out after the adult life-long discordance in physical activity habits, the physically inactive co-twins had 50% greater visceral fat area compared with the active co-twins (mean difference 55.5 cm2, 95% confidence interval (CI) 7.0-104.1, P=0.010). The liver fat score was 170% higher (13.2, 95% CI 3.5-22.8, P=0.030) and the intramuscular fat area 54% higher (4.9 cm2, 95% CI 1.9-7.9, P=0.002) among the inactive co-twins. All the trends were similar for MZ and DZ pairs. Peak oxygen uptake was inversely associated with visceral (r=-0.46, P=0.012) and intramuscular fat area (r=-0.48, P=0.028), with similar trends in intrapair difference correlations (r=-0.57, P=0.021 and r=-0.50, P=0.056, respectively). The intrapair difference correlation between visceral and intramuscular fat was also high (r=0.65, P=0.009). CONCLUSION: Regular physical activity seems to be an important factor in preventing the accumulation of high-risk fat over time, even after controlling for genetic liability and childhood environment. Therefore, the prevention and treatment of obesity should emphasize the role of regular leisure-time physical activity.

Mechanical properties and collagen cross-linking of the patellar tendon in old and young men.

Age-related loss in muscle mass and strength impairs daily life function in the elderly. However, it remains unknown whether tendon properties also deteriorate with age. Cross-linking of collagen molecules provides structural integrity to the tendon fibrils and has been shown to change with age in animals but has never been examined in humans in vivo. In this study, we examined the mechanical properties and pyridinoline and pentosidine cross-link and collagen concentrations of the patellar tendon in vivo in old (OM) and young men (YM). Seven OM (67 +/- 3 years, 86 +/- 10 kg) and 10 YM (27 +/- 2 years, 81 +/- 8 kg) with a similar physical activity level (OM 5 +/- 6 h/wk, YM 5 +/- 2 h/wk) were examined. MRI was used to assess whole tendon dimensions. Tendon mechanical properties were assessed with the use of simultaneous force and ultrasonographic measurements during ramped isometric contractions. Percutaneous tendon biopsies were taken and analyzed for hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP), pentosidine, and collagen concentrations. We found no significant differences in the dimensions or mechanical properties of the tendon between OM and YM. Collagen concentrations were lower in OM than in YM (0.49 +/- 0.27 vs. 0.73 +/- 0.14 mg/mg dry wt; P < 0.05). HP concentrations were higher in OM than in YM (898 +/- 172 vs. 645 +/- 183 mmol/mol; P < 0.05). LP concentrations were higher in OM than in YM (49 +/- 38 vs. 16 +/- 8 mmol/mol; P < 0.01), and pentosidine concentrations were higher in OM than in YM (73 +/- 13 vs. 11 +/- 2 mmol/mol; P < 0.01). These cross-sectional data raise the possibility that age may not appreciably influence the dimensions or mechanical properties of the human patellar tendon in vivo. Collagen concentration was reduced, whereas both enzymatic and nonenzymatic cross-linking of concentration was elevated in OM vs. in YM, which may be a mechanism to maintain the mechanical properties of tendon with aging.

Combination of hormone replacement therapy and high physical activity is associated with differences in Achilles tendon size in monozygotic female twin pairs.

Estrogen concentration has been suggested to play a role in tendon abnormalities and injury. In physically active postmenopausal women, hormone replacement therapy (HRT) has been suggested to decrease tendon diameter. We hypothesized that HRT use and physical activity are associated with Achilles tendon size and tissue structure. The study applied cotwin analysis of fourteen 54- to 62-yr-old identical female twin pairs with current discordance for HRT use for an average of 7 yr. Achilles tendon thickness and cross-sectional areas were determined by ultrasonography, and tendon structural organization was analyzed from the images using linear discriminant analysis (LDA). Maximal voluntary and twitch torques from plantar flexor muscles were measured. Serum levels of estradiol, estrone, testosterone, and sex hormone binding globulin were analyzed. Total daily metabolic equivalent score (MET-h/day) was calculated from physical activity questionnaires. Results showed that, in five physically active (MET > 4) pairs, the cotwins receiving HRT had greater estradiol level (P = 0.043) and smaller tendon cross-sectional area than their sisters (63 vs. 71 mm(2), P = 0.043). Among all pairs, Achilles tendon thickness and cross-sectional area did not significantly differ between HRT using and nonusing twin sisters. Intrapair correlation for Achilles tendon thickness was high, despite HRT use discordance (r = 0.84, P < 0.001). LDA distinguished different tendon structure only from two of six examined twin pairs who had a similar level of physical activity. In conclusion, the effect of HRT on Achilles tendon characteristics independent of genetic confounding may be present only in the presence of sufficient physical activity. In physically active twin pairs, the higher level of estrogen seems to be associated with smaller tendon size.

Abnormal response to physical activity in femurs after heterozygous inactivation of one allele of the Col2a1 gene for type II collagen in mice.

The objective of this study was to evaluate the influence of heterozygous inactivation of one allele of the type II collagen gene (Col2a1) on biomechanical properties and mineral density of bone under physical loading conditions. C57BL/6-TGN mice with heterozygous knockout (HZK) inactivation of Col2a1 gene and their nontransgenic littermate controls were housed in individual cages with running wheels for 9 and 15 months. The running activity of each mouse was monitored continuously throughout the experiment. Bone mineral density (BMD) of mice femora was measured using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). Biomechanical properties were determined using three-point bending tests. Vertebral bone samples were prepared for quantitative polarized light microscopy and digital densitometry of proteoglycans. The concentration of total collagen and collagen cross-links were analyzed using high-performance liquid chromatograpy (HPLC). The average daily running distance was shorter for the HZK mice between the age of 4 and 15 months as compared with normal runners (P < 0.05). The ultimate breaking force was 14.8% and 23.6% (9 vs. 15 months) lower in HZK-runners than in wild-type runners. BMD of the femur was 6.1% lower in HZK-runners at the age of 9 months (P < 0.05). Physical activity increased cortical BMD in wild-type runners but not in the HZK runners at the age of 9 months. The collagen network of the HZK mice was less organized. There were only minor changes in BMD and mechanical and structural properties between sedentary HZK mice and their wild-type controls. Increased physical activity induced significantly lower bone density, mechanical properties, and organization of collagen fibers in male HZK mice. However, there were no major differences in biomechanical parameters between sedentary HZK and wild-type male mice. This suggests an important guiding role of collagen type II in bone remodelling and maturation.

Synthesis and degradation of type IV collagen in rat skeletal muscle during immobilization in shortened and lengthened positions.

AIM: Type IV collagen is a major protein in basement membranes surrounding and supporting skeletal muscle cells. In the present study, we tested the hypotheses that immobilization down-regulates synthesis and up-regulates degradation of type IV collagen in skeletal muscle. METHODS: mRNA level and concentration of type IV collagen as well as mRNA levels and activities of proteins involved in its degradation were analysed from soleus (SOL), gastrocnemius (GAS) and extensor digitorum longus muscles after immobilization in shortened and lengthened positions for 1, 3 and 7 days. RESULTS: Following immobilization, type IV collagen mRNA level was decreased in SOL and GAS suggesting down-regulated synthesis of this protein. The mRNA level and activity of matrix metalloproteinase-2 (proMMP-2) were increased in all muscles, while the activity of tissue inhibitor of metalloproteinase-2 was decreased in SOL and GAS. These findings reflect an increased capacity for degradation of type IV collagen. CONCLUSIONS: As a consequence of decreased synthesis/degradation ratio immobilization reduced the concentration of type IV collagen in all muscles. The regulation of type IV collagen through synthesis and/or degradation seems, however, to be muscle specific. Immobilization in lengthened position seems to delay and partly decrease the net degradation of type IV collagen.

Regulation of synthesis of fibrillar collagens in rat skeletal muscle during immobilization in shortened and lengthened positions.

Immobilization has been shown to cause muscle atrophy and decreased total collagen synthesis in skeletal muscle. These changes can be counteracted by stretch. The purpose of this study was to find out the early effects of immobilization in shortened and lengthened positions on expression of type I and III collagen at pre- and post-translational level. The mRNA levels of type I and III collagen, prolyl 4-hydroxylase activity, total collagen concentration and the proportions of type I and III collagens were analysed in soleus (SOL), gastrocnemius (GM), extensor digitorum longus and tibialis anterior (TA) muscles during immobilization in shortened and lengthened positions for 1, 3 and 7 days. The mRNA levels for type I and III collagens decreased during 3-7 days in all muscles, except TA. In shortened GM and SOL, the mRNA level of type I collagen was lower than in the corresponding lengthened muscles. Prolyl 4-hydroxylase activity decreased in all muscles during 3-7 days. The activity in shortened GM was 30-37% lower than in the lengthened one during 3-7 days. Total collagen concentration and proportions of type I and III collagen showed no change during the 7-day immobilization period. The present study suggests that immobilization results in rapid down-regulation of total muscular collagen synthesis and that the timing and degree is roughly similar in type I and III collagens. Stretch seems to partially counteract these effects. Immobilization effect and the partially preventive effect of stretch on down-regulation of gene expression of prolyl 4-hydroxylase and fibrillar collagens during immobilization seems to be greater in weight-bearing SOL and GM than ankle joint dorsiflexors.

Acute exercise induced changes in rat skeletal muscle mRNAs and proteins regulating type IV collagen content.

This experiment tested the hypothesis that running-induced damage to rat skeletal muscle causes changes in synthesis and degradation of basement membrane type IV collagen and to proteins regulating its degradation. Samples from soleus muscle and red and white parts of quadriceps femoris muscle (MQF) were collected 6 h or 1, 2, 4, or 7 days after downhill running. Increased muscle beta-glucuronidase activity indicated greater muscle damage in the red part of MQF than in the white part of MQF or soleus. In the red part of MQF, type IV collagen expression was upregulated at the pretranslational level and the protein concentration decreased, whereas matrix metalloproteinase-2 (MMP-2), a protein that degrades type IV collagen, and tissue inhibitor of metalloproteinase-2 (TIMP-2), a protein that inhibits degradation, were increased in parallel both at mRNA and protein levels. Type IV collagen mRNA level increased in the white part of MQF and soleus muscle. The protein concentration increased in the white part of MQF and was unchanged in soleus muscle. MMP-2 and TIMP-2 changed only slightly in the white part of MQF and soleus muscle. The changes seem to depend on the severity of myofiber injury and thus probably reflect reorganization of basement membrane compounds.

The effect of supraphysiological doses of anabolic androgenic steroids on collagen metabolism.

We examined the effect of supraphysiological doses of anabolic androgenic steroids (AAS) on collagen metabolism and whether the changes reflect the alterations in muscle, bone, and tendon collagen metabolism, possibly in a tissue-specific manner. Serum carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP), aminoterminal propeptide of type III procollagen (PIIINP), urine hydroxylysylpyridinoline (HP), and lysylpyridinoline (LP) as well as urine creatinine were determined from 17 men abusing AAS. Measurements were made twice during the intake of AAS and twice during the subsequent withdrawal period. When the volunteers were on steroids, their serum PIIINP concentrations and urine HP/LP ratio were significantly higher and their serum ICTP concentrations were significantly lower than during the withdrawal period (p < 0.05). Serum PIIINP correlated with total cumulative doses of injectable intramuscular steroids, and serum ICTP correlated with the duration of the steroid intake period (p<0.05). The results suggest that high doses of AAS decrease the degradation and seem to increase the synthesis of type I collagen. Furthermore, high doses of AAS are suggested to enhance soft tissue collagen metabolism on the basis of increased type III collagen synthesis and elevated HP/LP ratio during the steroid administration period. Although the tissue-specific turnover of collagen of soft connective tissues remains unknown, the turnover of bone collagen seems not to change following the use of high doses of AAS, at least within the time interval of the present study.

Volumetric changes of articular cartilage during stress relaxation in unconfined compression.

The time-dependent lateral expansion and load relaxation of cartilage cylinders subjected to unconfined compression were simultaneously recorded. These measurements were used to (1) test the assumption of incompressibility for articular cartilage, (2) measure the Poisson's ratio of articular cartilage in compression and (3) investigate the relationship between stress relaxation and volumetric change. Mechanical tests were performed on fetal, calf, and adult humeral head articular cartilage. The instantaneous Poisson's ratio of adult cartilage was 0.49+/-0.08 (mean+S.D.), thus confirming the assumption of incompressibility for this tissue. The instantaneous Poisson's ratio was significantly lower for calf (0. 38+/-0.04) and fetal cartilage (0.36+/-0.04). The equilibrium Poisson's ratio, i.e. true Poisson's ratio of the solid matrix, was significantly higher for the adult tissue (0.26+/-0.11) compared to both the fetal (0.09+/-0.02) and calf (0.11+/-0.03) cartilage. A linear relationship between time-matched load and lateral expansion after the first minute of stress relaxation was observed.

Increased mRNAs for procollagens and key regulating enzymes in rat skeletal muscle following downhill running.

The purpose of the study was to investigate pre-translational regulation of collagen expression after a single bout of exercise. We analysed steady-state messenger ribonucleic acid (mRNA) levels for collagen types I, III and IV, alpha- and beta-subunits of prolyl 4-hydroxylase and lysyl oxidase (enzymes modifying procollagen chains), and enzyme activity of prolyl 4-hydroxylase from rat soleus muscle (MS) and the red parts of quadriceps femoris muscle (MQF) after 12 h and after 1, 2, 4, 7 and 14 days of downhill (-13.5 degrees ) treadmill running at a speed of 17 m.min-1 for 130 min. Histological and biochemical assays revealed exercise-induced muscle damage in MQF but not MS. Steady-state mRNA levels for the alpha- and beta-subunits of prolyl 4-hydroxylase in MQF, lysyl oxidase in MS and MQF were increased 12 h after running, whereas prolyl 4-hydroxylase activity did not increase until 2 days after exercise. The mRNA levels for the fibrillar collagens (I and III) and basement membrane type IV collagen significantly increased 1 day and 12 h after exertion, respectively. Peak mRNA levels were observed 2-4 days after running, the increases being more pronounced in MQF than in MS. No significant changes were observed in types I or III collagen at the protein level. Strenuous downhill running thus causes an increase in gene expression for collagen types I and III and their post-translational modifying enzymes in skeletal muscle in a co-ordinated manner. These changes, together with the increased gene expression of type IV collagen, may represent the regenerative response of muscle extracellular matrix to exercise-induced injury and an adaptive response to running exertion.

Remobilization does not fully restore immobilization induced articular cartilage atrophy.

The recovery of articular cartilage from immobilization induced atrophy was studied. The right hind limbs of 29-week-old beagle dogs were immobilized for 11 weeks and then remobilized for 50 weeks. Cartilage from the immobilized knee was compared with tissue from age matched control animals. After the immobilization period, uncalcified articular cartilage glycosaminoglycan concentration was reduced by 20% to 23%, the reduction being largest (44%) in the superficial zone. The collagen fibril network showed no significant changes, but the amount of collagen crosslinks was reduced (13.5%) during immobilization. After remobilization, glycosaminoglycan concentration was restored at most sites, except for in the upper parts of uncalcified cartilage in the medial femoral and tibial condyles (9% to 17% less glycosaminoglycans than in controls). The incorporation of 35SO4 was not changed, and remobilization also did not alter the birefringence of collagen fibrils. Remobilization restored the proportion of collagen crosslinks to the control level. The changes induced by joint unloading were reversible at most sites investigated, but full restoration of articular cartilage glycosaminoglycan concentration was not obtained in all sites, even after remobilization for 50 weeks. This suggests that lengthy immobilization of a joint can cause long lasting articular cartilage proteoglycan alterations at the same time as collagen organization remains largely unchanged. Because proteoglycans exert strong influence on the biomechanical properties of cartilage, lengthy immobilization may jeopardize the well being of articular cartilage.

Improved bone biomechanical properties in rats after oral xylitol administration.

The effects of 5, 10, and 20% dietary xylitol supplementations on the biomechanical properties, histological architecture, and the contents of collagen, pyridinoline, and deoxypyridinoline in long bones of rats were studied. Tibiae were used for the three-point bending test, and femurs were used for the torsion and loading test of the femoral neck. The 10 and 20% oral xylitol administrations caused a significant increase of tibial stress, femoral shear stress, and stress of the femoral neck as compared with the controls. Parallel, but not significant, effects were also seen in the 5% xylitol supplementation group. No significant differences in strain or Young's modulus of the tibiae were detected between the groups. An increased shear modulus of elasticity in femurs was detected in the 20% supplementation group as compared with the controls. The histomorphometrical data for the secondary spongiosa of the proximal tibia revealed that trabecular bone volume was significantly greater in all dietary xylitol supplementation groups as compared with the controls. The bone volume increased along with increasing xylitol content. No significant differences between the groups were detected concerning the amount of collagen per dry weight of organic matrix, the concentrations of pyridinoline or deoxypyridinoline in collagen, or the ratio of these crosslinks. This suggests no xylitol-dependent selective changes in these structures of bone collagen. In conclusion, dietary xylitol supplementation in rats improves the biomechanical properties of bone and increases the trabecular bone volume dose dependently.

Do more highly organized collagen fibrils increase bone mechanical strength in loss of mineral density after one-year running training?

The aim of this study was to evaluate the effects of long-term running training on the structural properties of bone. Ten beagle dogs ran according to a strenuous progressive program (up to 40 km/day) for 1 year. At the end of the training program, there was a significant reduction in bone mineral density (up to 9.7%) in the vertebrae of the runner dogs as compared with 10 sedentary control dogs. Polarized light microscopy of the vertebral trabecular bone, however, displayed proportionally higher retardation values of the collagen network of the runner dogs than of the sedentary dogs, suggesting a reorganization in a more parallel manner in the collagen fibrils. The concentration and cross-linking of collagen in the bones remained similar in both groups. No differences were observed in the force to failure of bones of the two groups nor in the histomorphometric analysis of the bones. We suggest that the collagen network in the bones accounted for the maintenance of the strength properties in the bones of the runner dogs despite the loss of mineral density.