Physical activity and strength of the femoral neck during the adolescent growth spurt: A longitudinal analysis

Loading of the femoral neck (FN) is dominated by bending and compressive stresses. We hypothesize that adaptation of the FN to physical activity would be manifested in the cross-sectional area (CSA) and section modulus (Z) of bone, indices of axial and bending strength, respectively. We investigated the influence of physical activity on bone strength during adolescence using 7 years of longitudinal data from 109 boys and 121 girls from the Saskatchewan Paediatric Bone and Mineral Accrual Study (PBMAS). Physical activity data (PAC-Q physical activity inventory) and anthropometric measurements were taken every 6 months and DXA bone scans were measured annually (Hologic QDR2000, array mode). We applied hip structural analysis to derive strength and geometric indices of the femoral neck using DXA scans. To control for maturation, we determined a biological maturity age defined as years from age at peak height velocity (APHV). To account for the repeated measures within individual nature of longitudinal data, multilevel random effects regression analyses were used to analyze the data. When biological maturity age and body size (height and weight) were controlled, in both boys and girls, physical activity was a significant positive independent predictor of CSA and Z of the narrow region of the femoral neck (P < 0.05). There was no independent effect of physical activity on the subperiosteal width of the femoral neck. When leg length and leg lean mass were introduced into the random effects models to control for size and muscle mass of the leg (instead of height and weight), all significant effects of physical activity disappeared. Even among adolescents engaged in normal levels of physical activity, the statistically significant relationship between physical activity and indices of bone strength demonstrate that modifiable lifestyle factors like exercise play an important role in optimizing bone strength during the growing years. Physical activity differences were explained by the interdependence between activity and lean mass considerations. Physical activity is important for optimal development of bone strength. (c) 2005 Elsevier Inc. All rights reserved.

RANKL protein is expressed at the pannus-bone interface at sites of articular bone erosion in rheumatoid arthritis

Objectives. Receptor activator of NF-kappa B ligand (RANKL) and osteoprotegerin (OPG) have been demonstrated to be critical regulators of osteoclast generation and activity. In addition, RANKL has been implicated as an important mediator of bone erosion in rheumatoid arthritis (RA). However, the expression of RANKL and OPG at sites of pannus invasion into bone has not been examined. The present study was undertaken to further elucidate the contribution of this cytokine system to osteoclastogenesis and subsequent bone erosion in RA by examining the pattern of protein expression for RANKL, OPG and the receptor activator of NF-kappa B (RANK) in RA at sites of articular bone erosion. Methods. Tissues from 20 surgical procedures from 17 patients with RA were collected as discarded materials. Six samples contained only synovium or tenosynovium remote from bone, four samples contained pannus-bone interface with adjacent synovium and 10 samples contained both synovium remote from bone and pannu-bone interface with adjacent synovium. Immunohistochemistry was used to characterize the cellular pattern of RANKL, RANK and OPG protein expression immediately adjacent to and remote from sites of bone erosion. Results. Cellular expression of RANKL protein was relatively restricted in the bone microenvironment; staining was focal and confined largely to sites of osteoclast-mediated erosion at the pannus-bone interface and at sites of subchondral bone erosion. RANK-expressing osteoclast precursor cells were also present in these sites. OPG protein expression was observed in numerous cells in synovium remote from bone but was more limited at sites of bone erosion, especially in regions associated with RANKL expression. Conclusions. The pattern of RANKL and OPG expression and the presence of RANK-expressing osteoclast precursor cells at sites of bone erosion in RA contributes to the generation of a local microenvironment that favours osteoclast differentiation and activity. These data provide further evidence implicating RANKL in the pathogenesis of arthritis-induced joint destruction.

Proprioceptive neuromuscular facilitation stretching - Mechanisms and clinical implications

Proprioceptive neuromuscular facilitation (PNF) stretching techniques are commonly used in the athletic and clinical environments to enhance both active and passive range of motion (ROM) with a view to optimising motor performance and rehabilitation. PNF stretching is positioned in the literature as the most effective stretching technique when the aim is to increase ROM, particularly in respect to short-term changes in ROM. With due consideration of the heterogeneity across the applied PNF stretching research, a summary of the findings suggests that an 'active' PNF stretching technique achieves the greatest gains in ROM, e.g. utilising a shortening contraction of the opposing muscle to place the target muscle on stretch, followed by a static contraction of the target muscle. The inclusion of a shortening contraction of the opposing muscle appears to have the greatest impact on enhancing ROM. When including a static contraction of the target muscle, this needs to be held for approximately 3 seconds at no more than 20% of a maximum voluntary contraction. The greatest changes in ROM generally occur after the first repetition and in order to achieve more lasting changes in ROM, PNF stretching needs to be performed once or twice per week. The superior changes in ROM that PNF stretching often produces compared with other stretching techniques has traditionally been attributed to autogenic and/or reciprocal inhibition, although the literature does not support this hypothesis. Instead, and in the absence of a biomechanical explanation, the contemporary view proposes that PNF stretching influences the point at which stretch is perceived or tolerated. The mechanism(s) underpinning the change in stretch perception or tolerance are not known, although pain modulation has been suggested.

Introducing amine functionalities on a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) surface: Comparing the use of ammonia plasma treatment and ethylenediamine aminolysis

Amine functionalities were introduced onto the surface of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) films by applying radio frequency ammonia plasma treatment and wet ethylenediamine treatment. The modified surfaces were characterized by X-ray photoelectron spectroscopy (XPS) for chemical composition and Raman microspectroscopy for the spatial distribution of the chemical moieties. The relative amount of amine functionalities introduced onto the PHBV surface was determined by exposing the treated films to the vapor of trifluoromethylbenzaldehyde (TFBA) prior to XPS analysis. The highest amount of amino groups on the PHBV surface could be introduced by use of ammonia plasma at short treatment times of 5 and 10 s, but no effect of plasma power within the range of 2.5-20 W was observed. Ethylenediamine treatment yielded fewer surface amino groups, and in addition an increase in crystallinity as well as degradation of PHBV was evident from Fourier transform infrared spectroscopy. Raman maps showed that the coverage of amino groups on the PHBV surfaces was patchy with large areas having no amine functionalities.

The v-MFG test: Investigating maternal, offspring and maternal-fetal genetic incompatibility effects on disease and viability

The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.

Hypothalamic regulation of cortical bone mass: Opposing activity of Y2 receptor and leptin pathways

NeuropeptideY-, Y2 receptor (Y2)-, and leptin-deficient mice show similar anabolic action in cancellous bone but have not been assessed in cortical bone. Cortical bone mass is elevated in Y2(-/-) mice through greater osteoblast activity. In contrast, leptin deficiency results in reduced bone mass. We show opposing central regulation of cortical bone.

Synthesis of soluble phosphate polymers by RAFT and their in vitro mineralization

Soluble linear (non-cross-linked) poly(monoacryloxyethyl phosphate) (PMAEP) and poly(2-(methacryloyloxy)ethyl phosphate) (PMOEP) were successfully synthesized through reversible addition-fragmentation chain transfer (RAFT)-mediated polymerization and by keeping the molecular weight below 20 K. Above this molecular weight, insoluble (cross-linked) polymers were observed, postulated to be due to residual diene (cross-linkable) monomers formed during purification of the monomers, MOEP and MAEP. Block copolymers consisting of PMAEP or PMOEP and poly(2-(acetoacetoxy) ethyl methacrylate) (PAAEMA) were successfully prepared and were immobilized on aminated slides. Simulated body fluid studies revealed that calcium phosphate (CaP) minerals formed on both the soluble polymers and the cross-linked gels were very similar. Both the PMAEP polymers and the PMOEP gel showed a CaP layer most probably brushite or monetite based on the Ca/P ratios. A secondary CaP mineral growth with a typical hydroxyapatite (HAP) globular morphology was found on the PMOEP gel. The soluble PMOEP film formed carbonated HAP according to Fourier transform infrared (FTIR) spectroscopy. Block copolymers attached to aminated slides showed only patchy mineralization, possibly due to the ionic interaction of negatively charged phosphate groups and protonated amines.

Therapies for axial disease in psoriatic arthritis. A systematic review

Prevalence rates for axial involvement in psoriatic arthritis (PsA) vary from 40% to 74% depending upon criteria for diagnosis. In the absence of trial evidence to assess axial involvement in PsA. the GRAPPA croup, by consensus, has suggested that outcome measures and therapies for axial disease ill ankylosing spondylitis (AS) be used. This systematic review addresses the management of axial disease in PsA, and provides treatment recommendations based oil the AS literature.

Vitamin D action and regulation of bone remodeling: Suppression of osteoclastogenesis by the mature osteoblast

Vitamin D acts through the immature osteoblast to stimulate osteoclastogenesis. Transgenic elevation of VDR in mature osteoblasts was found to inhibit osteoclastogenesis associated with an altered OPG response. This inhibition was confined to cancellous bone. This study indicates that vitamin D-mediated osteoclastogenesis is regulated locally by OPG production in the mature osteoblast.

In vivo demonstration of load-induced fluid flow in the rat tibia and its potential implications for processes associated with functional adaptation

Load-induced extravascular fluid flow has been postulated to play a role in mechanotransduction of physiological loads at the cellular level. Furthermore, the displaced fluid serves as a carrier for metabolites, nutrients, mineral precursors and osteotropic agents important for cellular activity. We hypothesise that load-induced fluid flow enhances the transport of these key substances, thus helping to regulate cellular activity associated with processes of functional adaptation and remodelling. To test this hypothesis, molecular tracer methods developed previously by our group were applied in vivo to observe and quantify the effects of load-induced fluid flow under four-point-bending loads. Preterminal tracer transport studies were carried out on 24 skeletally mature Sprague Dawley rats. Mechanical loading enhanced the transport of both small- and larger-molecular-mass tracers within the bony tissue of the tibial mid-diaphysis. Mechanical loading showed a highly significant effect on the number of periosteocytic spaces exhibiting tracer within the cross section of each bone. For all loading rates studied, the concentration of Procion Red tracer was consistently higher in the tibia subjected to pure bending loads than in the unloaded, contralateral tibia, Furthermore, the enhancement of transport was highly site-specific. In bones subjected to pure bending loads, a greater number of periosteocytic spaces exhibited the presence of tracer in the tension band of the cross section than in the compression band; this may reflect the higher strains induced in the tension band compared with the compression band within the mid-diaphysis of the rat tibia. Regardless of loading mode, the mean difference between the loaded side and the unloaded contralateral control side decreased with increasing loading frequency. Whether this reflects the length of exposure to the tracer or specific frequency effects cannot be determined by this set of experiments. These in vivo experimental results corroborate those of previous ex vivo and in vitro studies, Strain-related differences in tracer distribution provide support for the hypothesis that load-induced fluid flow plays a regulatory role in processes associated with functional adaptation.