Fibula: The Forgotten Bone-May It Provide Some Insight On a Wider Scope for Bone Mechanostat Control?

The human fibula responds to its mechanical environment differently from the tibia accordingly with foot usage. Fibula structure is unaffected by disuse, and is stronger concerning lateral bending in soccer players (who evert and rotate the foot) and weaker in long-distance runners (who jump while running) with respect to untrained controls, along the insertion region of peroneus muscles. These features, strikingly associated to the abilities of the fibulae of predator and prey quadrupeds to manage uneven surfaces and to store elastic energy to jump, respectively, suggest that bone mechanostat would control bone properties with high selective connotations beyond structural strength.

Meagre effects of disuse on the human fibula are not explained by bone size or geometry.

Fibula response to disuse is unknown; we assessed fibula bone in spinal cord injury (SCI) patients and able-bodied counterparts. Group differences were smaller than in the neighbouring tibia which could not be explained by bone geometry. Differential adaptation of the shank bones may indicate previously unknown mechanoadaptive behaviours of bone. INTRODUCTION: The fibula supports only a small and highly variable proportion of shank compressive load (-8 to +19 %), and little is known about other kinds of stresses. Hence, whilst effects of habitual loading on tibia are well-known, fibula response to disuse is difficult to predict. METHODS: Therefore, we assessed fibular bone strength using peripheral quantitative computed tomography (pQCT) at 5 % increments from 5 to 90 % distal-proximal tibia length in nine participants with long-term spinal cord injury (SCI; age 39.2 ± 6.2 years, time since injury 17.8 ± 7.4 years), representing a cross-sectional model of long-term disuse and in nine able-bodied counterparts of similar age (39.6 ± 7.8 years), height and mass. RESULTS: There was no group difference in diaphyseal fibula total bone mineral content (BMC) (P = 0.22, 95 % CIs -7.4 % to -13.4 % and +10.9 % to +19.2 %). Site by group interactions (P < 0.001) revealed 27 and 22 % lower BMC in SCI at 5 and 90 % (epiphyseal) sites only. Cortical bone geometry differed at mid and distal diaphysis, with lower endocortical circumference and greater cortical thickness in SCI than able-bodied participants in this region only (interactions both P < 0.01). Tibia bone strength was also assessed; bone by group interactions showed smaller group differences in fibula than tibia for all bone parameters, with opposing effects on distal diaphysis geometry in the two bones (all Ps < 0.001). CONCLUSIONS: These results suggest that the structure of the fibula diaphysis is not heavily influenced by compressive loading, and only mid and distal diaphysis are influenced by bending and/or torsional loads. The fibula is less influenced by disuse than the tibia, which cannot satisfactorily be explained by differences in bone geometry or relative changes in habitual loading in disuse. Biomechanical study of the shank loading environment may give new information pertaining to factors influencing bone mechanoadaptation.

Suboptimal methotrexate use in rheumatoid arthritis patients in Italy: the MARI study.

OBJECTIVES: Methotrexate (MTX) is the first choice in the treatment of rheumatoid arthritis (RA), but the doses and regimens vary significantly. For this purpose, we conducted an observational study on the use of MTX for RA in Italy (MARI study). METHODS: The MARI study included 1,327 RA patients on MTX treatment for at least 12 months, at 60 Italian rheumatology units. Concomitant medications with corticosteroids, other DMARDs or biological therapies were recorded. The clinical assessment included the Disease Activity Score 28 (DAS28) and the serological positivity for the rheumatoid factor or for the anti-citrullinated protein antibodies. RESULTS: The included patients were treated with either oral (n=288) or parenteral (n=1039) MTX. Only 15.5% of the total number of the patients was on adequate MTX dose (i.e. ≥ 15 mg for the oral route of administration and >12 mg for the parenteral one). The initially established MTX dose was modified in 37.1% of the patients, for intolerance or clinical criteria. A DAS28 remission (DAS28 <2.6) was observed only in 58.5% of the cases, while 52.9% of the patients still presenting an active form of the disease were on suboptimal doses of MTX. CONCLUSIONS: The weekly dose of MTX prescribed for the treatment of RA is often suboptimal, even in conditions of inadequate control of the disease activity. The recommendations for the use of MTX in RA patients should take into account the efficacy and tolerability data derived from its use in real clinical practice.

Electrical charging effects on the sliding friction of a model nano-confined ionic liquid.

Recent measurements suggest the possibility to exploit ionic liquids (ILs) as smart lubricants for nano-contacts, tuning their tribological and rheological properties by charging the sliding interfaces. Following our earlier theoretical study of charging effects on nanoscale confinement and squeezout of a model IL, we present here molecular dynamics simulations of the frictional and lubrication properties of that model under charging conditions. First, we describe the case when two equally charged plates slide while being held together to a confinement distance of a few molecular layers. The shear sliding stress is found to rise strongly and discontinuously as the number of IL layers decreases stepwise. However, the shear stress shows, within each given number of layers, only a weak dependence upon the precise value of the normal load, a result in agreement with data extracted from recent experiments. We subsequently describe the case of opposite charging of the sliding plates and follow the shear stress when the charging is slowly and adiabatically reversed in the course of time, under fixed load. Despite the fixed load, the number and structure of the confined IL layers change with changing charge, and that in turn drives strong friction variations. The latter involves first of all charging-induced freezing of the IL film, followed by a discharging-induced melting, both made possible by the nanoscale confinement. Another mechanism for charging-induced frictional changes is a shift of the plane of maximum shear from mid-film to the plate-film interface, and vice versa. While these occurrences and results invariably depend upon the parameters of the model IL and upon its specific interaction with the plates, the present study helps identifying a variety of possible behavior, obtained under very simple assumptions, while connecting it to an underlying equilibrium thermodynamics picture.

Analysis of the independent power of age-related, anthropometric and mechanical factors as determinants of the structure of radius and tibia in normal adults. A pQCT study.

To compare the independent influence of mechanical and non-mechanical factors on bone features, multiple regression analyses were performed between pQCT indicators of radius and tibia bone mass, mineralization, design and strength as determined variables, and age or time since menopause (TMP), body mass, bone length and regional muscles' areas as selected determinant factors, in Caucasian, physically active, untrained healthy men and pre- and post-menopausal women. In men and pre-menopausal women, the strongest influences were exerted by muscle area on radial features and by both muscle area and bone length on the tibia. Only for women, was body mass a significant factor for tibia traits. In men and pre-menopausal women, mass/design/strength indicators depended more strongly on the selected determinants than the cortical vBMD did (p<0.01-0.001 vs n.s.), regardless of age. However, TMP was an additional factor for both bones (p<0.01-0.001). The selected mechanical factors (muscle size, bone lengths) were more relevant than age/TMP or body weight to the development of allometrically-related bone properties (mass/design/strength), yet not to bone tissue 'quality' (cortical vBMD), suggesting a determinant, rather than determined role for cortical stiffness. While the mechanical impacts of muscles and bone levers on bone structure were comparable in men and pre-menopausal women, TMP exerted a stronger impact than allometric or mechanical factors on bone properties, including cortical vBMD.

Squeezout phenomena and boundary layer formation of a model ionic liquid under confinement and charging.

Electrical charging of parallel plates confining a model ionic liquid down to nanoscale distances yields a variety of charge-induced changes in the structural features of the confined film. That includes even-odd switching of the structural layering and charging-induced solidification and melting, with important changes of local ordering between and within layers, and of squeezout behavior. By means of molecular dynamics simulations, we explore this variety of phenomena in the simplest charged Lennard-Jones coarse-grained model including or excluding the effect a neutral tail giving an anisotropic shape to one of the model ions. Using these models and open conditions permitting the flow of ions in and out of the interplate gap, we simulate the liquid squeezout to obtain the distance dependent structure and forces between the plates during their adiabatic approach under load. Simulations at fixed applied force illustrate an effective electrical pumping of the ionic liquid, from a thick nearly solid film that withstands the interplate pressure for high plate charge to complete squeezout following melting near zero charge. Effective enthalpy curves obtained by integration of interplate forces versus distance show the local minima that correspond to layering and predict the switching between one minimum and another under squeezing and charging.

The pQCT 'Bone Strength Indices' (BSIs, SSI). Relative mechanical impact and diagnostic value of the indicators of bone tissue and design quality employed in their calculation in healthy men and pre- and post-menopausal women.

The pQCT-assessed Bone Strength Indices (BSI's, SSI) depend on the product of a 'quality' indicator, the cortical vBMD (vCtD), and a 'design' indicator, one of the cross-sectional moments of inertia or related variables (MIs) in long bones. As the MIs vary naturally much more than the vCtD and represent different properties, it could be that the variation of the indices might not reflect the relative mechanical impact of the variation of their determinant factors in different individuals or circumstances. To understand this problem, we determined the vCtD and MI's in tibia scans of 232 healthy men and pre- and post-MP women, expressed in SD of the means calculated for each group, and analyzed the independent influence of 1 SD unit of variation of each factor on that of the indices by multiple correlations. Results showed: 1. that the independent influence of the MIs on the indices was generally larger than that of the vCtD, and 2. that in post-MP women the influence of the vCtD was larger than it was in the other groups. This confirms the view that inter-individual variation of vCtD is comparatively small, and that mechanical competence of human bone is mostly determined by 'design' factors.

Mineralization- and remodeling-unrelated improvement of the post-yield properties of rat cortical bone by high doses of olpadronate.

Some pharmacologic effects on bone modeling may not be evident in studies of remodeling skeletons. This study analyzes some effects of olpadronate on cortical bone modeling and post-yield properties in femurs diaphyses (virtually only-modeling bones) of young rats by mid-diaphyseal pQCT scans and bending tests. We studied 20/22 male/female animals traetad orally with olpadronate (45-90 mg/kg/d, 3 months) and 8/9 untreated controls. Both OPD doses enhanced diaphyseal cross-sectional moments of inertia (CSMI) with no change in cortical vBMD and elastic modulus. Yield stiffness and strength were mildly increased. Post-yield strength, deflection and energy absorption were strikingly enhanced. Ultimate strength was enhanced mainly because of effects on bone mass/geometry and post-yield properties. The large improvement of post-yield properties could be explained by improvements in bone geometry. Improvements in bone mass/geometry over weight-bearing needs suggest an enhanced modeling-related response to mechanical stimuli. Effects on tissue microstructural factors (not measured) could not be excluded. Results reveal novel olpadronate effects on bone strength and toughness unrelated to tissue mineralization and stiffness, even at high doses. Further studies could establish whether this could also occur in modeling-remodeling skeletons. If so, they could counteract the negative impact of anti-remodeling effects of bisphosphonates on bone strength.

pQCT-assessed relationships between diaphyseal design and cortical bone mass and density in the tibiae of healthy sedentary and trained men and women.

In a pQCT study of running-trained and untrained men and women we had shown that bone mass distribution along the tibia was adapted to the usage-derived stress pattern. To study the possible association between the efficiency of diaphyseal design and bone material stiffness, we extend the analysis of the same sample to correlate pQCT indicators of the distribution (CSMIs), mass (BMC), and density (vBMD) of cortical bone tissue as descriptors of "distribution/mass" (d/m) or "distribution/quality" (d/q) relationships. The d/m and d/c curves followed positive (exponential) and negative (hyperbolic-like) equations, respectively. Distribution curves of r coefficients throughout the bone were all bell-shaped, reaching a maximum towards the mid-diaphysis. The CSMIs and BMC were higher, and vBMD was lower in men than women and in runners than non-runners. The d/m relationships were described by unique curves for all groups while d/q relationships were better adjusted to separate curves for men and women. Results support that: 1. diaphyseal design reflects the relative influence of bending/torsion stress along the bones, tending to minimize bone mass; 2. there is a trade-off between cortical bone "quality" and distribution; 3. d/m and d/q relationships are related to bone mechanical environment, and 4. d/q relationships are affected by sex.

Quantum interference of electrons in a ring: tuning of the geometrical phase.

We calculate the oscillations of the dc conductance across a mesoscopic ring, simultaneously tuned by applied magnetic and electric fields orthogonal to the ring. The oscillations depend on the Aharonov-Bohm flux and of the spin-orbit coupling. They result from mixing of the dynamical phase, including the Zeeman spin splitting, and of geometric phases. By changing the applied fields, the geometric phase contribution to the conductance oscillations can be tuned from the adiabatic (Berry) to the nonadiabatic (Ahronov-Anandan) regime. To model a realistic device, we also include nonzero backscattering at the connection between ring and contacts, and a random phase for electron wave function, accounting for dephasing effects.

Biomechanical background for a noninvasive assessment of bone strength and muscle-bone interactions.

New concepts and methods of study in bone biomechanics defy the prevailing idea that bone strength is determined by a systemically-controlled "mineralized mass" which grows until reaching a peak and then is lost at individually-specific rates. In case of bones, "mass" represents actually the substratum of a structure, the stiffness of which does not depend on the mass, but on the intrinsic stiffness and the spatial distribution of the mineralized material. A feed-back system called "bone mechanostat" seems to orient the osteoblastic and osteoclastic processes of bone, modeling and remodeling, according to the sensing by osteocytes of strains caused in the structure by mechanical usage of the skeleton, in specific directions as determined principally by the customary contractions of regional muscles and impact forces. The endocrine-metabolic systems, crucial for the normal skeletal development, modulate the work of osteocytes, blasts and clasts in a systemic way (i.e., not related to a specific direction of the stimuli). Therefore, they tend actually to interact with, rather than contribute to, the biomechanical control of bone structure. Furthermore, no feed-back loop enabling a cybernetic relationship of those systems with bone is known. Instead of passively letting hormones regulate their "mass" in order to optimize their strength, bones would actively self-regulate their architecture following an anisotropic pattern in order to optimize their stiffness (the only known variable to be ever controlled in the skeleton) and strength "despite of" the endocrine systems. Three practical questions derive from those ideas: 1. Osteoporoses are not "intense osteopenias" but "osteopenic fragilities". 2. The diagnosis of osteopenia could be solved densitometrically; but that of bone fragility is a biomechanical problem which requires auxiliary resources for evaluating the stiffness and the spatial distribution of the mineralized material. 3. Osteopenias and osteoporoses should be on time evaluated as related to the mass or strength of the regional muscles, respectively, in order to differentiate between the "primary" (intrinsic lesion of the mechanostat) or "secondary" (systemic) etiologies and the biomechanical origin (disuse) in each case, with important therapeutic implications.

Impact of parathyroid status and Ca and vitamin-D supplementation on bone mass and muscle-bone relationships in 208 Belarussian children after thyroidectomy because of thyroid carcinoma.

This observational study analyzes Ca-P metabolism and its impact on bone mass accrual and density and the muscle-bone mass/mass relationships in male and female children and adolescents who were parathyroidectomized because of thyroid carcinoma. Two hundred and eight children and adolescents (119 girls and 89 boys) from Gomel city (Belarus) and its rural surroundings were referred to our institution after having undergone total thyroidectomy for the treatment of advanced papillary thyroid cancer. A subgroup of children with demonstrated primary hypoparathyroidism received dihydrotachysterol (AT-10) and/or Ca supplementation. Among routine procedures over a maximum follow-up period of 5 years (average 3.7 years, maximum 8 visits), whole-body scans were taken using dual energy X-ray absorptiometry (DXA) at each visit in order to determine whole-body bone mineral content (TBMC), projected "areal" bone mineral density (TBMD), total lean mass (TLM) and total fat mass (TFM). The average serum Ca, P and AP concentrations over the whole observation period were significantly different between the groups; however, TBMC z-scores for all studied children were statistically similar in all visits. In girls, no between-group differences in height- and weight-controlled TBMC and TBMD or the TBMC/TLM ratio were observed (ANCOVA) and supplementation exerted no effect on these data, suggesting that the total bone mass accrual was not impaired by PTH deficiency in the studied conditions. However, non-supplemented boys showed lower values of the TBMC/TLM ratio than girls, and supplementation normalized these values in direct correlation with the induced improvement in serum P availability to bone. Results indicate that the primary impairment in parathyroid function and bone metabolism indicators in the thyroidectomized children was unrelated to any measurable change in crude bone mass values. However, in boys this condition impaired the TBMC/TLM ratio in such a way that the administered supplementation could normalize it as a function of improved P availability. Girls' skeleton seemed to have been naturally protected against the negative metabolic effect of the studied condition. An estrogen-induced enhancement of the biomechanical impact of muscle contractions on bone mass and structure could not be excluded in this group.

A DXA study of muscle-bone relationships in the whole body and limbs of 2512 normal men and pre- and post-menopausal women.

A whole-body DXA study of 1450 healthy Caucasian individuals [Bone 22 (1998) 683] found that mineral mass, either crude (BMC) or statistically adjusted to fat mass (FM-adjusted BMC), correlated linearly with lean mass (LM, proportional to muscle mass). The results showed similar slopes but decreasing intercepts (ordinate values) in the order: pre-MP women > men > post-MP women > children. This supports the hypothesis that sex hormones influence the control of bone status by muscle strength in all species. Now we further study those relationships in 2512 healthy Hispanic adults (307 men, 753 pre-MP women, 1452 post-MP women), including separate determinations in their upper and lower limbs. The slopes of the BMC or FM-adjusted BMC vs. LM relationships were parallel in all the studied regions. However, region-related differences were found between the ordinates of the curves. In the whole body, the crude-BMC/LM relationships showed the same ordinate differences as previously observed. In the lower limbs, those differences were smaller in magnitude but highly significant, showing the order: pre-MP women > men = post-MP women. In the upper limbs, the decreasing ordinate order was: men > pre-MP women > post-MP women. After fat adjustment of the BMC, order in both limbs was: men > pre-MP women > post-MP women. Parallelism of the curves was maintained in all cases. LM had a larger independent influence on these results than FM, body weight, or age. The parallelism of the curves supports the idea that a common biomechanical control of bones by muscles occurs in humans. Results suggest that sex-hormone-associated differences in DXA-assessed muscle-bone proportionality in humans could vary according to the region studied. This could be related to the different weight-bearing nature of the musculoskeletal structures studied. Besides the obvious anthropometric associations, FM would exert a mechanical effect as a component of body weight, evident in the lower limbs, while muscle contractions would induce a more significant, dynamical effect in both lower and upper limbs. Muscles seem to exert a larger influence than FM, body weight, and age on BMC in the whole body and lower limbs, regardless of the gender and reproductive status of the individual. The muscle-bone relationships studied may provide a rationale for a future differential diagnosis between disuse-related and other types of osteopenia.

Bone quality parameters of the distal radius as assessed by pQCT in normal and fractured women.

The aim of this study was to test the ability of some indicators of different aspects of bone quality (assessed by peripheral quantitative computed tomography in the distal radius) to discriminate between fractured and nonfractured individuals. The study compared 214 women aged 45-85 years, free of any bone-affecting treatment, of whom 107 had suffered a Colles' fracture in the previous 6 months and 107 did not. The determinations included bone tissue or mineral 'mass' indicators (trabecular, cortical and total volumetric mineral content, cortical bone area); bone 'density' estimates (trabecular, cortical and total volumetric mineral density), and the Cartesian (rectangular) and polar moments of inertia as influences of cross-sectional architecture on resistance to bending and torsional loads, respectively. The influences of body height, weight and age on the tomographic indicators were minimized by adjusting the data according to the partial coefficients of multiple stepwise regressions. The adjusted values of all the indicators were lower in fractured than in nonfractured groups. The prevalence of fractures was directly related to the actual values of the indicators, rather than the age or body habitus of the individuals. The significance of these differences between the assessed indicators decreased in the following order: trabecular 'mass' > trabecular 'density' > cortical or total 'mass' > cortical architecture > total or cortical 'density' indicators. Within the same type of bone, the tissue or mineral 'mass' indicators performed better than the 'density' indicators. The cortical bone density did not give useful information, probably because of technical difficulties. Odds-ratios and receiver-operating characteristic (ROC) analyses confirmed those features. The selected 'cut-off' values of the indicators as determined by the ROC curves (very close to those determined by the inflexion points of the logistic reression curves) may indicate reference limits to detect persons at risk of fracture according to the type of information provided by each variable. These results show that these tomographic indicators discriminate well between fractured and nonfractured individuals, and should be suitable to assess how total, cortical and trabecular bone strength in the distal radius could affect different kinds of strength regardless of the age or body habitus of the individual. Their ability to estimate fracture risk from different biomechanical points of view should be assessed by adequately designed, prospective studies.

Postmenopausal changes in the distribution of the volumetric BMD of cortical bone. A pQCT study of the human leg.

Three different regions of interest (ROIs) were defined in pQCT scans (XCT-3000 machine, Stratec, Germany) taken at the tibial mid-diaphyses of 12 pre-menopausal (pre-MP) and 12 post-menopausal (post-MP) women who were otherwise normal, according to the volumetric bone mineral density (vBMD) value of their corresponding pixels (voxels) as assessed by their respective attenuation values. They were classified as "low-vBMD" (LD-ROI, with a vBMD of 200-400 mg/cm(3)), corresponding chiefly to trabecular-subcortical bone; "medium-vBMD" (MD-ROI, vBMD = 400-800 mg/cm(3)), corresponding mainly to porous cortical bone or cortical-subcortical bone, and "high-vBMD" (HD-ROI, vBMD higher than 800 mg/cm(3)), corresponding to dense cortical bone. The fraction of the total cross-sectional bone area covered by the HD-ROI was 16% higher, and that covered by the MD-ROI 20% lower, in pre-MP than post-MP women. No differences concerning the LDROIs were found. A close, linearly negative relationship was found between the MD- and HD-ROI fractions in all the women together, with no inter-group differences in slope. The Stress-Strain Index (an indicator of the torsional stiffness and strength of the whole bones that involved both the vBMD and the spatial disposition of the HD bone in the cross-section - torsional moment of inertia -) correlated linearly and positively with the cross-sectional area of the HD-ROI, with a higher slope for pre-MP than post-MP women. Qualitatively, a. post-MP women showed a significantly more prevalent discontinuity of the voxels in the HD-ROI than pre-MP women, and b. the tendency of LD-ROIs to accumulate along the mechanically lesseffective (antero-posterior) axis of the image - a characteristic of pre-MP bones - was visually less evident in post-MP bones. These features describe non-invasively some changes induced by menopause in the human tibia that may be critical for defining the skeletal condition and to monitor the effects of treatments addressed either to protect or to improve mechanically the bone structure, beyond the possibilities of standard densitometry.

Analysis of biomechanical effects on bone and on the muscle-bone interactions in small animal models.

Animal models are suitable to study many aspects of bone structure and strength. This article reviews some general principles of current bone biomechanics and describes the scope of the available methodology for biomechanical studies of the musculoskeletal system employing those models. The analysis comprises bone and muscle "mass" indicators provided by standard densitometry (DEXA); bone 'mass', 'apparent density', geometry or architectural design and strength and muscle strength indicators that can be determined by peripheral quantitative computed tomography (pQCT), and bone material and structural (whole-bone) properties than can be directly assessed by destructive mechanical tests. Some novel interrelationships that can be investigated that way are discussed, namely, 1. the pathogenetic analysis of the effects on whole-bone strength, 2. the discrimination between mineralization and microstructural factors as determinants of changes in the bone material or structural properties, 3. the evaluation of the interaction of a treatment with the ability of bone 'mechanostat' to optimize the bone architectural design by 'distribution / mass' and 'distribution / quality' curves, and 4. the analysis of effects on the musclebone interactions for a differential diagnosis between 'physiological' or 'disuse' and 'true' osteopenias and osteoporoses.

Densitometric and tomographic analyses of musculoskeletal interactions in humans.

Previous studies with standard densitometry (DXA) have suggested that the bone mass is strongly dependent on the muscle mass in the species, following a similar relationship at any age and sex hormones or related factors potentiate that relationship. Studies with pQCT indicated that the surplus bone mass per unit of muscle mass previously observed in premenopausal women would be stored in skeletal regions with relatively little mechanical relevance, thus avoiding remotion through mechanically oriented remodelling by the bone mechanostat. Scanning the distal radius with pQCT has also showed a highly significant, linear relationship between SSI of the distal radius and the dynamometric maximal bending moment of the forearm in normal men and women. In order to investigate similar relationships in regions that are inaccessible to pQCT, we used spinal radiographs and axial QCT. This study affords additional evidence to the previous references concerning the direct, significant impact of the regional muscle strength on the determination of the tomographic indicators of bone mechanical quality and their indirect repercussion of the skeletal condition (curvature of the spine).

Gender-related differences in the relationship between densitometric values of whole-body bone mineral content and lean body mass in humans between 2 and 87 years of age.

The mineral, lean, and fat contents of the human body may be not only allometrically but also functionally associated. This report evaluates the influence of muscle mass on bone mass and its age-related changes by investigating these and other variables in both genders in the different stages of reproductive life. We have analyzed the dual-energy X-ray absorptiometry (DEXA)-determined whole-body mineral content (TBMC), lean body mass (LBM), and fat body mass data (FBM) of 778 children and adolescents of both genders, aged 2-20 years [previously reported in Bone 16(Suppl.): 393S-399S; 1995], and of 672 age-matched men and women, aged 20-87 years. Bone mass (as assessed by TBMC) was found to be closely and linearly associated with muscle mass (as reflected by LBM) throughout life. This relationship was similar in slope and intercept in prepubertal boys and girls. However, while keeping the same slope of that relationship (50-54 g increase in TBMC per kilogram LBM): (1) both men and women stored more mineral per unit of LBM within the reproductive period than before puberty (13%-29% and 33%-58%, respectively); (2) women stored more mineral than age-matched men with comparable LBM (17%-29%) until menopause; and (3) postmenopausal women had lower values of bone mineral than premenopausal women, similar to those of men with comparable LBM. Men showed no age effect on the TBMC/LBM relationship after puberty. Multiple regression analyses showed that not only the LBM, but also the FBM and body height (but not body weight), influenced the TBMC, in that decreasing order of determining power. However, neither the FBM nor body height could explain the pre/postpubertal and the gender-related differences in the TBMC/LBM relationship. Accordingly: (1) calculated TBMC/LBM and FBM-adjusted TBMC/LBM ratios were lower in girls and boys from 2-4 years of age until puberty; (2) thereafter, females rapidly reached significantly higher ratios than age-matched men until menopause; and (3) then, ratios for women and age-matched men tended to equalize. A biomechanical explanation of those differences is suggested. Sex hormones or related factors could affect the threshold of the feedback system that controls bone remodeling to adapt bone structure to the strains derived from customary mechanical usage in each region of the skeleton (bone "mechanostat"). Questions concerning whether the mineral accumulation in women during the reproductive period is related or not to an eventual role in pregnancy or lactation, or whether the new bone is stored in mechanically optimal or less optimal regions of the skeleton, are open to discussion.

The annular tinted contact lens syndrome: corneal topographic analysis of ring-shaped irregular astigmatism caused by annular tinted contact lenses.

PURPOSE: Irregular corneal astigmatism has been reported in association with annular tinted hydrogel contact lenses. We report the abnormal videokeratographic findings of five patients wearing annular tinted contact lenses, who presented with bilateral blurred vision and revealed a loss of best corrected visual acuity. METHODS/RESULTS: The corneal topographic analysis revealed a previously unreported distinct ring-shaped pattern of irregular astigmatism. The topographic circular band of irregular astigmatism was further characterized by concentric areas of relative steepening, flattening, and steepening with a diameter of approximately 4 mm. This pattern suggests that forces acting at the junctional zone between the tinted area and the clear pupillary area are inducing structural abnormalities of the corneal surface. At the time of presentation, the mean surface regularity index (SRI) was 2.06 (range: 0.61-5.88). The topography and best-corrected visual acuity returned to normal within days of discontinuing annular tinted lens use, and the mean SRI decreased to 0.44 (range: 0.21-1.16). Digital imaging of lenses obtained from our patients and of identical control lenses was performed. A masked analysis suggested that the study lenses contain greater amounts of pigment compared to the control lenses. CONCLUSIONS: We present ten characteristic signs and symptoms of this condition, which we have named "the annular tinted contact lens syndrome." Corneal topographic analysis is a powerful tool for detecting specific reversible irregularities of the corneal surface associated with the use of annular tinted contact lenses.

Long-bone biomechanics in mice selected for body conformation.

Two lines of mice divergently selected from the control strain (CBi) against the positive phenotypic correlation between body weight (b.w.) and tail (skeletal) length were obtained (CBi/C: high weight, short tail; CBi/L: low weight, long tail). The selected animals showed a different relationship between body and skeletal masses. To compare the adequacy between biomass and load-bearing ability of the skeleton, and to describe the eventual role of bone mechanostat in the production of these changes, cross-sectional and bending properties of both femur diaphyses were determined in CBi, CBi/C, and CBi/L adult mice of both genders. Cortical bone material quality (elastic modulus) was reduced in the selected lines (p < 0.001), significantly less in CBi/C than in CBi/L. In contrast, cross-sectional design (b.w.-adjusted values of moment of inertia, CSMI) was largely improved (p < 0.001), significantly more in CBi/C than in CBi/L. These effects determined a greater stiffness and strength in CBi/C than in CBi/L or CBi weight-paired mice. The elevations of the negative regression lines between elastic modulus and CSMI ("distribution/quality" curves) decreased in the order CBi/C > CBi/L > CBi. Data show that selection improved diaphyseal stiffness and strength in CBi/C animals because of an architectural overcompensation for the reduced bone material quality. Therefore, an inadequate control of long-bone architectural design as a function of the mechanical quality of cortical bone and b.w. bearing could have been induced in that line. Assuming bone mechanostatic regulation to be genetically programmed, some of the corresponding biological determinants should be transmitted independently, because artificial selection separately affected material quality and architectural design. The possibility of transmission of an inadequate mechanostatic function (inability to adapt bone modeling to bone material quality as a function of the biomass to be supported) was also shown, as some genotypes could express architectural modifications that largely exceed bone material quality deterioration.