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Arterial calcification is a common phenomenon in the elderly, in patients with atherosclerosis or renal failure and in diabetes. However, when present in very young individuals, it is likely to be associated with an underlying hereditary disorder of arterial calcification. Here, we present an overview of the few monogenic disorders presenting with early-onset cardiovascular calcification. These disorders can be classified according to the function of the respective disease gene into (1) disorders caused by an altered purine and phosphate/pyrophosphate metabolism, (2) interferonopathies, and (3) Gaucher disease. The finding of arterial calcification in early life should alert the clinician and prompt further genetic work-up to define the underlying genetic defect, to establish the correct diagnosis, and to enable appropriate therapy.

Singleton-Merten syndrome (SMS) is a type I interferonopathy characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, and psoriasis. A missense mutation in IFIH1 encoding a cytoplasmic viral RNA sensor MDA5 has recently been identified in the SMS patients as well as in patients with a monogenic form of lupus. We previously reported that Ifih1 gs/+ mice express a constitutively active MDA5 and spontaneously develop lupus-like nephritis. In this study, we demonstrate that the Ifih1 gs/+ mice also exhibit SMS-like bone abnormalities, including decreased bone mineral density and thin cortical bone. Histological analysis revealed a low number of osteoclasts, low bone formation rate, and abnormal development of growth plate cartilages in Ifih1 gs/+ mice. These abnormalities were not observed in Ifih1 gs/+ ・ Mavs -/- and Ifih1 gs/+ ・ Ifnar1 -/- mice, indicating the critical role of type I IFNs induced by MDA5/MAVS-dependent signaling in the bone pathogenesis of Ifih1 gs/+ mice, affecting bone turnover. Taken together, our findings suggest the inhibition of type I IFN signaling as a possible effective therapeutic strategy for bone disorders in SMS patients., (Copyright © 2019 by The American Association of Immunologists, Inc.)

RIG-I has a remarkable ability to specifically select viral 5'ppp dsRNAs for activation from a pool of cytosolic self-RNAs. The ATPase activity of RIG-I plays a role in RNA discrimination and activation, but the underlying mechanism was unclear. Using transient-state kinetics, we elucidated the ATPase-driven "kinetic proofreading" mechanism of RIG-I activation and RNA discrimination, akin to DNA polymerases, ribosomes, and T cell receptors. Even in the autoinhibited state of RIG-I, the C-terminal domain kinetically discriminates against self-RNAs by fast off rates. ATP binding facilitates dsRNA engagement but, interestingly, makes RIG-I promiscuous, explaining the constitutive signaling by Singleton-Merten syndrome-linked mutants that bind ATP without hydrolysis. ATP hydrolysis dissociates self-RNAs faster than 5'ppp dsRNA but, more importantly, drives RIG-I oligomerization through translocation, which we show to be regulated by helicase motif IVa. RIG-I translocates directionally from the dsRNA end into the stem region, and the 5'ppp end "throttles" translocation to provide a mechanism for threading and building a signaling-active oligomeric complex., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The annual cyclicality of cortical bone growth marks (BGMs) allows reconstruction of some important life history traits, such as longevity, growth rate or age at maturity. Little attention has been paid, however, to non-cyclical BGMs, though some record key life history events such as hatching (egg-laying vertebrates), metamorphosis (amphibians), or weaning (suggested for Microcebus and the hedgehog). Here, we investigate the relationship between non-cyclical BGMs and a stressful biological event in mammals: the moment of birth. In the present study, we histologically examine ontogenetic series of femora, tibiae and metapodia in several extant representatives of the genus Equus (E. hemionus, E. quagga and E. grevyi). Our analysis reveals the presence of a non-cyclical growth mark that is deposited around the moment of birth, analogous to the neonatal line described for teeth. We therefore refer to it as neonatal line. The presence of this feature within the bone cross-section agrees with a period of growth arrest in newborn foals regulated by the endocrine system. The neonatal line is accompanied by modifications in bone tissue type and vascularization, and has been identified in all bones studied and at different ontogenetic ages. Our discovery of a non-cyclical BGM related to the moment of birth in mammals is an important step towards the histological reconstruction of life histories in extant and fossil equids., Competing Interests: The authors have declared that no competing interests exist.

Purpose of Review: We give an update on the etiology and potential treatment options of rare inherited monogenic disorders associated with arterial calcification and calcific cardiac valve disease., Recent Findings: Genetic studies of rare inherited syndromes have identified key regulators of ectopic calcification. Based on the pathogenic principles causing the diseases, these can be classified into three groups: (1) disorders of an increased extracellular inorganic phosphate/inorganic pyrophosphate ratio (generalized arterial calcification of infancy, pseudoxanthoma elasticum, arterial calcification and distal joint calcification, progeria, idiopathic basal ganglia calcification, and hyperphosphatemic familial tumoral calcinosis; (2) interferonopathies (Singleton-Merten syndrome); and (3) others, including Keutel syndrome and Gaucher disease type IIIC. Although some of the identified causative mechanisms are not easy to target for treatment, it has become clear that a disturbed serum phosphate/pyrophosphate ratio is a major force triggering arterial and cardiac valve calcification. Further studies will focus on targeting the phosphate/pyrophosphate ratio to effectively prevent and treat these calcific disease phenotypes.

Patients: Singleton-Merten syndrome is an extremely rare autosomal dominant condition with less than 10 reported cases in the literature. It is characterized by abnormal aortic calcifications and dental abnormalities. The goal of this case report is to discuss the abnormal oral clinical features and the modified treatment protocol that was used in order to achieve osseointegration of dental implants in a patient having abnormal bone density and bone turnover associated with Singleton-Merten Syndrome., Discussion: Following extraction of the remaining teeth, titanium implants (Friadent GmbH, Mannheim, Germany and Straumann(®), Basel, Switzerland) were placed in the upper and lower jaw of the patient. The upper jaw which was treated with dental implants, received a bar supported implant retained prosthesis and the lower jaw an implant retained telescopic prosthesis. The patient was regularly followed up for the past 13 years during which, clinical and radiological evaluation of osseointegration was undertaken. All the loaded implants showed clinical and radiographic evidence of osseointegration. With a follow up of 13 years after insertion of the first implant, the patient reported functioning well with no complications., Conclusion: The treatment with dental implants in the extremely rare Singleton-Merten syndrome patients is a reasonable treatment option to rehabilitate maxillofacial aesthetics and establish normal function of the jaws., (Copyright © 2015 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.)

Carpal tunnel syndrome (CTS) is an idiopathic disease that results from increased fibrosis of the subsynovial connective tissue (SSCT). A recent study found overexpression of both transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) in the SSCT of CTS patients. This study investigated TGF-β and CTGF expression in a rabbit model of CTS, in which SSCT fibrosis is induced by a surgical injury. Levels of TGF-β1 and CTGF at 6, 12, 24 weeks after injury were determined by immunohistochemistry A significant increase in TGF-β1 and a concomitant significant increase in CTGF were found at 6 weeks, in addition to higher cell density compared to normal (all p<0.05), Interestingly, CTGF expression was reduced at 12 and 24 weeks, suggesting that an initial insult results in a time limited response. We conclude that this rabbit model mimics the fibrosis found in human CTS, and may be useful to study pathogenetic mechanisms of CTS in vivo.

The generation of bioengineered cartilage tissue suitable for transplantation is a potential therapy to treat damaged cartilage. We have shown previously that the physical and biomechanical properties of bioengineered cartilage can be improved by the application of 30 min of cyclic compression by a mechanism involving sequential upregulation of gene and protein levels of membrane type-1 matrix metalloproteinase (MT1-MMP) and MMP-13. In the current study, we demonstrated that MT1-MMP is critical to this response, as blocking the upregulation of MT1-MMP prevented the improvement in tissue formation. MT1-MMP seems to act by inducing tissue remodeling as evidenced by the presence of aggrecan degradation products by Western blot analysis and increased release of matrix molecules into the media. Release of these molecules was diminished when MT1-MMP upregulation was prevented. This matrix degradation was likely due to MT1-MMP, as under conditions where MMP-13 expression is maintained (stimulation in the presence of MT1-MMP siRNA) the release of these matrix molecules into the media was still prevented. It also appears that MT1-MMP does not regulate MMP-13 gene expression, as MT1-MMP-siRNA pretreatment had no effect on MMP-13 expression following mechanical stimulation. Further analysis of the anabolic genes and proteins involved in mechanically stimulated cartilage will lead to better understanding of the mechanism(s) underlying tissue formation yielding improved bioengineered cartilage., ((c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Dupuytren's disease, (DD), is a fibroproliferative condition of the palmar fascia in the hand, typically resulting in permanent contracture of one or more fingers. This fibromatosis is similar to scarring and other fibroses in displaying excess collagen secretion and contractile myofibroblast differentiation. In this report we expand on previous data demonstrating that POSTN mRNA, which encodes the extra-cellular matrix protein periostin, is up-regulated in Dupuytren's disease cord tissue relative to phenotypically normal palmar fascia. We demonstrate that the protein product of POSTN, periostin, is abundant in Dupuytren's disease cord tissue while little or no periostin immunoreactivity is evident in patient-matched control tissues. The relevance of periostin up-regulation in DD was assessed in primary cultures of cells derived from diseased and phenotypically unaffected palmar fascia from the same patients. These cells were grown in type-1 collagen-enriched culture conditions with or without periostin addition to more closely replicate the in vivo environment. Periostin was found to differentially regulate the apoptosis, proliferation, alpha smooth muscle actin expression and stressed Fibroblast Populated Collagen Lattice contraction of these cell types. We hypothesize that periostin, secreted by disease cord myofibroblasts into the extra-cellular matrix, promotes the transition of resident fibroblasts in the palmar fascia toward a myofibroblast phenotype, thereby promoting disease progression.

Background: The cutaneous antioxidants form an efficient protection system against the destructive potential of free radicals, produced by environmental factors, such as UV-sun irradiation, hazardous substances and lifestyle habits. Most of the antioxidants cannot be produced by the human organism. Thus, they have to be incorporated by food and beverages., Material and Methods: In the present manuscript, the distribution of carotenoids as a marker for antioxidative potential in human skin was investigated with two different in vivo Raman spectroscopy methods with an excitation wavelength of 785 nm (Skin Analyzer) and at 488 nm (resonance Raman spectroscopy). The carotenoid profile was assessed at three different anatomical locations (palm, forehead and volar forearm) in 12 healthy volunteers., Results: In untreated skin, the major fraction of the carotenoids is located in the upper part of the stratum corneum (SC). The amount of carotenoid is lower in the upper part of the SC on the forearm compared to forehead and palm shown with both methods. Both methods detect similar distinction patterns of carotenoid levels for the three anatomical locations., Conclusion: The present study supports the hypothesis that antioxidative substances; here carotenoids, are secreted via eccrine sweat glands and/or sebaceous glands to the skin surface. Raman spectroscopic methods are an efficient tool to analyze the distribution of carotenoids in the human skin over time and with the Skin Analyzer over different layers of the epidermis. Resonance Raman spectroscopy is suited to analyze deeper parts of the skin.

Aim: To determine the concentration of fluoride (F) in the metacarpi from ewes of varying age, which had been grazing pastures that had been regularly topdressed with phosphatic fertilisers, which contain F as a contaminant, for at least 30 years., Methods: Three groups of 10 ewes aged 6-8, 18-20 and 60-72 months were selected from seven research farms with a known fertiliser history, representing the major sheep farming regions of New Zealand. Lambs were born and remained on the property. The sheep were collected and slaughtered in autumn, and the right metacarpus removed for determination of F content. Representative samples of topsoil (0-30- and 30-60-mm depths) were also collected for determination of F content., Results: The total concentration of F in topsoil on the farms ranged from 161 to 712 mg/kg. The overall mean concentrations of F in metacarpi from 6-8-, 18-20- and 60-72-monthold ewes were 170 (SE 9.9), 308 (SE 13.9) and 480 (SE 28.4) mg/kg dry matter (DM), respectively. On six farms, lambs which had been exposed to limited or no ingestion of soil had the lowest concentration of F in their metacarpi. Generally, there was a curvilinear relationship between age and concentration of F in the metacarpi of sheep. On the seventh farm, the concentrations of F in the metacarpi from the 6-8- and 18-20-month-old sheep were similar but lower than those of the 60-72-month-old ewes. The area of soils on the farm where the 6-8-month-old-sheep were grazing had higher total concentrations of F in topsoil (271 mg/kg) than those soils grazed by the 18-20-month-old sheep (205 mg/kg), and this may be one reason for the elevated concentration of F in the metacarpi of the younger ewes. The concentrations of F in metacarpi, at any age, were not related to the concentration of F in topsoils., Conclusions: Many factors can influence the amounts of F in soil ingested by grazing sheep and the concentration of F in their bone. The concentration of F in the metacarpi of ewes generally increased curvilinearly with age, and the rate of accumulation of F in bone was greatest in young sheep. The potential risk of chronic fluorosis occurring in sheep grazing pastures in New Zealand is low for animals managed in a manner similar to the flocks studied, given the highest mean concentration of F was 601 mg/kg DM, observed in metacarpi from 60-72-month-old ewes, and that a concentration of at least 2,400 mg/kg DM is the threshold for chronic fluorosis.

Nonfocused extracorporeal shock wave therapy (ESWT) treatment protocol is commonly used in veterinary practice. This study investigated the effects of four nonfocused ESWT treatments, given 2 weeks apart, on bone radiopharmaceutical uptake and radiographic and thermographic appearance in the metacarpal and metatarsal regions in six adult untrained horses. There were no measurable treatment effects determined by thermography (daily), scintigraphy (at 2-week intervals), and radiography (before study initiation and at study completion) between treated and control limbs. It was concluded that no gross evidence of bone remodeling is detectable by conventional clinical assessment when nonfocused ESWT is applied to healthy equine metacarpal or metatarsal bone.

Functional adaptation of bone normally protects the skeleton from fracture during daily activity. Accumulation of microcracking and loss of osteocytes have been implicated in the regulation and initiation of targeted (reparative) remodeling of bone and, in certain situations, the development of fatigue or stress fracture. We performed a histologic study of the dorsal cortex of the mid-diaphysis of the third metacarpal (Mc-III) bone of Thoroughbred racehorses after bones were bulk-stained in basic fuchsin and transverse calcified sections were prepared. The Thoroughbred racehorse is an extreme athlete whose Mc-III bone experiences particularly high cyclic strains during training and racing. A group of non-athletic horses was also included in the experiment. The following variables were quantified: activation frequency (Ac.f); bone formation rate (BFR); resorption space density (Rs.N/T.Ar); microcrack density (Cr.Dn); microcrack mean length (Cr.Le); microcrack surface density (Cr.S.Dn); osteocyte density (Ot.N/T.Ar; Ot.N/B.Ar); and bone volume fraction (B.Ar/T.Ar). Ac.f and BFR were estimated using a mathematical algorithm. Using confocal microscopy, bones were examined for fine microcracks, diffuse matrix injury, and disruption of the osteocyte syncytium. Low values for Cr.Dn (#/mm2) were found in both groups (0.022+/-0.008 and 0.013+/-0.006 for racing Thoroughbreds and non-athletic horses, respectively). There was no significant relationship between Cr.Dn and Ot.N/T.Ar; Ot.N/B.Ar, B.Ar/T.Ar, and Ot.N/T.Ar; Ot.N/B.Ar, and remodeling (Ac.f, Rs.N/T.Ar) and Ot.N/T.Ar; Ot.N/B.Ar. Intense remodeling of the Mc-III dorsal cortex was found in the racing Thoroughbreds (Ac.f 12.8+/-7.4 #/mm2/year; BFR 31.5+/-15.6%; Rs.N/T.Ar 0.19+/-0.09 #/mm2) and was significantly increased compared with non-athletic horses. Overall, remodeling was weakly correlated with Cr.Dn (r2=0.15, P<0.05). Subtle matrix injury, not detectable by bright-field microscopy, was particularly evident adjacent to resorption spaces in Thoroughbred bone. In non-athletic horses, disruption of the dendritic cell processes of osteocytes associated with cement lines and interstitial fragments was more evident. Taken together, these findings suggest that site-specific (targeted) induction of remodeling during functional adaptation of bone in a high-strain skeletal site is not dependent on accumulation of microcracking or loss of osteocytes. We hypothesize that athleticism can directly influence bone turnover in this extreme athlete through pathways that do not involve classical linear microcracks.

Osteocytes, which are embedded in bone matrix, are the most abundant cells in bone. Despite the ideal location of osteocytes to sense the local environment and influence bone remodeling, their functions, and the relative importance of these functions, remain controversial. In this study, we tested several hypotheses that address the possibilities that population densities of osteocyte lacunae (Ot.Lc.N/B.Ar) correlate with strain-, remodeling- or metabolism-related aspects of the local biomechanical environments of mid-third diaphyseal equine radii and third metacarpals from skeletally mature animals. Ot.Lc.N/B.Ar data, quantified in multiple cortical locations, were analyzed for possible correlations with (1) structural and material characteristics (e.g., cortical thickness, percent ash, secondary osteon population density, mean osteon cross-sectional area, and predominant collagen fiber orientation), (2) strain characteristics, including prevalent/predominant strain magnitude and mode (tension, compression, shear), (3) hypothesized strain-mode-related microdamage characteristics, which might be perceived by osteocyte 'operational' networks, and (4) variations in remodeling dynamics and/or metabolism (i.e. presumably higher in endocortical regions than in other transcortical locations). Results showed relatively uniform Ot.Lc.N/B.Ar between regions with highly non-uniform strain and strain-related environments and markedly heterogeneous structural and material organization. These results suggest that population densities of these cells are poorly correlated with mechanobiological characteristics, including local variations in metabolic rate and strain magnitude/mode. Although osteocytes hypothetically evolved both as strain sensors and fatigue damage sensors able to direct the removal of damage as needed, the mechanisms that govern the distribution of these cells remain unclear. The results of this study provide little or no evidence that the number of osteocyte lacunae has a functional role in mechanotransduction pathways that are typically considered in bone adaptation.

The purpose of this study was to investigate the effect of alendronate on metacarpal and lumbar bone mineral density (BMD), bone resorption, and chronic back pain in postmenopausal women with osteoporosis. Eighty postmenopausal women with osteoporosis, 59-88 years of age, were divided into two groups of 40 each according to the site of BMD measurement: the metacarpus (M) and the lumbar spine (L). All of them were treated with alendronate (5 mg/day) for 12 months. Metacarpal or lumbar BMD was measured by computed X-ray densitometry or dual-energy X-ray absorptiometry in the M or the L group, respectively, at baseline and every 6 months. Urinary cross-linked N-terminal telopeptides of type I collagen (NTX) were measured by enzyme-linked immunosorbent assay, and chronic back pain was evaluated by face scale score at baseline and every 6 months in both groups. There were no significant differences in baseline characteristics, including age, body mass index, years since menopause, urinary NTX level, face scale score, or number of prevalent vertebral fractures per patient between the two groups. Urinary NTX level was reduced and chronic back pain was improved similarly in both groups. Whereas metacarpal BMD did not significantly change in the M group (0.20% increase), lumbar BMD increased by 8.15% in the L group. These results suggest that although alendronate increases BMD of the lumbar spine, which is rich in cancellous bone, and improves chronic back pain, with suppression of bone resorption in postmenopausal women with osteoporosis, it may fail to increase cortical BMD of the metacarpus, a distal site of the upper extremity.

Objective: Determine (1) the site-associated response of articular cartilage of the equine distal metacarpal condyle to training at a young age as assessed by changes in indentation stiffness and alterations in cartilage structure and composition, and (2) relationships between indentation stiffness and indices of cartilage structure and composition., Method: Experimental animals (n=6) were trained on a track (increasing exercise to 1km/day by 5 months); controls (n=6) were pasture-reared. Animals were euthanized at 18 months and four osteochondral samples were harvested per metacarpal condyle from dorsal-medial, dorsal-lateral, palmar-medial, and palmar-lateral aspects. Cartilage was analyzed for India ink staining (quantified as reflectance score (RS)), short-term indentation stiffness (sphere-ended, 0.4mm diameter), thickness, and biochemical composition., Results: Cartilage structural, biochemical and biomechanical properties varied markedly with site in the joint. Sites just medial and just lateral to the sagittal ridge showed signs of early degeneration, with relatively low RS, indentation stiffness, and collagen content, and relatively high water content. Effects of exercise and side (left vs right) were not detected for any measure. Overall, indentation stiffness correlated positively with RS and collagen content, and inversely with thickness and water content., Conclusion: Gentle exercise-imposed mechanical stimulation did not markedly affect articular cartilage function or structure. However, the marked site-associated variation suggests that biomechanical environment can initiate degenerative changes in immature cartilage during joint growth and maturation.

Unlabelled: A new trabecular bone explant model was used to examine osteocyte-osteoblast interactions under DHP loading. DHP loading enhanced osteocyte viability as well as osteoblast function measured by osteoid formation. However, live osteocytes were necessary for osteoblasts to form osteoids in response to DHP, which directly show osteoblast-osteocyte interactions in this in vitro culture., Introduction: A trabecular bone explant model was characterized and used to examine the effect of osteocyte and osteoblast interactions and dynamic hydrostatic pressure (DHP) loading on osteocyte viability and osteoblast function in long-term culture., Materials and Methods: Trabecular bone cores obtained from metacarpals of calves were cleaned of bone marrow and trabecular surface cells and divided into six groups, (1) live cores + dynamic hydrostatic pressure (DHP), (2) live cores + sham, (3) live cores + osteoblast + DHP, (4) live cores + osteoblast + sham, (5) devitalized cores + osteoblast + DHP, and (6) devitalized cores + osteoblast + sham, with four culture durations (2, 8, 15, and 22 days; n = 4/group). Cores from groups 3-6 were seeded with osteoblasts, and cores from groups 5 and 6 were devitalized before seeding. Groups 1, 3, and 5 were subjected to daily DHP loading. Bone histomorphometry was performed to quantify osteocyte viability based on morphology and to assess osteoblast function based on osteoid surface per bone surface (Os/Bs). TUNEL staining was performed to evaluate the mode of osteocyte death under various conditions., Results: A portion of osteocytes remained viable for the duration of culture. DHP loading significantly enhanced osteocyte viability up to day 8, whereas the presence of seeded osteoblasts significantly decreased osteocyte viability. Cores with live osteocytes showed higher Os/Bs compared with devitalized cores, which reached significant levels over a greater range of time-points when combined with DHP loading. DHP loading did not increase Os/Bs in the absence of live osteocytes. The percentage of apoptotic cells remained the same regardless of treatment or culture duration., Conclusion: Enhanced osteocyte viability with DHP suggests the necessity of mechanical stimulation for osteocyte survival in vitro. Furthermore, osteocytes play a critical role in the transmission of signals from DHP loading to modulate osteoblast function. This explant culture model may be used for mechanotransduction studies in long-term cultures.

We have evaluated the applicability of a new Digital X-ray Radiogrammetry (DXR) system in a Dutch Caucasian pediatric population. For this study we enrolled 535 healthy participants who all signed an informed consent form. In addition, 20 children suffering from inflammatory bowel disease (IBD) and juvenile chronic arthritis (JCA) were enrolled. Radiographs of the left hand were obtained from all participants. From the healthy population a subset of children with a history of forearm fractures were separately analyzed. Measurements consisted of DXR (X-posure; Pronosco-Sectra, Linköping, Sweden). Five hundred thirty-five subjects were enrolled in the study. Twenty-two subjects (4.3%) were discontinued (age 3-10 years), all because of a nonrecognizable radiograph by the DXR system. The short-term coefficient of variation of DXR in this population was 0.59%. Significant differences in DXR-BMD between boys and girls for the ages of 11, 12, 16, 17, and 18 years were found. There were also significant differences in DXR-BMD between the sequential Tanner stages. For 88 subjects repeat radiographs were available (mean interval 1.8 years). In all cases an increase in DXR-BMD was seen. Girls with IBD, JCA, or a history of forearm fractures and boys with IBD showed a significantly lower DXR-BMD compared with healthy controls. We show that DXR is an applicable technique in children. Also, in a small subpopulation it is possible to discriminate children with a high risk of low BMD.

Objective: To report tissue gentamicin concentrations after intraosseous (IO) perfusion in standing horses., Study Design: In vivo study., Animals or Sample Population: Twelve horses., Methods: Sedated horses had a cannulated cortical bone screw inserted into the dorsolateral aspect of the treated metacarpus and a tourniquet applied proximally. Gentamicin (2.2 mg/kg) diluted in sterile saline solution (0.1 mL/kg) was infused through the screw. Two horses were euthanatized at each time interval: 0, 2, 6, 12, 24, and 36 hours. Synovial fluid and bone samples were collected distal to the screw from both forelimbs. Gentamicin concentrations were measured using fluorescence polarization immunoassay., Results: The highest synovial fluid gentamicin concentrations were 385+/-273 microg/mL (mean+/-SD) in the metacarpophalangeal joint, 225+/-205 microg/mL in the proximal interphalangeal joint, 215+/-205 microg/mL in the distal interphalangeal joint, 382+/-195 microg/mL in the digital flexor tendon sheath, and 206+/-161 microg/mL in the navicular bursa. The highest bone concentrations of gentamicin were 55+/-30 microg/g in the distal metacarpus, 34+/-27 microg/g in the proximal, 16+/-15 microg/g in the middle, and 16+/-2.2 microg/g in the distal phalanges, and 27+/-17 microg/g in the proximal and 24+/-11 microg/g in the distal sesamoid bones., Conclusion: Standing IO perfusion of gentamicin resulted in local antibiotic concentrations in the synovial structures and bones of the distal aspect of the limb that exceed the reported minimum inhibitory concentration of pathogens commonly implicated in equine orthopedic infections., Clinical Relevance: Standing IO perfusion of gentamicin in the distal aspect of the limb should be considered for treatment of orthopedic infections of this region in horses.

The present study was designed to investigate the influence of modifiable risk factors (body weight and lifestyle) for bone loss on bone mineral density (BMD). We examined age-specific changes in metacarpal BMD, and its associations with body mass index and lifestyle among 532 community-dwelling postmenopausal Japanese women. Measurements of the second metacarpal BMD were obtained from the hand radiographs using computer-assisted radiographic absorptiometry. Body height and weight were measured, and body mass index (BMI) was calculated. Physical activity index was calculated using validated questionnaire. Daily calcium intake and amount of ingested alcohol were estimated by semiquantitative food frequency questionnaire. Current smoking status was obtained by questionnaire. Metacarpal BMD decreased significantly with increasing age. Simple correlation analysis indicated that metacarpal BMD correlated significantly with BMI and physical activity index. On the other hand, metacarpal BMD did not correlate with calcium intake and alcohol drinking. Metacarpal BMD in current smokers was not different from that in nonsmokers. Multiple regression analysis showed that increasing age was associated with decreased metacarpal BMD and greater BMI increased metacarpal BMD. However, physical activity, calcium intake, alcohol drinking and current smoking were not significant determinants of metacarpal BMD. Our findings suggest that maintenance of adequate body mass (prevention for leanness) is important for prevention of postmenopausal bone loss.

The effect of gastrointestinal nematode infections on bone development was investigated in growing sheep on pasture. Forty-five weaned lambs from six groups in a two-factorial design incorporating stocking rate (SR; low, medium and high) and presence or absence of infection on pasture were sampled in the late grazing season. Worm counts were performed at slaughter, and the left metacarpal bones were excised for bone assessment. Faecal egg counts and worm burdens, primarily of Ostertagia circumcincta and Trichostrongylus vitrinus, were considerably higher in the high SR infected group ("I-High") than in comparable animals at low or medium SRs, whereas uninfected groups showed negligible egg excretion. Clinical biochemistry revealed significantly reduced serum concentrations of albumin, calcium and alkaline phosphatase in infected lambs. Nematode infections were associated with significant reductions in bone mineral density (30% at high SR), measured by dual energy X-ray absorptiometry, and in bone size (9%). Histomorphometry indicated thinning of the trabecular structure and reduced bone formation in the infected groups, particularly the I-High group. Bone mineral density, bone tissue volume and structural changes were strongly associated with log-transformed worm counts. The study showed that lambs suffering from moderate to heavy degrees of naturally acquired gastrointestinal nematode infection developed marked osteopenia after weaning, i.eduring the later part of the grazing season., (Copyright Harcourt Publishers Ltd.)

The bone mineral density (BMD) of the second metacarpal bone of the left hand was measured in 57 patients with Turner syndrome by the digital image processing (DIP) method to study the relations between the treatment regimen and their bone mineral density. BMD SD score in the patients who had started the GH treatment before 10 years old was within +/-2SD of the standard before 14 years, but the score decreased to below -2SD after 14 years. In the patients who had started GH treatment after 10 years old, BMD score were significantly lower than -2SD, although there was tendency to increased. In the patients who had estrogen after 15 years old, BMD did not increase with GH alone and slowly increased after estrogen replacement. In the other two patients who had started sex steroid hormone replacement treatment before 15 years old, BMD maintained +/-2SD. In patients who received combined GH and LH-RH analog treatment, their BMD score did not increase during LH-RH analog treatment. It slowly increased but was still below -3SD after stop of LH-RH analog and start of estrogen treatment. In Turner syndrome, GH may play a role in maintaining prepubertal BMD levels [4], and estrogen plays an important role in pubertal BMD increment. It is recommended that estrogen treatment is started before 15 years of age for maintenance of normal BMD level.

The use of rigid fixation for fractures of the extremities has become commonplace. The short- and long-term effects of rigid fixation on the growing hand, however, have not been studied thoroughly. In this project, the use of rigid fixation across metacarpal growth plates (physes) in growing primate hands was examined. The hypothesis to be tested was that long-term placement of rigid fixation devices across physes during stabilization of mid-shaft osteotomies will cause the physes to close prematurely. Fixation devices with screws placed in the epiphysis and left in place for 4 months or 1 year resulted in open physes, in support of the null hypothesis. However, in physes plated for 1 year, biochemical changes associated with increased bone differentiation were apparent. Findings suggest that rigid fixation across physes for as long as 1 year can be used appropriately in growing individuals when necessary. However, until additional investigation establishes whether the open physes are still capable of producing bone-lengthening hypertrophic chondrocytes, caution should be used in long-term placement of rigid fixation devices.

This study proposed an assessment of the correlation of hand bone mineral density measured by dual energy x-ray absorbtiometry (DXA) with the carpo:metacarpal (C:MC) ratio and metacarpal cortical index (CI) in patients with rheumatoid arthritis (RA). The correlation of total hand BMD, CI and C:MC ratio with BMD at other sites, the Health Assessment Questionnaire (HAQ) and Larsen scores were also examined. The hand and axial BMD of 30 female patients were also compared with 29 age-matched healthy female controls. Total hand BMD values of patients were significantly lower than the control group. There was no significant difference between groups in axial measurements. CI correlated moderately with the second metacap (II.MC) midshaft and total hand BMD. The C:MC ratio correlated with II.MC midshaft and total hand BMD. Total hand BMD correlated moderately with the AP spine (L2-L4) and femoral neck BMD. Larsen scores showed weak negative correlation with II.MC midshaft BMD and CI. Grip strength correlated weakly only with total hand BMD. The results indicated that CI may reflect cortical bone mass of the hand accurately and did not predict bone density of the spine or hip in patients with RA. The C:MC ratio is a useful method for evaluating progression of wrist involvement and may be related to the loss of hand bone mineral density associated with disease process.

We studied the influence of vitamin E on intramuscular collagen characteristics and on metacarpal growth plate evolution in suckling lambs. Twenty-four 5-d-old Ile de France suckling male lambs were divided into four equal weight groups, and weekly i.m. injections of DL-alpha-tocopheryl acetate (Control group, 0 IU; Group 1, 625 IU; Group 2, 1,000 IU; and Group 3, 1,500 IU) were given until the lambs were 33 d old. Blood samples were withdrawn for plasma alpha-tocopherol, cholesterol, and triglyceride analyses when the lambs were slaughtered at 40 d of age. Hot carcass weight, metacarpal and metatarsal bone characteristics, and metacarpal growth plate width were measured. After 24 h at 2 to 4 degrees C, semitendinosus muscles were removed for intramuscular collagen analyses. Weight was not influenced by treatment, but lambs in Group 1 had a higher (P < .01) intramuscular collagen content than the other groups. A positive quadratic correlation was found between total collagen and vitamin E doses (r = .511; P < .05). Amount and percentage of soluble collagen increased in muscles of all three vitamin E-treated groups compared with the control group. However, hydroxylysyl pyridinoline concentration decreased with vitamin E injection, but the difference compared to control lambs was only significant for the group injected with 1,000 IU. Amount of soluble collagen was strongly correlated to total collagen concentration (r = .879; P < .0001). It was also related to the alpha-tocopherol/(cholesterol + triglycerides) ratio in plasma (r = .431; P < .04). However, the correlation between soluble collagen percentage and alpha-tocopherol concentration in plasma was not significant (r = .369; P < .08). Bone length, weight, and diameter did not change, but the thickness of metacarpal growth plate increased as the DL-alpha-tocopheryl acetate dose increased; in Groups 2 and 3, the growth plate was significantly wider than in Group 1 and the controls. Growth plate width correlated with alpha-tocopherol/(cholesterol + triglycerides) ratio in plasma (r = .481; P < .02).

Nationwide data on bone mass were collected from 33,992 subjects who underwent screenings for osteoporosis at 65 health care centers in 11 prefectures in Japan. Reference values in Japanese women were evaluated by the four convenient methods frequently used for the screening of osteoporosis based on healthy subjects, defined by their medical history. In addition, the prevalence of low bone mass was estimated in subjects 40 years or older by the four methods. Compared with the young normal subjects aged 20-29 years old, bone mass decreased after 30, 40, and 50 year in the calcaneus by quantitative ultrasound densitometry, the radius by dual energy X-ray absorptiometry (DXA), and the metacarpus by computed X-ray densitometer and digital image processing. The prevalence of a T-score <-1 was relatively similar (45.6-65.5% in the fifth decade and 81.3-94.3% in sixth) in each decade among the four methods. However, the use of a T-score

Although diffusion has been shown to be the major contributing mechanism for molecular transport in the extravascular spaces of organs and soft tissues, it is unlikely that diffusion alone can account for molecular transport in the porous, yet relatively impermeable matrix of bone. Rather, it has been proposed that fluid flow induced by the deformations that bone is subjected to during daily activities may promote molecular transport through convective mixing of fluids or enhancement of molecular transport from the capillaries to the outermost osteocytes within a given osteon. As the relative contribution of diffusive and convective transport in the bone matrix has not yet been elucidated, we conducted experiments to study the primary role of diffusion for molecular transport within bone and to establish a baseline for fluid transport whereby mechanical loading effects are negligible. Procion red and microperoxidase were utilized as short-term (i.e., low MW, transported on the order of minutes) and long-term (i.e., comparatively high MW, transported on the order of hours) molecular tracers, respectively, to elucidate in vivo the pathways and extent of transport in the metacarpus and tibia of 60-day-old (i.e., skeletally immature) and 180-day-old (i.e., skeletally mature) animals. The tracers were introduced intravenously and the animals were maintained in an anesthetized state for the duration of the experiment to prevent physiological loading. In short-term studies, procion red tracer distribution was highly dependent on bone structure, demarcating spaces apposing the vascular pathways in the trabecular bone of immature animals and vascular and extravascular pathways (i.e., specifically, the lacunocanalicular system) within compact bone of mature animals. In longer term studies using microperoxidase, reaction product was concentrated in soft tissues as well as along a subperiosteal and subendosteal band of bone. In contrast, little peroxidase reaction product was observed in the metacarpal and tibial cortices of either immature or mature animals. Based on the results of these studies, diffusive transport mechanisms may suffice to insure an adequate supply of small molecules, such as amino acids, to osteocytes in the midcortex within minutes. In contrast, diffusion alone may not be efficient for transport of larger molecules. Thus, another mechanism of transport, such as convective transport by means of load-induced fluid flow, may be necessary to provide a sufficient supply of larger molecules, such as proteins to osteocytes for the maintenance of metabolic activity, as well as for activation or suppression of modeling processes.

Despite excessive hip fractures in patients with Parkinson's disease (PD), little is known about bone changes in these patients. We measured bone mineral density (BMD; Z scores) in PD patients and analyzed its relation to serum biochemical indices and sunlight exposure. We measured BMD in 71 patients in the second metacarpals and divided the patients into two groups according to functional independence; group 1, Hoehn and Yahr stages 1 and 2; and group 2, stages 3 to 5. In four of 20 patients in group 1 (20%), the Z score was less than -1.0, indicating osteopenia. In 51 patients in group 2, 31 (61%) had a Z score less than -1.0. The group 1 patients showed a normal mean serum level of 25-hydroxyvitamin D (25-OHD; 21.7 ng/ml), while most group 2 patients were in a deficiency range (group mean 8.9 ng/ml). Many group 2 patients were sunlight deprived. Both groups had elevated serum ionized calcium levels correlating positively with Hoehn and Yahr stage and markedly depressed serum 1,25-dihydroxyvitamin D (1,25-[OH]2D) concentrations, indicating that immobilization-induced hypercalcemia had inhibited 1,25-[OH]2D production. Z scores correlated positively with 25-OHD levels and negatively with parathyroid hormone concentration and Hoehn and Yahr stage. Vitamin D deficiency due to sunlight deprivation and hypercalcemia induces compensatory hyperparathyroidism, which contributes to reduced BMD in PD patients, particularly those who are functionally dependent. Low BMD increases risk of hip fractures in patients with PD but may be improved by vitamin D supplementation.

Background: Osteoporosis is an age-related metabolic bone disease characterized by decreased mass and increased susceptibility to fracture. The literature suggests a relationship between oral bone loss and skeletal osteoporosis; however, most studies have produced conflicting results. The purpose of this study was to determine if a relationship exists among alveolar bone loss, alveolar bone density, second metacarpal density, salivary and gingival crevicular fluid interleukin 6 (IL-6), and IL-8 concentrations in premenopausal and postmenopausal healthy women receiving estrogen therapy., Methods: Twenty-eight healthy women (aged 23-78) were evaluated for this study. A vertical bitewing and hand radiographs were taken, and the subjects were evaluated for the presence of active periodontitis. The bitewing and hand radiographs were digitized, and measurements were made from the cemento-enamel junction to the alveolar crest from both arches. Bone density was evaluated in the maxillary and mandibular alveolar process and at the mid-shaft of the second metacarpal. Percent cortical area and the moment of inertia measurements were also determined. Stimulated whole saliva was collected for a 5-min period using a cube of paraffin as a stimulant and was analyzed for total protein by a colorimetric reaction and IL-6 and IL-8 by ELISA., Results: The results of the study showed that postmenopausal women on estrogen therapy had more alveolar bone loss, more missing teeth, and reduced alveolar and second metacarpal bone density than premenopausal women. In addition, postmenopausal women on estrogen therapy had higher salivary IL-6 concentrations than premenopausal women. Alveolar bone densities were also strongly correlated to second metacarpal densities., Conclusions: The results of the study suggest that changes in alveolar bone density and levels of bone resorptive cytokines in saliva may be secondary to changes in menopausal status. These changes may predispose loss of alveolar bone with resultant loss of teeth.

Rationale and Objectives: The authors verify whether metacarpal cortical striation can be used to assess longitudinal changes in bone turnover in Graves' disease., Methods: Eight patients with untreated Graves' disease (5 men, 3 women; age 36 +/- 12 years) and six patients with the disease in remission (1 man, 5 women; age 38 +/- 12) were studied. Posteroanterior radiographs of the bilateral hands were obtained using fine-grain mammography film and direct magnification. Three observers independently determined the grade of cortical striation (striation index; SI) of the second and third metacarpals in randomly presented radiographs., Results: The SI determined by all observers decreased significantly after the beginning of antihyperthyroid therapy compared with the SI before treatment (P < 0.05). Significant correlation was found between the observers' assessments (r = 0.74, P < 0.001). The average kappa value and percent agreement were 0.27 and 51.8%, respectively. Intraobserver variability provided relatively good kappa statistics (kappa: 0.56; percent agreement: 79.9%). Longitudinal decrease in the SI was in accordance with a decline in urinary pyridinoline cross-link excretion, a decline in serum osteocalcin, and an increase in bone mineral density of lumbar spine., Conclusions: The change in the SI can be used to detect increased and decreased bone turnover. Thus, the SI can be used as one index of bone turnover in patients with Graves' disease.

The zone of calcified cartilage (ZCC) forms an important interface between cartilage and bone for transmitting force, attaching cartilage to bone, and limiting diffusion from bone to the deeper layers of cartilage. The height of the ZCC is a relatively constant percent of articular cartilage and the height is maintained by a balance between progression of the tidemark into the unmineralized cartilage and changing into bone by vascular invasion and bony remodeling. During its formation, the cells that form the ZCC have properties similar to the cells of the growth plate. In the adult, the ZCC becomes quiescent but not inactive. The ZCC may be reactivated in osteoarthritis and may progressively calcify the unmineralized cartilage. This might contribute to cartilage thinning which would increase the concentration of forces across the uncalcified cartilage leading to more damage. Although the subchondral bony plate remodels extensively in osteoarthritis, there is little evidence that a change in the biomechanics of the plate directly initiates the osteoarthritic process in cartilage. However, increased repair by endochondral ossification of vertical cracks in the ZCC that penetrate into the marrow space could contribute to progression via changes in the ZCC.

Embryonic/neonatal bones in culture are commonly used for the study of osteoclastic resorption in vitro. For this purpose, the release of 45calcium (45Ca) from prelabeled bones is measured as an index of resorption. We studied 45Ca release from two types of long bone explants after different preparation methods: 17-day-old fetal mouse radii/ulnae with and without cartilage ends (intact radii/ulnae and shafts, respectively), and intact 18-day old metacarpals/metatarsals. In addition, we examined the effect of different culture conditions, such as cultures performed under the surface of the medium or at the interphase of medium and air, on 45Ca release and histology. When intact radii/ulnae were cultured under the surface of the medium, there was always a significant amount (10%) of net basal 45Ca release (corrected for physicochemical exchange) that was not due to osteoclastic resorption, as it could not be suppressed by inhibitors of resorption even at high concentrations. Moreover, histologically TRAcP-positive cells were almost absent after culture and the bone marrow/stromal cells in the center of the bone appeared necrotic, possibly due to a lack of oxygen. Under these culture conditions, osteoclasts could survive in shafts as well as in PTH-stimulated intact radii/ulnae, but a constant amount of 10% 45Ca, not due to resorption, was still released in the medium. When these explants were cultured at the interphase of medium and air, basal and stimulated 45Ca release originated from osteoclastic resorption. In contrast, in 18-day-old fetal mouse metacarpals/metatarsals, the experimental conditions applied did not affect 45Ca release, which was always due to resorption of the explants by osteoclasts.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical and physical characteristics of third metacarpal bones and liver and rib soft tissue composition from feedlot steers were determined. Steers were selected (32 from each experimental location) to represent the range in slaughter weight and composition for each treatment group in three (total n = 1,088) feedlot experiments. Steers were implanted with 0, 24, 36, 48, 60, 72, 84, or 96 mg of zeranol at approximately 140 d before slaughter. Cattle at each location were fed for the same number of days and slaughtered as a group. Zeranol dose had no effect on the chemical composition of bone, liver, or rib soft tissue with the following exceptions: zeranol decreased (P < .01) bone Ca concentration and increased (P < .07) liver P concentration. Zeranol implantation decreased medullary cavity anterioposterior (AP) diameters and AP cortical width (P < .08). Loads withstood by the bones up to flexure (P < .08) and the strain at flexure (P < .09) were inversely related to the quadratic of zeranol dose. However, modulus of elasticity at flexure and breaking increased numerically with zeranol dose. Stress withstood by bones at flexure was greater (P < .09) for implanted steers. Strain data indicate that metacarpals from steers receiving zeranol would exhibit less deformation upon loading to flexure (P < .09) than controls. These data indicate that administration of intermediate doses of zeranol altered bone deposition of Ca, which resulted in modified third metacarpal physical and mechanical characteristics.

Two experiments were conducted with pigs 1) to determine the effect of supplemental Zn on growth performance, bone Zn, and plasma Zn in pigs fed Zn-unsupplemented, corn-soybean meal diets and 2) to assess bioavailability of Zn from inorganic and organic Zn sources. In both experiments, weanling pigs were fed a diet with no supplemental Zn for 5 wk to deplete their Zn stores. In Exp. 1, 192 pigs were fed a corn-soybean meal diet (growing diet, 32 mg/kg of Zn; finishing diet, 27 mg/kg of Zn) supplemented with feed-grade ZnSO4.H2O to provide 0, 5, 10, 20, 40, and 80 mg/kg of supplemental Zn. Supplemental Zn did not affect weight gain, feed intake, or gain/feed during either the growing or the finishing period (P > .05). However, bone and plasma Zn concentrations increased linearly (P < .01) in response to supplemental Zn at dietary Zn levels between 27 mg/kg (basal) and 47 mg/kg (breakpoint). In Exp. 2, three levels of supplemental Zn from ZnSO4.H2O (0, 7.5, and 15 mg/kg of supplemental Zn) were used to construct a standard curve (metacarpal, coccygeal vertebrae, and plasma Zn concentrations regressed on supplemental Zn intake; R2 = .93, .89, and .82, respectively). From the standard curve, the bone and plasma Zn concentrations obtained from pigs fed 15 mg/kg of supplemental Zn from ZnO and 7.5 mg/kg of supplemental Zn from Zn-methionine (ZnMET) and Zn-lysine (ZnLYS) were used to calculate bioavailable Zn via multiple linear regression, slope-ratio analysis. The estimates of Zn bioavailability differed depending on which variable was used. Overall trends indicated the following rankings: ZnSO4.H2O > ZnMet > ZnO > ZnLys.

Computed radiography was used to make radiogrammetric measurements of the second metacarpal in 240 women, 180 considered normal and 60 osteoporotic. These measurements had a coefficient of variation for the external diameter of 0.74% in normal women and 0.75% in osteoporotic women, and for the internal diameter of 2.4% and 2.03%, respectively. The group of women with osteoporosis was divided according to external diameter and internal diameter into a group with osteoporosis due to increased bone resorption (61.1%, normal external diameter and increased internal diameter), and osteoporosis due to deficient bone formation (26.1%, decreased external diameter and normal internal diameter). In the remaining subjects (12.8%), osteoporosis was attributed to both mechanisms. There was a significant linear regression between internal diameter and tartrate-resistant acid phosphatase concentration (p < 0.0001) in the group of increased bone resorption, which was absent (p = ns) in the group with deficient bone mass formation. No changes were observed in the size of the two groups. The low coefficient of variation of radiogrammetric measurements with computed radiography validate it as an accurate technique for bone mass studies. Moreover, it has the additional advantage of permitting determination of the proportion of women with osteoporosis due to increased bone resorption and/or deficient bone mass formation.

Metacarpal bone mass (D2-d2)/D2 measured on radiographs, and bone mineral content (BMC) measured by photon absorptiometry, were studied in the forearms of 30 nondialyzed and 25 hemodialyzed patients with chronic failure and in a group of normal subjects. Metacarpal bone mass was reduced in nondialyzed women with chronic renal failure and the amount of bone mineral reduced both in males and females with chronic renal failure, whereas these measurements were normal in dialyzed patients with chronic renal failure. Bone mineral content in the forearm and metacarpal bone mass decreased with age, both in women with chronic renal failure and in normal women, the decrease being more pronounced in women with chronic renal failure than in normal women. No age-related decrease was seen in males. Bone mineral content corrected for the size of bone (BMC') decreased with age both in males and in females. Highly significant correlations were found between metacarpal bone mass and BMC' in nondialyzed and dialyzed patients with chronic renal failure, whereas no significant correlation could be demonstrated in normal subjects. The study indicates that changes in metacarpal bone mass and in BMC to some degree occur simultaneously in patients with chronic renal failure; an accelerated loss of bone mass and of bone mineral with age may be seen in women with chronic renal failure compared to normal women.

Premenopausal amenorrheic women may be at risk for the development of osteoporosis. In hyperprolactinemia, cortical bone mass is decreased and the magnitude of the decrease correlates with the severity of the estrogen deficiency. However, bone loss in women with amenorrhea from other causes has not been assessed. We have studied women with hypothalamic and hyperprolactinemic amenorrhea and premature ovarian failure. Bone mass in the peripheral cortical bone was only slightly decreased from age-matched controls, but spinal trabecular bone was decreased 20% to 30%. Estradiol levels were 20 to 80 pg/mL in these women, not different from normal early follicular levels. The decrease in bone mass in the spine did not correlate with serum estradiol at these levels. The hypothalamic amenorrhea group was made up of athletes in whom the bone mass decrease was an unexpected finding.

Positive correlation between the mineral content of the mid site of right third metacarpal and neck of femur has been established using the psi-ray absorption technique described by Shimmins et al. (1972b) to make measurements on excised human bones. An X-ray method (Anderson, Shimmins and Smith, 1966; Shimmins et al. 1972a) was used to measure the mineral content of the right third metacarpal in 101 female and 22 male patients with subcapital fracture of the ferum. When their metacarpal "whole bone densities" were compared with those of control subjects of the same age and sex, they were found to have significantly lower (P smaller than (0.025) average values. However, groups of patients defined according to Garden's classification of severity of fracture could not be distinguished one from the other on the basis of metacarpal whole bone density measurement.

Eighty crossbred boars were utilized in a 2 X 2 factorial arrangement of two energy levels (ad libitum and 75% ad libitum) and two Ca/P levels (100 and 150% of National Research Council daily requirement) to determine the effect of varying growth rate and Ca/P intake on performance and bone characteristics throughout the growth phase. Boars were fed the diets beginning postweaning at 5 wk of age and continuing until necropsy at 10 +/- 2-d intervals between 80 and 220 d of age, inclusive. Body weight of limit-fed boars was 72% that of ad libitum-fed boars. Daily gain and feed per gain ratio favored boars fed the 150% Ca/P levels. Although limit-feeding enhanced the development of longer, thicker and heavier metacarpals earlier in the growth period (between 80 and 150 d of age), there was little difference between limit-fed and ad libitum-fed boars at 220 d of age when values were corrected for differences in body weight. Mechanical bone characteristics, which were greater for ad libitum-fed than for limit-fed boars at the same age, were not different when values were corrected for body weight. Boars fed 150% Ca/P levels had heavier and thicker walled metacarpals that had greater bone strength than boars fed 100% Ca/P levels, with the magnitude of the difference not as great at 220 d of age and when values were corrected for body weight. Generally, boars fed the ad libitum-150% Ca/P diet had the heaviest and strongest bones. Ether extract, ash and Ca and P content of ash were generally higher for ad libitum-fed vs limit-fed and 150 vs 100% Ca/P diets at 80 and 150 d of age, but were not different at 220 d. Metacarpal weight, size, thickness, strength and ash content increased with age with a small decline in the rate of increase. Ether extract decreased with age. There was a very small increase in the Ca content of ash and a very small decrease in the P content with age, resulting in a slightly wider Ca:P ratio in older boars.

Hand bone calcium content [Ca] has been measured by local neutron analysis in hemodialyzed patients free of signs of osteomalacia before and 6-12 months after treatment with vitamin D metabolites, and it has been compared to some iliac bone histomorphometric parameters. With 1,25-(OH)2D3 alone, [Ca] increases significantly at the 6th month of treatment (p less than 0.001) but not from the 6th to the 12th month. With 1 alpha-(OH)D3 + 25-(OH)D3 the same phenomenon is observed at the 6th and 12th months of treatment. Before treatment, [Ca] was correlated negatively with the osteoid surfaces (OS) (r = -0.62, p = 0.01) and the number of osteoclasts per square millimeter (Ocl/mm2) (r = -0.79, p less than 0.001). At the 6th month of treatment, [Ca] was still correlated negatively with OS (r = -0.42, p = 0.05) and with Ocl/mm2 (r = -0.60, p less than 0.005). At the 12th month, the two negative correlations decreased but remained significant (r = -0.42, p = 0.05; r = -0.45, p = 0.05). These data suggest that (1) hand bone calcium analysis by neutron activation permits to follow up the peripheral bone mineral content in hemodialyzed patients and (2) the [Ca] increase only observed during the first months of treatment with vitamin D metabolites probably result from an attenuation of secondary hyperparathyroidism.

Cortical bone dimensions of the second metacarpal were analyzed relative to chronological age, skeletal maturity and body size in 280 ice hockey players 10 through 12 years of age. Defencemen had the largest cortical bone dimensions, followed by forwards and goalkeepers respectively. After removing the effects of height, weight, chronological age, and skeletal age by analysis of covariance procedures, boys at the forward position had larger estimated periosteal diameter, cortical thickness, and cortical area, than either defencemen of goalkeepers. Compared to non-athletic boys from Montreal and Philadelphia, the young hockey players had a larger periosteal diameter, cortical thickness, and cortical area for the same stature. The results suggest a possible role for the effects of physical activity on cortical bone deposition.

The osteoporosis which appears in paraplegics below the neurological lesion has been studied in 100 patients with the following parameters: quantitative X-rays, urinary hydroxyproline excretion, kinetic study of calcium metabolism by 45Ca, serum phosphorus and calcium, parathormone and calcitonin radio-immunoassay, quantitative histology, density fractionation of bone and amino-acid composition of fractionated bone analysis. All our results show that the important bone resorption occurring very early in the paraplegia is immediately followed by an increase of the bone repair. This osteoporosis below the neurological lesion in paraplegia represents an unbalance between the synthesis and the resorption of bone which possesses a large degree of activity. Furthermore, we demonstrated that the collagen of this bone is underhydroxylated. Following the quantitative X-rays and intraosseous phlebography results we have considered the aetiopathogenesis of this osteoporosis. It seems that vascular modifications due to the lesion of the autonomic nervous system play an important role and furthermore we believe that immobilisation represents only a minor factor in the aetiology of this osteoporosis.

In order to determine the pathogenesis and pathophysiology of post-oophorectomized osteopenia, we have investigated the bone mineral status and the serum levels of calcium regulating hormones in 250 females. The bone mineral status was measured in 250 [173 pre-menopausal females (controls) and 77 who received oophorectomy] females by microdensitometry in the metacarpal bone. Among these subjects, in some cases who were selected randomly, the serum levels of Alp, Ca, Pi, M-PTH, calcitonin (CT), bone gla protein (BGP), estrone, estradiol and delta 4-androstenedione, and the urinary excretion of Ca and hydroxyproline (OH-pro) as a function of the creatinine ratio were measured. The mineralization indices of bone such as GSmax, GSmin, and sigma GS/D in oophorectomized patients were significantly less than those in controls at ages up to 45 years. On the other hand, the index of periosteal bone resorption (MCI) in the oophorectomized group was less than that in controls at ages up to 50 years. Serum levels of Alp, Ca, Pi and BGP were higher in oophorectomized subjects than in controls. Despite these facts, the serum levels of calcium regulating hormones such as M-PTH and CT in these two groups were significantly different. Urinary Ca/cr and OH-pro/cr ratios were significantly higher in oophorectomized subjects at ages 40-44 than those in age matched controls. These data clearly indicate that oophorectomy causes high turn-over osteopenia.

The authors have already reported that the bone density of normal pregnant women might be kept at the same density as in normal non-pregnant women. However, it might be decreased in women with pregnancy induced hypertension (PIH) by estimating serum calcium levels, serum levels of calcium regulating hormones and calcium secretion into the urine. In order to demonstrate this theory, the degree of bone density in the second metacarpal bone of normal or PIH pregnant women was measured by X-ray using microdensitometry method (MD method). In MD method, six indices, such as MCI, d, GSmin, GSmax, sigma GS/D and densitometric pattern, are calculated by computer analysis of the X-ray of the bilateral hands. By the evaluation of the degree of bone atrophy, scores such as 0 better than the regression line of healthy women, which were prepared according to each age, 1 until 1 delta to the aggravation, 2 until 2 delta, and 3 more than 2 delta were totaled and evaluated as normal, initial stage of bone atrophy, 1st degree of bone atrophy, 2nd degree of bone atrophy and 3rd degree of bone atrophy for 0-3 scores, 4-9 scores, 10-12 scores and 13-18 scores, respectively (delta = 1 S.D.). The metacarpal index (MCI) of normal pregnant women in 3rd trimester was more than the mean in all cases, while cases more than 2 delta of the mean were noted in 29.4% of mild PIH and 11.8% of severe PIH, and a decreasing tendency of width of bone cortex was considered in PIH women. On the other hand, width of bone marrow (d) increased significantly in mild and severe PIH women. In the index for the density of only bone cortex area (GSmax) in PIH women, cases less than mean -1 delta were noted in 29.3% of mild types and in 11.8% of severe types respectively, and a high incidence was noted even though it was insignificant compared with 7.4% of normal pregnant women. In the index of the densities of bone cortex and bone marrow (GSmin), cases less than mean -1 delta were noted more frequently in PIH women than normal pregnant women, but in the index of bone density per unit length (sigma GS/D) no differences were noted between PIH and normal pregnant women.(ABSTRACT TRUNCATED AT 400 WORDS)