Skeletal Mineralization Research Articles

The Pathogenesis of Vascular Calcification in the Chronic Kidney Disease Mineral Bone Disorder: The Links Between Bone and the Vasculature

Considerable scientific progress in the pathogenesis of vascular calcification that has accrued in recent years is reviewed in this article. Factors regulating mesenchymal cell differentiation and their role in the neointimal calcification of atherosclerosis and the vascular media calcification observed in chronic kidney disease and diabetes are discussed, as is the role of bone regulatory proteins in bone mineralization and vascular calcification. This includes recent studies related to fetuin-A, and the discovery of a new circulating hormone involved in regulating phosphate homeostasis and sensing skeletal hydroxyapatite precipitation. Finally, the relationship between skeletal mineralization and vascular mineralization is discussed in terms of their links, especially through serum phosphate concentrations.

Experimental arthritis: Effect on growth parameters and total skeletal calcium

Aim of the study was to investigate the possible mechanisms leading to stunted growth and osteoporosis in experimental arthritis. Fourty-two female rats of 7–8 weeks of age were randomly assigned to three groups of 14 animals each: (a) controls; (b) adjuvant-inoculated (AA); and (c) adjuvant-inoculated rats receiving 10 mg cyclosporin A (CsA) orally for 30 days. Biological parameters studied were: hindpaw swelling; vertebral length progression expressed as Δ increments between days 1 and 30 as a parameter of skeletal growth, and estimation of total skeletal mineral content by dual energy X-ray absorptiometry ( n = 10 each group) on day 30. Endocrine parameters measured were pulsatile release of growth hormone (rGH) on day 30 following jugular cannulation and measurement of insulin-like growth factor (IGF-1) in pooled plasma from rGH profiles. Results can be summarized as follows: Untreated AA rats exhibited local signs of inflammation in comparison with controls (hindpaw diameter 8.1–8.9 mm vs. 5.3–5.6 mm in controls). Treatment with CsA normalized this parameter (4.9–5.6 mm). Vertebral growth was significantly retarded in AA rats in comparison with controls (214 ± 32 vs. 473 ± 33 μm; p < 0.001). Administration of CsA normalized vertebral size increment with a clear tendency to overgrowth (523 ± 43 μm, n.s.). There was also a marked reduction in total skeletal mineral content in diseased (AA) rats as compared to controls (5.8 ± 0.1 vs. 7.5 ± 0.1 g [OH-apatite]; p < 0.001), and a moderate but significant increment above controls in the group receiving CsA (8.0 ± 0.1 vs. 7.5 ± 0.1 g [OH-appatite]; p < 0.04). Integrated rGH profiles exhibited a significant fall in arthritic rats and were completely restored to normal under CsA treatment. A trend toward higher rGH values was observed in the latter group (2908 ± 554 in AA vs. 8317 ± 1492 ng/ml/240 min in controls; p < 0.001, and 10940 ± 222 ng/ml/240 min, n.s. in the CsA group). There was a good correlation between skeletal growth and rGH pulsatility ( r = 0.81; p < 0.001). IGF-1 followed a similar pattern (630 ± 44 in AA vs. 752 ± 30 ng/ml in controls; p < 0.04, and 769 ± 59 ng/ml in the CsA group, n.s. vs. controls). Thus, a clear tendency to skeletal overgrowth following treatment was observed in agreement with the hormonal data. It can therefore be concluded that, in experimental arthritis, attenuated GH-spiking and reduced circulating IGF-1 appear to be causally related to growth retardation, probably mimicking signs and symptoms observed in juvenile arthritis. Therapy with CsA is followed by normalization of hormonal and biological parameters accompanied by a catch up phenomenon in skeletal growth which is also observed clinically in juvenile arthritis. Generalized osteopenia is a prominent feature seemingly connected with the growth abnormalities as they parallel each other during the evolution of the disease and respond equally to therapy.

Management of phosphate in chronic kidney disease--Regulation of posphate homeostasis

Inorganic phosphate (Pi) is an essential nutrient in terms of both cellular metabolism and skeletal mineralization. Dietary Pi is absorbed by the intestine, deposited in the bone and filtered by the kidney. Regulation of Pi absorption/reabsorption is achieved by changing the apical abundance of Na/Pi transporters (NaPi- II a, II b, and II c) . The regulatory mechanisms involve several signaling factors, such as parathyroid hormone (PTH) , 1,25 (OH)2D3, and fibroblast growth factor (FGF) -23. FGF-23, produced in the osteocytes, binds with FGF receptor (FGFR) and klotho in target organs (kidney or parathyroid grand et al.) and acts as a Pi regulating factor.

Effect of a gluten-free diet on bone mineral density in children with celiac disease

The aim of the study was to assess the evolution of bone mineral density (BMD) in children with celiac disease and to evaluate the effect of a gluten-free diet (GFD). Altogether, 44 children (31 girls and 13 boys) were followed-up. BMD was measured by dual-energy X-ray absorptiometry of the lumbar spine (Hologic QDR 4500). Results are expressed as absolute values for BMD, and as Z scores for chronological age (BMD/CA) and bone age (BMD/BA). Patients were divided into two groups according to whether they followed a diet without (n=34) or with (n=10) gluten for at least 1 year. All patients were clinically free of symptoms at the end of the follow-up. At inclusion, 26 patients (59%) were delayed in bone age, 17 children (38%) had a BMD/CA< or =1 S.D. and six (13.6%) had a BMD/CA< or =2 S.D., whereas nine children (20%) had a BMD/BA< or =1 S.D. and three (6.8%) had a BMD/BA< or =2 S.D. During the follow-up, the BMD increase was greater in the GFD group, as determined by the BMD/CA/year (+0.05+/-0.3 vs -0.34+/-0.4 S.D.; P<0.01) and BMD/BA/year (-0.02+/-0.4 vs -0.4+/-0.6 S.D.; P<0.05). The gain in BMD/BA was smaller in the GFD group because of their need to catch up in bone maturation. Celiac children not following a GFD show delays in both bone maturation and mineralization. This prospective study confirms the importance of maintaining a GFD in children with celiac disease until the end of skeletal mineralization even in asymptomatic patients following a non-restricted diet.

Type IIc Sodium–Dependent Phosphate Transporter Regulates Calcium Metabolism

Primary renal inorganic phosphate (Pi) wasting leads to hypophosphatemia, which is associated with skeletal mineralization defects. In humans, mutations in the gene encoding the type IIc sodium-dependent phosphate transporter lead to hereditary hypophophatemic rickets with hypercalciuria, but whether Pi wasting directly causes the bone disorder is unknown. Here, we generated Npt2c-null mice to define the contribution of Npt2c to Pi homeostasis and to bone abnormalities. Homozygous mutants (Npt2c(-/-)) exhibited hypercalcemia, hypercalciuria, and elevated plasma 1,25-dihydroxyvitamin D(3) levels, but they did not develop hypophosphatemia, hyperphosphaturia, renal calcification, rickets, or osteomalacia. The increased levels of 1,25-dihydroxyvitamin D(3) in Npt2c(-/-) mice compared with age-matched Npt2c(+/+) mice may be the result of reduced catabolism, because we observed significantly reduced expression of renal 25-hydroxyvitamin D-24-hydroxylase mRNA but no change in 1alpha-hydroxylase mRNA levels. Enhanced intestinal absorption of calcium (Ca) contributed to the hypercalcemia and increased urinary Ca excretion. Furthermore, plasma levels of the phosphaturic protein fibroblast growth factor 23 were significantly decreased in Npt2c(-/-) mice. Sodium-dependent Pi co-transport at the renal brush border membrane, however, was not different among Npt2c(+/+), Npt2c(+/-), and Npt2c(-/-) mice. In summary, these data suggest that Npt2c maintains normal Ca metabolism, in part by modulating the vitamin D/fibroblast growth factor 23 axis.

Relationship between Plasma Fibroblast Growth Factor-23 Concentration and Bone Mineralization in Children with Renal Failure on Peritoneal Dialysis

Fibroblast growth factor (FGF)-23 is produced in bone, and circulating levels are markedly elevated in patients with end-stage kidney disease, but the relationship between plasma levels of FGF-23 and bone histology in dialysis patients with secondary hyperparathyroidism is unknown. The aim of the study was to evaluate the correlation between plasma levels of FGF-23 and bone histology in pediatric patients with end-stage kidney disease who display biochemical evidence of secondary hyperparathyroidism. We performed a cross-sectional analysis of the relationship between plasma FGF-23 levels and bone histomorphometry. The study was conducted in a referral center. Participants consisted of forty-nine pediatric patients who were treated with maintenance peritoneal dialysis and who had serum PTH levels (1st generation Nichols assay) greater than 400 pg/ml. There were no interventions. Plasma FGF-23 levels and bone histomorphometry were measured. No correlation existed between values of PTH and FGF-23. Bone formation rates correlated with PTH (r = 0.44; P < 0.01), but not with FGF-23. Higher FGF-23 concentrations were associated with decreased osteoid thickness (r = -0.49; P < 0.01) and shorter osteoid maturation time (r = -0.48; P < 0.01). High levels of FGF-23 are associated with improved indices of skeletal mineralization in dialyzed pediatric patients with high turnover renal osteodystrophy. Together with other biomarkers, FGF-23 measurements may indicate skeletal mineralization status in this patient population.

Vascular smooth muscle cells sense calcium: a new paradigm in vascular calcification

Calcification of arteries is a complex and dynamic process frequently seen in atherosclerosis, diabetes, and chronic kidney disease. This phenomenon, now considered a distinct inflammatory arteriopathy, has important clinical significance because arterial calcification is associated with increased cardiovascular events and is a strong predictor of poor cardiovascular outcomes.1,2 Patients with high coronary artery calcification scores have a five- to seven-fold increase in the risk of a hard coronary event compared with patients with low calcium scores, and patients with chronic kidney disease and vascular calcification have a 20- to 30-fold increase in cardiovascular mortality.2 Arterial calcification is a pathological process involving the vascular media and adventitia.3 Medial vascular smooth muscle cells (VSMCs) lose their ability to express smooth muscle-specific markers and undergo phenotypic transformation to osteoblast-like cells. Perivascular adventitial cells, microvascular pericytes, and adventitial mesenchymal stem cells also have the potential to express osteoblastic transcription factors, suggesting that, in addition to VSMCs, other vascular cell types contribute to calcification. The course of vascular calcification shares many features with that of bone mineralization, except that whereas skeletal mineralization is a physiological and highly regulated process, vascular calcification is a pathological phenomenon associated with extraskeletal mineralization in the vascular wall.2,3 Passive calcium phosphate deposition, active cell-mediated processes, and inflammatory responses contribute to vascular calcification.4 … *Corresponding author. Tel: +1 613 562 5800; fax: +1 613 562 5487. E-mail address : rtouyz{at}uottawa.ca

Micro‐CT evaluation of murine fetal skeletal development yields greater morphometric precision over traditional clear‐staining methods

Traditional techniques for quantification of murine fetal skeletal development (gross measurements, clear-staining) are severely limited by specimen processing, soft tissue presence, diffuse staining, and unclear landmarks between which to make measurements. Nondestructive microcomputed tomography (micro-CT) imaging is a versatile, well-documented tool traditionally used to generate high-resolution 3-D images and quantify microarchitectural parameters of trabecular bone. Although previously described as a tool for phenotyping fetal murine specimens, micro-CT has not previously been used to directly measure individual fetal skeletal structures. Imaging murine fetal skeletons using micro-CT enables the researcher to nondestructively quantify fetal skeletal development parameters including limb length, total bone volume, and average bone mineral density, as well as identify skeletal malformations. Micro-CT measurement of fetal limb lengths correlates well with traditional clear-staining methods (83.98% agreement), decreases variability in measurements (average standard errors: 6.28% for micro-CT and 10.82% for clear-staining), decreases data acquisition time by eliminating the need for tissue processing, and preserves the intact fixed fetus for further analysis. Use of the rigorous micro-CT technique to generate 3-D images for digital measurement enables isolation of skeletal structures based on degree of mineralization (local radiodensity), eliminating the complications of blurred stain boundaries and soft tissue inclusion that accompany clear-staining and gross measurement techniques. Microcomputed tomography provides a facile, accurate, and nondestructive method for determining the developmental state of the fetal skeleton using not only limb lengths and identification of malformations, but total skeletal bone volume and average skeletal mineral density as well.

The skeleton: Endocrine regulator of phosphate homeostasis

Phosphorus is an essential element in skeletal development, bone mineralization, membrane composition, nucleotide structure, and cellular signaling. Phosphate, the principal form in which phosphorus is found in the body, is regulated by the complex interplay of the hormones parathyroid hormone (PTH), calcitriol (1,25[OH](2) vitamin D(3)), and fibroblast growth factor 23 (FGF23). These collectively govern bone mineralization, absorption of phosphorus by the intestine, and renal tubular reabsorption of phosphate. The skeleton is the major storage pool for phosphate and the principal production site for FGF23, a major phosphate regulatory hormone. Recent advances in understanding the molecular basis of disorders of phosphate metabolism have revealed new phosphate-regulatory hormones and provided insight into how these regulators may interface with previously known phosphate-regulatory pathways. Here we outline the current knowledge about the regulation of normal phosphate homeostasis and present a review of the molecular basis of disorders of phosphate homeostasis.

Involvement of Cd Bioaccumulation in Spinal Deformities Occurrence in Natural Populations of Mediterranean Killifish

The aim of this study was to investigate the possible influence of environmental exposure to cadmium (Cd) on the spinal deformities occurrence in the Mediterranean killifish, Aphanius fasciatus (Pisces: Cyprinodontidae). For this purpose, some indicators of skeletal bone mineralization, Cd, and calcium (Ca) concentrations in spinal column as well as bioaccumulation of Cd from the water and the sediment have been compared in normal and deformed fish collected from polluted (S1) and nonpolluted (S2) areas in the Gulf of Gabès in Tunisia. When compared to the normal fish, the deformed fish showed signs of spinal column demineralization such as significant decrease in the ash weight/dry weight ratio, percentage of nonorganic components content, and Ca concentration. Cd concentrations in spinal column and liver were significantly higher in deformed fish than in normal fish. A highly significant negative correlation (r = -0.915, p < 0.01) between Cd and Ca concentrations was noted in spinal column of deformed fish. Bioaccumulation factors of Cd in the liver from the water and the sediment in deformed fish were also significantly higher (p < 0.0001) than in normal fish from S1 and S2. These findings suggest that the ability to accumulate large amount of Cd may represent a potential risk to induce spinal deformities in natural populations of Mediterranean killifish.

Effects of Nandrolone and TGF-β1 in growing rabbits with osteopenia induced by over-supplementation of calcium and vitamin D3

The study was undertaken to find out the effects of over supplementation of dietary calcium and vitamin D3 on the mineralization of growing skeleton, taking rabbit as an animal model; further to study the effects of Nandrolone deconoate and TGF-beta1 on the mineralization of osteopenic bones. Twenty four New Zealand White rabbits of either sex, 60 day old, were randomly divided in 4 equal groups, A, B, C and D. The animals of groups B, C and D were administered with oral supplementation of calcium (2000 mg/kg of standard rabbit feed) and vit-D3 (1000 IU/kg of standard feed) for 60 days. The animals of group A were given standard ration without any supplementation. After 60 days, the Ca-vit.D3 supplementation was discontinued; and the animals of group C were administered with TGF-beta1 (10 ng, i.m.) once in every three days and animals of group D were given Nandrolone deconoate (10 mg, i.m.) once every week for 30 days, whereas in animals of group B, no treatment was given. All the animals were evaluated based on different observations like body weight, radiographic observations, circulating biochemical and hormone profile (plasma Ca, IP, AP, OC and iPTH) every 15 days up to 60 days after initiation of treatment. The results indicated that the body weight of rabbits in different groups increased gradually and steadily at different intervals till the end of observation period, however, the increase was non-significantly more in group D. The CI in group A increased gradually at different intervals; whereas in groups B, C and D, there was no appreciable increase in the CI during the period of Ca-vit.D3 supplementation, suggesting development of osteopenia. Treatment with TGF-beta1 did not increase the CI significantly, whereas Nandrolone treatment resulted in significant increase in the CI on days 45 and 60. The plasma Ca levels showed slight but gradual increase from day 0 to 60 in almost all groups. Subsequently also, there was no marked change at different intervals in groups A and B; however, significant reduction in plasma Ca was noticed in group C on 15(th) day and in group D on 60(th) day after initiation of treatment. Plasma IP levels in groups B and C showed a decreasing trend up to day 60. After discontinuation of Ca-vit.D3 supplementation, in group B, it further decreased to remain significantly lower on 15(th) day, and in groups C and D, it increased significantly on 60(th) post-treatment day. There was no significant change in the AP activity during the entire period of study in group A; whereas significant reduction in AP activity was measured on 30(th) and 60(th) days of treatment in groups B and C, and on 15(th) day of treatment in group D. Plasma iPTH values did not show any significant change at any interval during the first 60 days in all groups. On 30(th) and 60(th) days of treatment, the mean iPTH level remained significantly lesser in group B. In all groups treated with over supplementation of Ca and vit.D3, there was a non-significant increase in the plasma OC levels up to day 60; however, there was no significant difference between the groups. It can be concluded that additional supplementation of Ca and vit.D3 results in osteopenia in growing rabbits. Administration of Nandrolone helps to increase the mineral density in osteopenic bones, whereas TGF-beta1 does not seem to have positive effect on the skeletal mineralization.

The Developmental Basis of Skeletal Cell Differentiation and the Molecular Basis of Major Skeletal Defects

Vertebrate skeletal differentiation retains elements from simpler phyla, and reflects the differentiation of supporting tissues programmed by primary embryonic development. This developmental scheme is driven by homeotic genes expressed in sequence, with subdivision of skeletal primordia driven by a combination of seven transmembrane-pass receptors responding to Wnt-family signals, and by bone morphogenetic family signals that define borders of individual bones. In sea-dwelling vertebrates, an essentially complete form of the skeleton adapted by the land-living vertebrates develops in cartilage, based on type II collagen and hydrophilic proteoglycans. In bony fishes, this skeleton is mineralized to form a solid bony skeleton. In the land-living vertebrates, most of the skeleton is replaced by an advanced vascular mineralized skeleton based on type I collagen, which reduces skeletal mass while facilitating use of skeletal mineral for metabolic homeostasis. Regulation of the mammalian skeleton, in this context, reflects practical adaptations to the needs for life on land that are related to ancestral developmental signals. This regulation includes central nervous system regulation that integrates bone turnover with overall metabolism. Recent work on skeletal development, in addition, demonstrates molecular mechanisms that cause developmental bone diseases.

Genetic Evidence of Serum Phosphate-Independent Functions of FGF-23 on Bone

Maintenance of physiologic phosphate balance is of crucial biological importance, as it is fundamental to cellular function, energy metabolism, and skeletal mineralization. Fibroblast growth factor-23 (FGF-23) is a master regulator of phosphate homeostasis, but the molecular mechanism of such regulation is not yet completely understood. Targeted disruption of the Fgf-23 gene in mice (Fgf-23−/−) elicits hyperphosphatemia, and an increase in renal sodium/phosphate co-transporter 2a (NaPi2a) protein abundance. To elucidate the pathophysiological role of augmented renal proximal tubular expression of NaPi2a in Fgf-23−/− mice and to examine serum phosphate–independent functions of Fgf23 in bone, we generated a new mouse line deficient in both Fgf-23 and NaPi2a genes, and determined the effect of genomic ablation of NaPi2a from Fgf-23−/− mice on phosphate homeostasis and skeletal mineralization. Fgf-23−/−/NaPi2a−/− double mutant mice are viable and exhibit normal physical activities when compared to Fgf-23−/− animals. Biochemical analyses show that ablation of NaPi2a from Fgf-23−/− mice reversed hyperphosphatemia to hypophosphatemia by 6 weeks of age. Surprisingly, despite the complete reversal of serum phosphate levels in Fgf-23−/−/NaPi2a−/−, their skeletal phenotype still resembles the one of Fgf23−/− animals. The results of this study provide the first genetic evidence of an in vivo pathologic role of NaPi2a in regulating abnormal phosphate homeostasis in Fgf-23−/− mice by deletion of both NaPi2a and Fgf-23 genes in the same animal. The persistence of the skeletal anomalies in double mutants suggests that Fgf-23 affects bone mineralization independently of systemic phosphate homeostasis. Finally, our data support (1) that regulation of phosphate homeostasis is a systemic effect of Fgf-23, while (2) skeletal mineralization and chondrocyte differentiation appear to be effects of Fgf-23 that are independent of phosphate homeostasis.

Heritability of bone density: Regional and gender differences in monozygotic twins

Bone mineral density (BMD) is a measure of a person's skeletal mineral content, and assessing BMD by dual x-ray absorptiometry (DEXA) can help to diagnose diseases of low bone density. In this study, we determine the heritability of BMD in male and female monozygotic twin subjects using DEXA in 13 specific anatomical regions. In an attempt to quantify the genetic contribution of gender and skeletal region to BMD heritability, we scanned 14 pairs of identical twins using DEXA and calculated the broad-sense heritability coefficient (H(2)) in each of the 13 different body regions. The region of the body that was most heritable for both genders was the head (H(2) >or= 95%). When males were compared to females, H(2) values for male hip (H(2) = 87%) and lower extremities (H(2) = 90%) were higher than those in females (H(2) = 49% and 56%, respectively). Conversely, H(2) value for the female pelvis (H(2) = 68%) was higher than that for males (H(2) = 26%). These data show that different regions of the skeleton exhibit different degrees of heritability, and that the variation depends on gender.

Phosphate and pyrophosphate mediate PKA-induced vascular cell calcification

Vascular calcification is associated with increased cardiovascular risk and occurs by osteochondrogenic differentiation of vascular cells. Many of the same regulatory factors that control skeletal mineralization, including the complex metabolic pathway controlling levels of the activator, inorganic phosphate, and the potent inhibitor, pyrophosphate, also govern vascular calcification. We previously found that the cAMP/PKA signaling pathway mediates in vitro vascular cell calcification induced by inflammatory factors including tumor necrosis factor-alpha 1 and oxidized phospholipids. In this report, we tested whether this signaling pathway modulates phosphate and pyrophosphate metabolism. Treatment of primary murine aortic cells with the PKA activator, forskolin, significantly induced osteoblastic differentiation markers, including alkaline phosphatase (ALP), osteopontin, and osteocalcin as well as the pyrophosphate generator, ectonucleotide-pyrophosphatase/phosphodiesterase-1 (Enpp1) and the pyrophosphate transporter, ankylosis protein, but not the sodium/phosphate cotransporter, Pit-1. In the presence of a substrate for ALP, beta-glycerophosphate, which generates inorganic phosphate, forskolin also enhanced matrix mineralization. Inhibitors of ALP or Pit-1 abrogated forskolin-induced osteopontin expression and mineralization but not forskolin-induced osteocalcin or ALP. These results suggest that phosphate is necessary for PKA-induced calcification of vascular cells and that the extent of PKA-induced calcification is controlled by feedback induction of the inhibitor, pyrophosphate.

Lumbar spine peak bone mass and bone turnover in men and women: a longitudinal study

Peak bone mass is an important determinant of bone mass in later life, but the age of peak bone mass is still unclear. We found that bone size and density increase and bone turnover decreases until age 25. It may be possible to influence bone accrual into the third decade. Peak bone mass is a major determinant of bone mass in later life. Bone growth and maturation is site-specific, and the age of peak bone mass is still unclear. It is important to know the age to which bone accrual continues so strategies to maximise bone mass can be targeted appropriately. This study aims to ascertain the age of lumbar spine peak bone mass. We measured lumbar spine BMC, estimated volume and BMAD by DXA and biochemical markers of bone turnover in 116 healthy males and females ages 11 to 40, followed up at an interval of five to nine years. The majority of peak bone mass was attained by the mid-twenties. Increases in BMC in adolescents and young adults were mostly due to increases in bone size. Bone turnover markers decreased through adolescence and the third decade and the decreasing rate of change in bone turnover corresponded with the decreasing rate of change in lumbar spine measurements. Skeletal maturation and bone mineral accrual at the lumbar spine continues into the third decade.

A computer-aided diagnosis system to screen for osteoporosis using dental panoramic radiographs

An eroded inferior cortex of the mandible detected on dental panoramic radiographs is useful for identifying post-menopausal women with low skeletal bone mineral density (BMD) or osteoporosis. The purposes of this study were to develop a computer-aided diagnosis (CAD) system that automatically determines cortical erosion of the mandible on dental panoramic radiographs and to assess the validation of this CAD system. A CAD system was developed based on mathematical morphology for identifying post-menopausal women with low skeletal BMD or osteoporosis, based on World Health Organization criteria, by identifying whether the endosteal margin of mandibular cortical bone was eroded. The sensitivity, specificity, predictive value, accuracy and likelihood for a positive risk result were calculated using dichotomous 2 x 2 tables using 100 panoramic radiographs. For identifying women with low skeletal BMD, the sensitivity and specificity were 76.8% and 61.1%, respectively, the positive and negative predictive values were 90.0% and 36.7%, accuracy was 74.0% and the likelihood for positive risk was 1.96. The respective values for identifying women with osteoporosis were 94.4% and 43.8%, the positive and negative predictive values were 48.6% and 93.3%, respectively, the accuracy was 62.0% and the likelihood for positive risk was 1.68. Our results suggest that a CAD system applied to dental panoramic radiographs may be useful for identifying post-menopausal women with low skeletal BMD or osteoporosis.

Bone-Targeted Replacement Therapy for Hypophosphatasia

Bone-Targeted Replacement Therapy for Hypophosphatasia

SCPP Gene Evolution and the Dental Mineralization Continuum

Many genes critical to vertebrate skeletal mineralization are members of the secretory calcium-binding phosphoprotein (SCPP) gene family, which has evolved by gene duplication from a single ancestral gene. In humans, mutations in some of these SCPP genes have been associated with various diseases related to dentin or enamel hypoplasia. Recently, systematic searches for SCPP genes of various species have allowed us to investigate the history of phylogenetically variable dental tissues as a whole. One important conclusion is that not all disease-associated SCPP genes are present in tetrapods, and teleost fish probably have none, even in toothed species, having acquired their complement of SCPP genes through an independent duplication history. Here, we review comparative analyses of mineralized dental tissues, with particular emphasis on the use of SCPPs, within and between tetrapods and teleosts. Current knowledge suggests a close relationship among bone, dentin, teleost fish enameloid (enamel-like hard tissue), and tetrapod enamel. These tissues thus form a mineralized-tissue continuum. Contemporary dental tissues have evolved from an ancestral continuum through lineage-specific modifications.

Maternal vitamin D in pregnancy may influence not only offspring bone mass but other aspects of musculoskeletal health and adiposity

Osteoporotic fractures, falls and obesity are major health problems in developed nations. Evidence suggests that there are antenatal factors predisposing to these conditions. Data are emerging from Australia and elsewhere to suggest that maternal vitamin D status in pregnancy affects intrauterine skeletal mineralisation and skeletal growth together with muscle development and adiposity. Given that low levels of vitamin D have been documented in many urbanised populations, including those in countries with abundant sunlight, an important issue for public health is whether maternal vitamin D insufficiency during pregnancy has adverse effects on offspring health. The developing fetus may be exposed to low levels of vitamin D during critical phases of development as a result of maternal hypovitaminosis D. We hypothesise that this may have adverse effects on offspring musculoskeletal health and other aspects of body composition. Further research focused on the implications of poor gestational vitamin D nutrition is warranted as these developmental effects are likely to have a sustained influence on health during childhood and in adult life. We suggest that there is a clear rationale for randomised clinical trials to assess the potential benefits and harmful effects of vitamin D supplementation during pregnancy.