Vertebral Sites Research Articles

Protein quality affects bone status during moderate protein restriction in growing mice

Adequate protein intake during development is critical to ensure optimal bone gain and to attain a higher peak bone mass later on. We hypothesized that the quality of the dietary protein is of prime importance for bone physiology during moderate protein restriction. The target population was growing Balb/C mice. We compared two protein restricted diets (6% of total energy as protein), one based on soy (LP-SOY) and one based on casein (LP-CAS). For comparison, a normal protein soy-based control group (NP-SOY) and a low protein group receiving an anabolic daily parathyroid hormone (PTH) 1-34 injection (LP-SOY+PTH) were included in the protocol. After 8weeks, LP-SOY mice had reduced body weights related to a lower lean mass whereas LP-CAS mice were not different from the NP-SOY group. LP-SOY mice were characterized by lower femoral cortical thickness, bone volume, trabecular number and thickness and increased medullar adiposity when compared to both the LP-CAS and NP-SOY groups. However, the dietary intervention had no effect on the vertebral parameters. The negative effect of the LP-SOY diet was correlated to an impaired bone formation as shown by the reduced P1NP serum level as well as the reduced osteoid surfaces and bone formation rate in the femur. PTH injection in LP-SOY mice had no effect on total weight or lean mass, but improved all bone parameters at both femoral and vertebral sites, suggesting that amino acid deficiency was not the primary reason for degraded bone status in mice consuming soy protein. In conclusion, our study showed that under the same protein restriction (6% of energy), a soy diet leads to impaired bone health whereas a casein diet has little effect when compared to a normal protein control.

The evolution of evolvability in microRNA target sites in vertebrates

The lack of long-term evolutionary conservation of microRNA (miRNA) target sites appears to contradict many analyses of their functions. Several hypotheses have been offered, but an attractive one—that the conservation may be a function of taxonomic hierarchy (vertebrates, mammals, primates, etc.)—has rarely been discussed. For such an analysis, we cannot use evolutionary conservation as a criterion of target identification, and hence, have used high confidence target sites in the cross-linking immunoprecipitation (CLIP) data. Assuming that a proportion, p, of target sites in the CLIP data are conserved, we define the evolvability of miRNA targets as 1-p. Genomic data from vertebrate species show that the evolvability between human and fish is very high, at more than 90%. The evolvability decreases to 50% between birds and mammals, 20% among mammalian orders, and only 6% between human and chimpanzee. Within each taxonomic hierarchy, there is a set of targets that are conserved only at that level of evolution. Extrapolating the evolutionary trend, we find the evolvability in any single species to be close to 0%. Thus, all miRNA target sites identified by the CLIP method are evolutionarily conserved in one species, but the conservation is lost step by step in larger taxonomic groups. The changing evolvability of miRNA targets suggests that miRNA-target interactions may play a role in the evolution of organismal diversity.

Posterior vertebral column resection in early onset spinal deformities

Early onset spinal deformities (EOSD) can be life-threatening in very young children. In the growing spine, surgical intervention is often unavoidable and should be carried out as soon as possible. A deformed section of the spine not only affects the development of the remaining healthy spine, but also that of the chest wall (which influences pulmonary function), the extremities and body balance. Posterior vertebral column resection (PVCR) represents an effective surgical solution to address such problems. However, reports in the literature concerning PVCR are mostly limited to its use in adolescents or adults. The purpose of this study was to illustrate our experience with PVCR in EOSD and to describe the surgical technique with respect to the unique anatomy of young children. Four children [mean age 3.7 (range 2.5-5.2) years] with severe spinal deformity underwent PVCR through a single approach. Multimodal intraoperative monitoring was used in all cases. Surgery included one stage posterior circumferential resection of one vertebral body along with the adjoining intervertebral discs and removal of all posterior elements. A transpedicular screw-rod system was used for correction and stabilisation. Fusion was strictly limited to the resection site, allowing for later conversion into a growing rod construct at the remaining spine, if necessary. Relevant data were extracted retrospectively from patient charts and long spine radiographs. The mean operation time was 500 (range 463-541) min, with an estimated blood loss of 762 (range 600-1,050) ml. Mean follow-up time was 6.3 (range 3.5-12.4) years. After PVCR, the mean Cobb angle for scoliosis was reduced from 69° (range 50-99°) to 29° (5-44°) and the sagittal curvature (kyphosis) from 126° (87-151°) to 61° (47-75°). The mean correction of scoliosis was 57% (18-92°) and of kyphosis, 51% (44-62°). There were no spinal cord-related complications. In three patients, spinal instrumentation for growth guidance (fusion less growing rod technique) was applied. Two patients had complications: one patient had a complication of anesthesia, halo pin failure, and revision surgery with extension of the instrumentation cranially due to loss of correction; the second patient had a postoperative infection, which required plastic reconstructive measures. PVCR appears to be an effective technique to treat severe EOSD. There are important differences in its use in young children when compared with older patients. In patients with EOSD, additional surgical procedures are often necessary during growth, and hence non-fusion instrumentation beyond the vertebral resection site is advantageous, as it permits spinal growth and the later addition of fusion.

Taphonomy of the reference Miocene vertebrate mammal site of Cerro de la Garita, Spain

This article reports a detailed taphonomic study of the reference Miocene vertebrate site of Cerro de la Garita, (Concud, Teruel, Spain). The sedimentary record of the site indicates that it was a palaeo-lakeshore, and this conclusion is supported by aquatic environment-related taphonomic modifications of its fossils (both on their surfaces and internally). The site provided a water source that appears to have been regularly visited by herbivores. It was, therefore, also likely to have been a good feeding ground for predators and scavengers. Hyaena coprolites have been found at the site, and tooth marks were identified on some fossil bone surfaces. Bone fragments 2–5 cm in length showed clear evidence of heavy digestion and probable regurgitation. Abundant trampling marks were seen on the surface of many of the fossil bones, traits that are congruent with a damp lakeshore environment. Most of the remains were broken, and only a few anatomical elements belonging to the same individual were found close together, although never articulated (i.e. in a manner reflecting their anatomical connections). The fossils showed no signs of selection (either by shape or size) or abrasion, although a certain re-orientation suggests the influence of wave or strand line activity. Despite being an open-air site, none of the fossils appeared to be weathered, further suggesting that the surrounding environment was a damp lakeshore probably shaded by vegetation. Indeed, abundant signs of root activity were observed. No evidence of reworking, that is, post-burial disturbance or diachronic mixing of fossils, was seen, confirming the international value of Cerro de la Garita as a reference site for continental Miocene mammal assemblages.

First Report of Coelacanth and Hybodont Remains from the Lower Permian Wellington Formation of Oklahoma

This is the first and only positive indication to date of the presence of the coelacanth, Spermatodus pustulosus, and the hybodont shark, Polyacrodus zideki, from the Wellington Formation of Oklahoma. This record documents the occurrence of both the coelacanth and hybodont in the Wellington Formation of North-central Oklahoma and it increases the stratigraphic distribution of both. The specimens were collected from a channel-fill conglomerate exposed in a south facing road cut. The site SNOMNH (Sam Noble Oklahoma Museum of Natural History) vertebrate site V 1627 is located in southern Noble County, north-central Oklahoma. The site has yielded numerous three-dimensional remains of fish, amphibians, and reptiles.

A Special Ingredient (VtR) Containing Oligostilbenes Isolated from Vitis thunbergii Prevents Bone Loss in Ovariectomized Mice: In Vitro and In Vivo Study.

Vitis thunbergii is used in Taiwan as a botanical supplement for inflammatory bone diseases. This study aims to examine its direct effect on bone metabolism. Three-month-old female mice were randomly divided into ovariectomized control (OVX), sham operated (SHAM), and ovariectomy treated with either 17β-estradiol or a special ingredient (VtR) fractionated from an ethanol extract of V. thunbergii started two weeks after ovariectomy. VtR treatment for 8 weeks significantly ameliorated the deterioration of bone mineral density and reversed all the ovariectomy-induced changes in μ-CT parameters. The antiosteoporotic effect of VtR accompanied decrease in serum levels of C-terminal telopeptides of type I collagen (CTx), interleukin-7, and ration of RANKL/osteoprotegerin (OPG) but rise in osteocalcin concentration. Sparse calcified microarchitecture and less alkaline-phosphatase- (ALP-) positive cells were observed at the femur and vertebral sites in OVX mice while VtR remarkably restored such variation. HPLC analysis showed (+)-vitisin-A, (−)-vitisin-B, and ampelopsin C predominated in VtR. Both (−)-vitisin B and ampelopsin C increased ALP activity and bone nodule formation in cultured osteoblasts. Instead of stimulating osteoblastogenesis, (+)-vitisin A dramatically repressed osteoclasts differentiation and bone resorption. The results suggested VtR composed of diverse components to reciprocally drive osteoblastogenesis and interdict osteoclastogenesis may serve as a potential botanic drug for osteoporosis therapy.

Estudio baritado del tubo digestivo alto en pacientes postoperados de cirugía bariátrica: Hallazgos normales y patológicos

Objective. To evaluate a barium study of the upper gastrointestinal tract in early postoperative monitoring of bariatric surgery patients, recording the anatomical characteristics of the gastric remnant and the frequency of complications such as leakage of contrast and emptying difficulties. Materials and Methods. We retrospectively evaluated the barium study of the upper gastrointestinal tract performed in 168 patients after gastric bypass (GBP) and 98 patients after vertical subtotal gastrectomy (VSG). All evaluated examinations were performed in the first five days after surgery. Gastric remnant volume was registered in relation to the T12 vertebral body (only in GBP), the presence and site of contrast leakage and gastric remnant emptying difficulties. Results. The average age of patients undergoing GBP was 43 years, and 37 years for VSG. The average volume of gastric remnant of patients with GBP was 1.5 T12 vertebral bodies. Two GBP operated patients (1.2%) had leakage of the contrast medium at the level of the gastroenteric anastomosis; in VSG operated patients the contrast leakage occurred in 7 cases (7.1%), the most frequent site being the left side cephalic portion of the gastric remnant. All cases with contrast leakage were subsequently studied using computed tomography, finding the presence of wound dehiscence or fluid collections adjacent to the gastric remnant. Emptying difficulty was observed in 12 patients operated for GBP (7.1%); there was no record of this complication in patients undergoing VSG. Conclusion. The upper gastrointestinal barium study is useful in patients after bariatric surgery to assess the early postoperative anatomy and volume of the gastric remnant, as well as to detect possible complications. It is a simple test, which should be applied as a routine control in these patients.

Primary hyperparathyroidism is associated with abnormal cortical and trabecular microstructure and reduced bone stiffness in postmenopausal women

Typically, in the milder form of primary hyperparathyroidism (PHPT), now seen in most countries, bone density by dual-energy X-ray absorptiometry (DXA) and detailed analyses of iliac crest bone biopsies by histomorphometry and micro-computed tomography (µCT) show detrimental effects in cortical bone, whereas the trabecular site (lumbar spine by DXA) and the trabecular compartment (by bone biopsy) appear to be relatively well preserved. Despite these findings, fracture risk at both vertebral and nonvertebral sites is increased in PHPT. Emerging technologies, such as high-resolution peripheral quantitative computed tomography (HRpQCT), may provide additional insight into microstructural features at sites such as the forearm and tibia that have heretofore not been easily accessible. Using HRpQCT, we determined cortical and trabecular microstructure at the radius and tibia in 51 postmenopausal women with PHPT and 120 controls. Individual trabecula segmentation (ITS) and micro-finite element (µFE) analyses of the HRpQCT images were also performed to further understand how the abnormalities seen by HRpQCT might translate into effects on bone strength. Women with PHPT showed, at both sites, decreased volumetric densities at trabecular and cortical compartments, thinner cortices, and more widely spaced and heterogeneously distributed trabeculae. At the radius, trabeculae were thinner and fewer in PHPT. The radius was affected to a greater extent in the trabecular compartment than the tibia. ITS analyses revealed, at both sites, that plate-like trabeculae were depleted, with a resultant reduction in the plate/rod ratio. Microarchitectural abnormalities were evident by decreased plate-rod and plate-plate junctions at the radius and tibia, and rod-rod junctions at the radius. These trabecular and cortical abnormalities resulted in decreased whole-bone stiffness and trabecular stiffness. These results provide evidence that in PHPT, microstructural abnormalities are pervasive and not limited to the cortical compartment, which may help to account for increased global fracture risk in PHPT.

Fractionated radiosurgery for painful spinal metastases: DOSIS - a phase II trial

BackgroundOne third of all cancer patients will develop bone metastases and the vertebral column is involved in approximately 70% of these patients. Conventional radiotherapy with of 1–10 fractions and total doses of 8-30 Gy is the current standard for painful vertebral metastases; however, the median pain response is short with 3–6 months and local tumor control is limited with these rather low irradiation doses. Recent advances in radiotherapy technology – intensity modulated radiotherapy for generation of highly conformal dose distributions and image-guidance for precise treatment delivery – have made dose-escalated radiosurgery of spinal metastases possible and early results of pain and local tumor control are promising. The current study will investigate efficacy and safety of radiosurgery for painful vertebral metastases and three characteristics will distinguish this study. 1) A prognostic score for overall survival will be used for selection of patients with longer life expectancy to allow for analysis of long-term efficacy and safety. 2) Fractionated radiosurgery will be performed with the number of treatment fractions adjusted to either good (10 fractions) or intermediate (5 fractions) life expectancy. Fractionation will allow inclusion of tumors immediately abutting the spinal cord due to higher biological effective doses at the tumor - spinal cord interface compared to single fraction treatment. 3) Dose intensification will be performed in the involved parts of the vertebrae only, while uninvolved parts are treated with conventional doses using the simultaneous integrated boost concept.Methods / DesignIt is the study hypothesis that hypo-fractionated image-guided radiosurgery significantly improves pain relief compared to historic data of conventionally fractionated radiotherapy. Primary endpoint is pain response 3 months after radiosurgery, which is defined as pain reduction of ≥ 2 points at the treated vertebral site on the 0 to 10 Visual Analogue Scale. 60 patients will be included into this two-centre phase II trial.ConclusionsResults of this study will refine the methods of patient selection, target volume definition, treatment planning and delivery as well as quality assurance for radiosurgery. It is the intention of this study to form the basis for a future randomized controlled trial comparing conventional radiotherapy with fractionated radiosurgery for palliation of painful vertebral metastases.Trial registrationClinicalTrials.gov Identifier: NCT01594892

Ce que les patientes doivent savoir sur le risque osseux et sa prévention

Post-menopausal osteoporosis is one of the classic complications of prolonged estrogen deficiency associated with menopause. It is defined as a state of the skeleton characterized by decreased bone strength with an increased risk of fracture. The natural history of osteoporosis and, in particular, the rapid increase in fracture recurrence after a first major fracture should justify a priori an approach for early detection of women at higher risk from the early postmenopausal phase. It is more of a chronic disease that requires support in the long term, in the absence of a truly curative treatment. Indeed, currently available therapies can at best reduce the incidence of fractures by about 50%, especially at the vertebral site, but do not cancel the disease. Moreover, duration of treatment is currently recommended for 5 to 10 years, which does not allow to consider that a single molecule could be taken "for the whole life". The fracture risk assessment based on the combination of densitometric measurement by DXA and the search for clinical risk factors is a prerequisite to any therapy. The first choice of treatment is especially important for a relatively young woman with high fracture risk. In early menopause (generally within the first decade of post-menopausal) and in the absence of contraindication, menopausal hormone therapy should remain the preferred option for first-line whenever possible. Raloxifene is an interesting alternative, due to its mechanisms of action and multiplicity of targets with, in particular, its preventive effect on the risk of estrogen receptor-positive breast cancer. It is only when there are contraindications to one or the other of these two molecules, that other osteoporosis treatments can be discussed. They should nevertheless be considered only in women whose 10-year-fracture risk is significantly increased. Indeed, it is mainly in this high risk of fracture, particularly because of an age greater than 65 years and a history of vertebral fracture, that their antifracture efficacy has been validated. In addition, it is mostly beyond this age that the question of the prevention of hip fracture has to be considered.

Palynomorphs of the Normapolles group and related plant mesofossils from the Iharkút vertebrate site, Bakony Mountains (Hungary)

Abstract Palynological and paleobotanical investigation of bonebeds and other strata of the Csehbanya Formation from the vertebrate locality at Iharkut (Bakony Mts, Hungary) reveals well-preserved Santonian palynological assemblages dominated by the Normapolles group, with a minor component consisting of other angiosperm pollen, some gymnosperm pollen, and spores. Eleven species of Normapolles-type pollen grains belonging to seven genera and fruit remains of a new taxon, Sphaeracostata barbackae gen. et sp. nov., are described. The new species is very abundant in the material, represented by ca. 1000 specimens. The genus Caryanthus Friis and an unnamed form previously reported from Haţeg by Lindfors et al. (2010) are also present. Plants producing Normapolles-type pollen grains diversified during the Late Cretaceous, with a bloom in the Santonian. The palynostratigraphy of the Upper Cretaceous terrestrial sediments in the studied region is based on Normapolles-related species. The studied assemblage is as...

Initial investigation of 18F-NaF PET/CT for identification of vertebral sites amenable to surgical revision after spinal fusion surgery

PurposeA pilot study was performed in patients with recurrent back pain after spinal fusion surgery to evaluate the ability of 18F-NaF PET/CT imaging to correctly identify those requiring surgical intervention and to locate a site amenable to surgical intervention.MethodsIn this prospective study 22 patients with recurrent back pain after spinal surgery and with equivocal findings on physical examination and CT were enrolled for evaluation with 18F-NaF PET/CT. All PET/CT images were prospectively reviewed with the primary objective of identifying or ruling out the presence of lesions amenable to surgical intervention. The PET/CT results were then validated during surgical exploration or clinical follow-up of at least 15 months.ResultsAbnormal 18F-NaF foci were found in 16 of the 22 patients, and surgical intervention was recommended. These foci were located at various sites: screws, cages, rods, fixation hardware, and bone grafts. In 6 of the 22 patients no foci requiring surgical intervention were found. Validation of the results by surgery (15 patients) or on clinical follow-up (7 patients) showed that 18F-NaF PET/CT correctly predicted the presence of an abnormality requiring surgical intervention in 15 of 16 patients and was falsely positive in 1 of 16.ConclusionIn this initial investigation, 18F-NaF PET/CT imaging showed potential utility for evaluation of recurrent symptoms after spinal fusion surgery by identifying those patients requiring surgical management.

Oral bisphosphonates reduce the risk of clinical fractures in glucocorticoid-induced osteoporosis in clinical practice

This study aims to estimate bisphosphonate effectiveness by comparing fracture incidence over time on therapy in glucocorticoid-induced osteoporosis (GIO). From this observational study, alendronate and risedronate decreased clinical vertebral and nonvertebral fractures over time. The effectiveness of each bisphosphonate is consistent with their efficacies demonstrated on surrogate markers in randomized controlled trials (RCTs). This study aims to estimate bisphosphonate effectiveness by comparing fracture incidence over time on therapy with fracture incidence during a short period after starting a therapy. The study population was a subgroup of a larger cohort study comprising two cohorts of women aged ≥65years, prescribed with alendronate or risedronate. Within the two study cohorts, 11,007 women were identified as having received glucocorticoids. Within each cohort, the baseline incidence of clinical fractures at nonvertebral and vertebral sites was defined by the initial 3-month period after starting therapy. Relative to these baseline data, we then compared the fracture incidence during the subsequent 12months on therapy. The baseline incidence of clinical nonvertebral and vertebral fractures was similar in the alendronate cohort (5.22 and 5.79/100 person-years, respectively) and in the risedronate cohort (5.51 and 5.68/100 person-years, respectively). Relative to the baseline incidence, fracture incidence was significantly lower in the subsequent 12months in both cohorts of alendronate (33% lower at nonvertebral sites and 59% at vertebral sites) and risedronate (28% lower at nonvertebral sites and 54% at vertebral sites). From this observational study not designed to compare drugs, both alendronate and risedronate decreased clinical vertebral and nonvertebral fractures over time. The reductions observed in fracture incidence, within each cohort, suggest that the effectiveness of each bisphosphonate in clinical practice is consistent with their efficacies demonstrated on surrogate markers in randomized controlled trials.

Palaeontological and palaeobiogeographical implications of the new Cenomanian vertebrate site of Algora, Guadalajara, Spain

A new Cenomanian fossil site has been located in Algora, in the Castilian Branch of the Iberian Ranges, central Spain. The outcrop is in the upper part of the Utrillas Formation in sediments that can be interpreted as sandy coastal deposits (bars and channels) with subtidal and intertidal events. The vertebrate fauna associated with this site is composed of mixed remains of fishes, turtles, crocodyliforms and dinosaurs, with Laurasian and Gondwanan affinities. The discovery of this site provides new palaeobiogeographical information and enriches the poorly known vertebrate faunas of the European Cenomanian.

Human bone marrow adiposity is linked with serum lipid levels not T1-diabetes

Increased marrow adiposity is often associated with bone loss. Little is known about the regulation of marrow adiposity in humans. Marrow adiposity is increased in several mouse models including type I (T1)-diabetic mice, which also display bone loss. However, the impact of metabolic disease on marrow adiposity in humans has yet to be examined. This study measured bone marrow adiposity levels with iterative decomposition of water and fat with echo asymmetry and least-squares estimation magnetic resonance imaging and determined their relationship with T1-diabetes, bone mineral density (BMD), and serum lipid levels. Participants were adult T1-diabetic patients (glycosylated hemoglobin averaging 7.70%±0.4%) and age- and body-mass-index-matched nondiabetic subjects. Consistent with previous reports, serum osteocalcin levels were lower in subjects with T1-diabetes compared to controls (reaching statistical significance in females) and negatively correlated with disease duration (r=−0.50, P<.01). Furthermore, femur neck BMD inversely correlated with diabetes severity (r=−0.417, P<.05). While marrow adiposity was not altered by T1-diabetes, there was a striking positive correlation between vertebral, femur, and tibia marrow adiposity and serum lipid levels (low-density lipoprotein, total cholesterol, cholesterol:high-density lipoprotein ratio, and triglyceride; r≥0.383), reaching a significance of P<.001 in some comparisons. Marrow adiposity also displayed strong intrasubject correlations at multiple bone sites (r≥0.411, P<.05), increased with age (r=0.410, P<.05 at vertebral sites), and was reciprocally related to bone density (r≥−0.378, P<.05). Taken together, our data suggest that marrow adiposity may be an indicator of elevated serum lipid levels and decreased bone density.

Targeted approaches in the treatment of osteoporosis: differential mechanism of action of denosumab and clinical utility.

Denosumab is a breakthrough biological drug approved by the Food and Drug Administration and European Medicines Agency for the treatment of osteoporosis in 2010. It is a fully human monoclonal antireceptor activator of nuclear factor kappa-B ligand antibody, which inhibits the activity of osteoclasts, resulting in an antiresorptive effect with a significant increase in bone mineral density. The FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial, comparing denosumab with no treatment in 7868 women with postmenopausal osteoporosis, showed an important reduction of fracture risk at hip, vertebral, and nonvertebral sites in the treated group, while no statistically significant difference in the incidence of adverse events was detected between denosumab and placebo groups. The specific action of denosumab directed against a key regulator of osteoclasts makes it a valuable tool in preventing the occurrence of skeletal events caused by bone destruction in patients with advanced malignancies. The drug was approved for postmenopausal osteoporosis in women at increased risk of fracture and for the treatment of bone loss associated with androgen deprivation therapy in men with prostate cancer.

Long-Term Effects of Neridronate and its Discontinuation in Patients with Primary Hyperparathyroidism

In patients with primary hyperparathyroidism (PHPT) not suitable for surgical correction, a skeletal protection with bisphosphonates is considered a reasonable option, but the long-term effects after treatment discontinuation are not well known. Sixty postmenopausal women with PHPT were given 400-600IU vitamin D(3) daily and 100mg neridronate IV every 2months for 2years with 2 additional years of follow-up without antiresorptive therapies. Bone mineral density (BMD) progressively rose by 6.7±7.6% (SD) and by 2.9±4.5% at the spine and femoral neck, respectively. During follow-up, mean BMD progressively fell, but after 2years it was still 3.9±5.5% higher than baseline values at the spine. Bone alkaline phosphatase and serum C-telopeptide of type I collagen decreased significantly within 6months (28 and 49% versus baseline, respectively) and rose to baseline values within 6-12months during follow-up. Serum PTH significantly rose from baseline during treatment, but it remained significantly higher than baseline during follow-up. The PTH changes were significantly correlated with serum 25-hydroxyvitamin D (25OHD) levels. In conclusion, in this study we observed that in patients with mild PHPT treatment with bisphosphonates is associated with the expected changes in bone-turnover markers and that the significant increases of both hip and spine BMD are partially maintained for at least 2years after treatment discontinuation at the vertebral site. The marked increases in serum PTH levels, particularly in subjects with low 25OHD levels, persist after treatment discontinuation and this raises the suspicion that this might reflect a worsening of PHPT.

Differential Habitat Use and Niche Partitioning by Pseudomonas Species in Human Homes

Many species of Pseudomonas have the ability to use a variety of resources and habitats, and as a result Pseudomonas are often characterized as having broad fundamental niches. We questioned whether actual habitat use by Pseudomonas species is equally broad. To do this, we sampled extensively to describe the biogeography of Pseudomonas within the human home, which presents a wide variety of habitats for microbes that live in close proximity to humans but are not part of the human flora, and for microbes that are opportunistic pathogens, such as Pseudomonas aeruginosa. From 960 samples taken in 20 homes, we obtained 163 Pseudomonas isolates. The most prevalent based on identification using the SepsiTest BLAST analysis of 16S rRNA (http://www.sepsitest-blast.de) were Pseudomonas monteilii (42 isolates), Pseudomonas plecoglossicida, Pseudomonas fulva, and P. aeruginosa (approximately 25 each). Of these, all but P. fulva differed in recovery rates among evaluated habitat types (drains, soils, water, internal vertebrate sites, vertebrate skin, inanimate surfaces, and garbage/compost) and all four species also differed in recovery rates among subcategories of habitat types (e.g., types of soils or drains). We also found that at both levels of habitat resolution, each of these six most common species (the four above plus Pseudomonas putida and Pseudomonas oryzihabitans) were over- or under-represented in some habitats relative to their contributions to the total Pseudomonas collected across all habitats. This pattern is consistent with niche partitioning. These results suggest that, whereas Pseudomonas are often characterized as generalists with broad fundamental niches, these species in fact have more restricted realized niches. Furthermore, niche partitioning driven by competition among Pseudomonas species may be contributing to the observed variability in habitat use by Pseudomonas in this system.

Evidence of Sustained Vertebral and Nonvertebral Antifracture Efficacy with Ibandronate Therapy: A Systematic Review

The antifracture efficacy of ibandronate at vertebral and nonvertebral sites was assessed. A literature review of randomized phase III clinical trials, meta-analyses or observational studies that reported fracture endpoints or surrogate markers, and compared ibandronate with placebo or an active comparator. In a phase III study, 2.5 mg daily oral ibandronate reduced the incidence of new vertebral fractures versus placebo and the relative risk reduction (RRR) was sustained over 3 years (62%; p = 0.0001). In two bridging studies, oral ibandronate 150 mg once monthly and 3 mg quarterly intravenous (i.v.) were superior to oral 2.5 mg daily in producing bone mineral density (BMD) increases at all sites over 2 years (p < 0.05). These improvements were sustained over 5 years. In meta-analyses of pivotal ibandronate studies, doses equivalent to annual cumulative exposure (ACE) ≥ 10.8 mg (including 150 mg once monthly and 3 mg quarterly i.v.) significantly reduced the incidence of nonvertebral fractures versus placebo or ACE 5.5 mg (2.5 mg daily) (RRR 29.9% and 38%, respectively; p < 0.05). Therefore, prevention of nonvertebral fractures was found in all patients with the commercially available highest doses, and not only in high-risk patients as observed in randomized clinical trials with lower doses. Finally, a 12-month, observational study of claims databases reported comparable rates of nonvertebral fractures and a statistically significantly lower rate of vertebral fractures (p < 0.01) with ibandronate versus weekly bisphosphonates. A large body of evidence suggests that ibandronate has sustained vertebral and nonvertebral antifracture efficacy in women with postmenopausal osteoporosis.

Current and Future Economic Burden of Osteoporosis in New Zealand

Osteoporosis is recognized as a serious health condition in developed as well as developing countries. There are no accurate estimates of the extent of the burden of osteoporosis in New Zealand. The purpose of this study was to estimate the economic burden of osteoporosis in New Zealand using data from international studies and population and health services information from New Zealand. To estimate the number of osteoporotic fractures and cost of treatment and management of osteoporosis and osteoporotic fractures to the health system in New Zealand in 2007 and to project the future burden in 2013 and 2020. Hospitalizations for hip fractures were combined with New Zealand census data and estimates from previous studies to estimate the expected number of osteoporotic vertebral, humeral, pelvic and other sites fractures in 2007. Health services usage and costs were estimated by combining data from New Zealand hospitals, the New Zealand Health Survey on the number of people diagnosed with osteoporosis, and the New Zealand Health Information Service (NZHIS) on pharmaceutical treatments. All prices are in New Zealand dollars ($NZ), year 2007 values. Losses in QALYs resulting from osteoporotic fractures were used to indicate the impact on morbidity and mortality. The lost QALYs and economic cost associated with osteoporosis were projected to 2013 and 2020 using population projections from the New Zealand census. There were an estimated 84 354 osteoporotic fractures in New Zealand in 2007, including 3803 hip and 27 994 vertebral fractures. Osteoporosis resulted in a loss of 11 249 QALYs. The total direct cost of osteoporosis was$NZ330 million, including $NZ212 million to treat the fractures, $NZ85 million for care after fractures and $NZ34 million for treatment and management of the estimated 70 631 people diagnosed with osteoporosis. Sensitivity analysis suggested the results were robust to assumptions regarding the number of fractures receiving medical treatment. Hospitalization costs represented a significant component of total costs. The cost of treatment and management of osteoporosis is expected to increase to over $NZ391 million in 2013 and $NZ458 million in 2020, with the number of QALYs lost increasing to 13 205 in 2013 and 15 176 in 2020. Osteoporosis and osteoporotic fractures create a significant burden on the health system in New Zealand. This study highlights the significant scope of the burden of osteoporosis and the potential gains that might be made from introducing interventions to mitigate the burden.