Effects of nasal calcitonin on bone mineral density following parathyroidectomy in patients with primary hyperparathyroidism

To investigate whether nasal salmon calcitonin (CT; 200 U/day) given in addition to calcium helps to restore the bone mass after parathyroidectomy (PTX) in patients with primary hyperparathyroidism (PHPT).

Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood

We report on a female who is compound heterozygote for two new point mutations in the CYP19 gene. The allele inherited from her mother presented a base pair deletion (C) occurring at P408 (CCC, exon 9), causing a frameshift that results in a nonsense codon 111 bp (37 aa) further down in the CYP19 gene. The allele inherited from her father showed a point mutation from G-->A at the splicing point (canonical GT to mutational AT) between exon and intron 3. This mutation ignores the splice site and a stop codon 3 bp downstream occurs. Aromatase deficiency was already suspected because of the marked virilization occurring prepartum in the mother, and the diagnosis was confirmed shortly after birth. Extremely low levels of serum estrogens were found in contrast to high levels of androgens. Ultrasonographic follow-up studies revealed persistently enlarged ovaries (19.5-22 mL) during early childhood (2 to 4 yr) which contained numerous large cysts up to 4.8 x 3.7 cm and normal-appearing large tertiary follicles already at the age of 2 yr. In addition, both basal and GnRH-induced FSH levels remained consistently strikingly elevated. Low-dose estradiol (E2) (0.4 mg/day) given for 50 days at the age of 3 6/12 yr resulted in normalization of serum gonadotropin levels, regression of ovarian size, and increase of whole body and lumbar spine (L1-L4) bone mineral density. The FSH concentration and ovarian size returned to pretreatment levels shortly (150 days) after cessation of E2 therapy. Therefore, we recommend that affected females be treated with low-dose E2 in amounts sufficient to result in physiological prepubertal E2 concentrations using an ultrasensitive estrogen assay. However, E2 replacement needs to be adjusted throughout childhood and puberty to ensure normal skeletal maturation and adequate adolescent growth spurt, normal accretion of bone mineral density, and, at the appropriate age, female secondary sex maturation.

Prevention of postmenopausal bone loss using tibolone or conventional peroral or transdermal hormone replacement therapy with 17beta-estradiol and dydrogesterone

Postmenopausal bone loss can be prevented by continuous or intermittent estradiol (E2) administration. Concomitant progestogen therapy is mandatory in nonhysterectomized women to curtail the risk of endometrial hyperplasia or cancer. However, the recurrence of vaginal bleeding induced by sequential progestogen therapy in addition to continuous estrogen administration is one of the reasons for noncompliance to hormone replacement therapy (HRT). Tibolone, a synthetic steroid with simultaneous weak estrogenic, androgenic, and progestational activity, which does not stimulate endometrial proliferation, has recently been proposed for the treatment of climacteric symptoms. To compare the efficacy of conventional oral and transdermal HRT with that of tibolone in the prevention of postmenopausal bone loss, 140 postmenopausal women (age, 52 +/- 0.6 years; median duration of menopause, 3 years) were enrolled in an open 2-year study. Volunteers had been offered a choice between HRT and no therapy (control group, CO). Patients selecting HRT were randomly allocated to one of the following three treatment groups: TIB, tibolone, 2.5 mg/day continuously, orally; PO, peroral E2, 2 mg/day continuously, plus sequential oral dydrogesterone (DYD), 10 mg/day, for 14 days of a 28-day cycle; TTS, transdermal E2 by patch releasing 50 microg/day, plus DYD as above. Bone densitometry of the lumbar spine, upper femur, and whole body was performed using dual-energy X-ray absorptiometry at baseline, and then 6, 12, 18, and 24 months after initiation of therapy. One hundred and fifteen women (82%) completed the 2 years of the study. The dropout rate was similar in each group. Over 2 years, bone preservation was observed in all three treatment groups as compared with controls, without significant differences among treatment regimens. In conclusion, tibolone can be regarded as an alternative to conventional HRT to prevent postmenopausal bone loss.

Micro and Macro Causes of Violence

The dominant emotion in violence-threatening situations is confrontational tension/fear (ct/f), which causes most violence to abort, or to be carried out inaccurately and incompetently. For violence to be successful, there must be a pathway around the barrier of ct/f. These pathways include: attacking the weak; audience-oriented staged and controlled fair fights; confrontation-avoiding remote violence; confrontation-avoiding by deception; confrontation-avoiding by absorption in technique. Successfully violent persons, on both sides of the law, are those who have developed these skilled interactional techniques. Since successful violence involves dominating the emotional attention space, only a small proportion of persons can belong to the elite which does most of each type of violence. Macro-violence, including victory and defeat in war, and in struggles of paramilitaries and social movements, is shaped by both material resources and social/emotional resources for maintaining violent organizations and forcing their opponents into organizational breakdown. Social and emotional destruction generally precedes physical destruction.

Cone Beam and Micro-Computed Tomography Validation of Manual Array Insertion for Minimally Invasive Cochlear Implantation

Delivering cochlear implants through a minimally invasive tunnel (1.8 mm in diameter) from the mastoid surface to the inner ear is referred to as direct cochlear access (DCA). Based on cone beam as well as micro-computed tomography imaging, this in vitro study evaluates the feasibility and efficacy of manual cochlear electrode array insertions via DCA. Free-fitting electrode arrays were inserted in 8 temporal bone specimens with previously drilled DCA tunnels. The insertion depth angle, procedural time, tunnel alignment as well as the inserted scala and intracochlear trauma were assessed. Seven of the 8 insertions were full insertions, with insertion depth angles higher than 520°. Three cases of atraumatic scala tympani insertion, 3 cases of probable basilar membrane rupture and 1 case of dislocation into the scala vestibuli were observed (1 specimen was damaged during extraction). Manual electrode array insertion following a DCA procedure seems to be feasible and safe and is a further step toward clinical application of image-guided otological microsurgery.

In vitro biomechanical testing of a micro external skeletal fixator

OBJECTIVE To biomechanically test the properties of three different Universal Micro External Fixator (UMEX™) configurations with regard to their use in very small animals (<5kg) and compare the UMEX system to the widely used IMEX External Skeletal Fixation (SK™) system in terms of stiffness, space needed for pin placement and weight. METHODS Three different UMEX configurations (type Ia, type Ib, and type II modified) and one SK configuration type Ia were used to stabilize Delrin plastic rods in a 1 cm fracture gap model. These constructs were tested in axial compression, craniocaudal bending, mediolateral bending, and torsion. Testing was conducted within the elastic range and mean stiffness in each mode was determined from the slope of the linear portion of the load-deformation curve. A Kruskal Wallis one-way analysis of variance on ranks test was utilized to assess differences between constructs (p <0.05). RESULTS The UMEX type II modified configuration was significantly stiffer than the other UMEX configurations and the SK type Ia, except in craniocaudal bending, where the SK type Ia configuration was stiffer than all UMEX constructs. The UMEX type Ia configuration was significantly the weakest of those frames. The UMEX constructs were lighter and smaller than the SK, thus facilitating closer pin placement. CONCLUSIONS Results supported previous reports concerning the superiority of more complex constructs regarding stiffness. The UMEX system appears to be a valid alternative for the treatment of long-bone fractures in very small animals.

Assessment of bone channels other than the nasopalatine canal in the anterior maxilla using limited cone beam computed tomography

PURPOSE The anterior maxilla, sometimes also called premaxilla, is an area frequently requiring surgical interventions. The objective of this observational study was to identify and assess accessory bone channels other than the nasopalatine canal in the anterior maxilla using limited cone beam computed tomography (CBCT). METHODS A total of 176 cases fulfilled the inclusion criteria comprising region of interest, quality of CBCT image, and absence of pathologic lesions or retained teeth. Any bone canal with a minimum diameter of 1.00 mm other than the nasopalatine canal was analyzed regarding size, location, and course, as well as patient gender and age. RESULTS A total of 67 accessory canals ≥1.00 mm were found in 49 patients (27.8%). A higher frequency of accessory canals was observed in males (33.0%) than in females (22.7%) (p = 0.130). Accessory canals occurred more frequently in older rather than younger patients (p = 0.115). The mean diameter of accessory canals was 1.31 ± 0.26 mm (range 1.01-2.13 mm). Gender and age did not significantly influence the diameter. Accessory canals were found palatal to all anterior teeth, but most frequently palatal to the central incisors. In 56.7%, the accessory canals curved superolaterally and communicated with the ipsilateral alveolar extension of the canalis sinuosus. CONCLUSIONS The study confirms the presence of bone channels within the anterior maxilla other than the nasopalatine canal. More than half of these accessory bone canals communicated with the canalis sinuosus. From a clinical perspective, studies are needed to determine the content of these accessory canals.

Piezoelectric alveolar ridge-splitting technique with simultaneous implant placement: a cohort study with 2-year radiographic results

PURPOSE Extended grafting procedures in atrophic ridges are invasive and time-consuming and increase cost and patient morbidity. Therefore, ridge-splitting techniques have been suggested to enlarge alveolar crests. The aim of this cohort study was to report techniques and radiographic outcomes of implants placed simultaneously with a piezoelectric alveolar ridge-splitting technique (RST). Peri-implant bone-level changes (ΔIBL) of implants placed with (study group, SG) or without RST (control group, CG) were compared. MATERIALS AND METHODS Two cohorts (seven patients in each) were matched regarding implant type, position, and number; superstructure type; age; and gender and received 17 implants each. Crestal implant bone level (IBL) was measured at surgery (T0), loading (T1), and 1 year (T2) and 2 years after loading (T3). For all implants, ΔIBL values were determined from radiographs. Differences in ΔIBL between SG and CG were analyzed statistically (Mann-Whitney U test). Bone width was assessed intraoperatively, and vertical bone mapping was performed at T0, T1, and T3. RESULTS After a mean observation period of 27.4 months after surgery, the implant survival rate was 100%. Mean ΔIBL was -1.68 ± 0.90 mm for SG and -1.04 ± 0.78 mm for CG (P = .022). Increased ΔIBL in SG versus CG occurred mainly until T2. Between T2 and T3, ΔIBL was limited (-0.11 ± 1.20 mm for SG and -0.05 ± 0.16 mm for CG; P = .546). Median bone width increased intraoperatively by 4.7 mm. CONCLUSIONS Within the limitations of this study, it can be suggested that RST is a well-functioning one-stage alternative to extended grafting procedures if the ridge shows adequate height. ΔIBL values indicated that implants with RST may fulfill accepted implant success criteria. However, during healing and the first year of loading, increased IBL alterations must be anticipated.

Fabric-mechanical property relationships of trabecular bone allografts are altered by supercritical CO2 treatment and gamma sterilization

Tissue grafts are implanted in orthopedic surgery every day. In order to minimize infection risk, bone allografts are often delipidated with supercritical CO2 and sterilized prior to implantation. This treatment may, however, impair the mechanical behavior of the bone graft tissue. The goal of this study was to determine clinically relevant mechanical properties of treated/sterilized human trabecular bone grafts, e.g. the apparent modulus, strength, and the ability to absorb energy during compaction. They were compared with results of identical experiments performed previously on untreated/fresh frozen human trabecular bone from the same anatomical site (Charlebois, 2008). We tested the hypothesis that the morphology–mechanical property relationships of treated cancellous allografts are similar to those of fresh untreated bone. The morphology of the allografts was determined by μCT. Subsequently, cylindrical samples were tested in unconfined and confined compression. To account for various morphologies, the experimental data was fitted to phenomenological mechanical models for elasticity, strength, and dissipated energy density based on bone volume fraction (BV/TV) and the fabric tensor determined by MIL. The treatment/sterilization process does not appear to influence bone graft stiffness. However, strength and energy dissipation of the bone grafts were found to be significantly reduced by 36% to 47% and 66% to 81%, respectively, for a broad range of volume fraction (0.14 < BV/TV < 0.39) and degree of anisotropy (1.24 < DA < 2.18). Since the latter properties are strongly dominated by BV/TV, the clinical consequences of this reduction can be compensated by using grafts with lower porosity. The data of this study suggests that an increase of 5–10% in BV/TV is sufficient to compensate for the reduced post-yield mechanical properties of treated/sterilized bone in monotonic compression. In applications where graft stiffness needs to be matched and strength is not a concern, treated allograft with the same BV/TV as an appropriate fresh bone graft may be used.

Finite element analysis for prediction of bone strength

Article preview View full access options BoneKEy Reports | Review Print Email Share/bookmark Finite element analysis for prediction of bone strength Philippe K Zysset, Enrico Dall'Ara, Peter Varga & Dieter H Pahr Affiliations Corresponding author BoneKEy Reports (2013) 2, Article number: 386 (2013) doi:10.1038/bonekey.2013.120 Received 03 January 2013 Accepted 25 June 2013 Published online 07 August 2013 Article tools Citation Reprints Rights & permissions Abstract Abstract• References• Author information Finite element (FE) analysis has been applied for the past 40 years to simulate the mechanical behavior of bone. Although several validation studies have been performed on specific anatomical sites and load cases, this study aims to review the predictability of human bone strength at the three major osteoporotic fracture sites quantified in recently completed in vitro studies at our former institute. Specifically, the performance of FE analysis based on clinical computer tomography (QCT) is compared with the ones of the current densitometric standards, bone mineral content, bone mineral density (BMD) and areal BMD (aBMD). Clinical fractures were produced in monotonic axial compression of the distal radii, vertebral sections and in side loading of the proximal femora. QCT-based FE models of the three bones were developed to simulate as closely as possible the boundary conditions of each experiment. For all sites, the FE methodology exhibited the lowest errors and the highest correlations in predicting the experimental bone strength. Likely due to the improved CT image resolution, the quality of the FE prediction in the peripheral skeleton using high-resolution peripheral CT was superior to that in the axial skeleton with whole-body QCT. Because of its projective and scalar nature, the performance of aBMD in predicting bone strength depended on loading mode and was significantly inferior to FE in axial compression of radial or vertebral sections but not significantly inferior to FE in side loading of the femur. Considering the cumulated evidence from the published validation studies, it is concluded that FE models provide the most reliable surrogates of bone strength at any of the three fracture sites.

Computational and experimental methodology for site-matched investigations of the influence of mineral mass fraction and collagen orientation on the axial indentation modulus of lamellar bone

Relationships between mineralization, collagen orientation and indentation modulus were investigated in bone structural units from the mid-shaft of human femora using a site-matched design. Mineral mass fraction, collagen fibril angle and indentation moduli were measured in registered anatomical sites using backscattered electron imaging, polarized light microscopy and nano-indentation, respectively. Theoretical indentation moduli were calculated with a homogenization model from the quantified mineral densities and mean collagen fibril orientations. The average indentation moduli predicted based on local mineralization and collagen fibers arrangement were not significantly different from the average measured experimentally with nanoindentation (p=0.9). Surprisingly, no substantial correlation of the measured indentation moduli with tissue mineralization and/or collagen fiber arrangement was found. Nano-porosity, micro-damage, collagen cross-links, non-collagenous proteins or other parameters affect the indentation measurements. Additional testing/simulation methods need to be considered to properly understand the variability of indentation moduli, beyond the mineralization and collagen arrangement in bone structural units.

HGF Expressing Stem Cells in Usual Interstitial Pneumonia Originate from the Bone Marrow and Are Antifibrotic

BACKGROUND Pulmonary fibrosis may result from abnormal alveolar wound repair after injury. Hepatocyte growth factor (HGF) improves alveolar epithelial wound repair in the lung. Stem cells were shown to play a major role in lung injury, repair and fibrosis. We studied the presence, origin and antifibrotic properties of HGF-expressing stem cells in usual interstitial pneumonia. METHODS Immunohistochemistry was performed in lung tissue sections and primary alveolar epithelial cells obtained from patients with usual interstitial pneumonia (UIP, n = 7). Bone marrow derived stromal cells (BMSC) from adult male rats were transfected with HGF, instilled intratracheally into bleomycin injured rat lungs and analyzed 7 and 14 days later. RESULTS In UIP, HGF was expressed in specific cells mainly located in fibrotic areas close to the hyperplastic alveolar epithelium. HGF-positive cells showed strong co-staining for the mesenchymal stem cell markers CD44, CD29, CD105 and CD90, indicating stem cell origin. HGF-positive cells also co-stained for CXCR4 (HGF+/CXCR4+) indicating that they originate from the bone marrow. The stem cell characteristics were confirmed in HGF secreting cells isolated from UIP lung biopsies. In vivo experiments showed that HGF-expressing BMSC attenuated bleomycin induced pulmonary fibrosis in the rat, indicating a beneficial role of bone marrow derived, HGF secreting stem cells in lung fibrosis. CONCLUSIONS HGF-positive stem cells are present in human fibrotic lung tissue (UIP) and originate from the bone marrow. Since HGF-transfected BMSC reduce bleomycin induced lung fibrosis in the bleomycin lung injury and fibrosis model, we assume that HGF-expressing, bone-marrow derived stem cells in UIP have antifibrotic properties.

Bone mineral density (BMD) and computer tomographic measurements of the equine proximal phalanx in correlation with breaking strength

Despite the fact that bone mineral density (BMD) is an important fracture risk predictor in human medicine, studies in equine orthopedic research are still lacking. We hypothesized that BMD correlates with bone failure and fatigue fractures of this bone. Thus, the objectives of this study were to measure the structural and mechanical properties of the proximal phalanx with dual energy X-ray absorptiometry (DXA), to correlate the data obtained from DXA and computer tomography (CT) measurements to those obtained by loading pressure examination and to establish representative region of interest (ROI) for in vitro BMD measurements of the equine proximal phalanx for predicting bone failure force. DXA was used to measure the whole bone BMD and additional three ROI sites in 14 equine proximal phalanges. Following evaluation of the bone density, whole bone, cortical width and area in the mid-diaphyseal plane were measured on CT images. Bones were broken using a manually controlled universal bone crusher to measure bone failure force and reevaluated for the site of fractures on follow-up CT images. Compressive load was applied at a constant displacement rate of 2 mm/min until failure, defined as the first clear drop in the load measurement. The lowest BMD was measured at the trabecular region (mean +/- SD: 1.52 +/- 0.12 g/cm2; median: 1.48 g/cm2; range: 1.38-1.83 g/cm2). There was a significant positive linear correlation between trabelcular BMD and the breaking strength (P = 0.023, r = 0.62). The trabecular region of the proximal phalanx appears to be the only significant indicator of failure of strength in vitro. This finding should be reassessed to further reveal the prognostic value of trabecular BMD in an in vivo fracture risk model.

Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression.

BACKGROUND: It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis. METHODS: We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression. RESULTS: No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does.

CT dose and image quality in the last three scanner generations.

AIM To compare the computed tomography (CT) dose and image quality with the filtered back projection against the iterative reconstruction and CT with a minimal electronic noise detector. METHODS A lung phantom (Chest Phantom N1 by Kyoto Kagaku) was scanned with 3 different CT scanners: the Somatom Sensation, the Definition Flash and the Definition Edge (all from Siemens, Erlangen, Germany). The scan parameters were identical to the Siemens presetting for THORAX ROUTINE (scan length 35 cm and FOV 33 cm). Nine different exposition levels were examined (reference mAs/peek voltage): 100/120, 100/100, 100/80, 50/120, 50/100, 50/80, 25/120, 25/100 and 25 mAs/80 kVp. Images from the SOMATOM Sensation were reconstructed using classic filtered back projection. Iterative reconstruction (SAFIRE, level 3) was performed for the two other scanners. A Stellar detector was used with the Somatom Definition Edge. The CT doses were represented by the dose length products (DLPs) (mGycm) provided by the scanners. Signal, contrast, noise and subjective image quality were recorded by two different radiologists with 10 and 3 years of experience in chest CT radiology. To determine the average dose reduction between two scanners, the integral of the dose difference was calculated from the lowest to the highest noise level. RESULTS When using iterative reconstruction (IR) instead of filtered back projection (FBP), the average dose reduction was 30%, 52% and 80% for bone, soft tissue and air, respectively, for the same image quality (P < 0.0001). The recently introduced Stellar detector (Sd) lowered the radiation dose by an additional 27%, 54% and 70% for bone, soft tissue and air, respectively (P < 0.0001). The benefit of dose reduction was larger at lower dose levels. With the same radiation dose, an average of 34% (22%-37%) and 25% (13%-46%) more contrast to noise was achieved by changing from FBP to IR and from IR to Sd, respectively. For the same contrast to noise level, an average of 59% (46%-71%) and 51% (38%-68%) dose reduction was produced for IR and Sd, respectively. For the same subjective image quality, the dose could be reduced by 25% (2%-42%) and 44% (33%-54%) using IR and Sd, respectively. CONCLUSION This study showed an average dose reduction between 27% and 70% for the new Stellar detector, which is equivalent to using IR instead of FBP.