Irregular Contour of Inner Ear Structures and Hypomineralized Areas at Otic Capsule: Are They Other Additional Imaging Findings of Incomplete Partition-III?

PURPOSE: Incomplete partition III (IP-III) characterized by congenital mixed or sensorineural hearing loss is a rare genetic disease transmitted through X-linked inheritance. Incomplete partition III can be easily achieved based on pathognomonic computed tomography findings. The aims of this study were to investigate the otic capsule abnormalities in IP-III and to report irregular contour of membranous labyrinth and hypomineralized areas at otic capsule, which have not previously been described. MATERIALS AND METHODS: The otic capsule features of 10 subjects (8 affected patients, 1 of whom is a female; 2 carrier mothers), who were diagnosed on clinical and typical radiologic findings, were analyzed. RESULTS: All patients had typical IP-III as described in the literature. Seven of 10 patients had irregular contour. Seven of 10 patients demonstrated hypomineralized areas, which were very hypodense to normally develop otic capsule areas. One affected patients and 2 carrier mothers had a normal-looking membranous labyrinth contour and normal mineralization at otic capsule. CONCLUSIONS: We report for the first time the irregular contour of inner ear structures and hypodense otic capsule areas in patients with IP-III. We think that though speculative, abnormal development of the inner endosteal layer results in irregular contour of inner ear structures. Hypomineralized areas at otic capsule could be explained by abnormal development of middle enchondral layer due to reduced or absent vascular supply from middle ear mucosa during fetal life. These findings may be accepted as additional criteria of IP-III.

Hearing impairment and osteogenesis imperfecta: Literature review.

The goal is to clarify the epidemiology of hearing loss in patients with osteogenesis imperfecta (OI), so as to improve management. A literature review analyzed data from 15 patient series. Hearing loss prevalence in OI varied widely, from 2% to 94.1%. Typically, hearing loss was conductive in young patients and sensorineural in older patients. Prevalence increased with age, but after 50 years the increase was slight, and seldom became total. Hearing loss was usually bilateral, but not necessarily symmetrical. There were no correlations between type of mutation (COL1A1 or COL1A2), prevalence, type or severity of hearing loss, or age of symptom onset; there was intra-familial variability. There was also no correlation between mutated gene, type of mutation and auditory phenotype. Frequency, type and severity of hearing loss were unrelated to other clinical parameters. Hearing loss prevalence depended on type of OI: higher in type I and lower in type IV. Incidence of otitis media was higher in children with OI, related to the associated craniofacial dysmorphia. Hearing screening before 5 years of age with long-term follow-up are recommended.

Asfotase alfa treatment for 1 year in a 16 year-old male with severe childhood hypophosphatasia.

We describe the clinical outcome of asfotase alfa therapy in a 16-year-old boy with severe childhood hypophosphatasia (HPP), who began therapy at age 15 years. The patient was diagnosed with HPP at age 2 years when he presented with genu varum and premature loss of primary teeth. He had a history of multiple fractures requiring 16 orthopedic surgeries with rod and pin placement in his lower extremities. He had chronic skeletal pain and used cane to ambulate with great difficulty. His height Z score at age 15 years was - 5. He had severe scoliosis and deformity of both legs. Bone radiograph showed hypomineralization and characteristic "tongues" of radiolucency in the distal radius and ulna. His serum alkaline phosphatase level was stable, with elevated serum pyridoxal 5'-phosphate and urine phosphoethanolamine, consistent with HPP. He was started on asfotase alfa 2 mg/kg given subcutaneously thrice weekly. He had marked clinical improvement in mobility with no report of pain after 3 months of treatment. At 6 month, he walked without cane and participated in outdoor activities with peers. Bone radiograph at 6 months showed striking improvement in previous radiolucent areas. At 9 months, his annualized growth velocity was 9.5 cm/year, while growth velocity of arm span was 12 cm/year. However, at 12 months, he was noted to have worsening scoliosis from 60 degrees before therapy to 110 degrees, with a slight decrease in height, necessitating a spinal fusion surgery. In conclusion, treatment with asfotase alfa significantly improved physical function, pain, overall quality of life, and skeletal radiographic findings in this patient. Close monitoring for progression of scoliosis in adolescents with HPP treated with asfotase alfa is recommended.

Ultrasound Characterization of Bone Demineralization Using a Support Vector Machine.

We propose an ultrasound-guided remote measurement technique, utilizing an acoustic radiation force beam as our excitation source and a receiving hydrophone, to assess non-invasively a bone's mechanical properties. Features, such as velocity, were extracted from the acoustic pressure received from the bone surface. The typical velocity of an intact bone (3540 m/s) was higher in comparison to that of a demineralized bone (2231 m/s). According to the receiver operating characteristic curve, the optimal velocity cutoff value of ≥3096 m/s yields 80% sensitivity and 82.61% specificity between intact and demineralized bone. Utilizing a support vector machine, the hours of bone demineralization were successfully classified with maximum accuracy >80% using 18% training data. The results indicate the potential application of our proposed technique and support vector machine for monitoring bone mechanical properties.

Bone mineralization and densitometric evaluation of vertebral fractures in women 6-21 years after the onset of anorexia nervosa symptoms. / Mineralizacja kosci i ocena densytometryczna zlaman kregoslupa u kobiet po uplywie 6­21 lat od pojawienia sie objawów jadlowstretu psychicznego.

OBJECTIVES: We attempted to assess bone mineralization and the frequency of fractures occurrence in women with a history of treatment of anorexia nervosa (AN) in adolescence. METHODS: 47 women (age 20-36.8 years) were re-examined 6.33-21,2 years after the onset of AN symptoms. Bone mineral density (BMD) of total body, lumbar spine, femoral neck, total hip (DXA) and densitometric Vertebral Fracture Assessment (VFA) were performed on 46 of women and BAP, P1NP, CTX, estradiol, testosterone, cortisol, IGF-1, leptin, DHEA-S on 45 of women entered for the current study. Current BMD results were compared with available baseline results from the time of hospitalization. RESULTS: Currently BMD Z-score <-1 examined at any location occurred in 28 from 46 women (including Z-score <-2 in 5 women). In 11 from 12 women with reduced BMD at the time of hospitalization current total body BMD was within the normal range. Lumbar spine BMD was normalized or improved respectively in 5 and 6 from 15 women. Currently increased levels/activity of bone formation markers: P1NP in 27 (60%) and BAP in 28 women (62.2%) were observed. In 7 women (15.6%) increased values of bone formation markers with increased marker of bone resorption (CTX) occurred. Osteoporotic fractures and fractures in the spine in VFA were not observed during the observation period. CONCLUSIONS: Despite early treatment of adolescent-onset AN and good outcomes of the treatment, decreased BMD was currently present in 60.9% of women. During follow-up normalization or significant improvement in BMD results (total body, lumbar spine) were observed in majority of cases.

Bone mineral density loss in clinically suspect arthralgia is associated with subclinical inflammation and progression to clinical arthritis.

OBJECTIVE: Peripheral bone mineral density (BMD) may be decreased in early rheumatoid arthritis (RA) but it is unknown whether BMD loss emerges before arthritis is clinically apparent. We aimed to study whether BMD loss occurs in patients with clinically suspect arthralgia (CSA), and whether it is associated with progression to clinical arthritis and magnetic resonance imaging (MRI)-detected subclinical inflammation. METHOD: Patients with CSA had arthralgia for <1 year and were at risk of progressing to RA according to their rheumatologists. At baseline, a 1.5 T MRI was performed of unilateral metacarpophalangeal, wrist, and metatarsophalangeal joints, and scored on synovitis, bone marrow oedema, and tenosynovitis;. summing these features yielded the total MRI inflammation score. Digital X-ray radiogrammetry (DXR) was used to estimate BMD on two sequential conventional hand radiographs (mean interval between radiographs 4.4 months). The change in BMD was studied; BMD loss was defined as a decrease of ≥2.5 mg/cm2/month. Patients were followed for arthritis development for a median of 18.4 months. RESULTS: In CSA patients (n = 108), change in BMD was negatively associated with age (ß = -0.03, p = 0.007). BMD loss in CSA patients was associated with arthritis development [adjusted for age hazard ratio (HR) = 6.1, 95% confidence interval (CI) 1.7 to 21.4] and was most frequently estimated in the months before clinical arthritis development. The total MRI inflammation scores were associated with the change in BMD (adjusted for age ß = -0.05, p = 0.047). The total MRI inflammation score and BMD loss were both independently associated with arthritis development (HR = 1.1, 95% CI 1.1 to 1.2, and HR = 4.6, 95% CI 1.2 to 17.2, respectively). CONCLUSION: In CSA patients, severe BMD loss is associated with MRI-detectable subclinical inflammation and with progression to clinical arthritis.

Bone demineralisation in a large cohort of Wilson disease patients.

AIMS AND BACKGROUND: We compared the bone mineral density (BMD) of adult Wilson disease (WD) patients (n = 148), with an age- and gender-matched healthy control population (n = 148). Within the WD cohort, correlations of BMD with WD disease parameters, lab results, type of treatment and known osteoporosis risk factors were analysed. METHODS: Hip and lumbar spine absolute BMD and T-score were measured by dual-energy X-ray absorptiometry. Osteoporosis and osteopenia were defined as a T-score ≤ -2.5, and between -1 and -2.5, respectively. RESULTS: There were significantly more subjects with abnormal T-scores in the WD population (58.8%) than in the control population (45.3%) (χ(2) = 6.65, df = 2, p = 0.036), as there were 50.0% osteopenic and 8.8% osteoporotic WD patients, vs. 41.2% and 4.1%, respectively, in the controls. Especially L2-L4 spine BMD measurements (BMD and T-scores) differed significantly between the WD population and matched controls. L2-L4 spine BMD for WD patients was on average 0.054 g/cm(2) (5.1%) lower than in matched normal controls (0.995 ± 0.156 vs 1.050 ± 0.135; p = 0.002). We found no significant correlation between BMD values and any of the WD disease parameters (e.g. the severity of liver disease), lab results, type of treatment or known osteoporosis risk factors. Duration of D-penicillamine treatment was negatively correlated with femoral BMD value, but in a clinically irrelevant manner, compared to age and gender. Importantly, BMD remained significantly lower in WD patients (n = 89) vs. controls after excluding WD patients with cirrhosis (p = 0.009). CONCLUSIONS: Our study suggests that WD is intrinsically associated with bone demineralisation.

Pulsed focused ultrasound treatment of muscle mitigates paralysis-induced bone loss in the adjacent bone: a study in a mouse model.

Bone loss can result from bed rest, space flight, spinal cord injury or age-related hormonal changes. Current bone loss mitigation techniques include pharmaceutical interventions, exercise, pulsed ultrasound targeted to bone and whole body vibration. In this study, we attempted to mitigate paralysis-induced bone loss by applying focused ultrasound to the midbelly of a paralyzed muscle. We employed a mouse model of disuse that uses onabotulinumtoxinA-induced paralysis, which causes rapid bone loss in 5 d. A focused 2 MHz transducer applied pulsed exposures with pulse repetition frequency mimicking that of motor neuron firing during walking (80 Hz), standing (20 Hz), or the standard pulsed ultrasound frequency used in fracture healing (1 kHz). Exposures were applied daily to calf muscle for 4 consecutive d. Trabecular bone changes were characterized using micro-computed tomography. Our results indicated that application of certain focused pulsed ultrasound parameters was able to mitigate some of the paralysis-induced bone loss.

Bone density in haemophilia: a single institutional cross-sectional study.

Haemophilia has been associated with low bone mineral density (BMD). However, prior clinical studies of this population have neither clearly elucidated risk factors for development of low BMD nor identified who may warrant screening for osteoporosis. The aim of the study was to evaluate the relationship between BMD and haemophilic arthropathy and other demographic and clinical variables. We undertook a cross-sectional study of BMD in adult men with haemophilia. Measures of predictor variables were collected by radiographic studies, physical examination, patient questionnaires and review of medical records. Among 88 enrolled subjects, the median age was 41 years (IQR: 20); median femoral neck BMD (n = 87) was 0.90 g cm(-2) (IQR: 0.24); and median radiographic joint score was 7.5 (IQR: 18). Among subjects <50 years (n = 62), after controlling for BMI, alcohol, HIV and White race, BMD decreased as radiographic joint score increased (est. ß = -0.006 mg cm(-2) ; 95% CI -0.009, -0.003; partial R(2) = 0.23). Among subjects ≥50 years (n = 26), 38% had osteoporosis (T score less than or equal to -2.5) and there was no association between BMD and arthropathy. Risk factors for low BMD in men with haemophilia <50 years include haemophilic arthropathy, low or normal BMI and HIV. Men with haemophilia over age 50 years should have routine screening for detection of osteoporosis.

Anatomo-radiological study of the superior semicircular canal dehiscence of 37 cadaver temporal bones.

PURPOSE: To assess the presence of dehiscence of the superior semicircular canal (SSCC) on computed tomography (CT) scanning and to study the microscopic anatomo-radiological correlation. MATERIALS AND METHODS: Thirty-seven temporal bones preserved in formalin, regardless of the clinical history of cadavers, were studied. A microscopic anatomical study was conducted with an operative microscope (20×). The settings of the CT permitted to obtain 0.6 mm slices contiguous reconstruction in Pöschl plane and in Stenvers plane. Three-dimensional (3D) reconstructions were performed if a radiological dehiscence was observed. The apex thickness was measured in Pöschl plane. The radiological positive criterion of SSCC dehiscence was an absence of bone coverage of more than 1 mm long in Pöschl and Stenvers planes. RESULTS: We observed three dehiscences of the 37 temporal bones on CT in Pöschl and Stenvers planes. However, no dehiscence was found microscopically. The 3D reconstruction was also positive in these three cases. Reconstructions in the Pöschl plane offered good results up to a bone thickness of 0.6 mm. When it was lower than 0.6 mm, the interpretation of the images appeared to be subjective. CONCLUSION: This study emphasizes the limitations of CT imaging, with a risk of false positives to take into account when interpreting the images. The 3D reconstructions also give too many false positives to be used alone and make an accurate diagnosis. The diagnosis of SSCC dehiscence will therefore remain clinical. Complementary and instrumental radiological examinations should be performed only to confirm this clinical suspicion.

Mandibular bone changes in 24 years and skeletal fracture prediction.

OBJECTIVES: The objectives of the investigation were to describe changes in mandibular bone structure with aging and to compare the usefulness of cortical and trabecular bone for fracture prediction. MATERIALS AND METHODS: From 1968 to 1993, 1,003 women were examined. With the help of panoramic radiographs, cortex thickness was measured and cortex was categorized as: normal, moderately, or severely eroded. The trabeculation was assessed as sparse, mixed, or dense. RESULTS: Visually, the mandibular compact and trabecular bone transformed gradually during the 24 years. The compact bone became more porous, the intertrabecular spaces increased, and the radiographic image of the trabeculae seemed less mineralized. Cortex thickness increased up to the age of 50 and decreased significantly thereafter. At all examinations, the sparse trabeculation group had more fractures (71-78 %) than the non-sparse group (27-31 %), whereas the severely eroded compact group showed more fractures than the less eroded groups only in 1992/1993, 24 years later. Sparse trabecular pattern was associated with future fractures both in perimenopausal and older women (relative risk (RR), 1.47-4.37) and cortical erosion in older women (RR, 1.35-1.55). RR for future fracture associated with a severely eroded cortex increased to 4.98 for cohort 1930 in 1992/1993. RR for future fracture associated with sparse trabeculation increased to 11.43 for cohort 1922 in 1992/1993. CONCLUSION: Dental radiographs contain enough information to identify women most at risk of future fracture. CLINICAL RELEVANCE: When observing sparse mandibular trabeculation, dentists can identify 40-69 % of women at risk for future fractures, depending on participant age at examination.

Use of X-ray microprobe to diagnose bone tissue demineralization after caffeine administration.

Caffeine is a methylxanthine which permeates the placenta. In studies on animals, it has been shown to produce teratogenic and embryotoxic effects in large doses. The objective of this study was to assess the influence of caffeine on the development of bone tissue, with particular reference to elemental bone composition using an X-ray microprobe. The research was conducted on rats. The fertilized females were randomly divided into an experimental and a control group. The experimental group was given caffeine orally in 30 mg/day doses from the 8th to the 21st day of pregnancy, while the control group was given water. The fetuses were used to assess the growth and mineralization of the skeleton. On the basis of double dyeing, a qualitative analysis of the bone morphology and mineralization was conducted. For calcium and potassium analysis, an X-ray microprobe was used. In 67 fetuses from the experimental group, changes in skeleton staining with the alcian-alizarin method were noticed. The frequency of the development of variants in the experimental group was statistically higher. In the experimental group,a significant decrease in the calcium level, as well as an increase in the potassium level, was observed. The X-ray microprobe's undoubted advantage is that is offers a quick qualitative and quantitative analysis of the elemental composition of the examined samples. Employing this new technique may furnish us with new capabilities when investigating the essence of the pathology process.

Comparison between amputation-induced demineralization and age-related bone loss using digital X-ray radiogrammetry.

Digital X-ray radiogrammetry (DXR) is a computer-assisted automatic osteodensitometric tool. This study was performed to compare DXR measurements between bone changes following amputation trauma and age-related bone loss. Thirty-five men, who had undergone finger amputations, received a baseline examination and 2--3 serial measurements. As a second group, 215 males older than 70yr were enrolled. All patients obtained standardized hand radiographs. The following DXR parameters evaluating metacarpals were considered: cortical bone mineral density (DXR-BMD), cortical thickness (DXR-CT), metacarpal index (DXR-MCI), outer bone diameter (width; DXR-W), and inner medullary diameter (DXR-MD). In the amputation group, the DXR parameters showed an accentuated initial decrease between first and second measurements (DRX-BMD--12.7%, DXR-CT--14.2%, DXR-W--8.6%, DXR-MCI--6.1%; p<0.001) followed by a less pronounced reduction between second and third radiographs (DRX-BMD--0.5%, DXR-CT--1.5%, DXR-W--0.1%, DXR-MCI--1.3%). DXR-MD revealed a reduction of--3.6% (p<0.05) between first and second estimates and a non-significant increase (+1.1%) between second and third measurements. When compared with the second and third estimates in the amputation group, men older than 70yr presented lower DXR-BMD, DXR-CT, and DXR-MCI values (p<0.001), but larger metacarpal outer and inner bone diameters (DXR-W and DXR-MD; p<0.001). DXR-MD of the elderly men group was also more extended when compared with the baseline measurements of the amputation cohort (p<0.001). The early accentuated cortical bone loss and particularly the pronounced decrease of the outer bone width seem to be characteristic for amputation-induced osteoporosis, suggesting that this might be a distinct secondary osteoporosis entity. When compared with amputation-associated osteoporosis, where the bone loss occurs to a higher extent in the outer bone diameter than in the medullary cavity, the age-related bone changes lead more to an increase of the medullary diameter than of the outer bone width.

Bone density and cortical structure after pediatric renal transplantation.

The impact of renal transplantation on trabecular and cortical bone mineral density (BMD) and cortical structure is unknown. We obtained quantitative computed tomography scans of the tibia in pediatric renal transplant recipients at transplantation and 3, 6, and 12 months; 58 recipients completed at least two visits. We used more than 700 reference participants to generate Z-scores for trabecular BMD, cortical BMD, section modulus (a summary measure of cortical dimensions and strength), and muscle and fat area. At baseline, compared with reference participants, renal transplant recipients had significantly lower mean section modulus and muscle area; trabecular BMD was significantly greater than reference participants only in transplant recipients younger than 13 years. After transplantation, trabecular BMD decreased significantly in association with greater glucocorticoid exposure. Cortical BMD increased significantly in association with greater glucocorticoid exposure and greater decreases in parathyroid hormone levels. Muscle and fat area both increased significantly, but section modulus did not improve. At 12 months, transplantation associated with significantly lower section modulus and greater fat area compared with reference participants. Muscle area and cortical BMD did not differ significantly between transplant recipients and reference participants. Trabecular BMD was no longer significantly elevated in younger recipients and was low in older recipients. Pediatric renal transplant associated with persistent deficits in section modulus, despite recovery of muscle, and low trabecular BMD in older recipients. Future studies should determine the implications of these data on fracture risk and identify strategies to improve bone density and structure.

Periprosthetic bone mineral density with a cementless triple tapered stem is dependent on daily activity.

PURPOSE: Periprosthetic bone loss around the femoral stem is frequently found after total hip arthroplasty. We have shown that periprosthetic bone mineral density (BMD) loss using the triple tapered stem is consistently much less in comparison with the straight type component. In this study, we compared periprosthetic BMD change with clinical factors. METHODS: Postoperative dual-energy X-ray absorptiometry was evaluated at follow-up. BMD was determined based on seven Gruen zones. We further compared BMD with clinical examination: body mass index (BMI), age, Harris hip score (HHS) or University of California at Los Angeles (UCLA) activity rating score. RESULTS: Periprosthetic BMD loss of the triple tapered stem was maintained. Especially, BMD in Gruen zone 1 which was maintained at 96% in comparison with the straight tapered stem. We compared the BMD change with clinical factors. There is no correlation between BMD and BMI, age or HHS. However, we found significant correlation between BMD and UCLA activity rating score in Gruen zones 1 and 2 of the triple tapered stem. Further, the correlation coefficient was increased at 48 months in comparison with 24 months. CONCLUSION: The cementless triple tapered stem maintains periprosthetic bone mineral density. Activity may reflect improving periprosthetic bone quality after THA using a triple tapered stem.

Inter-observer reliability of high-resolution ultrasonography in the assessment of bone erosions in patients with rheumatoid arthritis: experience of an intensive dedicated training programme.

OBJECTIVE: The present study was aimed at testing the ability of a rheumatologist without experience in ultrasound (US) who attended an intensive 4-week training programme focused on US assessing bone erosions in the hands and feet in patients with RA. METHODS: Twenty patients diagnosed with RA according to the ACR criteria were included in the study. All US examinations were performed bilaterally by two investigators (with different experience in the field of musculoskeletal US) at the following sites: the dorsal, lateral and volar aspect of the second metacarpal, ulnar and fifth metatarsal head; and the dorsal and volar aspect of the third metacarpal and second proximal heads. Each quadrant was scanning in longitudinal and transverse scans for assessing the qualitative, semiquantitative and quantitative US findings indicative of bone erosions according the OMERACT preliminary definition. RESULTS: Both κ-values and overall agreement percentages of qualitative and semiquantitative assessments showed moderate to excellent agreement between the two investigators. Similar results were obtained for the quantitative assessment with the concordance correlation coefficient value always significant. The only exception was the volar aspects, in particular those of the fifth metatarsal head. CONCLUSION: Our study suggests that after a 4-week dedicated training programme, a rheumatologist without experience in US is able to detect and score bone erosions in the hands and feet of patients with RA.

Bone demineralization in the lumbar spine of dogs submitted to prednisone therapy.

Glucocorticoids are drugs widely used in veterinary medicine; however, besides their clinical benefits, their use can trigger undesirable effects. A clinical trial was performed on eight healthy dogs with the intent of evaluating possible alterations in the bone mineral density after therapy with prednisone using a helical computed tomography. All animals received prednisone orally at a dose of 2 mg/kg of weight for 30 days. The bone mineral density was determined by obtaining the vertebral body radiodensity of the second lumbar vertebra values immediately before and after the administration of the medication. The experimental protocol allowed for the characterization of a significant (P < 0.01) reduction of the vertebral body radiodensity of the second lumbar vertebra. At the end of the experiment, it was characterized by a loss of bone mass of approximately 14%. None of the animals presented pathologic fracture at the end of the administration of the medication. This study verified that the alterations in the bone metabolism of the dogs submitted to the therapy with prednisone in a dosage of 2 mg/kg occur rapidly, which recommends a monitoring of the patients for the prevention of pathologic fractures.

[Hepatic osteodystrophy in patients with liver cirrhosis].

The article presents research data of BMD in 106 patients with liver cirrhosis. The core group of examined patients presented with LC patients the etiology of alcohol--37.7% and primary biliary cirrhosis--35.8%. In 68.9% of patients with established deficits of bone mineral density, by 24.6%--at the level of osteoporosis. Was detected influence of the etiology of the disease on the frequency of osteopenia and osteoporosis containment. Was made analysis of dependence of the frequency of osteopenia, and/or osteoporosis of population risk factors, duration of disease, grade of liver failure on the Child-Pugh. A comparative assessment of the effectiveness treatment of disorders of BMD active metabolite of vitamin D3--alpha caltsidol and drugs from the group of bisphosphonates.