Estimation of sex and age of "virtual skeletons"--a feasibility study

This article presents a feasibility study with the objective of investigating the potential of multi-detector computed tomography (MDCT) to estimate the bone age and sex of deceased persons. To obtain virtual skeletons, the bodies of 22 deceased persons with known age at death were scanned by MDCT using a special protocol that consisted of high-resolution imaging of the skull, shoulder girdle (including the upper half of the humeri), the symphysis pubis and the upper halves of the femora. Bone and soft-tissue reconstructions were performed in two and three dimensions. The resulting data were investigated by three anthropologists with different professional experience. Sex was determined by investigating three-dimensional models of the skull and pelvis. As a basic orientation for the age estimation, the complex method according to Nemeskéri and co-workers was applied. The final estimation was effected using additional parameters like the state of dentition, degeneration of the spine, etc., which where chosen individually by the three observers according to their experience. The results of the study show that the estimation of sex and age is possible by the use of MDCT. Virtual skeletons present an ideal collection for anthropological studies, because they are obtained in a non-invasive way and can be investigated ad infinitum.

Growth hormone (GH) deficiency type II: a novel GH-1 gene mutation (GH-R178H) affecting secretion and action

Context and Objective: Main features of the autosomal dominant form of GH deficiency (IGHD II) include markedly reduced secretion of GH combined with low concentrations of IGF-I leading to short stature. Design, Setting, and Patients: A female patient presented with short stature (height -6.0 sd score) and a delayed bone age of 2 yr at the chronological age of 5 yr. Later, at the age of 9 yr, GHD was confirmed by standard GH provocation test, which revealed subnormal concentrations of GH and a very low IGF-I. Genetic analysis of the GH-1 gene revealed the presence of a heterozygous R178H mutation. Interventions and Results: AtT-20 cells coexpressing both wt-GH and GH-R178H showed a reduced GH secretion after forskolin stimulation compared with the cells expressing only wt-GH, supporting the diagnosis of IGHD II. Because reduced GH concentrations found in the circulation of our untreated patient could not totally explain her severe short stature, functional characterization of the GH-R178H performed by studies of GH receptor binding and activation of the Janus kinase-2/signal transducer and activator of transcription-5 pathway revealed a reduced binding affinity of GH-R178H for GH receptor and signaling compared with the wt-GH. Conclusion: This is the first report of a patient suffering from short stature caused by a GH-1 gene alteration affecting not only GH secretion (IGHD II) but also GH binding and signaling, highlighting the necessity of functional analysis of any GH variant, even in the alleged situation of IGHD II.

[Follow-up in a boy with Leydig cell tumor after selective surgery]

A 8(6/12) year-old-boy presented with precocious puberty and a slightly enlarged left testis. After a detailed examination a Leydig cell tumour was diagnosed. Surgical exploration revealed an encapsulated tumour, 2.7 cm in length, which was selectively removed without orchidectomy. Within one year the clinical signs of pubertal precocity disappeared, the bone age did not further advance and height velocity declined from 8.2 cm / year (+3.9 SDS) to 4.1 cm/year (-1.0 SDS). Physiologically, he entered puberty at the chronological age of twelve years, presenting at that age, in comparison to his peer group, a slightly decreased pubertal growth spurt. However, bearing in mind that being precocious in puberty he started in fact his pubertal growth spurt at a far earlier age, therefore, this acceleration of height before operation has to be added to the centimetres gained during pubertal development thereafter resuiting consequently in an absolute normal pubertal growth spurt. This underlines the fact that the individual growth spurt and, therefore, the total amount of centimetres gained is very much robust. Ten years later, the patient ended up well within his familial target height and remained free of disease. We report on a long-term follow-up of a prepubertal boy after testis-sparing surgery for Leydig-cell-tumour.

Catch-up growth in autosomal dominant isolated growth hormone deficiency (IGHD type II)

OBJECTIVE: Data on the GH-induced catch-up growth of severely GH-deficient children affected by monogenetic defects are missing. PATIENTS: Catch-up growth of 21 prepubertal children (6 females, 15 males) affected with IGHD type II was analyzed in a retrospective chart review. At start of therapy, mean age was 6.2 years (range, 1.6-15.0), mean height SDS was -4.7 (-7.6 to -2.2), mean IGF-I SDS was -6.2 (-10.1 to -2.2). GH was substituted using a mean dose of 30.5microg/kg*d. RESULTS: Catch-up growth was characterized by a mean height gain of +0.92, +0.82, and +0.61 SDS after 1, 2, and 3 years of GH therapy, respectively. Mean height velocities were 10.7, 9.2 and 7.7cm/year during the first three years. Mean duration of complete catch-up growth was 6 years (3-9). Mean height SDS reached was -0.97 (-2.3 to +1.1), which was within the range of the estimated target height of -0.60 SDS (-1.20 to -0.15). The younger and shorter the children were at start of therapy the better they grew during the first year independent of the dose. Mean bone age was delayed at start by 2.1 years and progressed by 2.5 years during the first two years of therapy. Incomplete catch-up growth was caused by late initiation or irregular administration of GH in four cases. CONCLUSIONS: Our data suggest that GH-treated children with severe IGHD show a sustained catch-up growth over 6 years (mean) and reach their target height range. This response to GH is considered to be characteristic for young children with severe growth retardation due to IGHD.

Topographic and age-dependent distribution of subchondral bone density in the elbow joints of clinically normal dogs

OBJECTIVE: To investigate topographic and age-dependent adaptation of subchondral bone density in the elbow joints of healthy dogs by means of computed tomographic osteoabsorptiometry (CTOAM). Animals-42 elbow joints of 29 clinically normal dogs of various breeds and ages. PROCEDURES: Subchondral bone densities of the humeral, radial, and ulnar joint surfaces of the elbow relative to a water-hydroxyapatite phantom were assessed by means of CTOAM. Distribution patterns in juvenile, adult, and geriatric dogs (age, < 1 year, 1 to 8 years, and > 8 years, respectively) were determined and compared within and among groups. RESULTS: An area of increased subchondral bone density was detected in the humerus distomedially and cranially on the trochlea and in the olecranon fossa. The ulna had maximum bone densities on the anconeal and medial coronoid processes. Increased bone density was detected in the craniomedial region of the joint surface of the radius. A significant age-dependent increase in subchondral bone density was revealed in elbow joint surfaces of the radius, ulna, and humerus. Mean subchondral bone density of the radius was significantly less than that of the ulna in paired comparisons for all dogs combined and in adult and geriatric, but not juvenile, dog groups. CONCLUSIONS AND CLINICAL RELEVANCE: An age-dependent increase in subchondral bone density at the elbow joint was revealed. Maximal relative subchondral bone densities were detected consistently at the medial coronoid process and central aspect of the humeral trochlea, regions that are commonly affected in dogs with elbow dysplasia.

Prediction of hip fracture risk by quantitative ultrasound in more than 7000 Swiss women > or =70 years of age: comparison of three technologically different bone ultrasound devices in the SEMOF study

To compare the prediction of hip fracture risk of several bone ultrasounds (QUS), 7062 Swiss women > or =70 years of age were measured with three QUSs (two of the heel, one of the phalanges). Heel QUSs were both predictive of hip fracture risk, whereas the phalanges QUS was not. INTRODUCTION: As the number of hip fracture is expected to increase during these next decades, it is important to develop strategies to detect subjects at risk. Quantitative bone ultrasound (QUS), an ionizing radiation-free method, which is transportable, could be interesting for this purpose. MATERIALS AND METHODS: The Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk (SEMOF) study is a multicenter cohort study, which compared three QUSs for the assessment of hip fracture risk in a sample of 7609 elderly ambulatory women > or =70 years of age. Two QUSs measured the heel (Achilles+; GE-Lunar and Sahara; Hologic), and one measured the heel (DBM Sonic 1200; IGEA). The Cox proportional hazards regression was used to estimate the hazard of the first hip fracture, adjusted for age, BMI, and center, and the area under the ROC curves were calculated to compare the devices and their parameters. RESULTS: From the 7609 women who were included in the study, 7062 women 75.2 +/- 3.1 (SD) years of age were prospectively followed for 2.9 +/- 0.8 years. Eighty women reported a hip fracture. A decrease by 1 SD of the QUS variables corresponded to an increase of the hip fracture risk from 2.3 (95% CI, 1.7, 3.1) to 2.6 (95% CI, 1.9, 3.4) for the three variables of Achilles+ and from 2.2 (95% CI, 1.7, 3.0) to 2.4 (95% CI, 1.8, 3.2) for the three variables of Sahara. Risk gradients did not differ significantly among the variables of the two heel QUS devices. On the other hand, the phalanges QUS (DBM Sonic 1200) was not predictive of hip fracture risk, with an adjusted hazard risk of 1.2 (95% CI, 0.9, 1.5), even after reanalysis of the digitalized data and using different cut-off levels (1700 or 1570 m/s). CONCLUSIONS: In this elderly women population, heel QUS devices were both predictive of hip fracture risk, whereas the phalanges QUS device was not.

Effect of animal species and age on plate-induced vascular damage in cortical bone

Plates used for fracture fixation produce vascular injury to the underlying cortical bone. During the recovery of the blood supply, temporary osteoporosis is observed as a result of Haversian remodeling of the necrotic bone. This process temporarily reduces the strength of the bone. We tackled the postulate that quantitative differences exist between animal species, and in different bones within the same species, due to variations in the relative importance of the endosteal and periosteal blood supplies. Using implants scaled to the size of the bone, we found comparable cortical vascular damage in the sheep and in the dog, and in the tibia and femur of each animal. We observed a significant reduction in cortical vascular damage using plates that had a smaller contact area with the underlying bone. No significant difference in cortical vascular damage was noted in animals of different ages.

ChronOS Inject in Children with Benign Bone Lesions – Does It Increase the Healing Rate?

Benign bone lesions in children although rare, can result in a pathological fracture. Although their etiology and pathogenesis are not yet entirely clear, the phenomenon of spontaneous healing is well known. Nevertheless, some benign bone lesions are unlikely to heal spontaneously due to the patient's age or high risk of fracture and deformity due to the lesion's location or size. The following study presents our results after treatment of these bone cysts with chronOS Inject.

Reduced muscle mass and bone size in pediatric patients with inflammatory bowel disease

BACKGROUND: Decreased bone mineral density has been reported in children with inflammatory bowel disease (IBD). We used peripheral quantitative computed tomography (pQCT) to assess bone mineralization, geometry, and muscle cross-sectional area (CSA) in pediatric IBD. METHODS: In a cross-sectional study, pQCT of the forearm was applied in 143 IBD patients (mean age 13.9 +/- 3.5 years); 29% were newly diagnosed, 98 had Crohn's disease, and 45 had ulcerative colitis. Auxological data, cumulative glucocorticoid dose, disease activity indices, laboratory markers for inflammation, and bone metabolism were related to the results of pQCT. RESULTS: Patients were compromised in height (-0.82 +/- 1.1 SD), weight (-0.77 +/- 1.0 SD), muscle mass (-1.12 +/- 1.0 SD), and total bone cross-sectional area (-0.79 +/- 1.0 SD) compared to age- and sex-matched healthy controls (z-scores). In newly diagnosed patients, the ratio of bone mineral mass per muscle CSA was higher than in those with longer disease duration (1.00 versus 0.30, P = 0.007). Serum albumin level and disease activity correlated with muscle mass, accounting for 41.0% of variability in muscle mass (P < 0.01). The trabecular bone mineral density z-score was on average at the lower normal level (-0.40 +/- 1.3 SD, P < 0.05). CONCLUSIONS: Reduced bone geometry was explained only in part by reduced height. Bone disease in children with IBD seems to be secondary to muscle wasting, which is already present at diagnosis. With longer disease duration, bone adapts to the lower muscle CSA. Serum albumin concentration is a good marker for muscle wasting and abnormal bone development.

A 10-year retrospective analysis of radiographic bone-level changes of implants supporting single-unit crowns in periodontally compromised vs. periodontally healthy patients

AIM: To compare the 10-year peri-implant bone loss (BL) rate in periodontally compromised (PCP) and periodontally healthy patients (PHP) around two different implant systems supporting single-unit crowns. MATERIALS AND METHODS: In this retrospective, controlled study, the mean BL (mBL) rate around dental implants placed in four groups of 20 non-smokers was evaluated after a follow-up of 10 years. Two groups of patients treated for periodontitis (PCP) and two groups of PHP were created. For each category (PCP and PHP), two different types of implant had been selected. The mBL was calculated by subtracting the radiographic bone levels at the time of crown cementation from the bone levels at the 10-year follow-up. RESULTS: The mean age, mean full-mouth plaque and full-mouth bleeding scores and implant location were similar between the four groups. Implant survival rates ranged between 85% and 95%, without statistically significant differences (P>0.05) between groups. For both implant systems, PCP showed statistically significantly higher mBL rates and number of sites with BL> or =3 mm compared with PHP (P<0.0001). CONCLUSIONS: After 10 years, implants in PCP yielded lower survival rates and higher mean marginal BL rates compared with those of implants placed in PHP. These results were independent of the implant system used or the healing modality applied.

Obesity, age, sex, diagnosis, and fixation mode differently affect early cup failure in total hip arthroplasty: a matched case-control study of 4420 patients

Studies about the influence of patient characteristics on mechanical failure of cups in total hip replacement have applied different methodologies and revealed inconclusive results. The fixation mode has rarely been investigated. Therefore, we conducted a detailed analysis of the influence of patient characteristics and fixation mode on cup failure risks.

Abnormal bone geometry at the metacarpal bone shaft of rheumatoid arthritis patients with maintained muscle-bone relationship

OBJECTIVES:: Metacarpal juxta-articular bone is altered in Rheumatoid Arthritis (RA). However, a detailed analysis of disease related geometrical adaptations of the metacarpal shaft is missing. The aim of the present study was to assess the role of RA disease, forearm muscle cross-sectional area (CSA), age and sex on bone geometry at the metacarpal shaft. METHODS:: In 64 RA patients and 128 control subjects geometric properties of the third metacarpal bone mid-shaft and forearm muscle CSA were measured by peripheral quantitative computed tomography (pQCT). Linear models were performed for cortical CSA, total bone CSA, polar stress-strain Index (polar SSI, a surrogate for bone's resistance to bending and torsion), cortical thickness and Metacarpal Index (MI=cortical CSA/total CSA) with explanatory variables muscle CSA, age, RA status and sex. RESULTS:: Forearm muscle CSA was associated with cortical and total metacarpal CSA, and polar SSI. RA group status was associated with all bone parameters except cortical CSA. There was a significant interaction between RA status and age, indicating that the RA group had a greater age-related decrease in cortical CSA, cortical thickness and MI. CONCLUSIONS:: Bone geometry of the metacarpal shaft is altered in RA patients compared to healthy controls. While bone mass of the metacarpal shaft is adapted to forearm muscle mass, cortical thickness and MI are reduced but outer bone shaft circumference and polar SSI increased in RA patients. These adaptations correspond to an enhanced aging pattern in RA patients.

Age at hip or knee joint replacement surgery predicts likelihood of revision surgery

We compared revision and mortality rates of 4668 patients undergoing primary total hip and knee replacement between 1989 and 2007 at a University Hospital in New Zealand. The mean age at the time of surgery was 69 years (16 to 100). A total of 1175 patients (25%) had died at follow-up at a mean of ten years post-operatively. The mean age of those who died within ten years of surgery was 74.4 years (29 to 97) at time of surgery. No change in comorbidity score or age of the patients receiving joint replacement was noted during the study period. No association of revision or death could be proven with higher comorbidity scoring, grade of surgeon, or patient gender. We found that patients younger than 50 years at the time of surgery have a greater chance of requiring a revision than of dying, those around 58 years of age have a 50:50 chance of needing a revision, and in those older than 62 years the prosthesis will normally outlast the patient. Patients over 77 years old have a greater than 90% chance of dying than requiring a revision whereas those around 47 years are on average twice as likely to require a revision than die. This information can be used to rationalise the need for long-term surveillance and during the informed consent process.

18F-fluorodeoxyglucose uptake of bone and soft tissue sarcomas in pediatric patients

A high (18)F-fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT) imaging in sarcomas of adults has been reported. The current study aimed at defining the degree of (18)F-FDG uptake of pediatric sarcomas. This retrospective study included 29 patients (23 males, 6 females; mean age 14 ± 5 years) with soft tissue (n = 9) or bone (n = 20) sarcomas. Twenty-two patients (76%) underwent (18)F-FDG PET/CT and 7 (24%) had dedicated (18)F-FDG PET studies. Tumor (18)F-FDG uptake was quantified by standard uptake value (SUV)(max) and tumor-to-liver ratios (SUV ratios; tumor SUV(max)/liver SUV(mean)). Tumor SUV(max) and SUV ratios were correlated with tumor Ki-67 expression. SUV(max) ranged from 1.4 to 24 g/mL (median 2.5 g/mL) in soft tissue sarcomas and 1.6 to 20.4 g/mL (median 6.9 g/mL) in bone sarcomas (P = .03), and from 1.6 to 9.2 g/mL (median 3.9 g/mL) and 3.5 to 20.4 g/mL (median 12 g/mL) in Ewing sarcoma and osteosarcoma, respectively (P = .009). Tumor SUV ratios ranged from 0.8 to 8.7 (median 1.9) in soft tissue sarcomas and 1.4 to 8.9 (median 3.8) in bone sarcomas (P = .08). Ewing sarcoma had a significantly lower tumor SUV ratio than osteosarcoma (P = .01). Ki-67 expression correlated significantly with the (18)F-FDG uptake in bone but not in soft tissue sarcomas. All sarcomas were visualized by (18)F-FDG PET/CT imaging. A higher (18)F-FDG uptake was observed in osteosarcoma than in Ewing and soft tissue sarcomas. The results of this study suggest that the degree of tumor (18)F-FDG uptake is sufficient to allow for monitoring of therapeutic responses in pediatric sarcomas.